Research advances from the National Institutes of Health (NIH) Intramural Research Program (IRP) often make headlines. Read the news releases that describe our most recent findings:
BETHESDA, Md. (AP) — Sam Srisatta, a 20-year-old Florida college student, spent a month living inside a government hospital here last fall, playing video games and allowing scientists to document every morsel of food that went into his mouth.
From big bowls of salad to platters of meatballs and spaghetti sauce, Srisatta noshed his way through a nutrition study aimed at understanding the health effects of ultraprocessed foods, the controversial fare that now accounts for more than 70% of the U.S. food supply. He allowed The Associated Press to tag along for a day.
“Today my lunch was chicken nuggets, some chips, some ketchup,” said Srisatta, one of three dozen participants paid $5,000 each to devote 28 days of their lives to science. “It was pretty fulfilling.”
Examining exactly what made those nuggets so satisfying is the goal of the widely anticipated research led by National Institutes of Health nutrition researcher Kevin Hall.
“What we hope to do is figure out what those mechanisms are so that we can better understand that process,” Hall said.
NIH clinical trial results expand treatment options for this disease
Results from a large clinical trial show that treatment with an immunotherapy drug may nearly double the length of time people with high-risk, muscle-invasive bladder cancer are cancer-free following surgical removal of the bladder. Researchers found that postsurgical treatment with pembrolizumab (Keytruda), which is approved by the Food and Drug Administration (FDA) for treating at least 18 different cancers, was superior compared with observation. The study, led by researchers at the National Institutes of Health (NIH), was published Sept. 15, 2024, in New England Journal of Medicine.
“This study shows that pembrolizumab can offer patients another treatment option to help keep their disease from coming back,” said lead investigator Andrea B. Apolo, M.D., of NIH’s National Cancer Institute (NCI) Center for Cancer Research. “Extending the time that these patients are cancer-free makes a big difference in their quality of life.”
A diagnosis of muscle-invasive bladder cancer means the tumor in the bladder has invaded into and through the muscular layer of tissue that encases the bladder. The standard treatment for this form of bladder cancer is to surgically remove the entire bladder. To improve the chances of successful surgery and of eliminating any cancer cells that may have already escaped from the tumor, patients are given cisplatin-based chemotherapy for a period before surgery, known as neoadjuvant therapy, or after surgery, known as adjuvant therapy.
Adjuvant pembrolizumab helps people with muscle-invasive bladder cancer remain cancer free longer than with observation alone.
Increased risk among men in disadvantaged neighborhoods may be linked to chronic stress
West African genetic ancestry was associated with increased prostate cancer among men living in disadvantaged neighborhoods but not among men living in more affluent neighborhoods, according to a new study led by researchers at the National Institutes of Health (NIH). The findings suggest that neighborhood environment may play a role in determining how genetic ancestry influences prostate cancer risk. The study was published Sept. 16, 2024, in JAMA Network Open.
In the United States, most Black Americans have West African genetic ancestry, the researchers noted. Previous studies have shown that West African genetic ancestry is linked to increased prostate cancer risk among Black men, whose risk is higher than that of any other U.S. population group. However, it is unclear whether additional factors play a role in determining this ancestry-related risk.
To explore how the neighborhood environment and West African genetic ancestry may act together in influencing prostate cancer risk, researchers at NIH’s Center for Cancer Research at the National Cancer Institute (NCI) conducted a study with long-term follow-up that included 1,469 self-identified Black and White men from the greater Baltimore area. The researchers determined the men’s West African ancestry through genetic markers and neighborhood socioeconomic status through factors such as unemployment rate, income level, and percentage of households in poverty.
Study finds that sickle cell trait is prevalent among diverse human populations
National Institutes of Health (NIH) researchers and collaborators have found that being a carrier for sickle cell disease, known as having sickle cell trait, increases the risk of blood clots, a risk that is the same among diverse human populations that may not traditionally be associated with sickle cell disease. The study provides estimated clinical risks for people with sickle cell trait, which can inform clinical practice guidelines. Researchers examined the largest and most diverse set of people with sickle cell trait to date, which includes data from over 19,000 people of various ancestral backgrounds with sickle cell trait.
The study, published in Blood Advances, was led by researchers at the National Human Genome Research Institute (NHGRI), part of NIH, The Johns Hopkins University School of Medicine, Baltimore, and the company 23andMe, South San Francisco, California.
Previous research investigating the relationship between sickle cell trait and blood clots have only included individuals of African genetic ancestry and self-identified Black participants because of the incorrect assumption that the genetic carrier state only affects those who identify as Black or African American. While sickle cell trait in the United States is most prevalent in individuals who self-identify as Black or African American, individuals from all ancestral backgrounds may have sickle cell trait. Sickle cell trait is often found in individuals living in or from West and Central Africa, Mediterranean Europe, India and the Middle East.
“Because sickle cell trait is often associated with people who identify as Black or African American, it is not widely studied in other populations, a bias that has led to unintended harm for those with sickle cell trait,” says Vence Bonham Jr., J.D., who co-led the study and serves as acting deputy director and associate investigator at NHGRI. “In particular, the racialization of sickle cell trait has resulted in biased estimations of health risks. The results of our study will help clinicians properly contextualize the risk of blood clots amongst people with sickle cell trait without unintended bias.”
NIH study finds lung function remained stable or improved in adults after transplant.
So-called low-intensity blood stem cell transplants, which use milder conditioning agents than standard stem cell transplants, do not appear to damage the lungs and may help improve lung function in some patients with sickle cell disease (SCD), according to a three-year study of adults who underwent the procedure at the National Institutes of Health (NIH).
Damage to lung tissue and worsened lung function is a major complication and leading cause of death in people with sickle cell disease, a debilitating blood disorder. The new study, published today in the Annals of the American Thoracic Society, helps answer whether less intensive types of transplants, which tend to be better tolerated by many adults, by themselves either cause or promote further harm to the lungs.
“By using a low-intensity blood stem cell transplant for sickle cell disease, we may be able to stop the cycle of lung injury and prevent continued damage,” said study lead Parker Ruhl, M.D., an associate research physician and pulmonologist at NIH. “Without the ongoing injury, it’s possible that healing of lung tissue might occur, and this finding should help reassure adults living with sickle cell disease who are considering whether to have a low-intensity stem cell transplant procedure that their lung health will not be compromised by the transplant.”
Approach could have role in preventing malaria in pregnancy
Two National Institutes of Health (NIH)-supported trials of an experimental malaria vaccine in healthy Malian adults found that all three tested regimens were safe. One of the trials enrolled 300 healthy women ages 18 to 38 years who anticipated becoming pregnant soon after immunization. That trial began with drug treatment to remove malaria parasites, followed by three injections spaced over a month of either saline placebo or the investigational vaccine at one of two dosages. Both dosages of the vaccine candidate conferred a significant degree of protection from parasite infection and clinical malaria that was sustained over a span of two years without the need for a booster dose—a first for any malaria vaccine. In an exploratory analysis of women who conceived during the study, the vaccine significantly protected them from malaria in pregnancy. If confirmed through additional clinical trials, the approach modeled in this study could open improved ways to prevent malaria in pregnancy.
Spread by Anopheles mosquitoes, malaria parasites, including those of the species Plasmodium falciparum (Pf), can cause illness in people of any age. However, pregnant women, infants and very young children are especially vulnerable to life-threatening disease. Malarial parasitemia in pregnancy is estimated to cause up to 50,000 maternal deaths and 200,000 stillbirths in Africa each year.
The trials were co-led by investigators from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and the University of Sciences, Techniques and Technologies, Bamako (USTTB), Mali. The investigational vaccine used in both trials was PfSPZ Vaccine, a radiation-attenuated vaccine based on Pf sporozoites (a stage of the parasite’s lifecycle), manufactured by Sanaria Inc., Rockville, Maryland. Multiple previous clinical trials of PfSPZ Vaccine have shown it to be safe, including in malaria-endemic countries such as Mali. In results published in 2022, for example, an NIAID-sponsored, placebo-controlled trial of a three-dose regimen of PfSPZ Vaccine in Burkina Faso found that the vaccine had up to 46% efficacy that lasted at least 18 months.
NIH researchers find that large language models rely on concise, textbook-like language to evaluate medical questions
National Institutes of Health (NIH) researchers discover that while artificial intelligence (AI) tools can make accurate diagnoses from textbook-like descriptions of genetic diseases, the tools are significantly less accurate when analyzing summaries written by patients about their own health. These findings, reported in the American Journal of Human Genetics, demonstrate the need to improve these AI tools before they can be applied in health care settings to help make diagnoses and answer patient questions.
The researchers studied a type of AI known as a large language model, which is trained on massive amounts of text-based data. These models have the potential to be very helpful in medicine due to their ability to analyze and respond to questions and their often user-friendly interfaces.
“We may not always think of it this way, but so much of medicine is words-based,” said Ben Solomon, M.D., senior author of the study and clinical director at the NIH’s National Human Genome Research Institute (NHGRI). “For example, electronic health records and the conversations between doctors and patients all consist of words. Large language models have been a huge leap forward for AI, and being able to analyze words in a clinically useful way could be incredibly transformational.”
Researchers at the National Institutes of Health’s (NIH) Clinical Center and the National Heart, Lung and Blood Institute have developed and tested a new imaging method that will allow specific detection of Aspergillus fumigatus fungal infections in a timely manner in the future, without the need for invasive procedures. Delays in diagnosing fungal infections caused by Aspergillus and other fungi can put immunocompromised patients at risk for more serious illnesses or even death.
Due to their presence in the environment, many fungi evolved to use other sources of fuel besides glucose, such as by breaking down complex sugars into simple ones to produce energy. Aspergillus can break down a specific sugar, cellobiose, into two glucose molecules, while most other microbes and human cells cannot. The researchers developed a radioactive version of cellobiose which when injected in the blood, it can be visualized in the body using positron emission tomography (PET) scanners.
In this study, radioactive cellobiose ([18F]-Fluorocellobiose, [18F]-FCB) was injected in mice with fungal infections which were then imaged using a specialized PET scanner for small animals. The mice showed accumulation of radioactivity, while mice with bacterial infections or with noninfectious inflammation did not.
NIH researchers have developed and tested a new imaging method that will allow specific detection of Aspergillus fumigatus fungal infections.
While the overall numbers remain low, the findings spotlight the need to identify and help those at risk
Researchers at the National Institutes of Health (NIH) found that rates of preteen suicide (ages 8-12) have been increasing by approximately 8 percent annually since 2008. These increases were most pronounced among female preteens, American Indian/Alaska Native or Asian/Pacific Islander preteens, and Hispanic preteens. While the overall number of preteen suicides is small compared to teen and adult populations, the researchers say the findings from this analysis underscore the need for age-appropriate and culturally responsive prevention efforts that include suicide risk screening and lethal means safety counseling. The findings also highlight the need to better understand, identify, and help preteens who may be at risk for suicide.
Researchers from the National Institutes of Health (NIH) have discovered the source of dysfunction in the process whereby cells in the eye's retina remove waste.
A report by scientists at NIH and Johns Hopkins University, Baltimore, details how alterations in a factor called AKT2 affects the function of organelles called lysosomes and results in the production of deposits in the retina called drusen, a hallmark sign of dry age-related macular degeneration (AMD). According to the researchers, the findings suggest drusen formation is a downstream effect of AKT2-related lysosome dysfunction and points to a new target for therapeutic intervention.
Lysosomes are like cells' garbage disposals, and they play a crucial role in maintaining the eye's light-sensing retina. Key cells that make up the retinal pigment epithelium (RPE) provide oxygen and nutrients to the retina's energetically active neurons. They also collect and processes the retina’s waste products through lysosomes. Failure in the cells’ ability to process these waste products leads to the formation of drusen. As AMD progresses, drusen increase in number and volume. But despite intensive research, drusen formation is still largely a mystery.
AI model scored well on medical diagnostic quiz, but made mistakes explaining answers
Researchers at the National Institutes of Health (NIH) found that an artificial intelligence (AI) model solved medical quiz questions — designed to test health professionals’ ability to diagnose patients based on clinical images and a brief text summary — with high accuracy. However, physician-graders found the AI model made mistakes when describing images and explaining how its decision-making led to the correct answer. The findings, which shed light on AI’s potential in the clinical setting, were published in npj Digital Medicine. The study was led by researchers from NIH’s National Library of Medicine (NLM) and Weill Cornell Medicine, New York City.
“Integration of AI into health care holds great promise as a tool to help medical professionals diagnose patients faster, allowing them to start treatment sooner,” said NLM Acting Director, Stephen Sherry, Ph.D. “However, as this study shows, AI is not advanced enough yet to replace human experience, which is crucial for accurate diagnosis.”
The AI model and human physicians answered questions from the New England Journal of Medicine (NEJM)’s Image Challenge. The challenge is an online quiz that provides real clinical images and a short text description that includes details about the patient’s symptoms and presentation, then asks users to choose the correct diagnosis from multiple-choice answers.
GPT-4V, an AI model, often made mistakes when describing the medical image and explaining its reasoning behind the diagnosis — even in cases where it made the correct final choice.
