ROCHESTER, Minn. — Mayo Clinic researchers have identified an immune-regulating molecule that may help explain why some patients with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, do not respond to commonly used therapies. The findings, published in Cell Reports, describe a previously uncharacterized role for the molecule ST8Sia6 in regulating immune activity in the gut.

In preclinical models, researchers found that the absence of ST8Sia6 led to a marked increase in inflammatory immune cells in the intestines. The results suggest the molecule plays a key role in maintaining immune balance and may represent a distinct biological pathway from those targeted by existing treatments.

IBD affects nearly 3 million people in the United States, and its prevalence continues to rise. While the source of IBD is not known, researchers believe it may occur due to a combination of genetic and environmental factors. Recently introduced medications target a pro-inflammatory molecule known as TNF-alpha to reduce the autoimmune response in the intestines and help with symptoms such as diarrhea, bloating and bloody stools, but the treatment is not effective in all patients.

Discovering the role of the enzyme ST8Sia6 has provided the research team with a new view of IBD. "The normal function of ST8Sia6 in the gut had not been previously described," says Mayo Clinic immunology researcher Virginia Shapiro, Ph.D., principal investigator of the study. "We found ST8Sia6 regulates the abundance of immune cells and keeps them in the steady state of homeostasis. When the molecule is not present or even is reduced, the presence of inflammatory immune cells increases dramatically."

An intriguing enzyme in the immune system

The study of ST8Sia6 and its interactions with the immune system extend recent discoveries in Dr. Shapiro's research lab. Her team previously showed that ST8Sia6, an enzyme that adds sugar molecules to cell surfaces, enables a tumor to evade destruction by the immune system. The lab also found that ST8Sia6 can be used as a tool to help reduce the body's autoimmune attack on insulin-producing beta cells, as occurs in diabetes.

The leap to gastrointestinal disease occurred when the team noticed on an international database that a single mutation in the gene for ST8Sia6 turns up with greater frequency in people with Crohn's disease.

"The ST8Sia6 molecule is expressed pretty widely in different immune cells, but we weren't sure of its connection to this disease which involves chronic inflammation," says Sydney Crotts, a graduate student at Mayo Clinic Graduate School of Biomedical Sciences and first author of the study.

The team looked at preclinical models that lacked the ST8Sia6 gene. In the models, an abundance of immune cells gathered in the small intestine. The team also found that lower ST8Sia6 led to increased levels of messenger molecules that prompt an immune response. Together, the attributes increased susceptibility to intestinal inflammation.

"We think this might be a model of what's happening in patients with Crohn's disease who have a baseline of immune cells and are basically fine until they encounter a trigger and have a flare," says Crotts. She notes that the inflammation did not abate with TNF-alpha medication, suggesting this pathway may be distinct.

The study illuminates yet another action of ST8Sia6 on the immune system and presents a new avenue that may help IBD treatment. Further studies will be necessary to move the discovery toward the clinic.

"These findings mean researchers have an approach to better understand the source of TNF-resistant Crohn's disease, the pathways and molecules involved, and now may be able to develop additional ways to intervene to treat this disease," Crotts says.

For a complete list of authors, disclosures and funding, review the study.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

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• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

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ROCHESTER, Minn. — Mayo Clinic and Stanford Medicine researchers have developed the first blood test to map the complex ecosystem surrounding cancer cells, offering a more accurate way to predict which patients will benefit from immunotherapy. Their study's findings, published in Nature, represent a major advance in precision oncology and could help guide treatment decisions across multiple cancer types and treatments.

"This is a complete paradigm shift," says Aadel Chaudhuri, M.D., Ph.D., professor of radiation oncology at Mayo Clinic and co-senior author of the study. "Until now, liquid biopsies or blood tests have focused almost entirely on tumor cells. For the first time, we can use a simple blood test to understand the tumor's microenvironment, which is critical for determining how patients respond to modern cancer therapies."

Capturing and mapping the tumor environment

Immunotherapy has transformed cancer care, but only for some patients. Current tools used to predict tumor response, such as testing for the number of DNA mutations in a tumor and the levels of certain proteins on a cancer cell, aren't able to capture the level of detail needed.  

"One of the challenges is that these existing methods only have modest associations," Dr. Chaudhuri says. "They're essentially 'surrogates of surrogates' and don't fully capture what's happening inside the tumor environment."

To address this gap, the research team posed the question: Can a better readout of the tumor microenvironment be developed from a liquid biopsy of a patient's blood?

To start their investigation, they turned to spatial transcriptomics, an advanced technique that maps how different cells interact within a tumor. By analyzing tumor samples, they identified nine distinct cellular neighborhoods, or spatial ecotypes, each representing a unique immune and stromal (the noncancerous cells and structures surrounding the tumor) environment.

"Almost like geographic mapping, we were able to map where in the tumor microenvironment these neighborhoods of co-associated cells live," Dr. Chaudhuri explains. All 17 tested cancer types share these neighborhoods; some are more likely to occur at the border of the tumor and healthy tissue, while others were more likely found deeper inside the tumor. "Then, we showed that certain neighborhoods, or spatial ecotypes, are associated with survival and immunotherapy response outcomes."

Using AI to develop a simple blood test

To identify these tumor neighborhoods, the team collaborated with Aaron Newman, Ph.D., associate professor of biomedical data science at Stanford Medicine and co-senior author of the study. Newman's team developed methods to define these neighborhoods from tumor samples and an artificial intelligence (AI) framework to detect them in blood.

Using methylation — chemical markings on DNA that help control gene activity — on cell-free DNA shed by tumors into the bloodstream, the researchers created a liquid biopsy test that details the tumor microenvironment beyond its cancer cells. This means a blood draw, not an incision, is all it takes to profile the tumor's spatial ecotypes.

"This is the first time we've been able to noninvasively profile the tumor microenvironment at this level," says Dr. Chaudhuri.

In studies involving more than 1,300 patients across multiple cancers, including melanoma, lung, bladder and gastric cancers, specific spatial ecotypes were strongly associated with treatment outcomes. Certain ecotypes are predicted to respond positively to immunotherapy, while others were linked to treatment resistance and poorer survival. Standard biomarkers showed inferior predictive power.

Improving treatment decisions and avoiding side effects

The ability to predict immunotherapy response before starting treatment could have an immediate clinical impact.

Cancer therapy can be time-consuming and carry significant side effects. Identifying patients unlikely to benefit from immunotherapy could allow clinicians to choose more effective alternate therapies sooner.

"If a patient isn't going to respond, that's time we could be using a different treatment," Dr. Chaudhuri says. "Better upfront decision-making can directly improve outcomes."

Importantly, finding likely resistance to an immunotherapy is not necessarily bad news. It may help guide patients toward different treatments better suited to their tumor biology, further guided by the patient's personalized spatial ecotype profile.

Tracking cancer progress in real time

Because the test is blood-based, it also opens the door to ongoing monitoring of how a patient's tumor microenvironment evolves during treatment.

In early data, researchers observed that changes in spatial ecotypes could signal treatment response or resistance months before traditional imaging can.

"This gives us a window into how the tumor microenvironment is changing over time," says Dr. Chaudhuri. "We've never been able to see that before in a practical way."

Broadening the approach across cancers and other diseases

While the initial study focused primarily on patients with melanoma, the approach shows promise across many cancers, including lung cancer and bladder cancer, where treatment decisions are complex and time sensitive. The research team has new data beyond the published study showing the ability to predict complete responses to antibody drug conjugate (ADC)-based combination therapy. Researchers also believe the technology-assisted approach could eventually extend beyond cancer testing and treatment.

"This is not just about cancer," Dr. Chaudhuri says. "It could provide insights into a wide range of diseases by helping us understand complex biological environments in the body."

Further studies are underway to validate the test in larger patient populations and move it into clinical use. Researchers are also exploring how different tumor microenvironment patterns may predict response to other therapies beyond immunotherapy.

"This work opens up an entirely new way of thinking about disease," Dr. Chaudhuri says. "We've essentially uncovered a world that was invisible to us before — and now we can access it with a simple blood test."

Aadel Chaudhuri, M.D., Ph.D., has patent filings related to liquid biopsy and cancer biomarkers, and has ownership interests in Droplet Biosciences and LiquidCell Dx. Aaron Newman, Ph.D., has patent filings related to digital cytometry, liquid biopsy and cancer biomarkers. He has served as a consultant to, and has ownership interests in, CiberMed and LiquidCell Dx.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

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• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

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In a laboratory at Mayo Clinic, a machine that looks strikingly similar to a desktop printer is quietly reshaping the future of dermatology. Instead of ink, it dispenses living human cells. Instead of paper, it builds tissue — layer by layer — replicating one of the body's most complex organs: skin.

For Saranya Wyles, M.D., Ph.D., a dermatologist and researcher at Mayo Clinic, the journey into 3D bioprinting began not with an ambitious plan to reinvent tissue engineering, but with a practical problem. Her team needed a better way to test new therapies.

"We were trying to find a preclinical model to develop an FDA application," Dr. Wyles explains. Traditional approaches rely heavily on animal testing, but skin biology varies widely across species. Even commonly used preclinical models fall short when it comes to mimicking human skin conditions such as eczema.

At the same time, alternatives such as donated human skin samples — often surgical waste — can only survive for a few days in the lab. That limitation makes it difficult to study chronic diseases or long-term treatment effects.

Faced with these constraints, Dr. Wyles and her team asked a bold question: What if they could build human skin from scratch?

From printer to patient-specific model

The answer took shape through 3D bioprinting, an emerging technology that uses "bioinks" — mixtures of living cells and supportive materials — to construct tissues.

The concept sounds deceptively simple. Much like a standard printer uses different color cartridges, a bioprinter uses different cell types. In the case of skin, that includes fibroblasts, keratinocytes and melanocytes — the essential building blocks of the dermis and epidermis layers of the skin.

But translating that concept into living tissue proved anything but simple. Early attempts produced structures that looked nothing like real skin. "It was like a cartoon version," Dr. Wyles recalls. "Not even close."

What followed was nearly a year of intensive troubleshooting, bringing together clinicians, biomedical engineers and tissue engineers in a collaborative effort. The challenge wasn't just printing cells — it was keeping them alive, functional and organized.

Each cell type has its own needs, from nutrients to mechanical conditions. "It's like roommates," Dr. Wyles says. "They all want different things."

The team had to design new culture systems, optimize materials and even fine-tune the physical "stretch" of the printed tissue to mimic natural skin. These details matter. Skin's elasticity affects everything from wound healing to itch and aging. Gradually, iteration by iteration, the model improved.

Building skin, layer by layer

Today, the process resembles a carefully choreographed construction project. First, the printer lays down the dermis — the deeper layer of skin — using fibroblasts embedded in a collagen scaffold. After several days of maturation, the epidermis is printed on top, forming the outer protective layer.

The result is a structured tissue that mirrors key features of human skin, including stratified layers and pigment-producing cells. Crucially, the model uses entirely human-derived components, including a plant-based recombinant collagen that avoids the variability and immune risks associated with animal-derived materials.

The printed tissue can survive for weeks — far longer than traditional skin explants — allowing researchers to study disease progression and treatment responses over time. And because it's printed, it can be replicated with remarkable consistency.

"No two preclinical models are exactly the same," Dr. Wyles notes. "But we can print hundreds of nearly identical samples."

Improving how therapies are tested

The implications of this technology extend far beyond the lab bench. Preclinical testing has long been a cornerstone of drug development, yet it remains an imperfect predictor of how therapies will perform in humans — nearly 90% of drugs that succeed in preclinical testing ultimately fail in clinical trials.

Bioprinted human skin models offer a promising alternative — one that is not only more biologically relevant, but also faster, more scalable and more ethical.

"From both an ethical and a financial standpoint, the difference is enormous," Dr. Wyles says.

Regulators are beginning to take notice. The Food and Drug Administration has already engaged with the Mayo Clinic team on the technology, reviewing data demonstrating that the printed skin can replicate both the structure and function of human tissue.

That includes side-by-side comparisons of patient skin and lab-grown models, showing similar cellular architecture and biological responses. As a result, the model has been recognized as a promising alternative in certain preclinical contexts — potentially reducing the need for large animal studies.

Toward personalized and precision dermatology

Beyond its applications in preclinical research, the technology opens the door to a more personalized approach to medicine. Researchers are now developing ways to create patient-specific "maps" of skin by analyzing biopsies at a molecular level. These maps capture everything from cell distribution to markers of aging, such as cellular senescence.

Using this information, the team can program the bioprinter to recreate an individual's skin in the lab.

"We can essentially print your skin based on your own biological blueprint," Dr. Wyles says.

That capability could transform how treatments are developed and tested — allowing scientists to evaluate therapies on models that reflect specific patients, populations or conditions. It also has implications for studying aging, pigmentation and diseases such as atopic dermatitis, which can vary widely across individuals and skin types.

Expanding complexity

The current models represent a significant advance, but they are only the beginning. Human skin is a highly complex organ, responsible not just for protection, but also for sensation, temperature regulation and immune function. To more fully replicate that complexity, the Mayo team is working to add new features to their printed tissues.

Future versions may include blood vessels, immune cells and nerve structures — elements that would enable even more realistic modeling of disease and drug response. Researchers also are developing pigmented models to better represent diverse skin tones, addressing a long-standing gap in dermatologic research.

"Skin of color is an area where we need better models," Dr. Wyles says.

From innovation to impact

As interest in the technology grows, so does demand. Pharmaceutical and cosmetic companies are already exploring collaborations, drawn by the potential to accelerate product development while reducing reliance on animal testing.

To meet that demand, Mayo Clinic is working to scale the technology through collaborations and licensing, while continuing to refine the science.

At the same time, Dr. Wyles is mindful of the broader mission.

"We want to democratize this," she says. "The goal is to make it accessible so more people can use it, test more therapies and ultimately get treatments to patients faster."

A new frontier in regenerative medicine

The potential applications extend well beyond drug testing. Bioprinted skin could one day be used in regenerative medicine — for example, creating grafts for burn victims or patients with chronic wounds. It may also serve as a platform for studying aging and developing interventions to improve skin health over time.

For now, the focus remains on refining the models and expanding their capabilities.

"We're really just at the beginning of what this platform can do," Dr. Wyles says.

The post 3D-bioprinted human skin model expands options for preclinical research appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Research from Mayo Clinic is helping refine how multiple myeloma is diagnosed and treated, with findings that support more personalized therapies and identify promising immunotherapy strategies for aggressive forms of the disease.

The research led by Sikander Ailawadhi, M.D., Shaji Kumar, M.D., Akhilesh Pandey, M.D., Ph.D., and Richard Kandasamy, Ph.D. in the Mayo Clinic Comprehensive Cancer Center, focuses on tailoring treatment based on disease biology and improving outcomes for patients living longer with the cancer.

Treating multiple myeloma as a chronic disease

Multiple myeloma, a blood cancer that affects plasma cells in the bone marrow, can cause abnormal proteins to accumulate and damage organs. At Mayo Clinic, patients with multiple myeloma receive tailored treatment that varies from person to person based on how the disease develops and progresses.

Care strategies continue to evolve, including immunotherapy and clinical trials that study the most effective order to use available treatments. One approach uses monoclonal antibodies given in sequence to better target cancer cells and improve outcomes for patients whose disease has returned.

"We take into account the risks, but also what the patients' wants, needs and aspirations are, and make a decision about treatment that brings all this together," says Dr. Ailawadhi, a hematologist and oncologist. "Much has been learned about the best use of novel treatments such as CAR-T and other immunotherapy approaches."

New immunotherapy strategies show promise

In one area of research, Dr. Kumar, a hematologist, and colleagues published a study in the New England Journal of Medicine showing that an off-the-shelf dual-antibody immunotherapy can produce deep and durable responses in extramedullary multiple myeloma, a form of the disease with historically limited treatment options.

"We are seeing powerful responses in a disease that historically has resisted every therapy," says Dr. Kumar.

The approach uses two engineered antibodies to engage T cells through separate immune pathways, directing an immune response against myeloma cells. The treatment is administered in a standard infusion setting, in contrast to more complex cell therapies.

In early results, a majority of patients responded to the treatment, and many achieved no detectable disease, suggesting a potential new option for patients with resistant disease.

Seeing what standard tests miss

Understanding the full genetic profile of multiple myeloma remains a key challenge in care.

Dr. Pandey, a clinical pathologist in Laboratory Medicine and Pathology, and Dr. Kandasamy, a systems biologist, are collaborating with other researchers to study a potential new approach to defining the disease. Multiple myeloma is driven by changes in chromosomes that affect prognosis and treatment decisions. Standard testing uses fluorescence in situ hybridization, or FISH, which looks for specific known changes but may not capture the full picture.

A newer method, Genomic Proximity Mapping (GPM), analyzes a patient's entire genome. It can identify structural changes, gains or losses of genetic material and complex rearrangements, including high-risk features. In early studies, GPM confirmed results from standard testing and identified additional clinically important changes.

"This approach could improve risk assessment and help doctors choose treatments that are better tailored to each individual," says Dr. Pandey.

Researchers are now studying GPM testing in larger patient groups and exploring its use in other cancers.

“Beyond multiple myeloma, GPM can identify complex and hidden genetic changes. This means it could be useful across many types of cancer and help give a clearer picture of each person’s disease,” says Dr. Kandasamy.

Looking ahead toward precision care

As multiple myeloma care continues to evolve, new therapies will expand options for resistant disease and advances in testing will help guide treatment decisions. Comprehensive tools such as Genomic Proximity Mapping (GPM) may further refine risk assessment and support earlier, more precise care for patients.

Other clinical trials are evaluating the benefits of earlier use of immunotherapies in treatment and improved supportive care.

While multiple myeloma is considered treatable but not curable, these developments may help extend survival and improve quality of life, with a growing subset of patients achieving long-term remission.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

The post Improving how multiple myeloma is understood and treated appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — In a study published in the Journal of Heart and Lung Transplantation Open (JHLT Open), Mayo Clinic researchers found that remote patient monitoring (RPM) is a feasible and effective way to detect early health changes and support care decisions for lung transplant recipients during their first year after discharge from the hospital.

Lung transplant recipients require intensive, ongoing monitoring after transplant to detect complications such as rejection or infection.

"Many of these patients live far from the transplant center, making frequent in-person follow-up challenging," says Cassie Kennedy, M.D., co-senior author and medical director of the lung transplant program at Mayo Clinic in Rochester. "In recent years, we have transplanted patients from 25 states, including Hawaii. RPM allows us to stay closely connected to our patients — no matter where they live — after they return home and respond quickly when changes occur."

While remote patient monitoring has shown benefits in other patient populations, evidence in lung transplant recipients has been limited.

Throughout the 12-month study, researchers monitored 116 lung transplant recipients who lived a median distance of 234 miles from Mayo Clinic in Rochester. Patients used a home device kit to track symptoms and physiological data, including lung function, vital signs and weight, with results transmitted to their electronic health record and care team.

When abnormal values were detected, alerts were generated and reviewed by the clinical team to determine next steps. In total, nearly 470 alerts were triggered during the study. Most alerts were managed with continued monitoring, while about 1 in 4 prompted changes in care, including earlier clinic visits, diagnostic testing, medication adjustments or emergency evaluation.

"Just as important, when no abnormalities are detected, patients can be reassured and remain at home," says Dr. Kennedy.

Nearly half of hospitalizations among patients with available monitoring data were preceded by an RPM alert within the prior week, suggesting the system may help identify early signs of clinical deterioration and support earlier intervention.

"This study shows that a multiparameter, at-home monitoring approach can be successfully implemented in a high-risk population and generate actionable data to support clinical care," says Ali El Mokahal, M.D., first author and pulmonary and critical care medicine fellow at Mayo Clinic.

In addition to supporting earlier detection, the program demonstrated strong patient participation and ease of use. Of the 116 patients enrolled, only 15 discontinued participation during the study period.

"These findings provide important real-world evidence supporting the use of remote patient monitoring in lung transplant recipients," says Kelly Pennington, M.D., co-senior author and pulmonologist in the Division of Pulmonary and Critical Care Medicine at Mayo Clinic. "As these models evolve, they have the potential to transform how we deliver transplant care — expanding access, reducing burden and improving outcomes for patients."

The team will continue to monitor RPM program participants while exploring opportunities to expand this approach across Mayo Clinic sites and transplant programs.

For a complete list of authors, review the study.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

About Mayo Clinic Transplant Center
Mayo Clinic Transplant Center is one of the largest and most comprehensive transplant programs in the world. With programs in Arizona, Florida and Minnesota, Mayo Clinic provides seamless, coordinated care across adult heart, lung, liver, kidney and pancreas transplantation. Guided by a commitment to innovation, research and education, Mayo Clinic Transplant Center delivers world-leading outcomes, compassionate patient care and advances that shape the future of transplantation worldwide.

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• Kelley Luckstein, Mayo Clinic Communications, newsbureau@mayo.edu

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ROCHESTER, Minn. — A Mayo Clinic-developed artificial intelligence (AI) model can help specialists detect pancreatic cancer on routine abdominal CT scans up to three years before clinical diagnosis. It identifies subtle signs of disease before tumors are visible, when curative treatment may still be possible. The findings, published in Gut, mark a milestone in Mayo Clinic's multiyear research effort to enable earlier detection of one of the deadliest cancers.

The study validates this next-generation AI model using data and workflows that mirror clinical practice, including CT scans from multiple institutions, imaging systems and protocols.

Researchers used the AI model to analyze nearly 2,000 CT scans, including scans from patients later diagnosed with pancreatic cancer — all originally interpreted as normal. The system, called the Radiomics-based Early Detection Model (REDMOD), identified 73% of those prediagnostic cancers at a median of about 16 months before diagnosis — nearly double the detection rate of specialists reviewing the same scans without AI assistance.

The advantage was even greater at earlier time points. In scans obtained more than two years before diagnosis, the AI identified nearly three times as many early cancers that would otherwise go undetected.

Pancreatic cancer remains one of the deadliest cancers because it rarely causes detectable signs in its earliest stages. More than 85% of patients receive a diagnosis after the disease has already spread, and five-year survival rates remain below 15%, according to the National Cancer Institute. Projections show it will become the second-leading cause of cancer-related death in the U.S. by 2030.

"The greatest barrier to saving lives from pancreatic cancer has been our inability to see the disease when it is still curable," says Ajit Goenka, M.D., the study's senior author, and a Mayo Clinic radiologist and nuclear medicine specialist. "This AI can now identify the signature of cancer from a normal-appearing pancreas, and it can do so reliably over time and across diverse clinical settings." 

REDMOD measures hundreds of quantitative imaging features that describe tissue texture and structure, capturing faint biological changes as cancer begins to develop. The model is designed to analyze CT scans already obtained for other reasons — particularly in high-risk patients, such as those with new-onset diabetes — and flag elevated risk before any visible mass appears. 

The model runs automatically without time-intensive manual preparation. The team validated the model across CT scans from multiple institutions, imaging systems and protocols, demonstrating consistent performance beyond a single dataset.

The model's predictions also remained stable over time. In patients with multiple scans, the AI produced consistent results months apart, supporting its use for longitudinal monitoring and early detection. 

"This AI can now identify the signature of cancer from a normal-appearing pancreas, and it can do so reliably over time and across diverse clinical settings."  - Dr. Ajit Goenka

Researchers are advancing this work into clinical testing through Artificial Intelligence for Pancreatic Cancer Early Detection, or AI-PACED. This prospective study evaluates how clinicians can integrate AI-guided detection into care for patients at elevated risk. The study combines AI analysis of routine imaging with longitudinal follow-up to assess performance, including early detection, false positives and clinical outcomes. 

This research is part of Mayo Clinic's Precure initiative, which aims to predict and prevent disease by identifying the earliest biological changes in the body before symptoms begin. It also reflects Mayo Clinic's Clinical Impact strategy, accelerating the translation of discovery into patient care. 

The study was supported by the National Institutes of Health, the Hoveida Family Foundation, the Mayo Clinic Comprehensive Cancer Center and the Champions for Hope Pancreas Cancer Research Program of the Funk-Zitiello Foundation. 

For a complete list of authors, disclosures and funding, review the study. 

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About Mayo Clinic  
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.  

About Mayo Clinic Comprehensive Cancer Center  
Designated as a comprehensive cancer center by the National Cancer Institute, Mayo Clinic Comprehensive Cancer Center is defining the cancer center of the future, focused on delivering the world's most exceptional patient-centered cancer care for everyone. At Mayo Clinic Comprehensive Cancer Center, a culture of innovation and collaboration is driving research breakthroughs in cancer detection, prevention and treatment to change lives. 

Media contact:   

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu  

The post Mayo Clinic AI helps specialists detect pancreatic cancer up to 3 years before diagnosis in landmark validation study appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Mayo Clinic researchers have developed a blood-based method that may help detect germ cell tumors, the most common type of testicular cancer, including cases that do not show up on standard blood tests, according to a study published in Nature Communications.

Testicular cancer most often affects adolescents and young adults, and it is highly treatable, especially when found early. However, diagnosis can be challenging when tumors do not produce enough of the usual blood-based substances — called tumor markers — to show up on standard tests, which can make diagnosis harder.

To help solve this, researchers used a method that analyzes thousands of immune system signals in the blood at once. Using this approach, they developed a new test called GCT-iSIGN. In a study of 427 blood samples, the test identified 93% of individuals who had germ cell tumors and correctly ruled out cancer in 99% of people who did not. The test also detected 23 of 24 cases that standard blood tests missed. This gives doctors another way to find these cancers, especially in younger patients.

Researchers also developed a second test, called Sem-iSIGN, designed to distinguish between two main types of testicular cancer. This distinction matters because each type can require a different treatment approach.

The findings build on earlier work by the same research teams using immune profiling to identify biomarkers linked to paraneoplastic neurologic syndrome associated with testicular cancer, including KLHL11 IgG, which was described previously in The New England Journal of Medicine.

"When standard blood markers are negative, diagnosis and treatment planning can be delayed," says Divyanshu Dubey, M.B.B.S., senior and corresponding author of the study and a professor of laboratory medicine and pathology and a professor of neurology at Mayo Clinic. "Our findings show a promising path toward a more sensitive blood test approach, but additional studies are needed before it can be used routinely in patient care."

Co-first authors are M. Bakri Hammami, M.D., and Andrew M. Knight, Ph.D. Funding included support from the Department of Defense, as well as institutional and federal sources.

Mayo Clinic has a financial interest in the technology referenced in this news release. Any revenue received will be used to support Mayo Clinic's not‑for‑profit mission in patient care, education and research.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

The post Blood test shows promise for detecting testicular cancer when standard markers miss appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — A Mayo Clinic study found that both metabolic and bariatric surgery and GLP-1 medications improve cardiovascular health in people with obesity, but surgery was associated with significantly greater reductions in long-term cardiovascular risk. The findings were published in Annals of Surgery.

The study is a direct comparison of two leading obesity treatments, evaluating how each approach affects overall risk of cardiovascular disease.

"Both treatments are effective, but surgery appears to provide a greater reduction in long-term cardiovascular risk, especially when it leads to larger and more sustained weight loss," says Wissam Ghusn, M.D., a Mayo Clinic research collaborator and first author of the study.

Researchers analyzed outcomes for 812 adults with obesity, including 579 who underwent metabolic and bariatric surgery and 233 who received GLP-1 medications.

Key findings:

• Lifetime cardiovascular risk decreased more with surgery (declining 8.6% versus 1.7%).
• Weight loss was significantly greater with surgery, averaging nearly 28% of total body weight compared with about 11% among those treated with medications.

Obesity is a major contributor of heart disease, stroke and diabetes, making effective treatment critical for long-term health. While GLP-1 medications have gained attention for their role in weight management, the findings highlight differences in how treatment options may affect long-term outcomes.

Importantly, researchers say the findings are not about choosing one treatment over another, but about better aligning treatment decisions with long-term health goals.

"This study reinforces that obesity treatment should be viewed as a strategy to reduce cardiovascular risk, not just body weight," says Omar Ghanem, M.D., a metabolic surgeon and chair of the Division of Metabolic and Abdominal Wall Reconstructive Surgery at Mayo Clinic in Rochester. "It supports a more individualized, patient-centered approach where treatment decisions are based on long-term health impact."

The study also found that greater weight loss was closely linked to larger reductions in lifetime cardiovascular risk, particularly among patients who lost more than 20% of their body weight after surgery.

The findings may encourage earlier and more balanced discussions about treatment options, including considering surgery as a front-line option for some patients, rather than a last resort, while continuing to support the growing role of effective medications.

"Rather than thinking of these treatments as competing options, we should view them as complementary tools," says Dr. Ghanem. "Both surgery and medications play important roles in reducing long-term cardiovascular risk, and the right approach depends on the individual patient."

Researchers note that longer-term studies are needed to evaluate clinical outcomes such as heart attacks, strokes and survival, as well as the durability of medication-based therapies and the potential benefits of combining surgical and medical approaches.

For a complete list of authors, disclosures and funding, review the study.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Terri Malloy, Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic study finds bariatric surgery associated with greater long-term heart risk reduction than weight-loss medications  appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Subtle biological changes linked to Alzheimer’s disease may begin as early as the late 50s — decades before memory loss or other symptoms appear — according to new research from Mayo Clinic.

The study, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, maps when key brain and blood-based changes tend to accelerate across the lifespan, offering new insight into when detection and prevention efforts could have the greatest impact.

Alzheimer's disease, the most common form of dementia, affects about 6.9 million people in the U.S. aged 65 and older. It involves abnormal changes in proteins such as amyloid and tau that can begin years before symptoms, and it is associated with cognitive decline. There currently is no cure.

Mayo Clinic researchers identified when these changes tend to occur throughout the lifespan. Earlier detection can give patients and families more time to plan, to access care and to benefit from treatments that may slow progression.

Using data from 2,082 participants in the long-running Mayo Clinic Study of Aging, researchers analyzed a wide range of measures — including blood biomarkers, brain imaging and cognitive performance — to identify when Alzheimer’s-related changes begin to speed up.

"This population-based study provides an integrated view of age-related patterns across multiple Alzheimer's biomarkers measured in blood and imaging, plus cognition," says Mingzhao Hu, Ph.D., assistant professor in Mayo Clinic's Department of Quantitative Health Sciences and first author of the study. "By estimating the ages when changes in health markers become more noticeable, the results show that many of these shifts tend to happen from late 50s through early 70s."

The future of detecting Alzheimer's

"As Alzheimer’s research shifts toward prevention and earlier treatment, blood biomarkers will play a central role in identifying who is best suited for these therapies,” says Jonathan Graff-Radford, M.D., chair of Behavioral Neurology at Mayo Clinic and senior author of the study. "Knowing when these biomarkers start to change, and when they relate to cognitive impairment, helps point us to the ages when prevention screening could have the greatest impact."

Researchers found that many Alzheimer's-related biomarkers show that changes begin to accelerate at specific ages.

Measurable declines in cognitive performance were seen to accelerate in people who are in their late 50s, followed by more rapid amyloid accumulation in the brains of people in their early 60s — pointing to an early 60s window when cognitive and amyloid changes become more pronounced. The buildup of amyloid-beta proteins that clump together to form plaques in the brain is a primary hallmark of the disease.

By the late 60s to early 70s, biomarkers of tau pathology and neurodegeneration show more pronounced increases. Several blood-based markers — including plasma GFAP, NfL and p-tau — show steeper changes around ages 68 to 72, alongside more evident brain atrophy, particularly in memory-related regions. Two broad windows emerged, around the early 60s for cognition and amyloid PET, and around the late 60s to early 70s for several blood and neurodegeneration markers, highlighting these key transitional periods in the aging process.

Moving toward earlier detection 

Understanding the timeline of Alzheimer's disease progression could be critical for shifting care from late-stage treatment to earlier detection and prevention. Researchers point out that the findings reflect overall population trends, rather than precise predictions for any one individual. However, they offer direction for future research, including examining whether these "breakpoints" can predict cognitive decline, confirming the results in more diverse populations and tracking individuals over time to better understand how the disease progresses.

The results of the study also reinforce the growing role of blood tests in Alzheimer's research and care. These tests showed patterns similar to brain imaging, suggesting they could be used to monitor disease-related changes over time and identify people at higher risk.

"When you think about population screening, the critical issue is timing,” says Dr. Graff‑Radford. “You don’t want to start too early, before biomarkers change, and this work provides a way to begin addressing that," adds Dr. Graff-Radford.

The work also helps inform research into screening and monitoring by identifying age ranges when blood tests may be most informative. Additionally, several of the blood marker patterns were consistent across two commonly used laboratory platforms, supporting that the findings are not tied to a single assay. 

This research is part of a broader effort at Mayo Clinic known as the Precure initiative. It focuses on developing tools to help clinicians detect and address disease-related changes earlier, before symptoms appear or conditions become harder to treat.

For a complete list of authors, disclosures and funding, review the study.

Benefactor support for the Mayo Clinic Study of Aging included Duncan Alexander, Gates Ventures and the GHR Foundation.

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About Mayo Clinic
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Media contact:

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu

The post At what age does Alzheimer’s disease begin? Mayo Clinic study points to changes decades before symptoms appeared first on Mayo Clinic News Network.

Momentum is growing in the fight against amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two devastating neurological diseases now understood to be closely connected. At Mayo Clinic, researchers and clinicians are turning scientific breakthroughs into progress for patients and their families.

Watch: Dr. Bjorn Oskarsson explains work of ALS researchers

Journalists: Broadcast-quality soundbites are available for download at the end of this post. Please courtesy: "Mayo Clinic."

ALS, also known as motor neuron disease and Lou Gehrig's disease, affects nerves, leading to progressive weakness and loss of movement. FTD is a group of brain disorders that affect behavior, personality and language. Although these related conditions usually occur separately, they can occur together and pose significant challenges for patients and families.

While effective treatments remain limited, new approaches are emerging. Patients can receive supportive care to improve quality of life and extend survival, and recent advances include therapies for some genetic forms of ALS. These developments are making diagnostic testing increasingly important to identify potentially treatable causes.

Tools to diagnose ALS

Diagnosis of ALS typically includes a physical exam, medical history and electromyography (EMG), a specialized test of muscles and nerves that detects lower motor neuron degeneration. Mayo Clinic physicians are also using newer tools to improve detection.

"We now have an added blood test, neurofilament light, which is good at detecting ALS," says Bjorn Oskarsson, M.D., a neurologist and director of the ALS Clinic at Mayo Clinic in Florida. "The test measures a nerve protein that leaks into the blood and is significantly elevated in patients with this disease. Another test uses advanced imaging to detect a marker of upper motor neuron degeneration, allowing earlier diagnosis in some patients."

With ultra-high-resolution 7-Tesla MRI imaging, physicians and scientists can identify upper motor neuron degeneration in many people with ALS and help distinguish the disease from similar conditions. These tools, combined with genetic testing, help clinicians make more accurate diagnoses.

Research

Artificial intelligence shows promise in helping patients achieve greater independence. As ALS progresses, patients may lose the ability to speak. Voice-cloning technology recreates a person's voice from a previous recording, helping them continue communicating with loved ones through speaking devices.

This progress builds on a pivotal scientific discovery: In 2011, Mayo Clinic researchers helped discover that ALS and FTD can share a common underlying genetic cause, the C9orf72 mutation. This finding showed that the two conditions are part of a disease spectrum and transformed both research and clinical care. Neurogeneticist Rosa Rademakers, Ph.D., who was on the Mayo Clinic faculty from 2005 to 2019, received the 2026 Breakthrough Prize in Life Sciences for this discovery during her research at Mayo Clinic. She continues to collaborate with colleagues as a supplemental consultant in the Department of Neurosciences at Mayo Clinic.

Mayo Clinic researchers are developing new therapies that target the genetic and biological drivers of ALS and FTD. Clinical trials are underway that focus on treating the underlying disease mechanisms rather than symptoms alone.

Advances in genetic sequencing are providing new insights. Technologies that can read long stretches of DNA are allowing scientists to study the C9orf72 mutation in greater detail. Research led by Marka van Blitterswijk, M.D., Ph.D., a neuroscientist at Mayo Clinic in Florida, shows that variations in the length of this genetic repeat are linked to when symptoms begin, how quickly the disease progresses and the buildup of harmful proteins in the brain.

"It is a very exciting time to investigate ALS and FTD," says Dr. Van Blitterswijk. "New advances in genetic sequencing now enable us to look at the DNA and RNA at unprecedented resolution, creating tantalizing opportunities that will undoubtedly uncover novel causes, as well as much-needed biomarkers and therapeutic strategies for these debilitating diseases in the foreseeable future."

Researchers are also using advanced RNA analysis to better understand how genes function in diseased brain tissue. These findings could lead to earlier diagnosis and new treatments.

Additional research led by Wilfried Rossoll, Ph.D., a Mayo Clinic neuroscientist, is focused on proteins involved in disease progression. In ALS and FTD, a protein called TDP-43 forms clumps within brain cells. This pathology can disrupt essential functions, such as the cell's internal transport system, which can lead to cell damage or death. Mayo Clinic researchers have found that another protein, KPNB1, may help break apart these clumps and restore normal cell function.

Researchers are also working to identify additional genetic factors that influence ALS risk and progression. This work may improve understanding of neurodegenerative diseases and support the development of more precise clinical trials and targeted therapies.

A deeper understanding of ALS and FTD may lead to earlier intervention, more personalized care and improved outcomes for patients and families.

 Related:

• Mayo-clinic-researcher-awarded-breakthrough-prize-for-ALS-dementia-gene-discovery
• Florida dad receives first-in-world ALS treatment
• Mayo Clinic awarded federal grant to study experimental ALS drug
• Mayo researchers, collaborators affirm useful blood biomarker for group of brain disorders in new study

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