Mayo Clinic expert explains why it is important to act before perimenopause

JACKSONVILLE, Fla. — Weight gain is common in women during perimenopause and after menopause, but the physical changes underlying it start much earlier in adulthood. Daniela Hurtado Andrade, M.D., Ph.D., an endocrinologist and obesity expert at Mayo Clinic in Jacksonville, explains why it is important to start counteracting those changes before perimenopause arrives.  

"Weight changes are not only characteristic of midlife or menopause. Data have shown that weight gain starts early in adulthood," Dr. Hurtado says. "Around age 30, your muscle mass starts decreasing gradually as part of the natural aging process, and this is exacerbated in midlife due to menopause."

The decreasing muscle mass will lead to a lower metabolism, a risk factor for weight gain, Dr. Hurtado says.

Adding to the challenge of achieving a healthy weight before and after menopause are many of the features of modern life, Dr. Hurtado says. For example, an abundance of processed foods high in sugar and fat; technology such as escalators, elevators and cars that allows people to move from place to place without walking; and the difficulty of unplugging from devices that keep people connected to work and sedentary for longer hours, with less time spent on physical activity. 

Being aware that weight-related physical changes start earlier than midlife may help people be mindful about the importance of establishing and maintaining a healthy lifestyle, including adequate diet and exercise (at least 150 minutes per week), well ahead of menopause, Dr. Hurtado says. It may help to track what and how much you eat, to understand how much you need to eat to feel satisfied and avoid overeating, she adds.

To mitigate muscle mass loss that occurs with aging, a healthy diet should include enough protein and exercise should include resistance training and possibly high-intensity interval training, Dr. Hurtado says.  

"And this is even more important if we are engaging in a weight-loss intervention because we know that weight-loss interventions are also associated with muscle mass loss, which can have a significant impact on the weight-loss outcomes," she says. "One of the reasons why we hit a plateau when we are losing weight is because we are losing muscle mass and our metabolism slows down."

While a healthy lifestyle is essential, it may only get someone so far in pursuit of a healthy weight, Dr. Hurtado says. The body is genetically programmed to survive, so losing weight is perceived as  negative and our bodies will try to fight it. Some people can sustain low-calorie diets for a period of time and lose weight, but eventually they may start feeling hungry, eating more and gaining weight.

"As soon as some people even think about losing weight or restricting their calories, their brain overrides those thoughts: 'No, you're actually hungry, so you're going to eat as much as you need to make sure that you do not lose weight,'" Dr. Hurtado says. "There is a proportion of people in whom diet and exercise alone will work, but for the majority, they will not due to the complex regulation of energy balance."

Many people who live with overweight or obesity will need a tool such as a medication, an endoscopic bariatric procedure or bariatric surgery to help them achieve sustained weight loss, Dr. Hurtado says. In addition to nutritional and behavioral support, they also may benefit from physical therapy or occupational therapy to help them find ways to become physically active, she adds.

In the early 40s, and perhaps even earlier, it is important for women and their healthcare team to start discussing aging-related weight changes that are happening and will happen, Dr. Hurtado says.

"Every visit with a doctor is an opportunity, especially in these times when overweight and obesity are so highly prevalent," she says. "We want to prevent rather than treat something that may be more difficult to treat for several reasons. Lifestyle interventions are the core of all weight management interventions. While we need to understand that there is no magic pill, there are tools that can facilitate adhering to lifestyle changes."

Dr. Hurtado emphasizes that obesity is a disease.

"Starting the conversation about weight management with that message may help people have a different perspective: 'OK, so they are talking about something that is not my fault, but actually has a biological basis,'" Dr. Hurtado says. "Realizing that weight problems are a disease and not a character flaw can help them think about it differently and could be very impactful on the outcomes of weight loss interventions."

###

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:

• Sharon Theimer, Mayo Clinic Communications, newsbureau@mayo.edu

The post Aging-related weight gain in women: It may start earlier in life than you think appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — A multidisciplinary surgical team at Mayo Clinic has successfully treated an exceptionally rare and life-threatening cancer that invaded a patient's heart and airway. The procedure combined advanced cardiac surgery with complex airway reconstruction and represents a significant achievement in modern cancer care. 

Tami Channel's thyroid cancer was so advanced that her family had begun planning hospice care. The tumor had severely compromised her airway and had encased her carotid artery and jugular vein, two of the body's most vital blood vessels.  

Primary cancers of the heart are extremely rare. Most tumors that appear in the heart are benign, and malignant cardiac tumors such as sarcomas account for only a small fraction of all cancers. Airway tumors involving the throat or trachea are also uncommon and often detected late because early symptoms can resemble routine respiratory issues. When a malignant growth extends into both the heart and the airway, the risks multiply quickly because the tumor can narrow or block breathing passages and interfere with the heart's ability to function. 

Faced with a tumor that had grown into vital structures and left the patient's airway nearly the width of a toothpick, the care team, including Mabel Ryder, M.D., a Mayo Clinic endocrinologist, and Eric Moore, M.D., a Mayo Clinic head and neck surgeon, recognized that conventional treatment would not be enough. Tami needed a highly complex surgery — and it needed to happen quickly. As a matter of priority, Tami would undergo an unscheduled thoracotomy and bypass, an emergency open-chest operation that requires opening the chest cavity, supporting circulation through a heart-lung machine, and working around critical airways and blood vessels. Few hospitals could coordinate such a demanding procedure so quickly. 

"We were able to make it happen because it needed to be done," Dr. Moore says. "That's the Mayo difference." 

The operating room reflected Mayo's integrated model: anesthesiology, perfusion, bronchoscopy, cardiothoracic surgery, and head and neck surgery, with each discipline contributing seamlessly. 

"It felt like a choreographed ballet," Dr. Moore says. "This kind of multidisciplinary precision doesn't just happen — it's the Mayo model in action." 

During the same operation, specialists reconstructed the airway to restore safe breathing. Procedures of this complexity rely on close coordination among cardiac surgeons, thoracic and airway surgeons, ear, nose and throat specialists, anesthesiologists, oncologists, and critical care teams. Mayo Clinic Comprehensive Cancer Center experts are uniquely positioned to manage these cases because they can move quickly from diagnosis to complex surgery and recovery. 

This successful intervention shows what is possible when specialists collaborate on rare cancers that cross organ systems.  

### 

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 integrated care enables treatment for rare, complex cancer      appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — As rates of obesity, high blood pressure, type 2 diabetes and sleep apnea increase, cases of advanced chronic liver disease and resulting liver scarring or cirrhosis also are rising. Patients often are diagnosed based on symptoms, such as gastrointestinal bleeding, fluid retention or jaundice, which happen when liver disease has progressed to a late stage. This problem led Mayo Clinic researchers to develop an artificial intelligence (AI) model that resulted in twice the number of advanced chronic liver disease diagnoses in patients without symptoms, helping physicians treat them before the disease had progressed.

"Chronic liver disease is a progressive condition, so the sooner we can diagnose it, the sooner we can stop it from advancing to irreversible stages. Early intervention may decrease the likelihood that a patient will need a liver transplant in the future," says Doug Simonetto, M.D., a Mayo Clinic transplant hepatologist and lead author of the study published in Nature Medicine.

The heart and liver are closely linked. Liver scarring may lead to increased local pressure that can affect the heart. As a result, a heartbeat test called an electrocardiogram (ECG) can capture electrical signal changes in the heart connected to advanced liver disease. Dr. Simonetto and colleagues developed an AI model to analyze data from 11,513 Mayo Clinic patients undergoing routine ECGs. The model looked for patterns connected to advanced liver disease in the ECG data, and it found twice the number of patients who were diagnosed by standard methods. The diagnosis was confirmed by validated imaging or blood tests.

"As a family physician, I've often seen how advanced liver disease — which frequently has no symptoms until it becomes irreversible — can go undetected," says David Rushlow, M.D., Mayo Clinic Health System family physician and study co-author. "Many patients identified through the AI-ECG model had no idea they were living with advanced liver disease. By identifying these cases earlier, we were able to connect them to the right treatment — at a time when intervention can truly make a difference. For these patients, the technology helped us not only to uncover a diagnosis, it created an opportunity for better health outcomes and, in some cases, may have saved lives."

In this randomized clinical trial, 248 clinicians at Mayo Clinic in Rochester and throughout the Mayo Clinic Health System participated.

"The idea that a simple, noninvasive and inexpensive test could help identify patients at risk of developing advanced liver disease was very compelling. This study provided an opportunity to evaluate AI in our real-world clinical environment, where the true test of innovation is whether it improves care for patients in the community," says Dr. Rushlow. "We're only beginning to understand the full potential of AI-enabled tools like this and the promise they hold for preventive, personalized care."

In the next steps, the researchers will follow up with the patients, who were newly diagnosed with advanced liver disease, over the next two years.

The research is part of a larger effort at Mayo Clinic called the Precure initiative focused on developing tools that empower clinicians to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions.

Review the study for a complete list of authors, disclosures and funding.  

### 

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:

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

The post Mayo Clinic researchers develop AI-ECG model to diagnose liver disease earlier appeared first on Mayo Clinic News Network.

These discoveries reflect progress across three major innovation efforts at Mayo Clinic. Mayo Clinic clinicians and scientists are working together to develop tools to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions through the Precure initiative. They are advancing new cures for end-organ failure beyond traditional transplantation as part of the Genesis initiative. They are also uniting clinical insight with cutting-edge engineering to deliver novel neurological diagnostics and therapies through the Bioelectronics Neuromodulation Innovation to Cure (BIONIC) initiative. 
 

1. 'Virtual clinical trials' may predict success of heart failure drugs 

Mayo Clinic researchers have created "virtual clinical trials" that advance the discovery of therapies while reducing time, cost and the risk of failed studies by combining advanced computer modeling with real-world patient data as part of the Precure and Genesis initiatives. Through one virtual clinical trial, they have developed a new way to predict whether existing drugs could be repurposed to treat heart failure, one of the world's most pressing health challenges. 

"Clinical trials will always remain essential," says Cui Tao, Ph.D., the Nancy Peretsman and Robert Scully Chair of Artificial Intelligence and Informatics and vice president of Mayo Clinic Platform Informatics. "But this innovation demonstrates how AI can make research more efficient, affordable and broadly accessible. Integrating trial emulation, simulation, synthetic trials and biomedical knowledge modeling opens the door to a new paradigm in translational science." 

2. New discovery may unlock regenerative therapies for lung disease

Mayo Clinic researchers have uncovered the molecular "switch" that directs a small but powerful set of cells that choose whether to repair tissue or fight infection, a discovery that could inform regenerative therapies for chronic lung diseases, which is part of Mayo Clinic's Genesis initiative.
 
"We were surprised to find that these specialized cells cannot do both jobs at once," says Douglas Brownfield, Ph.D., senior author of the study. "Some commit to rebuilding, while others focus on defense. That division of labor is essential — and by uncovering the switch that controls it, we can start thinking about how to restore balance when it breaks down in disease." 

3. Stem cells may offer new hope for end-stage kidney disease treatment

Mayo Clinic researchers found that injecting patients' own stem cells from fat cells into the vein before hemodialysis, a treatment for end-stage kidney disease, often helped prevent inflammation and vein narrowing. This could help millions of people tolerate dialysis longer, extending the time before they require a kidney transplant as part of the Mayo Clinic Genesis initiative. 

"This approach has the potential to improve outcomes for millions of patients with kidney failure, reduce healthcare costs and inform new clinical guidelines for dialysis access management if validated in larger clinical trials," says Sanjay Misra, M.D., a Mayo Clinic interventional radiologist. 

4. Mayo Clinic physicians map patients' brain waves to personalize epilepsy treatment

Using detailed maps of each patient's unique brain wave patterns, Mayo Clinic physicians can now pinpoint where stimulation is most effective, moving beyond the traditional one-size-fits-all approach to epilepsy treatment. This research is part of the BIONIC initiative.

"The long-term goal is to quiet the seizure network, so it is eventually forgotten. Reorganizing the neuronal network could move us beyond controlling seizures to actually curing epilepsy," says Nick Gregg, M.D., a Mayo Clinic neurologist. 

5. New genetic biomarker flags aggressive brain tumors

Mayo Clinic researchers found when meningiomas — the most common type of brain tumor — show activity in a gene called telomerase reverse transcriptase (TERT), it tends to recur more quickly, even if it looks low grade under the microscope. This is part of the Mayo Clinic Precure initiative. 

"High TERT expression is strongly linked to faster disease progression," says Gelareh Zadeh, M.D., Ph.D., a neurosurgeon at Mayo Clinic and senior author of the study. "This makes it a promising new biomarker for identifying patients who may be at greater risk of developing aggressive disease."

6. Mayo Clinic researchers discover the immune system's 'fountain of youth'

Mayo Clinic researchers have found that some older people maintain "immune youth" – a new term coined by Mayo researchers to explain a young immune system in someone over age 60.  
 
"We observed that these patients have very young immune systems despite being in their 60s and 70s. But the price they pay for that is autoimmunity," says Cornelia Weyand, M.D., Ph.D., a Mayo Clinic rheumatologist and clinician-scientist. This is part of the Mayo Clinic Precure initiative.

7. Mayo Clinic tools predict, identify and diagnose Alzheimer's, dementia quicker

Mayo Clinic researchers have developed new tools to estimate a person's risk of developing Alzheimer's disease years before symptoms appear as part of the Precure initiative and to help clinicians identify brain activity patterns linked to nine types of dementia, including Alzheimer's disease, using one scan. They also confirmed the accuracy of an FDA-approved blood test that can be used at outpatient memory clinics to diagnose the disease in patients with a range of cognitive impairment. 

"Every patient who walks into my clinic carries a unique story shaped by the brain's complexity," says David T. Jones, M.D., a Mayo Clinic neurologist. "That complexity drew me to neurology and continues to drive my commitment to clearer answers."

8. Mayo Clinic research improves dense breast cancer screening and early detection

Nearly half of all women in the U.S. have dense breast tissue, which can make detecting breast cancer difficult with a mammogram. Mayo Clinic researchers found that adding another test, called molecular breast imaging, or MBI, to a 3D mammogram, improved the ability to find cancer in dense tissue by more than double. 
 
"Our research focuses on detecting the most lethal cancers, which can include invasive tumors that grow quickly. If these are detected earlier, we likely can save more lives," says Carrie Hruska, Ph.D., a Mayo Clinic professor of medical physics and lead author of the study. 

9. Mayo Clinic researchers find 'sugar coating' cells can protect those typically destroyed in type 1 diabetes

After identifying a sugar molecule that cancer cells use on their surfaces to hide from the immune system, Mayo Clinic researchers have found the same molecule may eventually help in the treatment of type 1 diabetes, once known as juvenile diabetes. 

"A goal would be to provide transplantable cells without the need for immunosuppression," says Virginia Shapiro, Ph.D., a Mayo Clinic immunology researcher. "Though we're still in the early stages, this study may be one step toward improving care."

10. New study calculates autoimmune disease prevalence

Mayo Clinic researchers and collaborators have described — for the first time — the prevalence of autoimmune diseases in the U.S. Their research reports that about 15 million people are estimated to have one or more of 105 autoimmune diseases. The study also found that autoimmune diseases occur most often in women, and it identified the top autoimmune diseases by prevalence, sex and age. 
 
"Knowing the number of patients with an autoimmune disease in the U.S. is critical to assess whether these diseases are increasing or decreasing over time and with treatment," says DeLisa Fairweather, Ph.D., vice-chair of translational research for the Department of Cardiovascular Medicine at Mayo Clinic in Florida and corresponding author of the study.

### 

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 A Year of Discovery: 10 Mayo Clinic research breakthroughs moving medicine forward  appeared first on Mayo Clinic News Network.

JACKSONVILLE, Fla. — A new multicenter study led by Mayo Clinic researchers has established a practical, evidence-based definition for rapidly progressive dementia (RPD), a rare but devastating form of cognitive decline that develops over months instead of years. The findings, published in Neurology, the medical journal of the American Academy of Neurology, may help clinicians recognize and treat RPD earlier, and enable researchers to work from a shared framework when studying the condition.

While most types of dementia progress gradually, RPD advances with alarming speed, often leading to significant cognitive decline or death within one to two years. Although it accounts for around 4% of dementia cases, RPD is difficult to diagnose. Symptoms can stem from numerous causes, including autoimmune disease, infections, neurodegenerative disorders such as Alzheimer's disease and rare conditions like Creutzfeldt-Jakob disease. This makes it challenging to consistently define the disorder across different settings.

"Clinicians need a clear, standardized way to identify patients whose decline is unusually fast," says Gregg Day, M.D., a behavioral neurologist at Mayo Clinic and senior author of the study. "This helps ensure that those with potentially treatable causes are recognized quickly, wherever they are seen. Furthermore, this is a necessary step before launching multicenter studies aimed at understanding why a small subset of dementia patients progresses rapidly and how to address this through clinical trials and treatments."

The new definition proposed by Dr. Day and his colleagues uses the Clinical Dementia Rating (CDR) scale, a well-established tool for assessing dementia severity. Criteria are based on the level of functional impairment involving memory, orientation, judgment, problem-solving, community affairs, home and hobbies, and personal care. Under the new framework, a person is considered to have rapidly progressive dementia if they develop mild dementia (CDR score of 1 or higher) within one year of symptom onset, or moderate-to-severe dementia (CDR score of 2 or higher) within two years. Researchers refer to this as the "1-in-1 or 2-in-2" rule.

To test this definition, the research team applied it to two large datasets. The first, known as the RaPID cohort, included 248 patients evaluated for suspected RPD at Mayo Clinic in Florida and Washington University in St. Louis. The second used data from the National Alzheimer's Coordinating Center, representing more than 19,000 participants across 46 research centers in the United States.

In the RaPID group, about 75% of patients met the new criteria. Nearly 1 in 3 had autoimmune or inflammatory causes — many of which are potentially reversible. In the broader national dataset, about 4% met the definition for RPD, with Alzheimer's disease being the most common underlying cause. Across both groups, people who met the RPD definition declined 3 to 4 times faster than those with typical dementia, based on changes measured using the CDR scale.

The new definition proved reliable across clinical and research settings, identifying both rare and common causes of RPD. It can be applied using a patient's clinical history instead of specialized testing, making it adaptable in diverse healthcare settings, including those with limited medical resources.

"By uniformly defining rapid progression, we can better identify patients who might benefit from treatment, improve consistency in research, and ultimately enhance care for people facing one of the most challenging forms of dementia," Dr. Day says.

For a complete list of authors, disclosures and funding, see the paper.

Related:

• Mayo Clinic researchers to study causes of rapidly progressive dementia
• Researchers identify new criteria to detect rapidly progressive dementia

###

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:

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

The post New Mayo-led study establishes practical definition for rapidly progressive dementia appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Mayo Clinic researchers have developed a smartwatch-based alert system that signals parents at the earliest signs of a tantrum in children with emotional and behavioral disorders — prompting them to intervene before it intensifies.  

In a new study published in JAMA Network Open, these alerts helped parents intervene within four seconds and shortened severe tantrums by an average of 11 minutes — about half the duration seen with standard therapy.  

In this system, a smartwatch worn by the child detects physiological stress signals, such as rising heart rate, or changes in movement or sleep, and sends them to an artificial intelligence (AI)-enabled app on the parent's smartphone. The app analyzes the data in real time and sends an alert as a cue for the parent to connect with their child. 

The findings demonstrate how smartwatch technology can help bridge a gap in pediatric mental healthcare by giving parents actionable support when professional help isn't immediately available. That need is widespread — nearly 1 in 5 U.S. children has a mental, behavioral or emotional health disorder, according to the Centers for Disease Control and Prevention.  

The approach shows how wearable technology, paired with patient-centric AI design, can support families beyond the clinic. 

Study design and results 

In the randomized clinical trial, 50 children aged 3 to 7 receiving Parent-Child Interaction Therapy at Mayo Clinic participated over 16 weeks. Half were assigned to use the smartwatch system, and half continued standard therapy. The study evaluated whether families would use the technology as intended and whether immediate alerts could measurably change parent response times and children's behavior. 

Notably, children wore the smartwatch for about 75% of the study period, demonstrating feasibility and family engagement. 

"This study shows that even small, well-timed interventions can change the trajectory of a child's emotional dysregulation episode," says Magdalena Romanowicz, M.D., a Mayo Clinic child psychiatrist who co-led the study. "These moments give parents a chance to step in with supportive actions — moving closer, offering reassurance, labeling emotions and redirecting attention before a tantrum intensifies." 

Building on earlier research 

This work builds on the team's earlier study, which used a machine learning algorithm to analyze smartwatch data — including heart rate, sleep and movement — to predict disruptive behaviors in hospitalized children receiving psychiatric care. 

That study, published in the Journal of Child and Adolescent Psychopharmacology, showed the algorithm could predict a child's behavioral state with 81% accuracy and provided a 30- to 60-minute advance warning of an impending outburst. 

"This work shows how basic science and clinical research can come together to transform patient care," says Arjun Athreya, Ph.D., who co-led the study and serves on the engineering faculty in Mayo Clinic's Department of Molecular Pharmacology and Experimental Therapeutics. "We've translated inpatient findings to outpatient care, and the results show how data from everyday smart devices can help families in real time." 

Empowering families with data-driven care 

Paul Croarkin, D.O., a Mayo Clinic child and adolescent psychiatrist and study co-author, says the findings highlight the power of data-driven care. "A smartwatch may seem simple, but when it's backed by evidence-based treatments and advanced analytics, it becomes a lifeline for families trying to manage severe behavioral symptoms at home."  

Julia Shekunov, M.D., medical director of Mayo Clinic's Child and Adolescent Psychiatry Inpatient Unit and also a study co-author, says the work addresses an urgent need. "We're seeing more children in crisis, and the severity is increasing. This system gives parents tools they can use immediately, even outside the clinic, to help their child regain control." 

Next steps 

Future studies will refine the system's predictive accuracy, test it in larger groups and assess its long-term benefits in routine outpatient care. 

This study was funded in part by a Mayo Clinic Clinical Trial Stimulus Fund and Mayo Clinic's Center for Individualized Medicine. For a complete list of authors, disclosures and funding, review the study.    

### 

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 smartwatch system helps parents shorten and defuse children’s severe tantrums early  appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Mayo Clinic researchers have uncovered how aging "zombie cells" trigger harmful inflammation that accelerates a severe and increasingly common form of fatty liver disease called metabolic dysfunction-associated steatohepatitis (MASH). As obesity rates rise worldwide, MASH is projected to increase and is already one of the leading causes of liver transplantation. 

"Liver scarring and inflammation are hallmarks of MASH. If left untreated, it can progress to liver cancer. This is why it's so important to understand the mechanisms driving the disease so that we can prevent it or develop more effective treatments," says Stella Victorelli, Ph.D., who is the lead author of the study published in Nature Communications.  

Dr. Victorelli and colleagues, who study aged or senescent "zombie" cells, identified a mechanism by which these cells drive liver scarring and inflammation. They found that small molecules called mitochondrial RNA, typically found within the cell's energy-producing mitochondria, can leak into the main part of the cell, where they mistakenly activate antiviral sensors called RIG-I and MDA5 — normally triggered when a virus infects a cell. In this case, the danger signal comes from the cell's own mitochondria, prompting a wave of inflammation that can damage nearby healthy tissue. 

When the researchers blocked the sensors, inflammation dropped sharply. The study also found that proteins BAX and BAK, which help open pores in the mitochondrial membrane, enable mitochondrial RNA to escape. In a preclinical MASH model, inhibiting BAX and BAK prevented RNA from escaping and was associated with less inflammation and healthier liver tissue. 

What are 'zombie' cells?

As we age, some cells enter senescence — a state in which they stop dividing but continue releasing inflammatory and tissue‑damaging molecules. When people are young, the immune system typically eliminates these senescent, or "zombie," cells. With age, however, they can persist and contribute to a range of age‑related health problems and diseases. 

While some research focuses on removing these cells, this team investigated how to quiet their harmful signals.  

"With age, we accumulate 'zombie' cells, which can lead to more disease," says João Passos, Ph.D., senior author of the study. "Our idea is that if we can quiet these cells earlier, we can prevent runaway inflammation and the development of many age‑related conditions, including liver disease. Understanding the mechanisms that drive disease allows us to target and delay those processes — potentially benefiting more than one condition." 

Dr. Passos and colleagues also are developing new technology to spatially map senescent cells throughout the body during aging. 

This research was conducted in partnership between the Robert and Arlene Kogod Center on Aging and the Center for Cell Signaling in Gastroenterology (C-SiG) at Mayo Clinic. 

The research is part of a larger effort at Mayo Clinic called the Precure initiative, which is focused on developing tools that empower clinicians to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions. 

Review the study for a complete list of authors, disclosures and funding.   

###  

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: 

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

The post ‘Zombie’ cells spark inflammation in severe fatty liver disease, Mayo Clinic researchers find  appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Resolutions to improve health typically include measures such as more exercise, a healthier diet and stopping smoking. But what about your gut microbiome? Taking steps to protect and improve it can benefit digestive health and more, says Purna Kashyap, M.B.B.S., a gastroenterologist at Mayo Clinic who specializes in the gut microbiome and gastrointestinal disorders.

"The microbiome is essentially a community of bacteria, fungi, viruses and all of their genes," Dr. Kashyap explains. "The skin, lungs and reproductive system each have their own microbiomes. The gut microbiome is probably the most diverse in our body. Its microbes perform several functions. The body's other microbiomes tend to be more specialized."

Your gut microbiome is as unique as your fingerprint. These bacteria perform important jobs, including breaking down fiber and starches; synthesizing vitamins and amino acids, such as vitamins B and K; and producing short-chain fatty acids (SCFA) that help prevent disease. They also maintain the intestinal barrier, a protective gut lining.

"For example, when you eat an apple, your stomach and small intestine break down some of it. The rest of the apple goes to your colon, where bacteria do the rest of the work for you," says Dr. Kashyap, the Bernard and Edith Waterman Director of the Microbiomics Program at the Mayo Clinic Center for Individualized Medicine.

"As the bacteria break down the apple's fiber, they produce substances that are good for the cells of the colon and the body."

If you lose these healthy bacteria, it creates an opportunity for some of the bacteria that cause disease to thrive. One example is Clostridioides difficile, or C. diff, a bacterium that can infect the colon, the longest part of the large intestine. Symptoms can range from diarrhea to life-threatening damage to the colon. Risk factors for C. diff infection include antibiotic use, hospitalization and certain medications that affect the immune system.

"If you take antibiotics, your microbiome might change for a short time, but it usually goes back to its original state," Dr. Kashyap says. "The same thing can happen with other changes or behaviors, such as traveling or eating a lot of fast food. Think of your microbiome like a rubber band. You can stretch it a bit, and it bounces back. But if you stretch it too much, it might get disrupted."

In addition to gut infections like C. diff, microbial imbalances are thought to play a role in other diseases and symptoms, including colon cancer; diabetes; depression and other mood disorders; Alzheimer's disease; Parkinson's disease; and cardiovascular disease. More research is needed to understand ties between the gut microbiome and these diseases, Dr. Kashyap says.

How far you can stretch your microbiome depends on several factors. Those include how long the disruption lasts. This is one reason it's important to avoid overusing antibiotics, Dr. Kashyap says.

Some underlying diseases, such as inflammatory intestinal diseases can affect which communities of bacteria can thrive in your gut and which can't. These include inflammatory bowel diseases such as Crohn's disease and ulcerative colitis.

Dr. Kashyap is studying the interactions between gut bacteria and dietary carbohydrates and how they influence the gastrointestinal system. His long-term goal is to develop new biomarkers and microbiota-targeted therapies for treatment of functional gastrointestinal disorders, including irritable bowel syndrome and chronic bloating, also known as functional bloating.

Lifestyle can also play an important role in the health of your gut microbiome, Dr. Kashyap adds: "Gut bacteria eat what you eat. If you eat a lot of sugary, salty, fatty foods such as snacks, sweets and highly processed foods or consume a lot of alcohol, you'll starve bacteria. As a result, they will try to get nutrients from your gut lining and will damage it in the process."

On the other hand, if your diet is loaded with a diverse array of fruits, vegetables and fiber, you'll nourish a diverse microbial community in your gut.

"The more diverse your gut microbes, the farther you can stretch things before you experience disruption," Dr. Kashyap says. "Happy bugs, happy life."

Other lifestyle habits will help to protect gut health:

• Drink plenty of healthy fluids such as water and limit or avoid alcohol.
• Exercise for at least 30 minutes most days.
• Don't smoke.
• Manage stress.

For more information about the microbiome and microbiome research at Mayo Clinic, visit Mayo Clinic Press and the Mayo Clinic Center for Individualized Medicine.

###

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:

• Sharon Theimer, Mayo Clinic Communications, newsbureau@mayo.edu
  

The post Get to know your microbiome: It can improve gut health and more, Mayo Clinic expert explains appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Photon therapy offers strong outcomes in treating oropharyngeal cancers; however, some radiation can reach and damage nearby healthy tissue. The damage can lead to side effects that may be severe for some patients. In a new nationwide study published in The Lancet that included Mayo Clinic, investigators found that patients with oropharyngeal cancer can live longer with fewer side effects if treated with proton beam radiation therapy.

Photon radiation therapy, which uses X-rays to cure cancers, is a standard treatment for a type of throat cancer called oropharyngeal cancer. Rates of oropharyngeal cancers are increasing in the U.S., mainly driven by HPV infection.

Reducing the toll of treatment 

Proton beam therapy has been used for years in children, where research shows it lowers both short- and long-term treatment-related side effects. "Protons have been studied extensively in pediatric populations and consistently demonstrate reduced short- and long-term toxicity," says Nadia Laack, M.D., chair of the Department of Radiation Oncology at Mayo Clinic in Rochester. "It has been more difficult to prove the benefits in adult cancer because many adult studies have not measured side effects as carefully or as long." 

To explore whether the same advantages apply to adults, investigators directly compared proton beam therapy with modern photon radiation called intensity-modulated radiation therapy (IMRT), which precisely targets tumors while limiting exposure to nearby healthy tissue. "It is effective as an oropharyngeal cancer treatment, but there's always some incidental dose to surrounding tissues because of the physical nature of X-rays," says Daniel Ma, M.D., radiation oncologist at Mayo Clinic and the Mayo site primary investigator of the study. This incidental dose of radiation can sometimes cause long-term complications, including pain, problems with swallowing and a weakened jawbone.

To alleviate these unwanted side effects, investigators studied proton beam radiation therapy as a treatment option. "Protons are charged particles that can stop at a certain depth, so the delivery is more focused," says Dr. Ma. "If you set up your proton fields thoughtfully, you can avoid irradiating critical structures like the mouth, voice box and swallowing muscles. That's the advantage of proton therapy and why we decided to investigate it within a clinical trial."

Mayo Clinic was one of 18 participating institutions around the U.S. that enrolled patients in the first-ever phase 3 randomized trial comparing the two types of radiation for oropharyngeal cancer. Dr. Ma collaborated with Robert Foote, M.D., emeritus professor of radiation oncology at Mayo Clinic and senior author of the study, and Samir Patel, M.D., radiation oncologist at Mayo Clinic, to help lead Mayo Clinic’s involvement in the study.

Study results found that proton beam therapy weakened the immune system by 15% less than photon therapy. It also lowered the risk of severe swallowing problems by 13% and reduced the need for feeding tubes by more than 13%.

An unexpected outcome 

The treatments were similar in effectiveness in controlling cancer growth and spread, so Dr. Ma expected survival to be approximately the same, but the survival results were surprising.  

"Unexpectedly, we found that the overall survival at five years was 91% with proton therapy and 81% with photon therapy," he says. 

These results weren't immediately apparent. "The survival benefit in our study didn't start separating out until three years and wasn't apparent until five years, so longer follow-up with patients was key," he says. 

Dr. Ma says this result is likely due to a variety of factors, including less toxicity and immune suppression. He adds, "Because of this, we feel strongly that proton therapy should be a standard treatment for oropharyngeal cancer patients who can tolerate and receive it." 

"This study is important because it confirms what we believe to be true in many adult cancer cases: reducing toxicity has a meaningful impact on quality of life and long-term outcomes," says Dr. Laack. "As our treatments improve and our patients live longer, reducing toxicity and improving quality of life is more important than ever." 

The study was led by The University of Texas MD Anderson Cancer Center. Review the study for a complete list of authors, disclosures and funding. 

###

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 Joint study finds proton beam therapy helps patients with throat cancer live longer with fewer side effects  appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — A new Mayo Clinic study published in the New England Journal of Medicine has uncovered that an off-the-shelf, dual-antibody therapy can generate deep and durable responses in extramedullary multiple myeloma — one of the most aggressive and treatment-resistant forms of the disease. 

"We are seeing powerful responses in a disease that historically has resisted every therapy," says Shaji Kumar, M.D., a Mayo Clinic Comprehensive Cancer Center hematologist and senior author of the study. "By recruiting T cells in two distinct ways at once, this dual-target antibody strategy can generate responses in patients who have had very few effective options." 

The approach combines two engineered antibodies, talquetamab and teclistamab, that simultaneously engage T cells and force them to attack myeloma cells through two separate immune pathways. Unlike CAR-T cell therapy, which requires custom manufacturing, this regimen is delivered as a standard infusion-center injection. 

In a trial involving 90 patients, 79% responded to treatment, and 54% achieved no detectable disease by imaging or blood testing. Among responders, nearly two-thirds maintained disease control at one year, a striking improvement for a subtype that typically carries a months-long prognosis. 

This is the first large, prospective study defined specifically by PET/MRI scan and focused exclusively on true extramedullary myeloma, not a mix of para- and extramedullary disease. Serious side effects were common. Infection was one serious side effect and underscores the importance of comprehensive supportive care alongside immunotherapy. 

The next big questions are whether this dual-target strategy can be moved earlier in the disease course, how safety can be optimized further through infection monitoring and prevention, and whether similar "two-locks, one-key" immune designs can be applied to other hard-to-treat cancers. 

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

### 

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 researchers find new hope for toughest myeloma through off-the-shelf immunotherapy  appeared first on Mayo Clinic News Network.