DALLAS – March 30, 2021 – UT Southwestern researchers have identified factors that put patients with childhood-onset lupus at elevated risk for poor outcomes, such as end-stage renal disease or death, as they transition from pediatric to adult health care. The findings, published online in Seminars in Arthritis and Rheumatism, emphasize the precarious nature of this period and shine a spotlight on areas prime for intervention to help protect these vulnerable patients. CREDIT UT Southwestern Medical Center

UT Southwestern researchers have identified factors that put patients with childhood-onset lupus at elevated risk for poor outcomes, such as end-stage renal disease or death, as they transition from pediatric to adult health care. The findings, published online in Seminars in Arthritis and Rheumatism, emphasize the precarious nature of this period and shine a spotlight on areas prime for intervention to help protect these vulnerable patients.

Patients with chronic diseases that used to be fatal early in life now often survive to live long lives. However, says study senior author Bonnie Bermas, M.D., professor of internal medicine at UTSW, while pediatric patients often have significant support in managing their conditions as children, they are expected to take much more responsibility for their health care as they transition to adult care.

Studies have shown that patients with chronic diseases such as HIV and sickle cell disease tend to have poor outcomes during this time. As an adult rheumatologist who cares for young adult patients with childhood-onset lupus erythematosus, an autoimmune disease, Bermas says she has witnessed a similar phenomenon. However, it’s unclear what factors put young lupus patients who transition to adult care at higher risk.

To explore this question, Nicole Bitencourt – a former UTSW pediatric and adult rheumatology fellow who is now on the faculty of the University of California Los Angeles Medical Center – along with Bermas and her UTSW colleagues used medical records to identify childhood-onset lupus patients who transitioned to adult care between 2010 and 2019. These 190 patients were seen at two different rheumatology clinics: One is a safety-net hospital that mainly treats patients with public insurance; the other is a university hospital that primarily sees patients with private insurance.

The researchers followed patients for an average of nearly 3.5 years and looked at three major outcomes: time to the first hospitalization following a patient’s final pediatric rheumatology visit; time to end-stage renal disease, a condition in which severe kidney failure necessitates dialysis; and death.

Of the 190 patients, 11 percent developed end-stage renal disease and 5 percent died during the follow-up period. Out of 114 patients with hospitalization data, 53 percent were hospitalized as young adults.

The research team found several factors linked with these poor outcomes. End-stage renal disease and death were associated with having public health insurance, a history of Child Protective Services involvement, and an unscheduled hospitalization during the final year of pediatric care. A shorter time to hospitalization in adult care was linked with a pediatric outpatient opioid prescription and Black race or Hispanic ethnicity.

Bermas, the Dr. Morris Ziff Distinguished Professor in Rheumatology, notes that these findings could help health care providers better target childhood-onset lupus patients who might be at higher risk of poor outcomes during their transition to make sure they have the support and resources needed to stay healthy after they become adults.

“Transitioning to young adulthood has its own challenges, but these patients are struggling with a chronic disease on top of that. We’re asking an awful lot of these patients to navigate the medical system, often with little support,” says Bermas. “By identifying those patients who may need more help, we can improve outcomes and even potentially save lives.”

Walking regularly and at greater intensity may help prevent Type 2 diabetes among 70 and 80 year olds, according to one of the first studies measuring steps and pace among this population.

The more steps a person takes, and the more intense, the lower their risk for developing diabetes, report researchers in a study published in the Jan. 20, 2022 issue of Diabetes Care.

“A key figure from our study is that for every 1,000 steps per day, our results showed a 6% lower diabetes risk in this population. What that means is, if the average older adult were to take 2,000 more steps every day in addition to what they were already doing, they might expect a 12% reduction in diabetes risk,” said first author Alexis C. Garduno, a third-year student in the University of California San Diego and San Diego State University joint doctoral program in public health.

A multi-institutional team of researchers analyzed data from the Women’s Health Initiative whose aim was characterizing physical activity and cardiovascular health in postmenopausal women.

For the current prospective study, a diverse cohort of women 65 and older, who did not have a diabetes diagnosis and who lived independently, were asked to wear a research-grade accelerometer for 24 hours per day over the right hip for one week. Their health was followed for up to seven years.

“We wanted to understand the extent to which stepping, or walking, is related to diabetes. And, is 10,000 steps a day really necessary for people to reduce their risk for diabetes?” said senior author John Bellettiere, PhD, MPH, assistant professor of epidemiology at the Herbert Wertheim School of Public Health and Human Longevity Science at UC San Diego.

The primary aim of the study was to assess associations between total steps taken per day and the development of diabetes. The secondary aim was to evaluate whether step intensity or cadence influenced diabetes risk.

Of the 4,838 women in the study, 395 or 8% developed diabetes.

Adults 65 and older often live with mobility or disability challenges. As physical activity drops their risk for Type 2 diabetes increases.

According to the American Diabetes Association, 1.5 million people are diagnosed with diabetes every year.

“If we estimate that one third of that population are older adults, that’s 500,000 older individuals who are newly diagnosed with diabetes every year. If all of them increase their steps by 2,000 steps per day and our 12% estimate is proven to be casual, we would expect 60,000 people each year to not get diabetes due to that increase in steps,” said Bellettiere.

Previous prevention studies have demonstrated that regular physical activity, along with improved diet, reduces the risk of diabetes in adults. In fact, the United States Department of Health and Human Services recommends at least 150 minutes of moderate to vigorous physical activity per week to reduce the risk of numerous chronic diseases, including diabetes.  

Age plays an important role in levels of physical activity intensity, Bellettiere said.

“What is moderate intensity activity for an older adult is very different than what is moderate intensity activity for a middle-aged or young adult. People who have mobility disability, do not have to walk as far, as fast or uphill to engage in moderate to vigorous intensity activity,” he said. “When we talk about moderate to vigorous intensity steps we are talking about the kind of steps that cause you to breathe a little heavy and make it harder to engage in a conversation. For the average person aged 70 to 80 years old, just walking around the block one time is moderate to vigorous intensity activity.”

Because all steps matter, not just those taken for exercise, the accelerometers used in the study count steps throughout the day, whether an individual is at home moving from room to room, taking a walk outdoors, or moving about a grocery store.

Additional randomized controlled trials are needed to determine the exact number of steps needed for risk reduction, the researchers said. In the future, clinicians may be able to personalize a physical activity plan by analyzing how an individual’s genetic risk or family history of diabetes influences the number of steps needed per day to reduce their risk for diabetes, said Garduno.

“It’s important, even if you have staved off diabetes, to keep with it and to incorporate regular stepping as part of your daily schedule and make it into a routine,” said Garduno. “It’s not enough for somebody to go on a walk once a week. Our study indicates that regular stepping is indicative of lower diabetes risk in older adults.”

Current treatments of MS focus on stopping inflammation, but they do not necessarily address the underlying cause. There is significant evidence that Epstein-Barr Virus (EBV) is part of the causal pathway of MS. ATA188 is an anti-EBV neurogenic t-cell therapy being developed by Atara Biotherapeutics, and in this video, I present their fascinating phase I data.

The autoimmune disease lupus may be triggered by a defective process in the development of red blood cells (RBCs), according to a study led by researchers at Weill Cornell Medicine. The discovery could lead to new methods for classifying and treating patients with this disease.

The researchers, who published their findings August 11 in Cell, found that in a number of lupus patients, maturing red blood cells fail to get rid of their mitochondria—tiny molecular reactors that help convert oxygen into chemical energy in most cell types, but are normally excluded from red blood cells. This abnormal retention of mitochondria can trigger the cascade of inappropriate and harmful immune activity that is characteristic of the disease.

“Our findings support that red blood cells can play a really important role in driving inflammation in a subgroup of lupus patients,” said senior author Dr. Virginia Pascual, the Drukier Director of the Gale and Ira Drukier Institute for Children’s Health and the Ronay Menschel Professor of Pediatrics at Weill Cornell Medicine. “So this adds a new piece to the lupus puzzle, and could now open the door to new possibilities for therapeutic interventions.”

The lead author of the study was Dr. Simone Caielli, assistant professor of immunology research at the Drukier Institute and the Department of Pediatrics at Weill Cornell Medicine.

Lupus, also known as systemic lupus erythematosus, is a chronic disorder that features intermittent and sometimes debilitating attacks by the immune system on the body’s own healthy tissues, including skin, joints, hair follicles, heart and kidneys. A common underlying factor is the abnormally elevated production of immune-activating proteins called type I interferons. Treatments, which often are taken long-term and have side effects, aim to suppress immune activity, including interferon-driven inflammation. There is no cure for lupus, and how it arises is still largely mysterious. It is estimated to affect roughly 200,000 people in the United States, the vast majority of whom are female.

Previous studies have shown defective mitochondria within immune cells of lupus patients. In the new study, the researchers examined red blood cells, which are supposed to have no mitochondria at all. They found that a large number of lupus patients had red blood cells with detectable levels of mitochondria—and these cells were especially frequent in patients with the most severe lupus symptoms. By contrast, healthy controls had no mitochondria-containing red blood cells.

Dr. Caielli then studied how human red blood cells normally rid themselves of mitochondria as they mature, as prior studies had mainly examined this in mice, and why this process could be defective in lupus patients.

Further experiments revealed how these abnormal red blood cells cause inflammation. In general, as red blood cells age or display signs of damage they are removed by scavenger immune cells called macrophages. Antibodies that bind red blood cells also facilitate their removal. Once ingested by macrophages, the red blood cells’ mitochondrial DNA stimulates a powerful inflammatory pathway called the cGAS/STING pathway, which in turn drives type I interferon production.  Underlining the relevance of these findings, “those lupus patients with mitochondria-containing red blood cells and evidence of circulating anti-RBC antibodies had higher interferon signatures compared to those who didn’t,” Dr. Caielli said.

The researchers are now continuing to study the complex process by which mitochondria are retained in red blood cells and end up driving abnormal immune activation. Identifying patients whose lupus symptoms are driven this way might permit to detect when they are likely to undergo lupus flares and to identify specific therapies for them.

Scrolling social media, reading websites, listening to podcasts, watching news. With so many options, it’s never been easier to follow American politics, but at what cost?

According to research from University of Nebraska–Lincoln political scientist Kevin Smith, all the political jockeying is harmful to our health, has been for some time, and even a change in party power didn’t help.

In a follow-up to the groundbreaking 2017 survey study where he first measured the effects of the political climate on Americans’ physical, social, mental and emotional health, Smith has published a new article in PLOS ONE. Smith repeated the same 32-question survey twice in 2020 — two weeks prior to the election, and two weeks after. The 2020 findings mirrored the 2017 results, and again found that a large proportion of American adults blame politics for causing them stress, loss of sleep, fractured relationships and more.

Similar to the 2017 findings, the 2020 surveys found that an estimated 40% of Americans identified politics as a significant source of stress. Additionally, between a fifth and a third of adults (50 to 85 million people) blamed politics for causing fatigue, feelings of anger, loss of temper and triggering compulsive behaviors. About a quarter of adults reported they’d given serious consideration to moving because of politics.

That the results remained mostly stable after nearly four years is cause for alarm, Smith said.

“This second round of surveys pretty conclusively demonstrates that the first survey was not out of left field — that what we found in that first survey really is indicative of what many Americans are experiencing,” Smith, chair and professor of political science, said. “It’s also unpleasant to think that in that span of time, nothing changed. A huge chunk of American adults genuinely perceive politics is exacting a serious toll on their social, their psychological and even their physical health.”

Smith repeated the survey with the same group of people both before and after the election to see if the election’s outcome — whatever it ended up being — would recast people’s perceptions.

“We wondered if a change in presidency, which indeed was the case, would shift attitudes, and the short answer is no,” Smith said. “If anything, the costs that people perceive politics is exacting on their health increased a little bit after the election.”

Most stunning to Smith was the repeated finding that 5% of Americans blame politics for having suicidal thoughts.

“One in 20 adults has contemplated suicide because of politics,” Smith said. “That showed up in the first survey in 2017, and we wondered if it was a statistical artifact. But in the two surveys since, we found exactly the same thing, so millions of American adults have contemplated suicide because of politics. That’s a serious health problem.”

Adults who were most likely to be negatively affected by politics were younger, more often Democratic-leaning, more interested in politics and more politically engaged.

“If there’s a profile of a person who is more likely to experience these effects from politics, it’s people with those traits,” Smith said.

Besides pointing to a possible health crisis, Smith warned the findings could be a bad recipe for democracy.

“There’s potential for a demobilization effect here,” Smith said. “If people view politics as so conflictual, and potentially a threat to their own well-being, they’ll say ‘heck with it, I don’t want to get involved.’ And democracies depend on participation. We need civically-engaged citizens.”

So, how can these effects be mitigated? Smith said that’s a question he plans to explore further in future research, though his team has identified one possible tool: becoming more politically knowledgeable.  

“People who were more politically knowledgeable were less likely to report these negative outcomes,” Smith said. “Something I’d really like to look at would be if you took somebody who’s politically interested, but not particularly politically knowledgeable, and they were given information about the political system, would that reduce these negative costs of politics? That could be a positive outcome of civic education that’s never been considered before.”