Publisher Health

A common gout medication, colchicine, significantly improved survival rates for patients hospitalized with worsening heart failure, a UVA Health study found. The researchers believe colchicine could also reduce the risk for heart attack and stroke in patients with a buildup of cholesterol in their arteries.
Researchers reviewed the records of more than 1,000 patients admitted to University of Virginia Medical Center between March 2011 and February 2020 for worsening heart failure. Patients who received colchicine for a gout flare had a survival rate of 97.9%, compared with a 93.5% survival rate for patients not receiving colchicine.
“These results highlight the importance of novel inflammatory mechanisms in heart failure,” said Kenneth Bilchick, MD, MS, Professor of Cardiovascular Medicine and a clinical investigator at UVA. “The signal for benefit with colchicine in these patients was very impressive, and I expect that these findings will have quite a significant impact on clinical care in heart failure and future research for patients with this condition.”
“Heart failure is more than just a failure of the pumping function of the heart. There are other processes that are involved, especially during an acute hospitalization phase such as elevated inflammation and neuro-hormonal process. Many of the therapeutic agents for heart failure target neuro-hormonal pathways, but few if any target inflammatory pathways,” said Sula Mazimba, MD, MPH, a UVA School of Medicine researcher and cardiologist specializing in heart failure. “Colchicine is a medication that has anti-inflammatory properties that could potentially attenuate the heightened inflammation that we see in patients who are hospitalized with heart failure.”
Treating Gout and Heart Failure
Heart failure occurs when the body fails to adequately pump blood throughout the body. Approximately 6 million Americans have heart failure, according to the American Heart Association, and the condition is responsible for more than 86,000 deaths annually.

In most mammals, females have two X chromosomes and males have one X and one Y chromosome in each of their cells. To avoid a double dose of X-linked genes in females, one of the Xs is silenced early in the developmental process. This silencing is critical, yet how it happens has been relatively mysterious. Two new U-M studies reveal more about this silencing process and insights that could improve stem cell research.
Human embryonic stem cells (hESCs) hold enormous promise for research into early development as well as for regenerative medicine for diseases ranging from type 1 diabetes to Parkinson’s disease. Yet, biologists working with female hESCs in the lab often run into a phenomenon wherein the normally inactivated X chromosome loses this suppression while growing in a culture dish.
“If you can’t maintain hESCs exactly as such in culture then you can’t use them for any downstream application,” said Sundeep Kalantry, Ph.D., associate professor of human genetics. He, along with Marissa Cloutier, a Ph.D. trainee, and their team set out to determine why X-inactivation erodes under certain experimental conditions over time.
Their primary suspect was the substance used to grow the cells in culture, called media. Cells are grown in media that supply them with chemical instructions called growth factors. These growth factors signal stem cells to keep dividing. One popular medium, called mTeSR1, appeared to be correlated with the loss of a key regulator of X-inactivation, a non-coding strand of RNA called XIST. Another medium, called Xenofree, did not lead to a loss of X-inactivation.
“We looked at the differences in the composition of these two media and identified lithium chloride as being present in mTeSR1 but not in Xenofree,” said Cloutier.
Lithium chloride is sometimes included in media to promote stem cell proliferation, however, it is known to interfere with many cell-signaling pathways by inhibiting GSK-3 proteins. (Inhibitors of GSK-3 proteins have been used to treat several diseases, and lithium, used to treat bipolar disorder, was one of the first natural GSK-3 inhibitors discovered.)
To confirm lithium chloride as the culprit, they added the compound to the Xenofree medium and saw a loss of X-inactivation. Their paper is published in Nature Communications.

Cannabis vaping is increasing as the most popular method of cannabis delivery among all adolescents in the U.S., as is the frequency of cannabis vaping, according to research at Columbia University Mailman School of Public Health. The study found that the frequency of vaping cannabis among adolescents from all demographic groups is reported at six or more times per month, and rising faster than occasional use. Those who vape and smoke nicotine are more than 40 times more likely to also vape and smoke cannabis.
Until now time trends in vaping use had largely been unexamined including trends in use frequency, emerging disparities, and co-occurring use of other substances, which are all critical for surveillance and public health programmatic efforts. The findings are published in the journal Addiction.
“Heavy and frequent use of cannabis is increasing among U.S. adolescents, and vaped systems for products for both cannabis and nicotine are growing in number so understanding the prevalence and patterns of frequent cannabis vaping is important public health information for prevention,” said Katherine Keyes, PhD, professor of epidemiology at Columbia Mailman School. “Given rising concerns about cannabis vaping in terms of safety, and potential for transition to cannabis use disorder especially at frequent levels of use, these results indicate a necessity for public health intervention and increased regulation.”
The findings are based on the U.S.-based representative annual survey, Monitoring the Future, a population of 51,052 school-attending adolescents. Schools were randomly selected and invited to participate for two years.
Past 30-day frequent cannabis use with vaping increased (2.1 percent to 5.4 percent), while occasional use with vaping rose from 1.2 to 3.5 percent from 2017 to 2019. Past 30-day frequent (3.8 to 2.1 percent) and occasional (6.9 to 4.4 percent) cannabis use without vaping declined. Certain groups, such as Hispanic/Latino or lower socioeconomic status adolescents, experienced particularly notable increases in frequent cannabis use with vaping (e.g., prevalence among Hispanic/Latino adolescents in 2017: 2.2 percent, 2019: 6.7 percent)
According to Keyes, tobacco use and e-cigarettes, as well as binge drinking, are strongly linked to frequent cannabis use — both vaping and non-vaping. The evidence indicates that young adults who use nicotine, especially through vaporizers, are more likely to subsequently use vaped cannabis.

New research from Queen Mary University of London, published in Nature Medicine, has shown that molecular profiling of the diseased joint tissue can significantly impact whether specific drug treatments will work to treat rheumatoid arthritis (RA) patients. The researchers also identified specific genes associated with resistance to most available drugs therapies, commonly referred to as refractory disease, which could provide the key to developing new, successful drugs to help these people.
While there has been much progress made over the past decades in treating arthritis, a significant number of patients (approximately 40%) do not respond to specific drug therapies, and 5-20% of people with the disease are resistant to all current forms of medication.
The researchers carried out a biopsy-based clinical trial, involving 164 arthritis patients, in which their responses to either rituximab or tocilizumab — two drugs commonly used to treat RA — were tested. The results of the original trial published in The Lancet in 2021 demonstrated that in those patients with a low synovial B-cell molecular signature only 12% responded to a medication that targets B cells (rituximab), whereas 50% responded to an alternative medication (tocilizumab). When patients had high levels of this genetic signature, the two drugs were similarly effective.
As part of the first-of-its-kind study, funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership, the Queen Mary team also looked at the cases where patients did not respond to treatment via any of the drugs and found that there were 1,277 genes that were unique to them specifically.
Building on this, the researchers applied a data analyses technique called machine learning models to develop computer algorithms which could predict drug response in individual patients. The machine learning algorithms, which included gene profiling from biopsies, performed considerably better at predicting which treatment would work best compared to a model which used only tissue pathology or clinical factors.
The study strongly supports the case for performing gene profiling of biopsies from arthritic joints before prescribing expensive so-called biologic targeted therapies. This could save the NHS and society considerable time and money and help avoid potential unwanted side-effects, joint damage, and worse outcomes which are common amongst patients. As well as influencing treatment prescription, such testing could also shed light on which people may not respond to any of the current drugs on the market, emphasising the need for developing alternative medications.
Professor Costantino Pitzalis, Versus Arthritis Professor of Rheumatology at Queen Mary University of London, said: “Incorporating molecular information prior to prescribing arthritis treatments to patients could forever change the way we treat the condition. Patients would benefit from a personalised approach that has a far greater chance of success, rather than the trial-and-error drug prescription that is currently the norm.
“These results are incredibly exciting in demonstrating the potential at our fingertips, however, the field is still in its infancy and additional confirmatory studies will be required to fully realise the promise of precision medicine in RA.
“The results are also important in finding solutions for those people who unfortunately don’t have a treatment that helps them presently. Knowing which specific molecular profiles impact this, and which pathways continue to drive disease activity in these patients, can help in developing new drugs to bring better results and much-needed relief from pain and suffering.”
The incorporation of these signatures in future diagnostic tests will be a necessary step to translate these findings into routine clinical care.
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Materials provided by Queen Mary University of London. Note: Content may be edited for style and length.

In a recent survey of more than 6,500 physicians from across the United States representing a broad spectrum of racial and ethnic diversity, nearly 30% of respondents reported experiencing discrimination and mistreatment from patients or patients’ family members or visitors.
Further, close to 20% of responding physicians had experiences in which patients or their family members or visitors refused to allow the physician to care for them because of the physician’s racial or ethnic attributes or gender.
“This is a staggering number,” says Lotte Dyrbye, MD, senior associate dean of faculty and chief well-being officer at the University of Colorado School of Medicine. “Simply having patients or family members say, ‘No, you can’t provide care because of the way you look’ — not because of competency – is really heartbreaking.”
In research published today, Dyrbye and her co-researchers surveyed more than 6,500 physicians nationwide about their experiences with mistreatment and discrimination in the course of doing their jobs. The research was conducted in collaboration with the American Medical Association (AMA).
“We wanted to understand how often it was happening, who it was happening to, and what are some of the intersections between race, ethnicity, and gender and physician mistreatment,” Dyrbye explains. “We were interested in exploring the relationship between having negative interactions with patients, visitors, and family members and physicians’ likelihood of being burned out.”
Physicians frequently experience discrimination
Throughout her career, Dyrbye, who joined CU this month in her new role, has conducted extensive research on clinician burnout. She co-authored “Taking Action Against Clinician Burnout: A Systems Approach to Professional Well-Being,” a consensus study for the National Academy of Medicine, and co-developed the Well-Being Index, a validated online self-assessment tool for clinicians.

After 20 years of perfecting their technique, the team behind the largest islet cell transplant program in the world reports the procedure is a safe, reliable and life-changing treatment for people with hard-to-control diabetes.
In results published this week in The Lancet Diabetes & Endocrinology, the researchers report on patient survival, graft survival, insulin independence and protection from life-threatening low blood sugars for 255 patients who have received a total of more than 700 infusions of islets at the University of Alberta Hospital over the past two decades.
“We’ve shown very clearly that islet transplantation is an effective therapy for patients with difficult-to-control Type 1 diabetes,” says James Shapiro, professor of surgery at the University of Alberta, Canada Research Chair in regenerative medicine and transplant surgery, and lead of the team that developed what has become known as the Edmonton Protocol. “This long-term safety data gives us confidence that we are doing the right thing.”
“This data shows really strong proof that cell-based therapies can deliver a meaningful and transformative impact for people with diabetes,” says Peter Senior, Charles A. Allard Chair in Diabetes Research and director of the Alberta Diabetes Institute at the U of A. “We are delivering something which all other treatments for diabetes don’t deliver — there’s a comfort, a predictability, a stability to blood sugar levels that don’t exist with anything else.”
Islets are clusters of cells which produce insulin, a hormone that allows the body to control the flow of energy from food, storing the excess after meals and releasing it to allow the body to function between meals. In Type 1 diabetes, the immune system mistakenly destroys the cells within islets so patients have to take insulin by injection. Patients with hard-to-control or “brittle” diabetes face life-threatening low or high blood sugars and long-term complications.
Between March 1999 and October 2019, 255 patients received islet transplants by infusion into their livers. Seventy per cent of the grafts survived for a median time of nearly six years. The researchers reported that a combination of two anti-inflammatory medications given during the first two weeks following transplant significantly increased long-term islet function.
The transplant recipients have to take lifelong immunosuppression drugs, which in some cases lead to skin cancer or infection, but most such complications were not fatal during the study period.
Seventy-nine per cent of the transplant recipients were able to stop taking insulin after two or more islet infusions and a median time of 95 days following the first transplant. Sixty-one per cent were still insulin-independent a year later, 32 per cent at five years and eight per cent after 20 years, the researchers reported. While most patients had to resume taking insulin injections, the doses were usually much smaller than their original needs and their diabetes control was better.
“Being completely free of insulin is not the main goal,” says Shapiro. “It’s a big bonus, obviously, but the biggest goal for the patient — when their life has been incapacitated by wild, inadequate control of blood sugar and dangerous lows and highs — is being able to stabilize. It is transformational.”
Edmonton’s is the world’s largest islet transplant program, but such transplants are now also carried out in other Canadian cities, Switzerland, France, Australia and the United Kingdom. Shapiro hopes the results will build confidence in the procedure in places where it is only available on an experimental basis, such as the United States.
Shapiro will continue to focus on finding a more plentiful supply of islet cells to replace the current reliance on deceased donors. Human trials have already shown success using stem cells programmed to produce insulin. Trials have just started to transplant cells that have been gene edited to make them invisible to the immune system.
“Islet transplant as it exists today isn’t suitable for everybody, but it shows very clear proof of concept that if we can fix the supply problem and minimize or eliminate the anti-rejection drugs, we will be able to move this treatment forward and make it far more available for children and adults with Type 1 and Type 2 diabetes in the future,” Shapiro says.
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Materials provided by University of Alberta. Original written by Gillian Rutherford. Note: Content may be edited for style and length.

Everyone eats the equivalent of three extra McDonald’s cheeseburgers a day than they admit — regardless of their waistline, University of Essex researchers have revealed.
The study shows obese and thin people all fib about food to the same amount regardless of the number on the bathroom scale and this could be undermining national health advice.
Researchers innovatively took into account the amount of energy a person burns in a day with everyone misreporting how many calories they consume by an average of 900 calories.
It found that as obese people burn more energy doing day-to-day tasks, they do not lie about food more than slimmer people.
Although the gap in reported meals and actual intake was bigger in obese people, they actually burn more calories than non-obese people.
This casts doubt on the official guidelines that claim Britain’s bulging waistlines are due to obese people not telling the truth about their diet.

Biomedical engineers at Duke University have developed a method to scan and image the blood flow and oxygen levels inside a mouse brain in real-time with enough resolution to view the activity of both individual vessels and the entire brain at once.
This new imaging approach breaks long-standing speed and resolution barriers in brain imaging technologies and could uncover new insights into neurovascular diseases like stroke, dementia and even acute brain injury.
The research appeared May 17 in the Nature journal Light: Science & Applications.
Imaging the brain is a balancing act. Tools need to be fast enough to capture rapid events, like a neuron firing or blood flowing through a capillary, and they need to show activity at different scales, whether it’s across the entire brain or at the level of a single artery.
“You can achieve these things individually, but it’s very difficult to do them all together,” said Junjie Yao, an assistant professor of biomedical engineering at Duke. “It’s like choosing between having a fast car that is small and uncomfortable to sit in, or a large, spacious car that doesn’t go over 30 miles an hour. For a long time, there wasn’t a way to get everything you wanted at once.”
In their new study, Yao and his team discuss how they’ve solved this long-standing trade-off by developing ultrafast photoacoustic microscopy, or UFF-PAM.

Glioblastomas (GBMs) are highly aggressive cancerous tumors of the brain and spinal cord. Brain cancers like GBM are challenging to treat because many cancer therapeutics cannot pass through the blood-brain barrier, and more than 90 percent of GBM tumors return after being surgically removed, despite surgery and subsequent chemo- and radiation therapy being the most successful way to treat the disease. In a new study led by investigators at Brigham and Women’s Hospital and Harvard Medical School, scientists devised a novel therapeutic strategy for treating GBMs post-surgery by using stem cells taken from healthy donors engineered to attack GBM-specific tumor cells. This strategy demonstrated profound efficacy in preclinical models of GBM, with 100 percent of mice living over 90 days after treatment. Results are published in Nature Communications.
“This is the first study to our knowledge that identifies target receptors on tumor cells prior to initiating therapy, and using biodegradable, gel-encapsulated, ‘off-the-shelf’ engineered stem cell based therapy after GBM tumor surgery,” said Khalid Shah, MS, PhD, director of the Center for Stem Cell and Translational Immunotherapy (CSTI) and the vice chair of research in the Department of Neurosurgery at the Brigham and faculty at Harvard Medical School and Harvard Stem Cell Institute (HSCI). “In the future, we will be applying this strategy to promptly identify target receptors after one receives a GBM diagnosis, then administer a gel-encapsulated, off-the-shelf, engineered stem cell therapeutic from a pre-made reservoir.”
Many cell-based therapies for cancer are derived from a patient’s own stem cells or immune cells. However, in a disease like GBM, most patients undergo surgery in the first week after receiving their diagnosis due to the disease’s rapid progression, granting little time to develop therapeutics from their own cell types. Instead, scientists developed a novel approach to use allogenic stem cells, or cells from healthy individuals, so that the remedy is readily available to administer immediately the time of surgery. Shah and colleagues evaluated the efficacy of several capsules that carry the stem-cell therapeutic in the brain and found a biodegradable hydrogel capsule to successfully transport the treatment without being washed away by cerebrospinal fluid.
Researchers first identified special receptors coined “death receptors” on circulating tumor cells (CTC) — or cancer cells in the bloodstream — using a genetic biomarker commonly expressed on tumor cells. Once identified, they took stem cells from the bone marrow of healthy human donors and engineered the cells to release a protein that binds to the death receptors and initiates cell death. They also built a safety switch into the stem cell system that allows tracking stem cells by PET imaging and, when activated, eradicates stem cells and further enhances cancer cell death. Finally, Shah’s team assessed the efficacy of the therapeutic bifunctional cells (MSCBif)in animal models of primary and recurrent GBM tumors post-surgery.
Notably, all mice that received the gel encapsulated stem cell-based therapeutic after surgery were still alive 90 days post-treatment, compared to mice that solely underwent surgery, which exhibited a mean survival time of 55 days. Investigators additionally assessed the safety of this clinical treatment by conducting several studies using different doses of the MSC therapy on mice. They found no signs of toxicity among mice with or without tumors.
The study’s findings pave a pathway to clinical testing in phase I clinical trials in patients with GBM undergoing brain surgery within next two years. Shah and colleagues note that this therapeutic strategy will be applicable to a wider range of solid tumors and that further investigations of its applications are warranted.
“Beyond this therapy’s significant exhibited success rate, these findings suggest that we can use stem cells from healthy individuals to treat cancer patients,” said Shah. “This work lays down a foundation to begin building an engineered therapeutic stem cell biobank targeting different receptors on tumor cells and the immune cells in the tumor microenvironment that we will one day be able to use to treat a wide range of difficult-to-treat cancers like GBM.”
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Materials provided by Brigham and Women’s Hospital. Note: Content may be edited for style and length.

A test for the common blood cancer multiple myeloma also holds clear clues that the patient has one of the most uncommon and deadly forms of this cancer, investigators say.
While there is a specific test for this rare IgD multiple myeloma, the clues from standard testing are sufficient to rapidly initiate aggressive treatment to reduce or prevent kidney destruction by the excessive number of circulating proteins called light chains it produces, says Dr. Gurmukh Singh, vice chair of clinical affairs for the Department of Pathology at the Medical College of Georgia.
Specific testing for IgD myeloma is available at a handful of reference labs across the country, but takes extra time and expense that may not be necessary and likely will delay the start of treatment, Singh says.
IgD myeloma accounts for about 1% of multiple myelomas and has a worse prognosis, says Singh, author of the study in the International Journal of Pathology and Clinical Research.
With multiple myeloma, the plasma cells that normally produce a wide range of antibodies to help us fight infection instead produce a single dysfunctional antibody, called an M spike, which leaves us vulnerable to infection and can even attack our bones.
Normally the classic Y-shape of the antibody has two light chains, proteins that form the arms of the Y with an antigen-binding site on their tips which is where healthy antibodies attach to whatever they are attacking. Light chains hook up with heavy chains, which are different, literally larger proteins that form the base of the Y.