Day: February 9, 2024

Apaxiban no Better than Aspirin for Preventing Recurrence in Cryptogenic Stroke and Atrial Cardiopathy

Trial comparing anticoagulant and antiplatelet therapy ends in a draw

Ischaemic and haemorrhagic stroke. Credit: Scientific Animations CC4.0

Administering apaxiban to patients with cryptogenic stroke and evidence of atrial cardiopathy to prevent recurrence was no more effective than giving aspirin, a large randomised trial has found. The trial, published in JAMA, did however find a possible slight advantage in safety of apaxiban over aspirin.

Cryptogenic stroke (CS) is cerebral ischaemia of obscure or unknown origin. One third of ischaemic strokes are cryptogenic. 

Atrial cardiopathy is defined as any complex of structural, architectural, contractile, or electrophysiologic changes affecting the atria with the potential to produce clinically relevant manifestations. Atrial cardiopathy is strongly associated with incident atrial fibrillation and plays a role in thromboembolism related to atrial fibrillation.

Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. But it was not known whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation. The Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial was therefore designed to determine whether anticoagulation is superior to antiplatelet therapy for preventing recurrent stroke in such patients.

From 2018 to 2023, the researchers conducted a multicentre, double-blind, phase 3 randomised clinical trial of 1015 participants with CS and evidence of atrial cardiopathy – defined as P-wave terminal force greater than 5000μV×ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250pg/mL, or left atrial diameter index of 3cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomisation.

The participants were randomised 1:1 to receive either apaxiban (5mg or 2.5 mg) twice daily or aspirin (81mg) once daily. The primary outcome measure of stroke occurrence was identical in both arms (40 patients, 4.4%).

There were zero intracranial haemorrhage events for apaxiban vs seven for aspirin, which is known to increase the risk of these. This supports a superior safety profile for apxiban over aspirin, but given the small number of events, the authors caution that this may be a chance finding.

Study limitations included a higher than expected dropout rate due to the COVID pandemic. Additionally, few patients met the atrial cardiopathy criterion of severe left atrial enlargement, but restricting the trial participants to this criterion would have rendered the trial infeasible.

Understanding How T Cells Target Tuberculosis will Enhance Vaccines and Therapies

Tuberculosis bacteria. Credit: CDC

La Jolla Institute for Immunology (LJI) is working to guide the development of new tuberculosis vaccines and drug therapies. Now a team of LJI scientists has uncovered important clues to how human T cells combat Mycobacterium tuberculosis, the bacterium that causes TB. Their findings were published recently in Nature Communications.

“This research gives us a better understanding of T cell responses to different stages in tuberculosis infection and helps us figure out is there are additional diagnostic targets, vaccine targets, or drug candidates to help people with the disease,” says LJI Research Assistant Professor Cecilia Lindestam Arlehamn, PhD, who led the new research in collaboration with LJI Professors Bjoern Peters, PhD, and Alessandro Sette, Dr.Biol.Sci.

The urgent need for TB research

According to the World Health Organization, more than 1.3 million people died of TB in 2022, making it the second-leading infectious cause-of-death after COVID. “TB is a huge problem in many countries,” says Lindestam Arlehamn.

Currently, a vaccine called bacille Calmette-Guerin (BCG) protects against some severe cases of TB. Unfortunately, BCG doesn’t consistently prevent cases of pulmonary TB, which can also be deadly.

Although there are drug treatments for TB, more and more cases around the world have proven drug resistant.

To help stop TB, Lindestam Arlehamn and her colleagues are learning from T cells. Instead of targeting an entire pathogen, T cells look for specific markers, called peptides sequences, that belong to the pathogen.

When a T cell recognises a certain part of a pathogen’s peptide sequence, that area is termed an “epitope.”

Uncovering T cell epitopes gives scientists vital information on how vaccines and drug treatments might take aim at the same epitopes to stop a pathogen.

T cells take aim at a range of TB epitopes

For the new study, the researchers worked with samples from patients who were mid-treatment for active TB. These samples came from study participants in Peru, Sri Lanka, and Moldova.

By looking at T cells in patients from three different continents, the researchers hoped to capture a wide diversity of genetics and environmental factors that can affect immune system activity.

In their analysis, the LJI team uncovered 137 unique T cell epitopes. They found that 16% of these epitopes were targeted by T cells found in two or more patients. The immune system appeared to be working hard to zoom in on these epitopes.

Going forward, Lindestam Arlehamn’s laboratory will investigate which of these epitopes may be promising targets for future TB vaccines and drug therapies.

A step toward better diagnostics

The new study is also a step toward catching TB cases before they turn deadly.

Because Mycobacterium tuberculosis is an airborne bacteria, a person can be exposed without ever realizing it. Once exposed, many people go months or years without any symptoms.

This inactive, or “latent,” TB can turn into active TB if a person’s immune system weakens, for example, during pregnancy or due to an infection such as HIV.

For the new study, the researchers also compared samples from active TB patients with samples from healthy individuals.

The scientists uncovered key differences in T cell reactivity between the two groups.

“For the first time, we could distinguish people with active TB versus those that have been exposed to TB – or unexposed individuals,” says Lindestam Arlehamn.

Lindestam Arlehamn says it may be possible to develop diagnostics that detect this tell-tale T cell reactivity that marks a person’s shift from latent to active TB. “Can we use this peptide pool to look for high-risk individuals and try and follow them over time?” she says.

Source: La Jolla Institute for Immunology

Exercise does not Cancel out Cardiovascular Risks of Sugary Drinks

Photo by Breakingpic on Pexels

Contrary to popular belief, the benefits of physical activity do not outweigh the risks of cardiovascular disease associated with drinking sugar-sweetened beverages, according to a new study led by Harvard T.H. Chan School of Public Health and published in The American Journal of Clinical Nutrition.

Sugar-sweetened beverages are the largest source of added sugars in the North American diet. Their consumption is associated with a higher risk of cardiovascular disease, the world’s leading cause of death.

“The marketing strategies for these drinks often show active people drinking these beverages. It suggests that sugary drink consumption has no negative effects on health if you’re physically active. Our research aimed to assess this hypothesis,” says co-author Jean-Philippe Drouin-Chartier, professor at Université Laval’s Faculty of Pharmacy.

For the study, the scientists used two cohorts totalling around 100 000 adults, followed for about 30 years.

The data show that those who consumed sugar-sweetened beverages more than twice a week had a higher risk of cardiovascular disease, regardless of physical activity levels.

The study found that even if the recommended 150 minutes of weekly physical activity protects against cardiovascular disease, it’s not enough to counter the adverse effects of sugar-sweetened beverages.

“Physical activity reduces the risk of cardiovascular disease associated with sugar-sweetened beverages by half, but it does not fully eliminate it,” says Drouin-Chartier.

The frequency of consumption considered in the study – twice a week – is relatively low but still is significantly associated with cardiovascular disease risk.

With daily consumption, the risk of cardiovascular disease is even higher. For this reason, Drouin-Chartier underlines the importance of targeting the omnipresence of sugar-sweetened beverages in the food environment.

This category includes soft and carbonated drinks (with or without caffeine), lemonade, and fruit cocktails. The study did not specifically consider energy drinks, but they also tend to be sugar-sweetened.

For artificially sweetened drinks, often presented as an alternative solution to sugar-sweetened beverages, their consumption was not associated with higher risk of cardiovascular diseases.

“Replacing sugar-sweetened beverages by diet drinks is good, because it reduces the amount of sugar. But the best drink option remains water,” explains Drouin-Chartier.

“Our findings provide further support for public health recommendations and policies to limit people’s intake of sugar-sweetened beverages, as well as to encourage people to meet and maintain adequate physical activity levels,” added lead author Lorena Pacheco, a research scientist in the Department of Nutrition at Harvard Chan School.

Source: Université Laval

Conquering Childhood Leukaemia: How You can Help

Preshthi Ishwarlal

Receiving the news that their child has been diagnosed with cancer is devastating for any parent, but this is even worse when they hear that, after 18 months of remission, their little one will need to battle the disease all over again.

This was the case for mom of two Arthie Ishwarlal. Back in 2021, her then two-year-old daughter, Preshthi, was diagnosed with Acute Lymphoblastic Leukaemia (ALL), a type of blood cancer that affects the bone marrow, white blood cells, red blood cells, and blood platelets. But, despite undergoing inpatient treatment, Preshthi experienced a relapse earlier this year with doctors saying that her only chance for survival is a stem cell transplant from a matching donor. Unfortunately, however, there is no match for her on the country’s stem cell registry at present.

As the world observes International Childhood Cancer Day (ICCD) on 15February, Palesa Mokomele, Head of Community Engagement and Communications at DKMS Africa explains that South Africans can potentially save Preshthi’s life. While there are currently over 73 000 donors on the South African registry, each only has a 1 in 100 000 chance of being a match for a blood cancer patient in need. But exacerbating the situation for little Preshthi is the lack of Indian donors since the best chance of a match comes from within one’s own ethnic group.”

She adds that it is not just Preshthi who needs a stem cell transplant for a second chance at life. “This is often the only treatment offering children with other blood cancers, like lymphomas, any hope of a cure.”

With leukaemia and lymphomas being two of the five most common cancers among South Africa’s youth, with the former accounting for 34% of childhood cancer cases and the latter 11%, Mokomele urges South Africans aged between 17 and 55 who are in good general health to register as donors. “In doing so, you might save a child’s life.”

Register at Registration is entirely free and takes less than five minutes.

For further information, get in touch with DKMS Africa at 0800 12 10 82.

New Study Suggests that Pumping Iron can Help Fight the Blues

Photo by Jonathan Borba on Unsplash

A new study has demonstrated the impact that resistance exercise training can have in the treatment of anxiety and depressive symptoms. The findings, published in Trends in Molecular Medicine, provide evidence to support the benefits of resistance exercise training can have on anxiety and depression and offers an examination of possible underlying mechanisms.

The research was carried out by Professor Matthew P. Herring at University of Limerick and Professor Jacob D. Meyer at Iowa State University.

“We are tremendously excited to have what we expect to be a highly cited snapshot of the promising available literature that supports resistance exercise training in improving anxiety and depression.

“Notwithstanding the limitations of the limited number of studies to date, there is exciting evidence, particularly from our previous and ongoing research of the available studies, that suggests that resistance exercise training may be an accessible alternative therapy to improve anxiety and depression.

“A more exciting aspect is that there is substantial promise in investigating the unknown mechanisms that may underlie these benefits to move us closer to maximizing benefits and to optimising the prescription of resistance exercise via precision medicine approaches,” Dr Herring added.

Professor Meyer, a co-author on the study, said: “The current research provides a foundation for testing if resistance training can be a key behavioural treatment approach for depression and anxiety.

“As resistance training likely works through both shared and distinct mechanisms to achieve its positive mood effects compared to aerobic exercise, it has the potential to be used in conjunction with aerobic exercise or as a standalone therapy for these debilitating conditions.

“Our research will use the platform established by current research as a springboard to comprehensively evaluate these potential benefits of resistance exercise in clinical populations while also identifying who would be the most likely to benefit from resistance exercise.”

Source: University of Limerick