Day: January 15, 2024

Foundations Laid for Standardised PET Examination of Diffuse Gliomas

Photo by Mart Production on Pexels

Diffuse gliomas are malignant brain tumours that cannot be optimally examined by means of conventional MRI imaging. So-called amino acid PET (positron emission tomography) scans are better able to image the activity and spread of gliomas. An international team of researchers from the RANO Working Group have drawn up the first ever international criteria for the standardised imaging of gliomas using amino acid PET. It has published its results in the journal The Lancet Oncology.

PET uses a radioactive tracer to measure metabolic processes in the body. Amino acid PET is used in the diagnosis of diffuse gliomas, with tracers that work on a protein basis (amino acids) and accumulate in brain tumours.

The Response Assessment in Neuro-Oncology (RANO) Working Group is an international, multidisciplinary consortium founded to develop standardised new response criteria for clinical studies relating to brain tumours.

Under the joint leadership of nuclear physician Nathalie Albert from LMU and oncologist Professor Matthias Preusser from the Medical University of Vienna, the RANO group has developed new criteria for assessing the success of therapies for diffuse gliomas.

Nathalie Albert explains: “PET imaging with radioactively labelled amino acids has proven extremely valuable in neuro-oncology and permits reliable representation of the activity and extension of gliomas. Although amino acid PET has been used for years, it had not been evaluated in a structured manner before now. In contrast to MRI-based diagnostics, there have been no criteria for interpreting these PET images.” According to the researchers, the new criteria allow PET to be used in clinical studies and everyday clinical practice and create a foundation for future research and the comparison of treatments for improved therapies.

New criteria for PET examinations of brain tumours

Diffuse gliomas are malignant brain tumorus that cannot be optimally examined by means of conventional MRI imaging. So-called amino acid PET scans are better able to image the activity and spread of gliomas.

These malignant brain tumours develop out of glial cells and are generally aggressive and difficult to treat.

The RANO group has developed criteria that permit evaluation of the success of treatment using PET. Called PET RANO 1.0, these PET-based criteria open up new possibilities for the standardised assessment of diffuse gliomas.

Source: Ludwig-Maximilians-Universität München

A Universal Coronavirus Vaccine could Save Millions of Lives in a Future Pandemic

Photo by Mika Baumeister on Unsplash

What if in the years prior to the COVID pandemic, scientists had developed a universal coronavirus vaccine, one that targets parts common to coronaviruses, offering some protection against all strains? Would it have been of help during the pandemic?

A new study suggests if such a vaccine were available at the start of the pandemic, it could have saved millions of lives, prevented suffering, and saved billions of dollars in direct medical and other costs until the strain-specific (ie, SARS-CoV-2) vaccine went through the entire development, testing, and emergency use authorisation process that lasted 10 months.

In this study, published in The Lancet’s eClinicalMedicine, researchers show that having a universal vaccine at the start of the pandemic would have had substantial health and economic benefits under almost all scenarios tested.

In order to determine the value of investing in developing and stockpiling a universal coronavirus vaccine, the team developed a computational model that simulated the entire US population, the introduction and spread of a novel coronavirus like SARS-CoV-2 in 2020 and the resulting health (eg, infections, hospitalisations) and economic (eg, direct medical costs, productivity losses) outcomes.

The experiments simulated what would happen if a universal coronavirus vaccine was available at the start of the COVID pandemic.

Vaccinating with a universal coronavirus vaccine as a standalone intervention (e.g., no face mask use or social distancing) was cost-saving even when its efficacy was as low as 10% and only 10% of the U.S. population received the vaccine.

For example, when a universal coronavirus vaccine has 10% efficacy, vaccinating a quarter of the U.S. population within two months of the start of the pandemic averts an average of 14.6 million infections and saves over $27 billion in direct medical costs.

Such low vaccine coverage at the start of the pandemic could occur if a vaccine were only made available to certain high-risk subpopulations (eg, 65 years and older, the immunocompromised, frontline workers), similar to the approach when mRNA vaccines became available in December 2020.

“COVID-19 was the third major and serious coronavirus epidemic or pandemic following SARS in 2002 and MERS in 2012, thus, we should anticipate a fourth coronavirus outbreak within the next decade or so,” says Peter J. Hotez, MD, PhD, dean of Baylor’s National School of Tropical Medicine and co-director of the Texas Children’s Hospital Center for Vaccine Development.

“A universal vaccine is cost-effective and cost-saving and a priority for advancement.”

A universal coronavirus vaccine was also shown to be highly cost-effective even if a more specific and more efficacious vaccine came to market.

For example, the study shows if it takes four months or longer for a strain-specific vaccine to reach the market, using a universal vaccine was still cost cost-saving.

In a scenario where a strain-specific vaccine has 90% efficacy but is unavailable for two months after the start of the pandemic, the results from the model show that vaccinating only 10% of the population with a universal vaccine that has 10% efficacy at the start of the pandemic can save over $2 billion in societal costs (eg, direct medical costs and productivity losses from absenteeism). Given the time required to develop a strain-specific vaccine during a pandemic to match circulating strains of the virus, this highlights the importance of having a universal vaccine readily available as a stopgap.

“Our study shows the importance of giving as many people as possible in a population at least some degree of immune protection as soon as possible,” explains Bruce Y. Lee, MD, MBA, executive director of PHICOR and professor at CUNY SPH.

“Having a universal vaccine developed, stockpiled, and ready to go in the event of a pandemic could be a game-changer even if a more specific vaccine could be developed three to four months later.”

Generally, results from the model found that a universal vaccine would end up saving money if the cost to get a person vaccinated (eg, cost of the vaccine itself, distribution, administration, storage, research, and development) is as high as $10 390 from a societal perspective.

Source: CUNY Graduate School of Public Health and Health Policy

Liraglutide Results in Increased Insulin Sensitivity Independent of Weight Loss

Photo by Photomix Company on Pexels

A new Vanderbilt University study published in the journal Diabetes demonstrates that a glucagon-like peptide-1 receptor (GLP-1R) agonist, a member of a class of medication used to treat Type 2 diabetes and obesity, can lead to a rapid improvement in insulin sensitivity.

Insulin sensitivity is how responsive cells are to insulin; reduced insulin sensitivity or insulin resistance is a feature of Type 2 diabetes, so improving it can reduce the risk of developing the disease or improve its treatment.

GLP-1R agonists are medications that influence metabolism, such as decreasing blood sugar levels by promoting insulin secretion. Dipeptidyl peptidase 4 (DPP-4) inhibitors block the degradation of the body’s own endogenous GLP-1, as well as other peptide hormones such as glucose-dependent insulinotropic peptide (GIP).

“We know that GLP-1R agonists promote weight loss, but we were surprised to find that the GLP-1R agonist liraglutide also has rapid effects on insulin sensitivity, independent from weight loss,” said Mona Mashayekhi MD, PhD, assistant professor of Medicine in the Division of Diabetes, Endocrinology and Metabolism.

“This effect requires activation of the GLP-1 receptor, but increasing the body’s own endogenous GLP-1 through the use of the DPP4 inhibitor sitagliptin does not achieve similar effects.”

“Our research suggests that liraglutide, and presumably other GLP-1R agonists, are having important metabolic effects in a way that’s different from increasing endogenous GLP-1 levels, even though they’re using the same receptor. Future research will focus on potential mechanisms of how GLP-1R agonists are improving insulin sensitivity independent of weight loss.”

Eighty-eight individuals with obesity and pre-diabetes were randomized for 14 weeks to receive the GLP-1R agonist liraglutide, the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin, or weight loss without drug using a low-calorie diet.

To further investigate the GLP-1R-dependent effects of the treatments, the GLP-1R antagonist exendin and a placebo were given in a two-by-two crossover study during mixed meal tests.

Crossover studies allow the response of a subject to treatment A to be compared with the same subject’s response to treatment B.

Liraglutide was shown to rapidly improve insulin sensitivity as well as decrease blood glucose within two weeks of beginning treatment and before any weight loss.

“GLP-1R agonists are an exciting class of medications, given their strong glucose-lowering effects combined with tremendous weight-loss benefits, and they have transformed how we manage diabetes and obesity in the clinic,” Mashayekhi said.

“Since the number of medications in this class is rapidly expanding, a deeper understanding of the mechanisms of benefit is crucial so we can design the right drugs for the desired effects in the right patients.”

The investigators’ prior research demonstrated that liraglutide, but not sitagliptin or diet, improves measures of heart disease and inflammation.

This matches the clinical findings of reduced cardiovascular disease with GLP-1R agonist treatment.

Future studies will continue to explore both receptor- and weight loss-dependent effects of GLP-1R agonists in humans.

Source: Vanderbilt University Medical Center

A New Pain-free Way to Treat Ventricular Arrhythmia

Source: CC0

A breakthrough study sets the foundation of a ground-breaking treatment regimen for treating ventricular arrhythmia. The study, published in Nature Communications, demonstrates the design and feasibility of a new hydrogel-based pacing modality.

The urgent need for an effective therapeutic regimen for ventricular arrhythmia inspired a team led by Dr. Mehdi Razavi at The Texas Heart Institute (THI), to collaborate The University of Texas at Austin (UT Austin) Cockrell School of Engineering led by Dr. Elizabeth Cosgriff-Hernandez, to co-develop an innovative strategy that addresses the pathophysiology of re-entrant arrhythmia.

Ventricular arrhythmia, which occurs in the lower chambers of the heart or ventricles, is the leading cause of sudden cardiac death in the United States.

When heart rhythm abnormality occurs in a self-sustained manner, it is called re-entrant arrhythmia, which is usually fatal.

“Re-entry occurs mainly from delayed conduction in scarred heart tissues, usually after coronary artery occlusion during a heart attack, which can be corrected by enabling pacing in these regions,” said Dr. Razavi, a practicing cardiologist and cardiac electrophysiologist.

“These hydrogels then can access the scarred tissue, thereby enabling direct pacing of the otherwise inaccessible regions of the heart.”

Given hydrogels’ biostability, biocompatibility, tunable properties, and the ease of incorporating electrical conductivity, the scientists are exploring them as potential electrodes that can be easily delivered inside coronary veins.

A clinical advantage of the unique system is that ischemia can be avoided by delivering the hydrogel using the veins.

The researchers successfully deployed the innovative hydrogel technology through minimally invasive catheter delivery in a pig model.

“The hydrogels have significant conductive properties that enable simultaneous pacing from multiple sites along the length of the hydrogel and create a conduction highway similar to those in Purkinje fibers,” according to Dr. Cosgriff-Hernandez.

Today, arrhythmia is treatable with medicines and procedures that control the irregular rhythms.

The current anti-arrhythmic drugs on the market are not always effective; although the drugs slow the conduction velocity, they facilitate re-entry arrhythmia.

Moreover, these drugs can be toxic and can lead to the destruction of tissues near the diseased regions of the heart.

Even with the widely used interventional ablation therapies, arrhythmia recurs in a significant proportion of patients. None of these procedures address the mechanism of re-entry.

Cardiac defibrillators implanted to compensate for the shortfalls in the current therapy options are painful when delivering electric shocks to restore heart rhythm and can severely deteriorate the patient’s quality of life.

If left untreated, arrhythmia can damage the heart, brain, or other organs, leading to stroke or cardiac arrest, during which the heart suddenly and unexpectedly stops beating.

“When injected into target vessels, the conductive hydrogel conforms to the patient’s vessel morphology. Adding a traditional pacemaker to this gel allows for pacing that resembles the native conduction in the heart — effectively mimicking the native electrical rhythm of the heart — and extinguishes the cause for arrhythmia, providing painless defibrillation,” added Dr. Cosgriff-Hernandez.

The work demonstrates for the first time the ability to confer direct electrical stimulation of the native and scarred mid-myocardium through injectable hydrogel electrodes as a pacing modality.

With minimally invasive catheter delivery and standard pacemaker technologies, this study indicates the feasibility of a novel pacing modality that resembles native conduction, potentially eliminating lethal re-entrant arrhythmia and providing painless defibrillation, which can be successfully adopted in a clinical workflow.

The scientific advance is significant considering pain management is highly relevant to overall wellness for patients with heart, lung, and blood diseases.

Such innovation in painless defibrillation and preventing arrhythmia could revolutionize cardiac rhythm management.

Source: Texas Heart Institute 

Choice of Breast Cancer Surgery Facilities may Drive Inequality

Photo by Michelle Leman on Pexels

Including patients as partners for making decisions about their medical treatments is an important aspect of patient-centred care. A new study from England examined choices that patients with breast cancer make when considering where to have surgery for their condition and assessed how policies that offer such choices might affect inequalities in the health care system. The findings are published in CANCER.

For the study, investigators analysed data from the National Health Service (NHS), the publicly funded health care system in the United Kingdom that offers patients with cancer the opportunity to select any hospital providing cancer treatment, and identified all women diagnosed with breast cancer from 2016 to 2018 who had breast-conserving surgery or a mastectomy.

Records showed that 22 622 of 69,153 patients undergoing breast-conserving surgery (32.7%) and 7179 of 23 536 patients undergoing mastectomy (30.5%) bypassed their nearest hospital to receive surgery farther away from home. Women who were younger, without additional medical conditions, of white ethnic background, or lived in rural areas were more likely to travel to more distant hospitals.

Patients were more likely to be treated at hospitals classified as specialist breast reconstruction centres even if they personally were not undergoing breast reconstruction after surgery. Patients who had a mastectomy and immediate breast reconstruction were more likely to travel to hospitals that had surgeons with a strong media reputation for breast cancer surgery, and patients were less likely to travel to hospitals with shorter surgical waiting times. Patients did not seem to make choices based on hospitals’ research activity, quality rating, breast re-operation rates (to remove additional cancer cells that were missed), or status as a multidisciplinary cancer centre (where patients can receive all their care at one location).

The investigators noted that this separation – elderly patients, those with comorbidities, and those from ethnic minority backgrounds receiving care at their local hospital, while others travel to other hospitals and specialist centres – could further drive inequalities in access to quality care.

“As marginalized groups already face barriers to high-quality care, it is important for policy makers to consider measures that mitigate against the risks of increasing inequalities in access and outcomes, by for example providing free transport, accommodation, or even protection against loss of income,” said co-author Lu Han, PhD, of the London School of Hygiene & Tropical Medicine. “Moreover, patients prefer to access information on the quality of breast cancer care of the hospitals in their region at the start of the management pathway when a diagnosis is sought. Such information should be easy to understand and presented in a format that can support the trade-offs that patients have to make.”

Source: Wiley