Day: August 25, 2021

Weight Loss in 80% Following Series of Different Diets

Photo by i yunmai on Unsplash

In a study testing three successive and varying diets, nearly 80 percent of participants in a lost a “clinically significant” amount of body weight in less than two years.

The participants adhered to a sequence of a calorie-restrictive diet, a low-carb/high-fat diet and an intermittent fasting diet, losing 11.1 kilograms on average.

The results were published in the journal Nutrition.

“Almost 80 percent of participants lost a clinically significant amount of weight,” said study leader Rebecca Christensen, a PhD candidate at the Dalla Lana School of Public Health. “This is important because losing just five percent of your body weight is associated with improvements in cardiometabolic function and other health concerns.

“That lets us know that we have a lot of different tools in the toolbox to pick from when initiating a dietary intervention.”

Christensen says that staying on the same diet can be tough, which is why she is pleased that the study’s findings suggest there may be an alternative.

“It can be quite hard for patients to maintain dietary interventions,” she said. “This might be where successive diets have an advantage as changing things up makes it easier to stick to a diet.”

As more people attempt to shed their pandemic weight, Christensen said she also found that there is no right month to start your diet. Rather, it is just about getting started, adding that reaching a very low body mass index (BMI) need not be the goal.

“We know that that’s not necessarily feasible,” she said. “But the very least they are reaching the weight that we know is beneficial for their health which is why we want to do the intervention.”

Source: University of Toronto

Tissue Memory T Cells Could be the Future of Vaccination

Source: Pixabay

Researchers have described how tissue-resident memory T (TRM) cells  behave in different tissues around the body, in a step towards novel, long-lasting vaccines.

Applications include second generation COVID vaccines, that would target lung tissue directly.

TRM cells are an immune cell that are exclusively found in tissues, not in circulation or the blood, and have been found to be critical for immune protection against viral infection and are also able to control melanoma growth in the skin.

In this study, led by University of Melbourne Professor Laura Mackay and published in Nature Immunology, examined the behaviour of TRM cells in a number of different body tissues.

By comparing barrier organs that are exposed to the environment, like the skin, to solid organs such as the liver, the team found that the location in which TRMs are raised significantly impacts the way they contribute to immunity, demonstrating that “one size does not fit all” when it comes to these cells.

Postdoctoral researcher Dr Susan Christo said that discovering the distinct molecular signatures and behaviours of TRM cells in specific tissues will help the development of effective T cell-based vaccines and immunotherapies.

“For example, if you want effective T-cell mediated immunity against a respiratory virus like SARS-CoV-2 or influenza, you want to induce TRM cells in the lung. That way, the memory of the infection exists at the site of potential pathogen encounter,” Dr Christo said.

“We found that TRM cells act like chameleons when they enter into a new tissue — they rapidly adapt to the molecules and proteins around them and can take on a new ‘image’ or phenotype.

“The tissue surroundings also control how these cells behave — TRM cells in the skin are suppressed by a particular protein called TGF-b which acts like a handbrake to stop these cells from unnecessary activation that may cause autoimmunity, such as psoriasis, but still allows them to fight against dangers like melanoma.

“One key advantage of skin TRM cells is that they can last a really long time and will be ready to attack when the body is in true danger.

The team found the TRMs inside the liver do not have this TGF-b brake, and so have a greater ability to form a bigger pool of cells.

“You could think of them as generating a large army of soldiers that fight the infection. However liver TRMs have a shorter half-life and might not be around to fight future battles,” Dr Christo explained.

“To give the example of malaria, if you want to target immune cells in the liver, you need to work out what needs to be done to make those cells live longer.

“This is also the case for short-lived TRM cells in the lung, which has significant implications on the durability of vaccines against the flu and COVID. Therefore, our study provided the first evidence of what our immune cells need to last the distance and protect us for a long time.”

Source: Medical Xpress

CT Scans Reveal Lung Destruction in Asthmatics

Source: Pixabay CC0

A new study using CT scans have revealed significant changes indicating lung destruction in some asthmatics.

Clinicians have long thought that some people with asthma experience declines in their lung function, called fixed airflow obstruction (FAO), due to changes to their airways. In this study published in The Journal of Allergy and Clinical Immunologyresearchers have found that this issue could extend to the surrounding lung tissue.

Respirologist Kaoruko Shimizu at Hokkaido University said, “Bronchial asthma is considered to be mainly due to inflammation and remodeling of the larger respiratory airways. But not all asthmatics improve with the typical treatments prescribed to alleviate this condition. We wanted to know if changes to the surrounding lung tissue induced a decline in pulmonary function over time in this subgroup of patients.”

Shimizu and her colleagues applied a novel computer tomography (CT)-based approach to detect changes in lung tissue. In this approach, the scientists examined CT scans employing an index called “exponent D” for areas of reduced lung density with increasing coalescence of neighbouring airspaces, which indicates emphysema, or the destruction of air sacs. Airway obstruction was measured by testing the ability of people with asthma to forcefully exhale air in one second. This ability is reduced when the airways are narrower.

The tests examined around 200 smokers and non-smokers with varying degrees of asthma, who were then followed up annually for five years.

People with asthma who experienced persistent airflow limitation, regardless of the severity of their asthma or their smoking status, exhibited constricted airways and also showed signs of lung tissue destruction, the researchers found.

The observed changes to lung tissue in this subgroup of asthmatic patients were not associated with the typical inflammatory markers linked to bronchial asthma. This is important, because it could explain why conventional anti-inflammatory treatments are not as successful in this group.

Future studies should investigate lung destruction in asthma, enabling more personalised management, said Shimizu.

Source: Hokkaido University

Periodontitis Linked to Risk of Cardiovascular Disease

Source: Unsplash CC0

A new study has found that periodontitis is associated with an increased risk of cardiovascular disease: the more severe the periodontitis, the higher the risk. Those who had a previous heart attack showed an even stronger association.

Study author Dr Giulia Ferrannini of the Karolinska Institute said: “Our study suggests that dental screening programmes including regular check-ups and education on proper dental hygiene may help to prevent first and subsequent heart events.”

Periodontitis, a disease of the tissue surrounding the tooth structure, has been associated with a number of diseases. The Swedish PAROKRANK (Periodontitis and its Relation to Coronary Artery Disease) study previously demonstrated that there was a significantly higher prevalence of periodontitis in first time heart attack patients compared to their healthy peers.

In this long-term follow-up of PAROKRANK, participants investigated whether the periodontitis, both in heart attack patients and their healthy peers, was related to an increased risk of new cardiovascular events over time.

The analysis included 1587 participants aged an average of 62 years. Participants underwent a dental examination between 2010 and 2014: 985 were classified as healthy, 489 had moderate periodontitis, and 113 had severe periodontitis. Participants were followed up for the occurrence of cardiovascular events and death. The primary endpoint was a composite of all-cause death, non-fatal heart attack or stroke, or severe heart failure. Follow-up data were collected until the end of 2018 from Swedish national death and patient registries.

Over an average 6.2 years of follow-up, there were 205 primary endpoint events. In the overall cohort, participants with periodontitis at baseline had 49% higher odds of the primary endpoint compared to those with healthy gums, increasing with periodontitis severity.
Assessing heart attack patients and healthy controls separately, graded relationship between gum disease severity and the primary endpoint was significant only for the patients group.

Dr Ferrannini said: “The risk of experiencing a cardiovascular event during follow-up was higher in participants with periodontitis, increasing in parallel with the severity. This was particularly apparent in patients who had already experienced a myocardial infarction.”

She added: “We postulate that the damage of periodontal tissues in people with gum disease may facilitate the transfer of germs into the bloodstream. This could accelerate harmful changes to the blood vessels and/or enhance systemic inflammation that is harmful to the vessels.”

“It is important to underline that the quality of care in Sweden is high, as confirmed by the overall low number of total events during follow-up. Despite this, gum disease was linked with an elevated likelihood of cardiovascular disease or death,” Dr Ferrannini concluded.

Source: European Society of Cardiology

Small Trial Sees ‘Astounding’ Effect of Fenofibrate in Severe COVID

Source: Fusion Medical Animation on Unsplash

A small interventional trial with 15 severely ill COVID patients showed an ‘astounding’ effect of fenofibrate as a treatment.

Recently, Professor Yaakov Nahmias’ team at the Hebrew University of Jerusalem (HU) reported that COVID causes abnormal accumulation of lipids, known to initiate severe inflammation through a process called lipotoxicity. In 2020, the researchers conducted lab testing of fenofibrate, a lipid-lowering drug, showing it both reduced lung cell damage while blocked virus replication. These results have since been confirmed by other studies, and in October 2020 an observational study was reported to support the original findings. This led to an interventional, single-arm open-label study to validate the findings.

The study recruited 15 severe-hospitalised COVID patients with pneumonia requiring oxygen support, who were given 145 mg/day of fenofibrate for 10 days in addition to standard care and continuously monitored for disease progression and outcomes. 

‘Astounding’ results
“The results were astounding,” Prof Nahmias declared. “Progressive inflammation markers, that are the hallmark of deteriorative COVID, dropped within 48 hours of treatment. Moreover, 14 of the 15 severe patients didn’t require oxygen support within a week of treatment, while historical records show that the vast majority severe patients treated with the standard of care require lengthy respiratory support,” he added. 

No ‘silver bullet’
Fenofibrate is a well-known, FDA-approved drug for the treatment of hypertriglyceridemia, primary hypercholesterolemia, or mixed dyslipidemia and has a good safety profile. “There are no silver bullets,” cautioned Nahmias, “but fenofibrate is far safer than other drugs proposed to date, and its mechanism of action makes is less likely to be variant-specific.”

“All patients were discharged within less than a week after the treatment began and were discharged to complete the 10-day treatment at home, with no drug-related adverse events reported,” noted Professor Shlomo Maayan, head of Infectious Disease Unit at Barzilai, where the study was conducted. “Further, fewer patients reported COVID side effects during their 4-week follow-up appointment,” he added. These preliminary findings are promising for patients who severe the acute phase of severe COVID.

However, the researchers stressed that while the results were extremely promising, only randomised placebo-controlled studies can serve as basis for clinical decisions. “We entered the second phase of the study and are actively recruiting patients,” explained Prof Nahmias, noting that two Phase 3 studies are already being conducted.

The findings, which are currently under peer review, were released on Research Square.

Source: Medical Xpress

Abrocitinib Promising in Teen Atopic Dermatitis

Credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health

Following treatment with the investigational oral Janus kinase (JAK) inhibitor abrocitinib plus topical therapy, teenagers with moderate or severe atopic dermatitis (AD) showed significant improvement to placebo, according to a new study published in JAMA Dermatology.

Up to 20% of children and adolescents are affected by AD, which has an adverse impact on QoL, academic performance, and social relationships, as well as the QoL of caregivers. Subcutaneous dupilumab is safe and effective in moderate-to-severe AD in adolescents, but there is a lack of an oral option, they said.

Nearly half of the patients had clear or almost clear skin by clinician assessment (IGA), and about 70% of patients treated with either of two doses of the JAK inhibitor had at least 75% improvement in the Eczema Area and Severity Index (EASI-75). In contrast, a fourth of patients who received placebo in addition to topical therapy met the clinician assessment outcome and about 40% met EASI-75 criteria.

Abrocitinib, a JAK-1-selective inhibitor, had already shown to be tolerable and effective in adults. The present trial included 285 patients aged 12 to 17, with coprimary endpoints being an IGA score of 0/1 with at least a two-grade improvement from baseline, plus an EASI-75 response, with both outcomes assessed at 12 weeks. Secondary endpoints included improvement in pruritis.

An IGA 0/1 response was seen in 46.2% of patients treated with abrocitinib 200 mg and 41.6% of those assigned to abrocitinib 100 mg, compared to 24.5% in the placebo group. The proportion of patients who met EASI-75 response criteria was 72% with abrocitinib 200 mg, 68.5% with abrocitinib 100 mg, and 41.5% with placebo. Significant improvement was seen in pruritis compared to placebo, showing an improvement in pruritis. The researchers noted that improved indicators could lead to better sleep and QoL indicators.

AE rates were 62.8% with the higher dose of abrocitinib, 56.8% with the lower dose, and 52.1% in the placebo group, with nausea occurring more often with abrocitinib 200 mg than with abrocitinib 100 mg (18.1% vs 7.4%).

These results suggest abrocitinib has great potential for treating teenage AD, said John C. Browning, MD, of Texas Dermatology and Laser Specialists in Dallas. Current there are no JAK inhibitors indicated for AD, and an oral option is very exciting he to MedPage Today via email. “Not everyone responds to current systemic therapies, so there is a definite need for new treatments.”

“I think more teens will be open to trying an oral option, but they will need to be committed to taking it every day,” he said, adding that compliance is an issue. “Both abrocitinib and dupilumab are effective, so there is not a tradeoff in going from injections to oral therapy.”

Source: MedPage Today