Day: August 24, 2021

Categories : Cardiovascular Disease Diet and NutritionTags :

Gut Microbiome Moderates BP Benefits of Flavonoids

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Flavonoid-rich foods, such as berries, apples, pears and wine, seem to reduce hypertension due in part to characteristics of the gut microbiome, according to a new study published in Hypertension.

“Our gut microbiome plays a key role in metabolising flavonoids to enhance their cardioprotective effects, and this study provides evidence to suggest these blood pressure-lowering effects are achievable with simple changes to the daily diet,” said lead researcher Aedín Cassidy, PhD, chair and professor in nutrition and preventive medicine at the Institute for Global Food Security at Queen’s University.

Flavonoids are compounds found naturally in fruits, vegetables and plant-based foods such as tea, chocolate and wine. They have miscellaneous favourable biochemical and antioxidant effects associated with various diseases such as cancer, Alzheimer’s disease, atherosclerosis, etc. Flavonoids are broken down by the body’s gut microbiome. Recent studies found a link between gut microbiota, the microorganisms in the human digestive tract, and cardiovascular disease (CVD). Gut microbiota are highly individual, and seem to be associated with CVD.

With studies suggesting flavonoids may reduce heart disease risk, the researchers investigaged the role of the gut microbiome in this. 
Researchers drew on a group of 904 adults between the ages of 25 and 82, 57% men from Germany’s PopGen biobank. Researchers evaluated the participants’ food intake, gut microbiome and blood pressure levels together with other clinical and molecular phenotyping at regular follow-up examinations.

Participants’ intake of flavonoid-rich foods during the previous year was calculated from a self-reported food questionnaire detailing the frequency and quantity eaten of 112 foods.

Participants’ gut microbiomes were assessed by faecal bacterial DNA in stool samples. After an overnight fast, participants’ blood pressure levels were measured. Researchers also collected participants’ lifestyle information, and measured BMI and other physical characteristics,

The analysis found that:

  • Study participants with the highest intake of flavonoid-rich foods, including berries, red wine, apples and pears, had lower systolic blood pressure levels, as well as greater gut microbiome diversity than the participants with the lowest levels of flavonoid-rich food intake.
  • Up to 15.2% of the association between flavonoid-rich foods and systolic blood pressure could be explained by the diversity found in participants’ gut microbiome.
  • Eating 1.6 servings of berries per day (one serving = 80 grams, or 1 cup) was associated with an average reduction in systolic blood pressure levels of 4.1 mm Hg. 12% of the association was explained by gut microbiome factors.
  • Drinking 2.8 glasses (125 ml of wine per glass) of red wine a week was associated with an average of 3.7 mm Hg lower systolic blood pressure level, of which 15% could be explained by the gut microbiome.

“Our findings indicate future trials should look at participants according to metabolic profile in order to more accurately study the roles of metabolism and the gut microbiome in regulating the effects of flavonoids on blood pressure,” said Cassidy. “A better understanding of the highly individual variability of flavonoid metabolism could very well explain why some people have greater cardiovascular protection benefits from flavonoid-rich foods than others.”

While this study suggests potential benefits to consuming red wine, the American Heart Association suggests that if you don’t drink alcohol already, you shouldn’t start.

Study limitations include not being able to account for all factors, such as genetics and lifestyle. The authors noted the focus of this study was on specific foods rich in flavonoids, not all food and beverages with flavonoids.

Source: Medical Xpress

Categories : COVID HospitalsTags :

Prone Positioning Reduces Need for Mechanical Ventilation

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Source: Martha Dominguez de Gouveia on Unsplash

A ‘meta-trial’ of 1100 hospitalised COVID patients requiring high-flow nasal cannula oxygen therapy suggests that prone positioning soon after admission can significantly reduce the need for mechanical ventilation.

While acute respiratory distress syndrome patients have been placed prone for years by critical care specialists, this study provides clinical evidence needed to support the use of prone positioning for patients with COVID requiring high-flow nasal cannula oxygen therapy.

The findings, published today in the Lancet Respiratory Medicine, were conducted on severely ill COVID patients between April 2020 and January 2021.

“Breathing in the prone position helps the lungs work more efficiently,” explained the study’s lead author Dr. Jie Li, associate professor and respiratory therapist at Rush University Medical Center. “When people with severe oxygenation issues are laying on their stomachs, it results in better matching of the blood flow and ventilation in the lungs which improves blood oxygen levels.”

Prof Li noted that several interventions are available to improve oxygenation in critically ill patients, but that there was little outcomes-focused clinical evidence to show that prone positioning prior to mechanical ventilation is beneficial.

Adult patients with COVID needing respiratory support from a high-flow nasal cannula agreed to participate in this clinical trial, and were randomly assigned to the supine or prone positioning groups. They were asked to stay in that position for as long as they could tolerate. Both positioning groups received high-flow oxygen therapy and standard medical management.

Patients were continually monitored to determine if mechanical ventilation was needed. This study’s data showed that patients in the prone positioning group were significantly less likely to require mechanical ventilation (33% in the awake prone positioning group vs 40% in the supine group).

Another study lead author, Stephan Ehrmann, MD, PhD, said that “for the clinical implications of our study, awake prone positioning is a safe intervention that reduces the risk of treatment failure in acute severe hypoxemic respiratory failure due to COVID-19. Our findings support the routine implementation of awake prone positioning in critically ill patients with COVID19 requiring high flow nasal cannula oxygen therapy. It appears important that clinicians improve patient comfort during prone positioning, so the patient can stay in the position for at least 8 hours a day.”

Reducing the need for mechanical ventilation cuts down on resources needed. “Ventilators can indeed save the lives of people who are no longer able to breathe on their own. That said, we now have strategies to keep patients off the ventilator, saving those devices for the sickest patients who truly need them.” Prof Li added.

Source: Medical Xpress

Categories : Cardiovascular DiseaseTags :

Parental History Not The Only Premature Heart Attack Risk

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A new study has shown that, while parental history is a contributing factor, young heart attack victims are more likely to be smokers, obese, and have high blood pressure or diabetes compared to their peers.

“The findings underline the importance of preventing smoking and overweight in children and adolescents in order to reduce the likelihood of heart disease later in life,” said study author Professor Harm Wienbergen of the Bremen Institute for Heart and Circulation Research.

“Understanding the reasons for heart attacks in young adults is important from a societal perspective due to their employment and family responsibilities,” he continued. “However, there are limited data on the predictors of heart events in this group.”

The researchers compared the clinical characteristics of consecutive patients admitted to hospital with acute myocardial infarction at 45 years of age or younger against randomly selected individuals from the German population. Cases and controls were matched according to age and gender. The case-control study enrolled a total of 522 patients with 1191 matched controls from a national database.

The researchers found that the proportion of active smokers was more than three-fold higher in the young heart attack group compared to the general population (82.4% vs 24.1%). Patients were more likely to have high blood pressure (25.1% vs 0.5%), diabetes (11.7% vs 1.7%) and a parental history of premature heart attack (27.6% vs 8.1%) compared to their peers. Patients were more often obese, with a median body mass index (BMI) of 28.4 kg/m2 compared to 25.5 kg/m2 for controls. In contrast, the proportion consuming alcohol at least four times a week was higher in the general population (11.2%) compared to heart patients (7.1%).

The researchers analysed the independent risk factors for the occurrence of acute myocardial infarction at 45 years of age or younger. The analysis was adjusted for age, sex, high blood pressure, diabetes, active smoking, body mass index, alcohol consumption, years of school education, and birth in Germany.

Hypertension was associated with an 85-fold odds of a heart attack aged 45 or under. The corresponding odds of a premature heart attack associated with active smoking, diabetes mellitus, parental history and obesity (BMI 30 kg/m2 or above) were 12, 5, 3 and 2. Alcohol consumption was associated with a lower odds of heart attack at a young age with an odds ratio of 0.3.

Prof Wienbergen said: “Our study shows that smoking and metabolic factors, such as hypertension, diabetes and obesity, are strongly associated with an increased likelihood of premature acute myocardial infarction. A protective effect of moderate alcohol consumption has been described by other studies and is confirmed in the present analysis of young patients.”

He concluded: “Our study suggests that family history is not the only predisposing factor for early heart attacks. The findings add impetus to the argument that young people should be educated about why it is important to avoid smoking and have a healthy body weight.”

Source: European Society of Cardiology

Categories : Cancer PaediatricsTags :

A Brief Window of Opportunity to Halt Certain Paediatric Gliomas

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Photo by Jeffrey Riley on Unsplash

In a pre-clinical study, investigators identified a vulnerability in a developmental signaling pathway that can be hijacked to drive paediatric low-grade glioma (pLGG) formation.

The study, published in Developmental Cell, demonstrated that targeted treatment prevents tumor formation, long before irreversible damage to the optic nerve can cause permanent loss of vision. This finding will inform chemo-prevention therapeutic trials in the future.

Brain tumours are the most common solid tumours in children, the most prevalent of which are pLGGs, of which 10 to 15% arise in patients with the familial cancer predisposition syndrome known as neurofibromatosis type 1 (NF1). Thi increases risks of developing tumours along the nerves and in the brain.

Almost 20% of children with NF1 develop pLGGs along the optic pathway, also known as NF1-associated optic pathway glioma (NF1-OPG). Despite many advances in cancer therapy, there are no definitive therapies available that prevent or alleviate the neurological deficits (i.e. vision loss) and that could improve the quality of life.

“The evidence presented can inform chemoprevention therapeutic trials for children with NF1-OPG. This therapeutic strategy may also be applicable to children with the developmental disorders that are at high risk of developing pediatric tumors, such as other RASopathies,” said Yuan Zhu, PhD, scientific director and Gilbert Family Endowed professor at the Gilbert Family Neurofibromatosis Institute and associate director of the Center for Cancer and Immunology Research.

The mechanism of vulnerability to pLGGs during development is not fully understood. It could be that the cell population of origin for this debilitating tumour is transiently proliferative during development. The NF1 gene produces a protein that inhibits MEK/ERK signalling, thereby helping regulate normal cell proliferation, survival and differentiation. With loss of NF1 function, it abnormally activates the MEK/ERK signalling pathway, leading to tumour formation.

Certain transient cells present during development of the brain and optic nerve are vulnerable to tumour formation because they depend on MEK/ERK signalling. Researchers identified cells dependent on the pathway and grew during a transient developmental window as the lineage-of-origin for NF1-OPG in the optic nerve. They then used a genetically engineered pre-clinical model to design a transient, low-dose chemo-preventative strategy, which prevented these tumours entirely.

“When we provided a dose-dependent inhibition of MEK/ERK signaling, it rescued the emergence and increase of brain lipid binding protein-expressing (BLBP+) migrating GPs glial progenitors, preventing NF1-OPG formation,” the researchers wrote. “Equally importantly, the degree of ERK inhibition required for preventing NF1-OPG formation also greatly improved the health and survival of the NF1-deficient model.”

Clinical trials using MEK inhibitors (MEKi) are underway for children as young as 1 month old, making the design of a chemo-preventative trial using a MEKi to treat children with NF1 more feasible. This treatment approach might not only prevent OPG formation, but also other NF1-associated and RASopathies-associated developmental defects and tumours.

Source: Children’s National Hospital

Categories : Diseases, Syndromes and ConditionsTags :

Another COVID-scale Pandemic in 59 Years ‘Statistically Likely’

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A new study based on 400 years of historical records asserts that extreme pandemic events such as COVID are more common than believed.

The Duke University study, published in Proceedings of the National Academy of Sciences, used records of past outbreaks to estimate the intensity of those events and the yearly probability of them recurring.

It found the probability of a pandemic with similar impact to COVID is about 2% in any year, meaning that someone born in the year 2000 by now would have about a 38% chance of experiencing one. That probability is only increasing, highlighting the need to adjust perceptions of pandemic risks and expectations for preparedness, the researchers said.

“The most important takeaway is that large pandemics like COVID and the Spanish flu are relatively likely,” said study co-author William Pan, PhD, associate professor of global environmental health at Duke. The understanding that pandemics are not so rare should raise the priority of future prevention and control efforts, he said.

The study employed new statistical methods to measure the scale and frequency of disease outbreaks for which there was no immediate medical intervention over the past four centuries. Their analysis, including deadly pathogens including plague, smallpox, cholera, typhus and novel influenza viruses, found pandemics occurred with great variability in the past. But they also identified patterns that allowed them to describe the probabilities of similar-scale events happening again.

In the case of a pandemic like the Spanish flu, which killed more than 30 million people between 1918 and 1920, the probability of a pandemic of similar magnitude occurring ranged from 0.3% to 1.9% per year over the time period studied. Taken together, it is statistically likely that such a massive pandemic would occur within the next 400 years.

However, the data also show that the risk of intense outbreaks is increasing rapidly. Based on the increasing rate at which novel pathogens such as SARS-CoV-2 have broken loose in human populations in the past 50 years, the study estimates that the probability of novel disease outbreaks will likely triple in the next few decades.

With this increased risk factor, the researchers estimate that a COVID-scale pandemic is likely within a span of 59 years (by the year 2090), a result they write is “much lower than intuitively expected.” Although not included in the paper, they also calculated the probability of a pandemic capable of eliminating all human life, finding it statistically likely within the next 12 000 years. 

That does not mean it will be 59 years before the next COVID-like pandemic, nor that the Spanish flu for another 300 years. Such events are equally probable in any year during the span, said Duke University Professor Gabriel Katul, another of the paper’s authors.

“When a 100-year flood occurs today, one may erroneously presume that one can afford to wait another 100 years before experiencing another such event. This impression is false. One can get another 100-year flood the next year,” explained Prof Katul.

Dr Pan noted that population growth, changes in food systems, environmental degradation and more frequent contact between humans and disease-harboring animals all may be significant factors for increasing frequency of pandemics. However, he stresses that the statistical techniques are not to explain the pandemics.

However, he hopes the study will spark deeper exploration of the factors that may be making devastating pandemics more likely – and how to counteract them.

“This points to the importance of early response to disease outbreaks and building capacity for pandemic surveillance at the local and global scales, as well as for setting a research agenda for understanding why large outbreaks are becoming more common,” Dr Pan said.

Source: Duke University

Categories : COVIDTags :

Pfizer Vaccine Fully Approved in US

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On Monday, the US Food and Drug administration approved the Pfizer/BioNTech COVID vaccine, the first vaccine against the novel coronavirus to receive full approval.

The vaccine, which will be marketed as Comirnaty, can be used for individuals ages 16 and older for COVID prevention. However, the vaccine is still under emergency use authorisation (EUA) for adolescents ages 12-15, the agency said.

FDA Acting Commissioner, Janet Woodcock, MD, said in a statement: “While this and other vaccines have met the FDA’s rigorous, scientific standards for emergency use authorisation, as the first FDA-approved COVID vaccine, the public can be very confident that this vaccine meets the high standards for safety, effectiveness, and manufacturing quality the FDA requires of an approved product.”

At a media briefing, Peter Marks, MD, PhD, the director for the Center for Biologics Evaluation and Research at FDA, detailed the meticulous process used for conducting a review of a biologics license application for full approval, including invidivual analysis of adverse events.

Since 11 December, 2020, the vaccine has been under an EUA for individuals ages 16 and older. Evidence for the full approval comes from expanded phase III trial safety and efficacy data released by the manufacturer this April. An analysis of 927 confirmed cases in the trial’s 44 000 participants found that 7 days after the second dose, Comirnaty had a 91.3% efficacy against symptomatic COVID through 6 months.

More than half of the participants had over 4 months of safety data, including 12 000 people who were followed up through 6 months. Injection site pain, fatigue, headache, muscle or joint pain, and fever were the most common adverse events. A slight increase in risk for myocarditis and pericarditis up to 7 days after the second dose was noted, particularly in males under 40 (peaking in ages 12-17), but symptoms resolved completely.

Trial data was collected before the Delta variant became the dominant strain in the US, Dr Marks noted, Israeli “real world” suggest the vaccine still retains effectiveness but wanes. This is something the agency will follow. 

Former FDA commissioner Dr. Mark McClellan, who now directs the Duke-Margolis Center for Health Policy, spoke to the media about the approval, saying surveys showed that it will help sway vaccine holdouts.

“I do think it will make a difference. Maybe not a large number of people running out and getting a vaccine today. At this point we’ve got a little bit over 70 percent of Americans who are eligible for the vaccine have gotten at least one dose. That’s about 87 million Americans who are eligible who haven’t. Out of those, according to some recent surveys, about 30 percent say the full approval of the Pfizer vaccine would make a difference in their decisions.”

Source: MedPage Today