Month: June 2022

Norovirus and Other Enteric Viruses can Spread via Saliva

A microscopic view of salivary gland acinar epithelial cells (pink) infected with rotavirus (green), a type of enteric virus, in a mouse. Credit: Nihal Altan-Bonnet (NIH/NHLBI)

Enteric viruses can grow in the salivary glands of mice and spread through their saliva, scientists at the National Institutes of Health have discovered. Enteric viruses transmission through saliva suggests that coughing, talking, sneezing, sharing food and utensils, and even kissing all have the potential for spreading the viruses.

The findings, which appear in the journal Nature, could lead to better ways to prevent, diagnose, and treat diseases caused by these viruses, potentially saving lives.

Enteric viruses, such as noroviruses and rotaviruses, have long been known to spread by eating food or drinking liquids contaminated with faecal matter containing these viruses. Enteric viruses were thought to bypass the salivary gland and target the intestines, exiting later through faeces. Though another route of transmission was suspected, this theory remained largely untested until now.

Now researchers will need to confirm that salivary transmission of enteric viruses is possible in humans. If they find that it is, the researchers said, they may also discover that this route of transmission is even more common than the conventional route. A finding such as that could help explain, they said, why the high number of enteric virus infections each year worldwide fails to adequately account for faecal contamination as the sole transmission route.

“This is completely new territory because these viruses were thought to only grow in the intestines,” said senior author Nihal Altan-Bonnet, PhD. “Salivary transmission of enteric viruses is another layer of transmission we didn’t know about. It is an entirely new way of thinking about how these viruses can transmit, how they can be diagnosed, and, most importantly, how their spread might be mitigated.”

Dr Altan-Bonnet, who has studied enteric viruses for years, said the discovery was completely serendipitous. Her team had been conducting experiments with enteric viruses in infant mice, which are the animal models of choice for studying these infections because their immature digestive and immune systems make them susceptible to infections.

For the current study, the researchers fed a group of newborn mice that were less than 10 days old with either norovirus or rotavirus. The mouse pups were then returned to cages and allowed to suckle their mothers, who were initially virus-free. After just a day, one of Dr Altan-Bonnet’s team members, NHLBI researcher and study co-author Sourish Ghosh, PhD, noticed something unusual. The mouse pups showed a surge in IgA antibodies – important disease-fighting components – in their guts. This was surprising considering that the immune systems of the mouse pups were immature and not expected to make their own antibodies at this stage.

Ghosh also noticed other unusual things: The viruses were replicating in the mothers’ milk duct cells at high levels. When Dr Ghosh collected milk from the breasts of the mouse mothers, he found that the timing and levels of the IgA surge in the mothers’ milk mirrored the timing and levels of the IgA surge in the guts of their pups. It seemed the infection in the mothers’ breasts had boosted the production of virus-fighting IgA antibodies in their breast milk, which ultimately helped clear the infection in their pups, the researchers said.

Eager to know how the viruses got into the mothers’ breast tissue in the first place, the researchers conducted additional experiments and found that the mouse pups had not transmitted the viruses to their mothers through the conventional route – by leaving contaminated faeces in a shared living space for their mothers to ingest. That’s when the researchers decided to see whether the viruses in the mothers’ breast tissue might have come from the saliva of the infected pups and somehow spread during breastfeeding.

To test the theory, Dr Ghosh collected saliva samples and salivary glands from the mouse pups and found that the salivary glands were replicating these viruses at very high levels and shedding the viruses into the saliva in large amounts. Additional experiments quickly confirmed the salivary theory: suckling had caused both mother-to-pup and pup-to-mother viral transmission.

Source: National Institutes of Health

Sleep Now Part of American Heart Association’s Cardiovascular Health Score

Sleeping man
Photo by Mert Kahveci on Unsplash

Sleep duration is now considered an essential component for ideal heart and brain health. Life’s Essential 8™ cardiovascular health score replaces Life’s Simple 7™, according to a new American Heart Association advisory published in Circulation.

Other updates to the measures of optimal cardiovascular health, now for anyone ages 2 and older, include a new guide to assess diet; accounting for exposure to second-hand smoke and vaping; using non-HDL cholesterol instead of total cholesterol to measure blood lipids; and expanding the blood sugar measure to include haemoglobin A1c to assess Type 2 diabetes risk.

“The new metric of sleep duration reflects the latest research findings: sleep impacts overall health, and people who have healthier sleep patterns manage health factors such as weight, blood pressure or risk for Type 2 diabetes more effectively,” said American Heart Association President Professor Donald M. Lloyd-Jones, MD, who led the advisory writing group. “In addition, advances in ways to measure sleep, such as with wearable devices, now offer people the ability to reliably and routinely monitor their sleep habits at home.”

The Association first defined the seven metrics for cardiovascular health in 2010 to identify the specific health behaviours and health factors that drive optimal heart and brain health.

After 12 years and more than 2400 scientific papers on the topic, new discoveries in heart and brain health and in the ways to measure cardiovascular health provided an opportunity to revisit each health component in more detail. Four of the original metrics have been redefined for consistency with newer clinical guidelines or compatibility with new measurement tools. Also, the scoring system can now be applied to anyone ages 2 and older.

The Life’s Essential 8™ components of optimal cardiovascular health are divided into two major areas: health behaviours (diet, physical activity, nicotine exposure and sleep) and health factors (BMI, cholesterol levels, blood sugar and blood pressure). “The idea of optimal cardiovascular health is important because it gives people positive goals to work toward at any stage of life,” said Lloyd-Jones.

“Life’s Simple 7™ has served as a proven, powerful tool for understanding how to achieve healthy aging and ways to improve cardiovascular health while decreasing the risks of developing heart disease and stroke, as well as cancer, dementia and many other chronic diseases,” he said. “Given the evolving research, it was important to address some limitations to the original metrics, particularly in ways they’ve been applied to people from diverse racial and ethnic populations.”

Prof Lloyd-Jones explained that some of the previous metrics, such as diet, were not as sensitive to differences among people, or as responsive to changes over time within a single individual. “We felt it was the right time to conduct a comprehensive review of the latest research to refine the existing metrics and consider any new metrics that add value to assessing cardiovascular health for all people.”

Life’s Essential 8™ includes:

  1. Diet (updated):  A new guide to assess diet quality for adults and children at the individual level (for individual health care and dietary counselling) and at the population level (for research and public health purposes).
  2. Physical activity (no changes): The optimal level is 150 minutes of moderate physical activity or more per week or 75 minutes per week of vigorous-intensity physical activity for adults; 420 minutes or more per week for children ages 6 and older; and age-specific modifications for younger children.
  3. Nicotine exposure (updated): Use of inhaled nicotine-delivery systems, which includes e-cigarettes or vaping devices, is added since the previous metric only monitored traditional, combustible cigarettes. This reflects use by adults and youth and their implications on long-term health. Life’s Essential 8™ also includes second-hand smoke exposure for children and adults.
  4. Sleep duration (new): Sleep duration is associated with cardiovascular health. Measured by average hours of sleep per night, the ideal level is 7-9 hours daily for adults. Ideal daily sleep ranges for children are 10-16 hours per 24 hours for ages 5 and younger; 9-12 hours for ages 6-12 years; and 8-10 hours for ages 13-18 years.
  5. Body mass index (no changes): The writing group acknowledges that body mass index (BMI) is an imperfect metric, yet it is easily calculated and widely available; therefore, BMI continues as a reasonable gauge to assess weight categories that may lead to health problems. BMI of 18.5–24.9 is associated with the highest levels of cardiovascular health. The writing group notes that BMI ranges and the subsequent health risks associated with them may differ among people from diverse racial or ethnic backgrounds or ancestry. This aligns with the World Health Organization’s recommendations to adjust BMI ranges for people of Asian or Pacific Islander ancestry because recent evidence indicates their risk of conditions such as  CVD or Type 2 diabetes is higher at a lower BMI.
  6. Blood lipids (updated): The metric for blood lipids (cholesterol and triglycerides) is updated to use non-HDL cholesterol as the preferred number to monitor, rather than total cholesterol. Other forms of cholesterol, when high, are linked to CVD risk. This shift is made because non-HDL cholesterol can be measured without fasting beforehand (thereby increasing its availability at any time of day and implementation at more appointments) and reliably calculated among all people.
  7. Blood glucose (updated): This metric is expanded to include the option of haemoglobin A1c readings or blood glucose levels for people with or without Type 1 or Type 2 diabetes or prediabetes. Haemoglobin A1c can better reflect long-term glycaemic control.
  8. Blood pressure (no changes): Blood pressure criteria remain unchanged from the Association’s 2017 guidelines that established levels less than 120/80 mm Hg as optimal, and hypertension defined as 130-139 mm Hg systolic pressure (the top number in a reading) or 80-89 mm Hg diastolic pressure (bottom number).

Each component of Life’s Essential 8™, which is assessed by the My Life Check tool, has an updated scoring system ranging from 0 to 100 points. The overall cardiovascular health score from 0 to 100 points is the average of the scores for each of the 8 health measures. Overall scores below 50 indicate “poor” cardiovascular health, and 50-79 is considered “moderate” cardiovascular health. Scores of 80 and above indicate “high” cardiovascular health. The advisory recommends measuring cholesterol, blood sugar, blood pressure, height and weight at least every five years for the most complete and accurate Life’s Essential 8™ score.

The writing group also reviewed data about the impacts of stress, mental health and social determinants of health, such as access to health care, income or education level, and structural racism, which are critical to understanding the foundations of health, particularly among people from diverse racial and ethnic populations.

“We considered social determinants of health carefully in our update and determined more research is needed on these components to establish their measurement and inclusion in the future,” said Lloyd-Jones. “Nonetheless, social and structural determinants, as well as psychological health and well-being, are critical, foundational factors in an individual’s or a community’s opportunity to preserve and improve cardiovascular health. We must consider and address all of these issues for people to have the opportunity for a full, healthy life as measured by Life’s Essential 8™.”

Source: American Heart Association

Greater Hospitalisation or ED Visit Risk for Cannabis Users

Photo by RODNAE Productions from Pexels

Compared to non-users, cannabis users have 22% higher rates in emergency department (ED) visits and hospitalisations, according to new research findings. The study, published in BMJ Open Respiratory Research revealed that serious physical injury and respiratory-reasons were the two leading causes of ED visits and hospitalisations among cannabis users.

The findings suggest an association between cannabis use and negative health events, which the researchers say should underline the need to educate and remind the public of the harmful impacts of cannabis on health.

“Our research demonstrates that cannabis use in the general population is associated with heightened risk of clinically serious negative outcomes, specifically, needing to present to the ED or be admitted to hospital,” said Dr Nicholas Vozoris, lead author, a respirologist at St. Michael’s and an associate scientist at the hospital’s Li Ka Shing Knowledge Institute.

“Unlike tobacco, there is some uncertainty or controversy regarding the adverse health impacts of cannabis. Some individuals may perceive that cannabis has some health benefits and is otherwise benign. Our research highlights to those using – or considering to use – cannabis, that this behaviour is associated with important negative health events.”

To compare health outcomes among cannabis users and individuals who don’t use cannabis, researchers used data collected in a survey of individuals who self-reported cannabis use and linked it with health administrative data for Ontario residents.

Using propensity score matching, researchers compared the health outcomes of nearly 4800 individuals who reported any cannabis use in the preceding 12 months with the health outcomes of over 10 000 individuals never-users, or having used cannabis only once and more than 12 months ago. Researchers incorporated 31 different variables while matching study participants to minimise an unfair comparison, including demographics, multiple physical and mental health diseases, and tobacco, alcohol and illicit drug use.

The study’s main aim was to see if there was a link between cannabis use and respiratory-related hospitalisation or ED visits. No significant associations were found between cannabis use and respiratory-related ED visits, hospitalisations, or death from any cause. However, they did find that overall visits to the ED or hospitalisations for any reason was significantly higher among cannabis users.

In addition to having greater odds of ED visits or hospitalisation, the findings show that one of every 25 cannabis users will go to the emergency department (ED) or be admitted to hospital within a year of using cannabis.

Among the reasons for ED visits or hospitalisations of cannabis users, acute trauma was the most common, with 15% of cannabis users who got medical attention receiving it for this reason, and 14% receiving care for respiratory reasons.

“The results of our research support that health care professionals and government should discourage recreational cannabis consumption in the general population,” noted Dr Vozoris.

Source: EurekAlert!

Omicron Viral Load Shedding May Be Unaffected by Vaccination

SARS-CoV-2 virus
SARS-CoV-2 virus. Source: Fusion Medical Animation on Unsplash

A small study published in the New England Journal of Medicine has found that viral load shedding of the omicron variant is similar to other strains, and is not significantly affected by vaccination status.

The SARS-CoV-2 omicron variant has a shorter incubation period and a higher transmission rate than previous variants. Recently, the Centers for Disease Control and Prevention recommended shortening the strict isolation period for infected persons from 10 days to 5 days after symptom onset or initial positive test, followed by 5 days of masking. However, the viral delay kinetics and load shedding of omicron is still unclear.

Using nasal swabs to measure viral load, sequencing, and viral culture, they enrolled 66 participants, including 32 with delta variant and 34 with omicron. Participants who received COVID–specific therapies were excluded; only one participant was asymptomatic.

The characteristics of the participants were similar in the two variant groups except that more participants with omicron infection had received a booster vaccine than had those with delta infection (35% vs 3%). After adjustments for age, sex, and vaccination status, the number of days from an initial positive polymerase-chain-reaction (PCR) assay to a negative PCR assay and the number of days from an initial positive PCR assay to culture conversion were similar in the two variant groups.

The median time from the initial positive PCR assay to culture conversion was 4 days in the delta group and 5 days in the omicron group; the median time from symptom onset or the initial positive PCR assay, whichever was earlier, to culture conversion was 6 days and 8 days, respectively. There were no appreciable between-group differences in the time to PCR conversion or culture conversion according to vaccination status, although the sample size was quite small, which led to imprecision in the estimates.

In these participants with nonsevere COVID, the viral decay kinetics were similar with omicron infection and delta infection. No large differences in the median duration of viral shedding was seen among participants who were unvaccinated, vaccinated but not boosted, and those who were vaccinated and boosted.

Discussing limitations, the authors cautioned that the small sample size limits precision, and there are possible residual confounding variables. Further studies are need to properly correlate culture positivity with infectivity.

They conclude by saying: “Our data suggest that some persons who are infected with the omicron and delta SARS-CoV-2 variants shed culturable virus more than 5 days after symptom onset or an initial positive test.”

Could Carbon Monoxide Treat Inflammation?

Photo by Samuel Ramos on Unsplash

While carbon monoxide is associated with asphyxiation cases, in small doses it also has beneficial qualities, helping reduce inflammation and stimulate tissue regeneration.

But now, a team of researchers have devised a novel way to deliver carbon monoxide to the body without its hazardous effects. Inspired by techniques used in molecular gastronomy, they were able to incorporate carbon monoxide into stable foams that can be delivered to the digestive tract.

In a mouse study, the researchers showed that these foams reduced inflammation of the colon and helped to reverse acute liver failure caused by acetaminophen overdose. The researchers said that their new technique, described today in a Science Translational Medicine paper, could also be used to deliver other therapeutic gases.

“The ability to deliver a gas opens up whole new opportunities of how we think of therapeutics. We generally don’t think of a gas as a therapeutic that you would take orally (or that could be administered rectally), so this offers an exciting new way to think about how we can help patients,” said Giovanni Traverso, a professor at MIT and a gastroenterologist at Brigham and Women’s Hospital.

Inspired by fine cuisine

Since the late 1990s, Leo Otterbein, a professor of surgery at Harvard Medical School and Beth Israel Deaconess Medical Center, has been studying the therapeutic effects of low CO doses. The gas has been shown to impart beneficial effects in preventing rejection of transplanted organs, reducing tumour growth, and modulating inflammation and acute tissue injury. 

When inhaled at high concentrations, CO binds to haemoglobin in the blood and prevents the body from obtaining enough oxygen, which can be fatal in same cases. However, at lower doses, it has beneficial effects such as reducing inflammation and promoting tissue regeneration, Prof Otterbein said.

“We’ve known for years that carbon monoxide can impart beneficial effects in all sorts of disease pathologies, when given as an inhaled gas,” he saud. “However, it’s been a challenge to use it in the clinic, for a number of reasons related to safe and reproducible administration, and health care workers’ concerns, which has led to people wanting to find other ways to administer it.”

Prof Traverso’s lab specialises in developing novel methods for delivering drugs to the gastrointestinal tract. They came up with the idea of incorporating the gas into a foam, much the way that chefs use carbon dioxide to create foams infused with fruits, vegetables, or other flavours.

Culinary foams are usually created by adding a thickening or gelling agent to a liquid or a solid that has been pureed, and then either whipping it to incorporate air or using a specialised siphon that injects gases such as carbon dioxide or compressed air.

The MIT team created a modified siphon that could be attached to any kind of gas canister, allowing them to incorporate CO into their foam. To create the foams, they used food additives such as alginate, methyl cellulose, and maltodextrin. Xantham gum was also added to stabilise the foams. By varying the amount of xantham gum, the researchers could control the release rate of CO gas from the foam.

After showing that they could control the timing of the gas release in the body, the researchers decided to test the foams for a few different applications. First, they studied two types of topical applications, analogous to applying a cream to soothe itchy or inflamed areas. In a study of mice, they found that delivering the foam rectally reduced inflammation caused by colitis or radiation-induced proctitis (inflammation of the rectum that can be caused by radiation treatment for cervical or prostate cancer).

Current treatments for colitis and other inflammatory conditions such as Crohn’s disease usually involve drugs that suppress the immune system, which can make patients more susceptible to infections. Treating those conditions with a foam that can be applied directly to inflamed tissue offers a potential alternative, or complementary approach, to those immunosuppressive treatments, the researchers said. While the foams were given rectally in this study, it could also be possible to deliver them orally, the researchers say.

Controlling the dose

The researchers then investigated possible systemic applications to deliver CO to remote organs, such as the liver, because of its ability to diffuse from the GI tract elsewhere in the body. For this study, they used a mouse model of acetaminophen overdose, which causes severe liver damage. They found that gas delivered to the lower GI tract was able to reach the liver and greatly reduce the amount of inflammation and tissue damage seen there.

In these experiments, the researchers did not find any adverse effects after the carbon monoxide administration. A healthy individual has CO levels of ~1% in the bloodstream, and studies of human volunteers have shown that levels as high as 14% can be tolerated without adverse effects.

“We think that with the foam used in this study, we’re not even coming close to the levels that we would be concerned about,” Otterbein says. “What we have learned from the inhaled gas trials has paved a path to say it’s safe, as long as you know and can control how much you’re giving, much like any medication. That’s another nice aspect of this approach — we can control the exact dose.”

In this study, the researchers also created carbon-monoxide containing gels, as well as gas-filled solids, using techniques similar to those used to make Pop Rocks, the hard candies that contain pressurised carbon dioxide bubbles. They plan to test those in further studies, in addition to developing the foams for possible tests in human patients.

Source: MIT

Antibiotic Stewardship and Sepsis Management: Achieving the Best of Both

Photo by Anna Shvets on Pexels

Lessening sepsis’s deadly effects means quickly recognising its signs and symptoms, and initiating antibiotic treatments, but some experts have wondered whether this may contribute to antibiotic overuse, especially with time-to-treatment performance measures. A new study published in JAMA Internal Medicine showed that it was possible to effectively treat sepsis while engaging in antibiotic stewardship.

The study led by Hallie Prescott, MD, of the University of Michigan Health Division of Pulmonary and Critical Care and Vincent Liu, MD, of Kaiser Permanente Division of Research, looked at data from more than 1.5 million patients from 2013–2018. Patients included came to the emergency department with signs of systemic inflammatory response syndrome (SIRS), which includes increased heart rate, abnormal body temperature, among other signs.

The research team analysed antibiotics use in these patients, including number receiving antibiotics, when treatment started, treatment duration medications and the broadness of spectrum of the antibiotics.

“We showed in the overall cohort, that antibiotic use decreased. There was a slight decrease in the proportion treated within 48 hours, a more impressive decrease in the average number of days of antibiotic treatment, and also a decrease in the use of broad-spectrum antibiotics,” said Dr Prescott.

About half of the people who met the criteria for SIRS received antibiotics within 12 to 48 hours after admission, a practice that decreased slightly over time. At the same time, 30-day mortality, length of hospitalisation, and the development of multi-drug resistant bacteria also decreased.

“This study adds to our national conversation about how to combat sepsis most effectively. It also confirms that we now need to look for new opportunities to mitigate sepsis by finding patients at high risk before they arrive at the hospital, identifying hospitalised patients most likely to benefit from specific treatments, and enhancing their recovery after they survive sepsis,” said Dr Liu.

Dr Prescott agrees: “The pushback has been [time-to-treatment for sepsis] should not be a performance measure because it’s going to cause more harm than good, and I think our data shows it probably does more good than harm. We have shown that 152 hospitals have been able to make improvements in stewardship and sepsis treatment at the same time, contrary to popular belief.”

Source: Michigan Medicine – University of Michigan

A Soft Robotic Design for Diabetic Amputee Pain Relief

Proof-of-concept rendering (left) and photo (right) of the prototype of the new microfluidics-enabled soft robotic prosthesis for lower limb amputees.
Credit: Waterloo Microfluidics Laboratory at University of Waterloo

Diabetic amputations often involve neuropathy, and patients detect damage resulting from an ill-fitting prosthesis, leading to further amputation. To solve this, in Biomicrofluidics, scientists described a new type of prosthetic using microfluidics-enabled soft robotics that reduces skin ulcerations and pain in patients who have had an amputation between the ankle and knee.

More than 80% of lower-limb amputations are due to diabetic foot ulcers, and the lower limb is known to swell at unpredictable times, resulting in volume changes of 10% or more.

Typically, the prosthesis used after amputation includes fabric and silicone liners that can be added or removed to improve fit. The amputee needs to manually change the liners, but neuropathy leading to poor sensation makes this difficult and can lead to more damage to the remaining limb.

“Rather than creating a new type of prosthetic socket, the typical silicon/fabric limb liner is replaced with a single layer of liner with integrated soft fluidic actuators as an interfacing layer,” said author Carolyn Ren, from the University of Waterloo. “These actuators are designed to be inflated to varying pressures based on the anatomy of the residual limb to reduce pain and prevent pressure ulcerations.”

The scientists started off with pneumatic actuators to adjust the pressure of the prosthetic socket, but it was quite heavy.

To reduce weight, the group miniaturised the actuators, designing a microfluidic chip with 10 integrated pneumatic valves to control each actuator. The full system is controlled by a miniature air pump and two solenoid valves that provide air to the microfluidic chip. The control box is small and light enough to be worn as part of the prosthesis.

Prosthetics experts provided a detailed map of desired pressures for the prosthetic socket. The group carried out extensive measurements of the contact pressure provided by each actuator and compared these to the desired pressure for a working prosthesis.

All of the actuators produced the right pressures suggesting the new device will work well in the field, with the next step being a more accurate biological model.

The group plans additional research to integrate pressure sensors directly into the prosthetic liner, perhaps using newly available knitted soft fabric that incorporates pressure sensing material.

Source: American Institute of Physics

Post-operative AF Linked to Risk of Hospitalisation for Heart Failure

Associations between post-operative atrial fibrillation and incident heart failure hospitalisations. Credit: European Heart Journal

A study of over three million patients found that people who develop an atrial fibrillation (AF) after undergoing surgery have an increased risk of subsequent hospitalisation for heart failure.

The study, which is published in the European Heart Journal, showed that the risk of hospitalisation for heart failure among patients who developed AF after surgery increased regardless of whether or not the surgery was for a heart condition.

Among 76 536 patients who underwent heart surgery, 18.8% developed post-operative AF and the risk of hospitalisation for heart failure increased by a third compared to patients who did not develop AF. Among 2 929 854 patients without a history of heart disease who had surgery for non-heart-related conditions, 0.8% developed AF and the risk of hospitalisation for heart failure doubled.

The study’s first author, Dr Parag Goyal, Associate Professor of Medicine at Weill Cornell Medicine, said: “Our study, which to our knowledge is the largest study to date, shows that post-operative atrial fibrillation is associated with future heart failure hospitalisations. This could mean that atrial fibrillation is an important indicator of underlying but not yet detected heart failure; or it could mean that atrial fibrillation itself contributes to the future development of heart failure. While this study could not specifically address which of these mechanisms are at play, our hope is that this study will inspire future work into exploring the underlying mechanism seen in our important findings.

“Regardless of the mechanism, our study shows that post-operative atrial fibrillation is clearly an important entity that merits attention and incorporation into decision making. Most importantly, patients and doctors need to be more vigilant about heart failure symptoms among patients who develop post-operative atrial fibrillation. Those who do develop the condition may require more aggressive treatments for other risk factors for heart failure, such as high blood pressure, diabetes and narrowing of the arteries.”

Post-operative AF occurs in up to 40% of patients undergoing heart surgery and 2% of patients undergoing non-cardiac surgery. Doctors have tended to view it as a benign event, triggered by the stress of the surgery – but evidence is emerging that post-operative AF is linked to longer term problems such as stroke and death from any cause. Until now, there has been limited evidence regarding its association with subsequent heart failure.

For the current, retrospective study, the researchers collected data on hospital health claims from 2016 to 2018, adjusting for factors that could affect the results such as age, sex, race, insurance status, medical history and body mass index.

Study limitations include its observational nature which can only establish association, not causation. The study relies on administrative claims data and medical codes to identify medical conditions; it lacks more detailed information like management strategies for post-operative AF, and on the function and size of the left ventricle, which could affect the likelihood of developing AF.

The researchers hope to conduct further studies to understand the underlying mechanism and to investigate ways of preventing future hospitalisations for heart failure among patients who develop post-operative AF.

The researchers wrote in the conclusion that “In the meantime, clinicians should be aware that POAF [post-operative AF] may be a harbinger of HF.”

In an accompanying editorial, Dr Melissa Middeldorp and Professor Christine Albert, both from the Smidt Heart Institute at Cedars-Sinai, California, USA, write: “These data add to a growing body of literature suggesting that POAF is not just a transient response to surgery but may be reflective of underlying atrial and myocardial structural changes that not only predispose to the acute AF event but to other potentially related adverse cardiovascular events, such as HF hospitalisation.”

They write that further studies are needed for a better understanding of the mechanisms involved in placing people at greater risk of AF and post-operative heart failure is needed in order to reduce hospitalisation and deaths after surgery.

“With a greater understanding of patients’ full risk factor profile, we may advocate for early aggressive intervention at the initial manifestation of POAF, to improve outcomes and reduce rehospitalisation following cardiac and non-cardiac surgery,” they concluded.

Source: European Society of Cardiology

Highly Resistant MRSA Strain in Pigs Can Jump to Humans

Methicillin-resistant Staphylococcus aureus (MRSA) bacteria. Credit: CDC

A new study published in eLife has found that a highly antibiotic-resistant strain of methicillin resistant Staphylococcus aureus (MRSA) has emerged in livestock in the last 50 years, likely a result of widespread antibiotic use in pig farming.

The strain, CC398, has become the dominant type of MRSA in European livestock in the past fifty years. It is also a growing cause of human MRSA infections.

The study found that CC398 has maintained its antibiotic resistance over decades in pigs and other livestock. And it is capable of rapidly adapting to human hosts while maintaining this antibiotic resistance. Increasing numbers of humans have been infected with the strain.

“Historically high levels of antibiotic use may have led to the evolution of this highly antibiotic resistant strain of MRSA on pig farms,” said Dr Gemma Murray, a lead author of the study.

She added: “We found that the antibiotic resistance in this livestock-associated MRSA is extremely stable – it has persisted over several decades, and also as the bacteria has spread across different livestock species.”

Antibiotic use in European livestock is much lower than it has been in the past. But despite policy changes reducing antibiotic use on pig farms, this strain of MRSA in pigs is unlikely to be impacted because it is so stable.

CC398 is found in a range of livestock but mostly in pigs. Its rise has been particularly evident in Danish pig farms where the proportion of MRSA-positive herds has increased from less than 5% in 2008 to 90% in 2018. MRSA doesn’t cause disease in pigs.

“Understanding the emergence and success of CC398 in European livestock – and its capacity to infect humans – is vitally important in managing the risk it poses to public health,” said Dr Lucy Weinert in the University of Cambridge’s Department of Veterinary Medicine, senior author of the paper.

The success of CC398 in livestock and its ability to infect humans is linked to three mobile genetic elements in the MRSA genome. These are chunks of genetic material that give the MRSA certain characteristics, including its resistance to antibiotics and its ability to evade the human immune system.

The researchers reconstructed the evolutionary history of two particular mobile genetic elements called Tn916 and SCCmec that confer antibiotic resistancein MRSAand found they have persisted in a stable way in CC398 in pigs over decades. They also persist when CC398 jumps to humans — carrying with them high levels of resistance to antibiotics commonly used in farming.

In contrast, a third mobile genetic element called ?Sa3, which enables the CC398 strain of MRSA to evade the human immune system, was found to have frequently disappeared and reappeared over time, in both human-associated and livestock-associated CC398. This suggests that CC398 can rapidly adapt to human hosts.

“Cases of livestock-associated MRSA in humans are still only a small fraction of all MRSA cases in human populations, but the fact that they’re increasing is a worrying sign,” said Weinert.

Intensification of farming, combined with high levels of antibiotic use in livestock, has led to particular concerns about livestock as reservoirs of antibiotic-resistant human infections.

Zinc oxide has been used for many years on pig farms to prevent diarrhoea in piglets. Due to concerns about its environmental impact and its potential promotion of antibiotic resistance in livestock, the European Union will ban its use from this month. But the authors say this ban may not help reduce the prevalence of CC398 because the genes conferring antibiotic resistance are not always linked to the genes that confer resistance to zinc treatment.

Source: University of Cambridge

Long COVID Cognitive Impairment More Widespread than Thought

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Scientists following COVID patients up to 12 months after diagnosis have found that mild cognitive impairment is common even after mild to moderate COVID. The study results, currently in preprint on the medRxiv server awaiting peer review, suggest that cognitive impairment, though barely noticeable, may affect large portions of the global population.

The finding comes as the US Centers for Disease Control reported that up to 1 in 5 Americans experienced at least one symptom that could be attributable to Long COVID.

SARS-CoV-2 is believed to cause lasting cognitive impairment in some cases, though the exact nature of it was not clear. Severe COVID cases risk damage through hypoxia, stroke, as well as the immune and inflammatory response to SARS-CoV-2. Mild to moderate COVID cases are still at risk of brain dysfunction, and cognitive deficits, providing a window into the potential mechanisms of brain injury without the confounding role of severe disease and its complications. Given the large numbers of people who had mild to moderate COVID disease, there would be significant implications for public health.

To assess the effects of the disease, the researchers studied 128 SARS-CoV-2 positive patients, assessing cognition and olfaction at set intervals after COVID diagnosis, along with lung capacity and blood biomarkers including the kynurenine pathway (KP).

After correcting for demographics, mild to moderate cognitive impairment was present in 26% on year post diagnosis, respectively. Overall cognitive performance declined mildly, but was statistically significant. KP metabolites quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine were significantly associated with cognitive decline.

“The immune system reacts first with the virus … tries to basically get rid of the virus,” she said to ABC News. “Then it goes a little bit into overdrive and this overdrive does not fully calm down.”

The KP pathway was seen to be disturbed similarly to the way inflammation is caused by viruses such as HIV.

“I think we’re seeing something a bit akin here, where this low level of inflammation is more and more understood as being able to traffic to the brain, or even being within the brain and affecting those regions of the brain where we process information that demand speed, extra attention and extra cognitive demands,” she explained.

Dr Cysique emphasises that the cognitive decline recorded among most participants in the study is mild and they may not even notice it.

The researchers suggested that as a unique biomarker, the KP offers a potential therapeutic target for COVID-related cognitive impairment.