Day: August 20, 2021

Bacterial Superinfections in COVID Rarer Than Expected

Only 21 percent of patients with severe pneumonia caused by SARS-CoV-2 have a documented bacterial superinfection at the time of intubation, resulting in potential overuse of antibiotics, according to new research.

Superinfection occurs when another, usually different, infection is superimposed on the initial infection. In this case, it is bacterial pneumonia during severe viral pneumonia.

Dr Wunderink and co-authors reported their findings in a study published online in the Journal of Respiratory and Critical Care Medicine, which shows that the usual clinical criteria used to diagnose bacterial pneumonia could not distinguish between those with bacterial superinfection and those with severe SARS-CoV-2 infection only.

According to the authors, there is weak evidence behind current guidelines recommending that patients with SARS-CoV-2 pneumonia receive empirical antibiotics on hospital admission for suspected bacterial superinfection. In other published clinical trials of patients with SARS-CoV-2 pneumonia, rates of superinfection pneumonia are unexpectedly low.
“More accurate assessment other than just reviewing clinical parameters is needed to enable clinicians to avoid using antibiotics in the majority of these patients, but appropriately use antibiotics in the 20-25 percent who have a bacterial infection as well,” said Dr Wunderink.

The team conducted an observational study to determine the prevalence and cause of bacterial superinfection at the time of initial intubation and the incidence and cause of subsequent bacterial ventilator-associated pneumonia (VAP) in 179 patients with severe SARS-CoV-2 pneumonia which required mechanical ventilation.

The researchers analysed 386 bronchoscopic bronchoalveolar lavage fluid samples from patients, and actual antibiotic use was compared with guideline-recommended therapy. Bacterial superinfection within 48 hours of intubation was detected in 21 percent of patients; 72 patients (44.4 percent) developed at least one VAP episode; and 15 (20.8 percent) of initial VAPs were caused by difficult-to-treat bacteria.

The authors found that in patients with severe SARS-CoV-2 pneumonia, bacterial superinfection at the time of intubation occurred in less than 25 percent of patients. Guideline-based empirical antibiotic management at the time of intubation would have resulted in antibiotic overuse.

The researchers believe that their findings have multiple implications for antibiotic guidelines: “Rapid diagnostic tests are important for helping identify suspected pneumonia in intubated patients. This can have major clinical implications because the current approach of using clinically defined risk factors for suspected methicillin-resistant staphylococcus aureus (MRSA) or pseudomonas bacteria as the cause of pneumonia still grossly overestimate the true incidence of these pathogens. In addition, the recommendation for empirical antibiotic treatment of worsening viral community-acquired pneumonia (now requiring intubation) may need to be revisited. This is not only true for SARS-CoV-2 but potentially for severe influenza as well.”

“An accurate diagnosis of suspected pneumonia allows clinicians to safely avoid or use narrow spectrum antibiotics for many patients,” Dr Wunderink added.  “While multiple interventions impact mortality in these critically ill patients, the low mortality in our study with more limited antibiotic treatment suggests that our approach was safe.”

Source: American Thoracic Society

A Leak-proof, Biocompatible Intestinal Patch

Researchers at Empa have developed a patch that stably seals two sutured pieces of intestine and thus prevents dangerous leaks.

A burst appendix or a life-threatening intestinal volvulus are emergencies that need to be treated by surgeons immediately. However, operations carry risks: highly acidic digestive juices and intestinal bacteria can leak out, causing peritonitis and sepsis.

Sealing sutured tissue with a plaster has already been tried, but the first were not well tolerated or were even toxic. Currently, these plasters are made of biodegradable proteins, which have variable clinical results. These is because they are mainly intended to support the healing process, and dissolve too quickly when in contact with digestive juices and don’t always hold tight. “Leaks after abdominal surgery are still one of the most feared complications today,” explained Empa researcher Inge Herrmann, who is also professor for nanoparticulate systems at ETH Zurich.

Searching for a material that could reliably seal intestinal injuries and surgical wounds, Hermann’s team found a synthetic composite material made up of four acrylic substances that, together, form a chemically stable hydrogel. Additionally, the patch actively cross-links with the intestinal tissue until it is fluid-tight. The quadriga of acrylic acid, methyl acylate, acrylamide and bis-acrylamide works in perfect synergy, as each component conveys a specific feature to the final product: a stable bond to the mucosa, the formation of networks, resistance to digestive juices and hydrophobicity. This new technology is detailed in Advanced Functional Materials.

In lab experiments, the researchers found the polymer system met their expectations. “Adhesion is up to ten times higher than with conventional adhesive materials,” said researcher Alexandre Anthis from Empa’s Particles-Biology Interactions lab in St. Gallen. “Further analysis also showed that our hydrogel can withstand five times the maximum pressure load in the intestine.” The material’s design uses its tailored effect: The rubbery composite selectively reacts with digestive juices that might leak through intestinal wounds, expands and closes all the more tightly. The inexpensive, biocompatible super glue, could thus shorten hospital stays and save healthcare costs, and Anthis is making plans to bring it to market.

Source: Empa

Some Cognitive Abilities Improve With Age

Image by Mar Lezhava on Unsplash

While it has long been held that all cognitive abilities decline with age, new research shows that some of these abilities can actually improve over a lifetime.

The findings, published in Nature Human Behavior, show that two key brain functions, focusing and attending to new information, can in fact improve in older individuals. These functions underlie key aspects of cognition including memory, decision making, and self-control, and even navigation, math, language and reading.

“These results are amazing, and have important consequences for how we should view aging,” said senior investigator, Michael T Ullman, PhD, a professor in the Department of Neuroscience and director of Georgetown’s Brain and Language Lab.

“People have widely assumed that attention and executive functions decline with age, despite intriguing hints from some smaller-scale studies that raised questions about these assumptions,” he said. “But the results from our large study indicate that critical elements of these abilities actually improve during aging, likely because we simply practice these skills throughout our life.”

“This is all the more important because of the rapidly aging population, both in the U.S. and around the world,” Ullman said, adding that with further research, it may be possible to deliberately improve these skills to protect against cognitive decline.

The research team explored three separate components of attention and executive function in a group of 702 participants aged 58 to 98. This age range was chosen since this is when cognition often changes the most during aging.

The components they studied are the brain networks involved in alerting, orienting and executive inhibition. Each has different characteristics and relies on different brain areas and different neurochemicals and genes. Therefore, Ullman and Veríssimo reasoned, the networks may also show different aging patterns.

Alerting is characterised by a state of enhanced vigilance and preparedness, while orienting involves shifting brain resources to a particular location in space. The executive network inhibits distracting or conflicting information, allowing us to focus on what’s important.

“We use all three processes constantly,” Veríssimo explains. “For example, when you are driving a car, alerting is your increased preparedness when you approach an intersection. Orienting occurs when you shift your attention to an unexpected movement, such as a pedestrian. And executive function allows you to inhibit distractions such as birds or billboards so you can stay focused on driving.”

Surprisingly, only alerting abilities declined with age while both orienting and executive inhibition actually improved.

The researchers hypothesis is that because orienting and inhibition are simply skills that allow selective attention, these skills can improve with lifelong practice. Ullman and Veríssimo suggest that these gains can be large enough to outweigh the underlying neural declines. Alerting declines, they believe, because this basic state of vigilance and preparedness cannot improve with practice.  
“Because of the relatively large number of participants, and because we ruled out numerous alternative explanations, the findings should be reliable and so may apply quite broadly,” Veríssimo said, adding that “because orienting and inhibitory skills underlie numerous behaviors, the results have wide-ranging implications.”

“The findings not only change our view of how aging affects the mind, but may also lead to clinical improvements, including for patients with aging disorders such as Alzheimer’s disease,” said Ullman. 

Source: Georgetown University Medical Center

Antibody COVID Prophylactic Cocktail Performs Well in Trials

Source: NCI on Unsplash

A COVID prophylactic cocktail of long-acting antibodies cut the risk of developing symptomatic disease in a high-risk unvaccinated patient population, AstraZeneca announced on Friday.

Initial phase III trial data showed that AZD7442 (tixagevimab and cilgavimab) as pre-exposure prophylaxis significantly reduced the risk of developing COVID symptoms by 77% versus placebo, meeting the trial’s primary endpoint.
AstraZeneca further noted there were no cases of severe COVID or COVID-related deaths in the intervention group, while there were three cases of severe COVID and two deaths in the placebo group.

No safety concerns were noted by the manufacturer, as the treatment was well-tolerated and adverse events were balanced between groups.

A key feature of the trial was that 75% of participants had comorbidities, including being “at risk of an inadequate response to active [immunisation],” such as older adults and those with immunosuppressive disease or on immunosuppressive medication.

“With these exciting results, AZD7442 could be an important tool in our arsenal to help people who may need more than a vaccine to return to their normal lives,” the trial’s principal investigator, Myron Levin, MD, of the University of Colorado School of Medicine, said in a statement.

AZD7442 was derived from the B cells of convalescent patients. PROVENT was a phase III randomised trial conducted in the US and Europe. Participants were 5197 adults “who would benefit from prevention” with the long-acting antibody, were unvaccinated at the time of enrollment, and tested negative for SARS-CoV-2.
Participants were randomised 2:1 to receive a single 300 mg dose of AZD7442 or placebo. AstraZeneca noted that 43% of participants were ages 60 and older. The company noted that the drug is active in lab studies against emerging strains, including the Delta variant.

Patients were followed for 183 days, though subjects are slated to be followed for 15 months, AstraZeneca said. Data will be submitted for peer-reviewed publication while the company seeks approval for AZD7442.

Source: MedPage Today

One Woman’s Journey of Recovery from Cardiac Arrest

Photo from Olivier Collett on Unsplash
Photo from Olivier Collett on Unsplash

At age 37, Mary Gordon was fit and healthy but could not explain the fatigue she began experiencing. Shortly before Christmas 2019, she woke up feeling out of sorts. During Christmas shopping, she nearly passed out at one point.

“Everything went blank,” Gordon recalled. “But it was so quick that I questioned if it really happened.”

Gordon put it down to dehydration and tiredness. But over the next week, she nearly passed out three more times, once while driving. Just before flying home, she managed to get a last-minute appointment on New Year’s Eve with her doctor’s physician assistant. By this point, she half expected to be admitted to hospital.
The physician assistant performed a test on her heart, which looked normal. But her blood pressure was through the roof. She advised Gordon to cancel her flight and to start wearing a heart monitor so the medical team could gather more information.

Gordon was familiar with the heart monitor because in university, her doctor detected a heart murmur and diagnosed her with mitral valve prolapse: extra tissue caused the mitral valve leaflets to expand into the left atrium when her heart contracted. In the severe cases, it can lead to blood leaking back through the valve, potentially resulting in arrhythmia. However, when the doctor reviewed the data, he told her to not worry about it. And an electrocardiogram years later seemed to confirm the diagnosis.

But now, leaving the visit with the physician assistant, Gordon collapsed near the elevator, in cardiac arrest. Fortunately a receptionist found her. For six minutes, the physician assistant and a doctor performed CPR , and also used an automated external defibrillator. The first thing she remembered was being in the emergency room, with her boyfriend, Matt Costakis, and several doctors at the foot of her bed.
She was confused for the first few days.

“My brain was not retaining information,” she said. “It took a few days before things were sinking in. Everything was a blur.”

An implantable cardioverter defibrillator was implanted in her chest, followed by a minimally invasive surgery the week after to repair her mitral valve.

“It wasn’t until the surgery that it was fully recognized she has something that’s particularly rare called mitral annular disjunction,” said Dr. Paula Pinell-Salles, Gordon’s cardiologist at Virginia Heart in Falls Church. “That variant is the most prone to significant prolapse and may be more closely associated with the kind of arrhythmia she presented with.”

Gordon was discharged after a two-week hospital stay. Though fatigued, she eagerly started her cardiac rehab, relishing the supportive environment. 

“The thought of raising my heart rate or being able to ever run again was so foreign,” she said. “It was awesome to know there’s a way to slowly ease back into that with the safety of people watching you.”

When COVID ended in-person rehab, she continued to push herself walking long distances but she still feared exercising alone.

“It was a weird transition and very emotional,” she said, pointing to the emergency ID tag she now wears. “But I got to the point where I could go off by myself.”

Eight months after the cardiac arrest, she was running again. And on the one-year anniversary, Gordon and Costakis, along with her dog, hiked her favourite trail to the top of a mountain, where Costakis proposed to her. 

Now happily engaged and largely recovered, Gordon promotes CPR training and wants to raise awareness about the difference between heart attacks and cardiac arrest.

As defined by the American Heart Association and the American College of Cardiology, “(sudden) cardiac arrest is the sudden cessation of cardiac activity so that the victim becomes unresponsive, with no normal breathing and no signs of circulation. If corrective measures are not taken rapidly, this condition progresses to sudden death. Cardiac arrest should be used to signify an event as described above, that is reversed, usually by CPR and/or defibrillation or cardioversion, or cardiac pacing. Sudden cardiac death should not be used to describe events that are not fatal.”

“It doesn’t hurt to learn it again, or watch the video and just build your confidence,” she said. “If I can do something to help the next person, that’s all I can ask for.”

Source: American Heart Association

Study Evaluates Efficacy and Tolerability of Ultrafiltration

A new study evaluates the efficacy and renal tolerability of ultrafiltration in acute decompensated heart failure.

Acute decompensated heart failure (ADHF) is a life-threatening and costly disease. Controversy remains regarding the efficacy and renal tolerability of ultrafiltration for treating ADHF. This article by Yajie Liu and Xin Yuan from the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China, and published in Cardiovascular Innovations and Applications, evaluated this clinical issue.

After searching databases for relevant trials, their quality and outcomes were evaluated with the use of the risk of the bias assessment tool and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, respectively. Risk ratio and the standardised or weighted mean differences were computed and pooled with fixed-effects or random-effects models.

The 19-study meta-analysis, involving 1281 patients, found that ultrafiltration was superior to control for weight loss (1.24kg) and fluid removal (1.55L) and was associated with a significant increase in serum creatinine level compared with the control treatments (0.15 mg/dL).
No significant effects were found for serum N-terminal prohormone of brain natriuretic peptide level, length of hospital stay, all-cause mortality, or all-cause rehospitalisation in the ultrafiltration group.

Overall, the meta-analysis found that use of ultrafiltration in patients with ADHF is superior to control treatments for weight loss and fluid removal but has adverse renal effects and lacks significant effects on long-term prognosis.

Source: News-Medical.Net