Tag: 17/3/22

Categories : COVIDTags :

Losartan is Not Effective in Reducing Lung Injury from COVID

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

In a study published in JAMA Network Open, researchers reported that the blood pressure medication losartan is not effective in reducing lung injury in patients with COVID.

This drug was investigated based on early reports suggesting benefit in preclinical models of the 2003 SARS virus, a close family member to the current SARS-CoV-2 virus.

The research team sought to determine if a common blood pressure medication might decrease lung injury in patients hospitalised with COVID. Their results found that losartan treatment did not reduce lung injury in patients admitted with COVID, and had no effect on mortality.

In addition, critically-ill patients treated with losartan needed additional, temporary blood pressure support. However, this did not result in worse outcomes overall.

“Even though this particular drug was not effective for the treatment of COVID-19, repurposing inexpensive and relatively safe medications remains an important approach to contain healthcare costs,” said study co-author Michael Puskarich, MD, an associate professor in emergency medicine.

“Finding effective treatments for COVID that can be widely used across both the developed and developing world remains an important ongoing area of investigation,” Dr Puskarich added.

The researchers noted that more studies of protein and cellular signalling from ALPS-COVID trial participants are ongoing.

“We hope that future study findings of these proteins may show insights into why the body responds the way it does to COVID,” said co-author Christopher Tignanelli, MD, MS, FACS, FAMIA, an assistant professor in surgery. “Critically, this will help us understand why some people develop severe disease following COVID infection and others are asymptomatic.”

Source: University of Minnesota Medical School

Categories : Regenerative MedicineTags :

Cell Fusion Jump-starts Retinal Regeneration

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Genetics
Image source: Pixabay

Researchers have reported that they have successfully fused human retinal cells with adult stem cells, in a novel potential regenerative therapy to treat retinal damage and visual impairment.

The resulting hybrid cells stimulate the regenerative potential of human retinal tissue, something previously only thought to be found in cold-blood vertebrates.

Cell fusion events, where two different cells combine into one single entity, are known to be a possible mechanism contributing to tissue regeneration. These cell fusions result in four sets of chromosomes instead of the usual two. Though a rare phenomenon in humans, it has been reliably detected in the liver, brain, and gastrointestinal tract. Now, cell fusion events have been found also take place in the human retina, as reported in eBioMedicine.

Seeking to see if cell fusion events could differentiate into neurons, the researchers fused Müller glia, cells that play a secondary but important role in maintaining the structure and function of the retina, with adult stem cells.

“We were able to carry out cell fusion in vitro, creating hybrid cells. Importantly, the process was more efficient in the presence of a chemical signal transmitted from the retina in response to damage, resulting in rates of hybridisation increasing twofold. This gave us an important clue for the role of cell fusion in the retina,” said first author Sergi Bonilla.

The hybrid cells were injected into a growing retinal organoid, a model that closely resembles the function of the human retina. The researchers found that the hybrid cells successfully engrafted into the tissue and differentiated into cells that closely resemble ganglion cells, a type of neuron essential for vision.

“Our findings are important because they show that the Müller Glia in the human retina have the potential to regenerate neurons,” said lead researcher Professor Pia Cosma. “Salamanders and fish can repair damage caused to the retina thanks to their Müller glia, which differentiate into neurons that rescue or replace damaged neurons. Mammalian Müller glia have lost this regenerative capacity, which means retinal damage or degradation can lead to visual impairment for life. Our findings bring us one step closer to recovering this ability.”

Further work will be to understand why these hybrid cells, which have four complete sets of chromosomes, don’t result in chromosomal instability and cancer development. The authors of the study believe the retina may have a mechanism regulating chromosome segregation similar to the liver, which contains tetraploid cells that act as a genetic reservoir, undergoing mitosis in response to stress and injury.

Source: Center for Genomic Regulation

Categories : Diseases, Syndromes and ConditionsTags :

An Unexpected Ally: Pathogen Enhances Antifungal Drug

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Scanning Electron Micrograph of Pseudomonas aeruginosa.
Credit: CDC/Janice Carr

While pathogens usually work against drug treatments, sometimes, they can actually strengthen them, according to a new University of Maine study published in the journal Infection and Immunity.

Polymicrobial infections, which are a combination of bacteria, viruses, fungi and parasites, are challenging to treat because it is not well understood how pathogens interact during infection and how these interactions affect the drugs treating them.

In a study published in Infection and Immunity, University of Maine researchers examined two common pathogens that often occur at similar sites, particularly in cystic fibrosis and mechanically ventilated patients: Candida albicans and Pseudomonas aeruginosa.

Candida is the fourth most common hospital-acquired pathogen, and many antifungal agents only slow it rather than kill it outright. Meanwhile, P. aeruginosa infects 90% of all adult cystic fibrosis patients. Combined, C. albicans and P. aeruginosa cause more serious disease in cystic fibrosis and ventilated patients.

The researchers investigated the effectiveness of the antifungal drug fluconazole in vitro and then during infection of the zebrafish with both pathogens. Fluconazole slows fungal growth, but Candida can become tolerant to the drug and not only survive, but also evolve tolerance that leads to therapy failure and, potentially, death.

The results showed that P. aeruginosa in fact works with fluconazole to eliminate drug tolerance and clear the C. albicans infection in the culture and the zebrafish.

“Polymicrobial infections are challenging to treat not only because of the lack of understanding of how invading microorganisms interact but also because we don’t know how these interactions affect treatment efficacy. Our work demonstrates that polymicrobial interactions can indeed affect treatment efficacy and, most importantly, it highlights the importance of nutrient availability in the environment -; such as iron in our study -; and how it modulates treatment efficacy,” explained Siham Hattab, lead author of the study.

What’s more, the bacteria also enhance the drug’s ability against a second pathogenic Candida species that tends to be more resistant to the drug.

The increased effectiveness of the drug suggests to the researchers that there is still much more to learn about how current drugs work when targeting these dangerous and complex polymicrobial infections.

Senior study author, Robert Wheeler, associate professor of microbiology said: “We are really excited to have revealed that sometimes drugs against fungal infection can work even better in a more ‘real-world’ situation than in the test tube. There is still a lot to learn about how pathogens interact during infection, and it will be interesting to see how the bacteria manage to work with the drugs to target Candida.”

Source: University of Maine

Categories : Obstetrics & GynaecologyTags :

WHO Warns of Lethal Tranexamic Acid Mix-ups in Intrathecal Administration

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Intravenous IV drip in woman's hand
Photo by Anna Shvets on Pexels

The World Health Organization is alerting health care professionals about the risk of lethal administration errors that can potentially occur with tranexamic acid (TXA) injection. There have been reports of TXA being mistaken for obstetric spinal anaesthesia used for caesarean deliveries resulting in inadvertent intrathecal administration.

Intrathecal TXA is a potent neurotoxin and neurological sequelae are manifested, with refractory seizures and 50% mortality. The profound toxicity of intrathecal TXA was described in 1980. In a 2019 review, Patel et al. identified 21 reported cases of inadvertent intrathecal injection of TXA since 1988, of which 20 were life-threatening and 10 fatal. It appears that mortality risk is greater after caesarean delivery. Sixteen were reported between 2009 and 2018.

WHO recommends early use of intravenous TXA within three hours of birth in addition to standard care for women with clinically diagnosed postpartum haemorrhage (PPH) following vaginal births or caesarean section. TXA should be administered at a fixed dose of 1g in 10 ml (100 mg/ml) IV at 1 ml per minute, with a second dose of 1g IV if bleeding continues after 30 minutes. In South Africa, the incidence of maternal bleeding after caesarean delivery has been characterised as a national emergency, and obstetric haemorrhage remains the third most common cause of maternal mortality at 17%.

However, problems can arise as TXA is frequently stored in close proximity with other medicines, including injectable local anaesthetics indicated for spinal analgesia (eg, for caesarean section). The presentation of some of the local anaesthetics is similar to the TXA presentation (transparent ampoule containing transparent solution), which can be administered in error instead of the intended intrathecal anaesthetic, and resulting in serious undesirable adverse effects.

Obstetricians from several countries have recently reported inadvertent intrathecal TXA administration and related serious neurological injuries. In a South African clinical alert, Bishop et al. highlighted the different appearances of TXA used in state and private hospitals, with one example in private hospitals appearing very similar (white label, red text) at first glance to spinal bupivacaine and stored in the same container. Applicable recommendations were provided by the authors.

TXA is a lifesaving medicine, however, this potential clinical risk should be considered and addressed by all operating theatre staff. Reviewing of existing operating theatre drug handling practice is required in order to decrease this risk, such as storage of TXA away from the anaesthetic drug trolley, preferably outside the theatre.

Source: World Health Organization

Categories : Cardiovascular Disease Lab Tests and ImagingTags :

Cardiac CT Matches Coronary Angiography with Fewer Complications

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Coronary artery showing atherosclerosis. Image source: Wikimidia CC0

A clinical trial found that cardiac computed tomography (CT) offers similar diagnostic accuracy to catheterisation – the current standard diagnostic test for intermediate-risk patients – in people with suspected coronary artery disease, as well as being associated with a lower risk of complications. The trial’s findings were published in the New England Journal of Medicine.

The current standard diagnostic test for coronary artery disease (CAD) is coronary angiography (often along with cardiac catheterisation). This minimally invasive procedure uses dye marker visible on X-ray imaging to detect arterial narrowing. Any narrowing detected in this manner can be treated during the procedure itself using stents, which prop open the newly widened blood vessels. More than 3.5 million of these procedures are carried out in European catheterisation laboratories every year, and more are carried out every year. Approximately two million of these do not involve immediate treatment in the cath lab. In these cases, the procedure is able to rule out narrowed or blocked coronary arteries.

The main question addressed by the DISCHARGE Trial Group was whether the low-risk, non-invasive coronary CT method can provide a safe alternative to catheterization in certain patients with suspected CAD. In order to test the effectiveness of both of these diagnostic imaging techniques in patients with stable chest pain, the project followed more than 3500 patients for a duration of four years. Patients were randomised to either computed tomography or cardiac catheterisation. If their initial evaluation ruled out obstructive coronary artery disease, participants were discharged back to their referring physician for further treatment – a step which gave the trial its name: DISCHARGE. Patients who were diagnosed as having the disease were managed in accordance with European guidelines at the time of the study.

Discussing the long-term results, trial leader Professor Dr Marc Dewey said: “The trial confirmed that a CT-based management is safe in patients with stable (ie, non-acute) chest pain and suspected coronary artery disease.”

Evaluation of safety was based on the incidence of major cardiovascular events over a period of up to four years. He added: “Among the patients referred for cardiac catheterisation and included in this trial, the risk of major adverse cardiovascular events was found to be similar in both the CT and catheterisation groups, occurring in 2.1% and 3.0% of patients, respectively. The incidence of major procedure-related complications was found to be four-times lower in patients managed with an initial CT strategy.”

Other outcome measures were included in the DISCHARGE trial, such as improvements in chest pain and quality of life over the course of the trial. This new strategy could help relieve pressure on health care systems by helping to reduce the volume of catheterisation procedures. Prof Dewey said: “Now that CT has been standardised and quality-tested as part of the DISCHARGE trial, this method could be made more widely available as part of the routine clinical care of people with intermediate CAD risk.”

As a next step, the trial’s method for estimating a person’s clinical risk of having coronary artery disease will need to be further evaluated to determine whether it can improve referral and indication for CT in routine clinical care. Health economics are an important component in making decisions about reimbursement in health care systems. As mentioned in the discussion of the publication, further methodologically very rigorous cost-effectiveness analyses of CT and cardiac catheterisation are necessary and will be conducted by the DISCHARGE Trial Group.

Source: University of Glasgow