Year: 2021

Categories : Diseases, Syndromes and Conditions Hospitals PaediatricsTags :

Children with Sepsis Respond Better to ‘Relaxed’ Care Bundle

On By ModernMedia

Following a ‘relaxed care bundle’ was linked to lower 30-day mortality and shorter hospital stays among children with sepsis, according to preliminary data from the Improving Pediatric Sepsis Outcomes (IPSO) FACTO trial.

The study findings were presented virtually at the Society of Critical Care Medicine’s Critical Care Congress.

Sepsis is the leading cause of death in children, with an estimated 7.5 million deaths a year. Childhood sepsis includes severe pneumonia, severe diarrhoea, severe malaria, and severe measles. Some 25-40% of children who recover from sepsis still have long-term consequences.

The ‘relaxed’ sepsis bundle is based on a group of best evidence-based interventions. It involves an initial fluid bolus delivery within 60 minutes, as opposed to 20 minutes; and antibiotic delivery within 180 instead of 60 minutes. Accepted sepsis recognition protocols (screen, huddle, or care order) were also involved with the bundle.

This trial data came from about 40 000 patients with sepsis or suspected sepsis at a range of children’s hospitals across the US, from 2017 to 2019. Raina M Paul, MD, of Advocate Children’s Hospital, Illinois, USA reported the data, saying that the relaxed bundle saw better outcomes than the more original bundle which was more time-restrictive. 
Sepsis-attributable mortality fell by 48.9% among the relaxed bolus-compliant versus non-compliant group (3.1% vs 3.5%), and by 13.7% in original bundle-compliant vs non-compliant cases. Following all aspects of the relaxed bundle was associated with a reduction in median days in hospital from 9 to 6 days.

In a separate presentation, Kayla Bronder Phelps, MD, of CS Mott Children’s Hospital in Michigan, USA, reported the results of a study that showed children hospitalised for severe sepsis were likely to have longer hospital stays if they were from lower-income neighbourhoods. Using a national database, she identified 10 130 cases of children with severe sepsis. Severe sepsis hospitalisations were also highest among the lowest-income quartile, reflecting the fact that there were more children living in low-income neighbourhoods.

Overall, 8.4% of children in the cohort died of sepsis during hospitalisation, with no association between mortality rates and income level. However, children in the lowest-income areas spent a median 9 days in the hospital, while children from the highest-income areas spent 8 days.

Bronder Phelps noted that the study is among the first to examine the impact of poverty on paediatric sepsis outcomes. Poverty is a known risk factor for a wide range of paediatric diseases, such as neonatal bacterial infection, asthma, and migraine, and in adults, poverty is associated with poorer outcomes including higher mortality rates.

Source: MedPage Today

Presentation information 1: Paul R, et al “Improving pediatric sepsis outcomes for all children together (IPSO FACTO): Interim results” SCCM 2021; Abstract 32.

Presentation information 2: Phelps K, et al “The association of socioeconomic status and pediatric sepsis outcomes” SCCM 2021; Abstract 37.

Categories : AgeingTags :

APLS1 Inhibitors Eliminate Senescent Cells to Ameliorate Ageing

On By ModernMedia

A new technique has been developed to eliminate senescent cells that are involved in many age-related diseases, according to a study by researchers at the University of Tokyo.

As ageing progresses, cancers emerge, motor function declines through muscle loss, and metabolic disorders occur due to adipose tissue atrophy. Senescent cells accumulating in organs are behind many of these problems; their telomeres having shortened through divisions as a result of multiple stresses and now at their replication limit, they now no longer function effectively. Previous research using genetic engineering to knock out senescent cells in mice was able to put the onset of age-related diseases such as arteriosclerosis and renal damage, and extended life expectancy. However, the research did not yield a drug which could be given as a treatment.

To tackle this problem, the researchers created a way to produce large numbers of purified senescent. cells to search for genetic targets for drugs. One of the ways they found involved GLS1, a gene involved in glutamine. On testing with GLS1 inhibitors, senescent cells were vulnerable due to damage to the lysosomal membrane and lower intracellular pH. Lysosomes are organelles which produce enzymes to destroy defunct cell parts, bacteria and viruses if needed, and the cell itself if apoptosis is triggered. They also have an essential role in the regulation of intracellular pH, and are very acidic, having to be protected from the rest of the cell by a membrane. Analysing the dynamics of lysosomes, the team found that damage to the lysosomal membranes in senescent cells decreases intracellular pH.

When they administered GLS1 inhibitors to old mice, knocking out senescent cells, their ageing was significantly improved. The symptoms of obese diabetes, arteriosclerosis, and fatty liver disease were ameliorated. GLS1 inhibitors are already being used in trials as cancer treatments.
“We hope that innovative anti-aging therapies and treatments for geriatric diseases will be developed that can remove senescent cells by treatment with GLS1 inhibitors,” said Professor Nakanishi.

Source: News-Medical.Net

Journal information: Johmura, Y., et al. (2021) Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders. Science. doi.org/10.1126/science.abb5916.

Categories : COVID General InterestTags :

Drone Company to Start New Rural Vaccine Delivery Service

On By ModernMedia

Zipline, a company that has made its name using drones to deliver medicines to remote locations in countries like Rwanda, has announced that it is to expand its capability to include all COVID vaccines.

In a press release, Zipline said that it is partnering with a COVID vaccine manufacturer, the identity of which was not disclosed, to add on the ability to deliver vaccines that require ultra cold temperatures in specialised refrigerated containers.

For remote rural locations, the Pfizer/BioNTech vaccine is not an option because of  its stringent temperature storage requirements of minus 70 degrees celsius. In such situations, the choice of COVID vaccines is limited to the more expensive Moderna vaccine, which still requires freezing temperatures, or vaccines like those from Johnsons & Johnson or AstraZeneca, which don’t have as high effectiveness but are able to be stored at normal refrigerator temperature ranges.

Zipline is planning to add these ultracold storage refrigerators at all of its drone bases. A clinic in its network would be able to request a few dozen doses of vaccine, and the company’s drones would be able to deliver it in a special refrigerated container.

Zipline operates fixed-wing, battery-powered drones that can make a round trip of up to 80 kilometres. Each base that the drones operate from can service an area of over 22 500 square kilometres, completely ignoring difficult terrain and lack of road access which may endanger drivers. A trip which could take hours in a 4 by 4 can be done in under an hour.
The drones can deliver a 1.75kg payload by parachute at a designated location, and return to base. Since the drone navigates by GPS, it can do so in a range of weather conditions, and by day or night.

Zipline CEO Keller Rinaudo said that his company wants to help rural areas that have been hard hit by COVID. “Where you live shouldn’t determine whether or not you get a COVID-19 vaccine,” he said in the release. “We can help health systems bypass infrastructure and supply chain challenges through instant delivery.”

Source: Bloomberg

Categories : COVIDTags :

UK to Look at Mixing of Different Vaccines

On By ModernMedia

The UK is launching a trial to explore the mixing of vaccines can be combined. Some, like Russia’s Sputnik vaccine, already combine two different types of vaccines, but these were specifically designed and tested to work together. 

Current guidance in the UK says that anyone who receives a Pfizer-BioNTech or Oxford-AstraZeneca vaccine dose should get the second dose of that same vaccine. Only in exceptional circumstances such as not knowing what vaccine was given will a different vaccine be administered.

The main aim was to enhance logistical flexibility. The Oxford/AstraZeneca, Johnson & Johnson and Novavax vaccines can all be stored at normal refrigerator temperatures, while the Moderna vaccine must be stored at -20C, within normal freezer range, and Pfizer/BioNTech’s vaccine needs an ultra-cold -70C. Not requiring a second dose of the same vaccine could ease up storage requirements. 

However, with previous vaccines, mixing different vaccine types worked and even strengthened their overall effectiveness. Some Ebola immunisation programmes, for example, combine two different vaccines to achieve greater protection.

The trial will comprise some 800 participants aged 50 or older, receiving a combination of Oxford/AstraZeneca and Pfizer/BioNTech in either order.

Some vaccines that work by using a virus to deliver the antigens, and there is some evidence to suggest that the immune system starts to focus on the viral delivery system instead of the antigen. Thus, combining vaccines will keep the immune system’s attention on the antigens.

Chief investigator, Prof Matthew Snape from the University of Oxford, said the “tremendously exciting study” would provide critical information for vaccine rollouts.

Animal studies have shown “a better antibody response with a mixed schedule rather than the straight schedule” of vaccine doses, he said.

“It will be really interesting to see if the different delivery methods actually could lead to an enhanced immune response [in humans],” he said, “or at least a response that’s as good as giving the straight schedule of the same doses”.

Source: BBC News

Categories : Cancer GeneticsTags :

RNA Knockout Halts the Spread of Triple-negative Breast Cancer

On By ModernMedia

The University of Westminster has released a new study showing that taking out small chunks of human DNA called microRNA can reverse the spread of triple negative breast cancer cells.

The study also suggested that microRNAs could be targeted to spot and treat triple negative breast cancer. Breast cancer is the most common cancer in women, and triple negative breast cancer makes up 10-20% of cases.

MicroRNAs (miRs) have important roles in cellular functioning and signalling, and are heavily involved in the growth and metastasis of cancers. The researchers found that miR-21, a major breast cancer-related RNA, is increased in triple negative breast cancer and is also associated with metastasis.

Using CRISPR/Cas9, the researchers knocked out miR-21 from the cancer cells, and discovered that the cancer cells’ metastatic properties were reversed. They also observed that they released smaller vesicles, which release lipid blobs that play an important part in cancer spread. There was also less miR-21 carried in the vesicles, which also carry disease-related molecules to other cells.

Lead researcher Dr Pinar Uysal-Onganer of the University of Westminster, said: “This is an important study which contributes to better understanding of roles of miRs in aggressive cancer types such as triple negative breast cancer. We are now aiming to clarify the relationships between miR-21 and cancer drug resistance, which is another important factor that limits cancer cure.”

Source: Medical Xpress

Journal information: Elif Damla Arisan et al. MiR-21 is Required for the Epithelial–Mesenchymal Transition in MDA-MB-231 Breast Cancer Cells, International Journal of Molecular Sciences (2021). DOI: 10.3390/ijms22041557

Categories : HospitalsTags :

Life-saving Benefits of Telemedicine in ICUs

On By ModernMedia

A study in Cleveland, USA, showed that at hospitals without 24/7 on-site intensivists, those that had intensivists available to deliver telemedicine had lower ICU mortality rates.

Presented at the Society of Critical Care Medicine’s virtual 50th Critical Care Congress, Cleveland Clinic intensivist Dr Chiedozie Udeh, commented that the COVID pandemic has thrust ICU telemedicine into the spotlight.

“In an ideal world, patients would have an intensivist at the bedside 24/7, but the reality is that even if we had all of the money in the world, we don’t have enough trained professionals to do the job,” Udeh said.

Out of patients treated at one of nine hospitals within the Cleveland Clinic Health System, patients receiving ICU telemedicine were 18% less likely to die and were discharged 2 days sooner than patients who received traditional ICU care, without 24/7 on-site intensivist care.  

The unadjusted 30-day mortality among the telemedicine patients was 5.5%, while in the standard care group it was significantly higher at 6.9%.ICU length of stay was significantly shorter in the ICU telemedicine group, as was the length of total hospital stay.

Udeh said that an intensivist monitoring patients via telemedicine has access to relevant data and can perform the same functions as an on-site clinician, short of physical contact. Intensivists can monitor multiple patients and have two-way communication with bedside nurses. Dedicated software is available, including tools to identify deteriorating patients needing care.

Speaking to MedPage Today, Udeh said ICU telemedicine offers an intermediate treatment strategy between large academic centres with 24/7 on-site intensivist care, and smaller hospitals without such care. More research is needed to understand how telemedicine leads to reduced mortality, he added.

“If I had to speculate I would imagine this would probably be due to patients’ receiving more timely needed interventions,” he said.

“We think these findings provide further reassurance about the value of ICU telemedicine, particularly in light of our collective experience in 2020,” said Udeh. “With the COVID-19 pandemic, telemedicine in general assumed greater prominence.”

CU telemedicine can benefit both large hospital systems and smaller, individual hospitals, he said.

“Smaller hospitals may have no intensivist at all or they may have only one,” he said. He added that, according to one recent survey, about half of US hospitals do not have an intensivist on staff.

ICU telemedicine still has considerable expenses associated with it, however; at $50 000 per bed in first year costs, it may be hard to justify for resource-constrained hospitals.

Source: MedPage Today

Presentation information: Udeh CI, et al “ICU telemedicine and clinical risks associated with 30-day mortality: a retrospective cohort study” SCCM2021.

Categories : COVIDTags :

Viral Load Drives the Transmission of COVID

On By ModernMedia

Knowing what factors drive the transmission of COVID is crucial to informing schemes to contain and adapt to its spread.

There is abundant data on location and duration of exposure to COVID, but there is precious little on any other factors, the researchers noted.

The SARS-CoV-2 virus is detectable in respiratory tract samples 1-2 days before symptom onset, and can continue for several weeks afterward. But the detection of viral RNA is not necessarily related to infectiousness, and no studies had established the connection between viral load and COVID transmission, although viral load had been linked to COVID mortality.

The researchers used linked index cases of COVID to determine that viral load was the principle factor behind COVID transmission, and is the largest such study to date. This emphasises the need for initiating proper contact tracing.

The researchers conducted a post-hoc analysis of 314 cases during the initial COVID wave in Spain, of whom 90% (282) had at least one close contact, resulting in a total of 753 contacts. Viral load was the key indicator of COVID transmission.

The overall secondary attack rate (proportion of COVID-positive contacts) during the study period was 17%. However, this rate varied from 12% when the viral load of the index case was lower than 1×10⁶ copies per mL, to 24% when it was 1×10¹⁰ copies per mL or higher.

Running multivariate analyses, the researchers found no association between sex, age, diabetes, cardiovascular disease, or respiratory disease and the risk of or time to developing symptomatic COVID. There was a significant association of incubation time with initial viral load, increasing from five days among patients with a high viral load to seven days among participants with a low viral load.

The researchers wrote: “Taken together, our results indicate that the viral load, rather than symptoms, might be the predominant driver of transmission.”

They conclude that all cases should be considered potential transmitters of the virus. They also suggest viral load assessment in patients with large numbers of contacts, and risk stratification by time to symptom appearance based on viral load. 

Source: News-Medical.Net

Journal information: Marks M, et al. Transmission of COVID-19 in 282 clusters in Catalonia, Spain: a cohort study. The Lancet Infectious Disease, 2021. DOI: https://doi.org/10.1016/S1473-3099(20)30985-3, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30985-3/fulltext

Categories : CancerTags :

New Ultrasonic Tumour Therapy

On By ModernMedia

A new technique has been developed that uses ultrasound to vapourise encased nano-droplets, at the tumour site. This technology could be used to image the tumour, damage it or even deliver chemotherapy drugs with precision.

Existing applications of ultrasound therapy include thermal excitation of tissues, for example to dilate blood vessels, and creating cavitation to break up kidney stones. Ultrasonic toothbrushes have also been shown to remove dental plaque with better efficiency than conventional toothbrushes, and about the same as that of mechanical electrical toothbrushes. Micrometre-sized droplets, encased in a stabilising shell, can already be visualised with ultrasound, but these are too large to enter tumours. Nanometre-sized droplets can do so, however.

Vapourisation is tricky to control in reality, since the process requires a point of nucleation. The researchers demonstrated an efficient way to achieve vapourisation: by applying a frequency at the exact resonant frequency of the droplet, the pressure inside suddenly drops and the liquid vapourises. This is much the same principle as shattering a crystal glass by bombarding it with sound at its resonant frequency.

The researchers used hydrofluorocarbons,  which have a very low boiling point,   for the droplets. The resonance of the droplet being six times higher makes vapourisation much easier. The speed of sound of the droplet fluid being lower than the speed of sound in the bodily fluids surrounding it.
This resonant droplet vapourisation technology has a number of possible medical applications. The bubbles from the bursting droplets could be used to physically damage the tumour. Or, the droplets could contain chemotherapy drugs and made to break open precisely inside the tumour and reducing exposure of the rest of the body.

Source: News-Medical.Net

Journal information: Lajoinie, G. et al. (2021) High-Frequency Acoustic Droplet Vaporization is Initiated by Resonance’ by Guillaume Lajoinie, Tim Segers, and Michel Versluis. Physical Review Letters. doi.org/10.1103/PhysRevLett.126.034501.

Categories : Injury & Trauma TransplantsTags :

First Successful Face and Double Hand Transplant

On By ModernMedia

Doctors in New York have performed the world’s first successful face and double hand transplant.

The patient, 22 year-old Joe DiMeo, had suffered burns over 80% of his body in a 2018 crash, resulting in his fingers being amputated. His eyelids and lips were also amputated. He had been driving home from a night shift when he fell asleep at the wheel and his car crashed, bursting into flames. He spent four months in a burns unit, much of it in an induced coma. After 20 reconstructive surgeries, he still had only limited use of his hands and face.

In a 23-hour operation, doctors attached the donor’s face and hands. He then spent 45 days in ICU, then a further two months in hospital. Mr DiMeo learned to open his new eyelids and move his hands, and is now spending up to five hours a day in rehab.

Eduardo Rodriguez, director of the Face Transplant Program, said: “We wanted to give him not only an operation that made him look better, but it ultimately had to work ideally, especially with the hands.” He added that Mr DiMeo is the most motivated patient he had met.

The doctors waited to ensure that the transplant had taken before calling it successful. While a face and double hand transplants had been performed before, one patient died from complications and the other had to have their hands amputated when they failed to thrive.

Hand transplants have progressed a great deal since the first successful one in 1998. Enormous strides have been made in immunosuppression since then, requiring fewer drugs with less resultant toxicity and side effects. There is also a protocol for using donor bone marrow and stem cells to modulate the immune system in place of typical immunosuppression.

Mr Dimeo says that he can now exercise and make breakfast unaided.

“This is a once-in-a-lifetime gift, and I hope the family can take some comfort knowing that part of the donor lives on with me,” Mr Dimeo said. “My parents and I are very grateful that I’ve been given this second chance.”

Source: BBC News

Categories : COVIDTags :

Pfizer Vaccine 90% Effective After a Single Dose

On By ModernMedia

A study from the University of East Anglia (UEA) reported that the Pfizer vaccine provides “very high” protection after a single dose.

The researchers drew on Israeli data, where the vaccine had been widely administered, and found that the vaccine was 90% effective at 21 days after the initial dose. This supports the plan that the UK and other nations have of delaying a second dose to achieve maximum coverage. However, they also noted that infection rates increased eight days after the first dose, which they attribute to people becoming less cautious as a result of the vaccination. The study is available on the medRxiv preprint server, and has not been peer reviewed, as it is a rapid response to the ongoing COVID pandemic.

Lead researcher and COVID expert Prof Paul Hunter, from UEA’s Norwich Medical School, said: “A second dose of the Pfizer vaccine would normally be given 21 days or more after the first to top up and lengthen the effect of the first dose.

“But here in the UK, the decision was made to delay the timing of the second injection until 12 weeks after the first.

“The logic behind this is to protect more people sooner and so reduce the total number of severe infections, hospitalisations, and deaths.

“But this decision caused criticism from some quarters due in part to a belief that a single injection may not give adequate immunity.”

Prof Hunter explains the motivation for the study was previous flawed research on the Pfizer vaccine, also using Israeli data. But the study did not consider effectiveness past day 18.

The researchers observed that case incidence rose up til day eight by which time it had doubled, then fell. Prof Hunter said: “We found that the vaccine effectiveness was still pretty much zero until about 14 days after people were vaccinated. But then after day 14 immunity rose gradually day by day to about 90 percent at day 21 and then didn’t improve any further. All the observed improvement was before any second injection.

“This shows that a single dose of vaccine is highly protective, although it can take up to 21 days to achieve this.”

Although the vaccine’s effectiveness beyond this is not known, it still supports the UK’s decision to space out vaccine doses, Prof Hunter concluded.

Source: Medical Xpress

Journal information: “Estimating the effectiveness of the Pfizer COVID-19 BNT162b2 vaccine after a single dose. A reanalysis of a study of ‘real-world’ vaccination outcomes from Israel” is published on the medRxiv pre-print server: www.medrxiv.org/content/10.110 … 021.02.01.21250957v1