Human colon cancer cells. Credit: National Cancer Institute
Tumours often contain areas of oxygen-deficient tissue that frequently withstand conventional therapies. This is because the drugs applied in tumours require oxygen to be effective. An international research team has developed a novel mechanism of action that works without oxygen: polymeric incorporated nanocatalysts target the tumour tissue selectively and switch off the glutathione that the cells need to survive. The team published their findings in the journal Nature Communications.
Why tumours shrink but don’t disappear
Study leader Dr Johannes Karges from Ruhr University Bochum, Germany, explained: “As tumours grow very quickly, consume a lot of oxygen and their vascular growth can’t necessarily keep pace, they often contain areas that are poorly supplied with oxygen.” These areas, often in the centre of the tumour, frequently survive treatment with conventional drugs, so that the tumour initially shrinks but doesn’t disappear completely. This is because the therapeutic agents require oxygen to be effective.
The mechanism of action developed by Karges’ team works without oxygen. “It’s a catalyst based on the element ruthenium, which oxidises the naturally present glutathione in the cancer cells and switches it off,” explains Karges. Glutathione is essential for the survival of cells and protects them from a wide range of different factors. If it ceases to be effective, the cell deteriorates.
Compound accumulates in tumour tissue
All cells of the body need and contain glutathione. However, the catalyst has a selective effect on cancer cells as it is packaged in polymeric nanoparticles that accumulate specifically in the tumour tissue. Experiments on cancer cells and on mice with human tumours, that were considered incurable, proved successful. “These are encouraging results that need to be confirmed in further studies,” concludes Johannes Karges. “Still, there’s a lot of research work to be done before it can be used in humans.”
There were no differences in quality of life, symptoms, hospital admissions or mortality between a group of patients with pulmonary disease and low oxygen levels in the blood that received oxygen therapy at home for 24 hours a day, and a group that received the same therapy for 15 hours a day, according to a study in the New England Journal of Medicine.
“This has considerable significance for patients with chronic obstructive pulmonary disease and other pulmonary diseases who are undergoing long-term oxygen therapy at home,” says study leader Magnus Ekström of Lund University.
Every year, there are about a million patients in the US alone with severe sub-optimal oxygen levels who begin oxygen therapy at home. The patient must wear a nasal oxygen mask 24 hours a day, which is often felt to be restrictive and burdensome. In addition, the gas is cold and dry, which may cause problems such as dryness, ulcers and inflammation of the airways. Using the equipment may also be perceived as stigmatising by patients.
The aim of the therapy is to prolong life, but its application differs and the scientific evidence for the therapy’s efficacy has been inadequate.
In a randomised, controlled large multicentre study, the researchers have now examined the effect of different durations of oxygen therapy on important health outcomes. A total of 241 patients with chronic and severely low oxygen levels in the blood from 20 different clinics in Sweden were randomised to receive oxygen therapy for either 24 hours a day or 15 hours a day. The patients were followed for one year, and all completed the study. There was a high level of compliance with the prescribed daily therapy duration.
“There were no differences between the groups regarding hospital admission or the risk of dying. And again, when we compare self-reported quality of life and physical activity, symptoms and fatigue between the groups, we see no differences or indication of advantages if oxygen is used for more than 15 hours a day,” says Magnus Ekström, researcher in respiratory andpalliative medicine at Lund University.
The results differ from previous studies conducted in the 1970s, which suggested that therapy for 24 hours a day could increase the survival rate.
“The older studies were small and only included patients with chronic obstructive pulmonary disease, not least because it is difficult to recruit such seriously ill individuals for a randomised study. Also, the patients included in the older studies differ from those who start oxygen therapy at home nowadays. The strength of this study is that we have been able to include twice as many patients, and that it represents the reality nowadays in which many of those receiving oxygen therapy at home are older, also have cardiovascular diseases and are women,” says Josefin Sundh, adjunct senior lecturer at Örebro University and pulmonologist at the University Hospital in Örebro, who was co-leader of the study.
“The group treated with oxygen 15 hours a day received this during the night when, in general, oxygenation is poorer. The results show that it seems to be safe for this type of patient to be without oxygen for quite a large part of the day. This is important as it may reduce the side effects of the therapy and mean that the patients can adapt it more to their everyday life,” says Magnus Ekström.
The researchers based the study on data from Swedevox, the Swedish National Registry for Respiratory Failure.
The researchers are now moving on to examine whether therapy using a high flow rate of warmed-up, more humidified oxygen at night can improve prognoses and patient well-being.
New evidence shows higher oxygen concentrations may help prevent deaths of preterm babies
Photo by Hush Naidoo on Unsplash
Giving very premature babies high concentrations of oxygen soon after birth may reduce the risk of death by 50%, compared to lower levels of oxygen says new research led by University of Sydney researchers.
Premature babies sometimes need assisted breathing because their lungs haven’t finished developing, so doctors may give them supplemental oxygen via a breathing mask or breathing tube.
The study, published in JAMA Pediatrics, examined clinical trial data and outcomes of over one thousand premature babies who were given different oxygen concentrations. This included low concentrations of oxygen (~30%), intermediate (~50–65%) or high (~90%).
The study found for babies born prematurely, at less than 32 weeks starting resuscitation with high concentrations of oxygen (90% or greater), could increase chances of survival compared to low levels (21–30%).
When a doctor provides oxygen to babies that need help breathing, there is a device that regulates how oxygen is mixed together to reach the desired concentration. The researchers believe higher initial levels of oxygen may jump-start independent breathing, but more research is required to explore the underlying cause for this effect.
The researchers emphasise that additional large studies will be important to confirm this finding, and that even when starting with high oxygen, it needs to be adjusted to lower levels quickly to avoid hyperoxia (oxygen poisoning).
How the oxygen is delivered during the first 10 minutes of the infant’s life is critical. Doctors may give the baby high levels of oxygen at the start but then monitor vital signs and continually adjust the oxygen to avoid over or under exposure.
If confirmed in future studies, the findings challenge current international recommendations that suggest giving preterm babies the same amount of oxygen as babies born at term, 21%–30% oxygen (room air), rather than extra oxygen.
This study also demonstrates that there may not be a one-size-fits-all approach, and babies born prematurely may have different needs than babies born at term.
“Ensuring very premature infants get the right treatment from the beginning sets them up to lead healthy lives. There is no better time to intervene than immediately after birth,” said lead author Dr James Sotiropoulos from the University of Sydney’s NHMRC Clinical Trials Centre.
“The goal is to find the right balance – how do we give enough oxygen to prevent death and disability, but not damage vital organs.”
“Whilst promising and potentially practice-changing, these findings will need to be confirmed in future larger studies.”
Historically, oxygen with a 100% concentration was used to resuscitate all newborn infants. But due to studies that found high concentrations of oxygen over time can lead to hyperoxia and subsequent organ damage, in 2010 it prompted changes in international treatment recommendations for the use of blended oxygen (starting with low oxygen) for preterm infants.
Hyperoxia still a danger
However, researchers say the change was mainly based on evidence for full-term infants, who have fully developed lungs and who are often not as sick as premature infants. To date, there is little conclusive evidence to guide best practice for premature infants. The researchers emphasise the findings should not minimise the dangers of hyperoxia.
“The debate around exactly how much oxygen is best for extremely premature babies is still ongoing but, ultimately, everyone has the same shared goal of determining the best treatment for newborns,” said Dr Anna Lene Seidler from the NHMRC Clinical Trials Centre.
“Our findings, together with all the other research that is currently happening, may help the most vulnerable preterm infants have the best chance of survival.”
“We are very lucky to work with a highly collaborative international group on this question, some of whom have been studying it for decades. The group’s diverse expertise and experience is a major strength of this work,” said Dr Sotiropoulos.
Scientists studying the impact of oxygen supplementation on motor learning have found a promising treatment that could help patients who have experienced neurological trauma recover lost motor skills.
“A simple and easy to administer treatment with 100% oxygen can drastically improve human motor learning processes,” said Dr Marc Dalecki, now at the German University of Health and Sports in Berlin, senior author of the study in Frontiers in Neuroscience.
Repurposing a frontline treatment
Brains have a high oxygen demand, and hypoxia causes cognitive function to decrease, while in high-oxygen contexts it recovers, and the delivery of 100% oxygen is already used to help preserve as much of the brain as possible in patients with neurological injuries.
Motor learning is particularly dependent on oxygen-reliant information processing and memory functions: humans learn by trial and error, so the ability to remember and integrate information from previous trials is critical to efficient and effective motor learning. So could supplementing oxygen while learning a motor task help people learn faster and more effectively, offering hope for neurorehabilitation patients?
“I had this idea in my mind for almost a decade and promised myself to investigate it once I got my own research lab,” said Dalecki, who led the experimental research at the School of Kinesiology at Louisiana State University. “And with Zheng Wang, now Dr Zheng Wang, I had the perfect doctoral student to run it – a keen physiotherapist with a clinical background and stroke patient experience.”
Hand-eye coordination
Dalecki and Wang recruited 40 participants, 20 of whom received 100% oxygen at normobaric pressure and 20 of whom received medical air (21% oxygen) through a nasal cannula during the “adaptation” or learning phase of a task.
Dalecki and Wang selected a simple visuomotor task which involved drawing lines between different targets on a digital tablet with a stylus. The task was designed to test how quickly the participants were able to integrate information from the eye and hand, a crucial part of motor learning. After the task had been learned, the alignment of the cursor and the stylus was altered to see how effectively the participants adapted to the inconsistency, and then realigned for a final session to see how they adapted to the realignment.
“The oxygen treatment led to substantially faster and about 30% better learning in a typical visuomotor adaptation task,” said Wang, first author of the study and now at the Mayo Clinic in Rochester. “We also demonstrate that the participants were able to consolidate these improvements after the termination of the oxygen treatment.”
Oxygen improved learning by 30%
The scientists found that the participants who had received oxygen learned faster and performed better, improvements which extended into later sessions of the task when oxygen was not administered.
The oxygen group moved the pen more smoothly and more accurately, and when the cursor was adjusted in a deliberate attempt to throw them off, they adapted more quickly. They also made bigger mistakes when the alignment of the stylus was corrected, suggesting they had integrated the previous alignment more thoroughly than the other group.
Dalecki and Wang plan to investigate the long-term effects of this supplementation on learning and test the intervention with other motor learning tasks: it is possible that the relevant brain functions for this task in particular benefit from high ambient oxygen levels, leading to the observed advantages in performance. They also hope to bring the oxygen treatment to elderly and injured people, in the hope that it will help them re-learn motor skills.
“Our future plan is to investigate whether this treatment can also improve motor recovery processes following brain trauma,” said Dalecki. “Since it worked in the young healthy brain, we expect that the effects may even be larger in the neurologically impaired, more vulnerable brain.”
Supplies of medical oxygen in Ukraine are dangerously low due to disruption caused by the Russian invasion, the World Health Organization has warned.
Due to the crisis, the WHO estimates that the country needs an additional 20–25% increase in oxygen supplies over and above its normal needs. As it currently stands, the transport of oxygen cylinders across the country is being disrupted, especially into the capital Kyiv. As of 27 February, many hospitals across the country, including in Kyiv, had less than 24 hours’ supply remaining.
Furthermore, oxygen production facilities are experiencing shortages of zeolite, which is needed for the safe production of oxygen in the pressure swing absorption process.
Prior to the conflict, the WHO had worked with Ukraine to improve its oxygen supply infrastructure, especially during the COVID pandemic. “Of the over 600 health facilities nationwide assessed by WHO during the pandemic, close to half were directly supported with supplies, technical know-how and infrastructure investments, enabling health authorities to save tens of thousands of lives,” the WHO said. This progress is threatening to be undone.
“Compounding the risk to patients, critical hospital services are also being jeopardised by electricity and power shortages, and ambulances transporting patients are in danger of getting caught in the crossfire,” the WHO said in its press release.
To offset this, the WHO is working through regional networks to bring in oxygen, as well as providing trauma treatment supplies. These would be brought in through a safe logistics corridor in Poland.
Médecins Sans Frontières (MSF) has announced that it is suspending activities in Ukraine. “These included care for people living with HIV in Severodonetsk; care for patients with tuberculosis in Zhytomyr; and improving access to healthcare access in Donetsk, in eastern Ukraine, where we have been providing much-needed healthcare, including for mental health, to conflict-affected communities,” the organisation said in an announcement.
However, it is working to ensure some continuity of its operations, and are working to provide trauma training to certain hospitals and have provided some trauma supplies.
The Ukrainian capital of Kyiv has also put out a call for donations of medicines, such as the antiviral amixin, the antibiotic nifuroxazide and the haemostatic agent aminocaproic acid.
A newly installed solar-powered medical oxygen system at a hospital in central Somalia is proving effective in saving lives, Somali and World Health Organization doctors told Voice of America.
The innovative solar oxygen system, the first of its kind in the country, was installed at Hanaano hospital, in the central town of Dhusamareb a year ago. Doctors say the system is having an impact and helping save the lives of very young patients.
“This innovation is giving us promise and hopes,” says Dr Mamunur Rahman Malik, WHO Somalia Representative.
According to Dr Malik, 171 patients received oxygen at the hospital from the solar-powered system from February to October 2021. Of these, only three patients died, and five others were referred to other hospitals.
Every year some 15 000 to 20 000 deaths occur in Somalia among children under five years of age due to pneumonia, said Dr Malik, making it the deadliest disease among under-fives.
The director of Hanaano hospital, Dr Mohamed Abdi, said the innovation is making a difference.
“It has helped a lot, it has saved more than a hundred people who received the service,” he said to VOA Somali.
“It was a problem for the children under one year and the children who are born six months to get enough oxygen. Now we are not worried about oxygen availability if the electricity goes out because there are the oxygen concentrators.”
One patient was Abdiaziz Omar Abdi, admitted to the hospital on January 16 with severe pneumonia and was struggling to breathe normally. The oxygen rate in his body had dropped to 60%, Dr Abdi said. Doctors immediately put him on oxygen along with ampicillin and dexamethasone medications. When discharged three days later, he was breathing normally. His oxygen was up to 90%.
Dr Malik said the oxygen is being used to treat a wide range of medical conditions – asphyxia, pneumonia, injuries, trauma, and road traffic accidents.
“We have seen in other countries that use of solar-powered medical oxygen (if applied in a timely manner) can save up to 35% of deaths from childhood pneumonia,” he said, adding that it could save the lives of at least 7000 children who die “needlessly” due to pneumonia.
The initiative to install solar-powered bio-medical equipment at Hanaano hospital emerged during the height of COVID in 2020, at a time when people were dying due to respiratory problems. Hospitals were unable to keep up with case loads and the cost of a cylinder of oxygen rose to between $400 to $600, and only 20% of health facilities had any kind of access to oxygen, said Dr Malik.
“If you look at the current situation, as of today Somalia needs close to 3000 or 4000 cubic metres of oxygen per day. So, oxygen was the biggest need in all the hospitals.”
Solar power can also be used for medical refrigerators, and their use is becoming widespread in Africa.
At the virtual launch of Global Citizen’s Recover Better Together Campaign, access to vaccines and medical resources was highlighted as a key area to address.
“Covid-19 has threatened the lives and livelihoods of everyone on the planet. To respond, we must take several urgent actions. The only way that we will be able to recover better, together is by defeating the virus everywhere through universal access of vaccines, diagnostics, and therapeutics,” said World Health Organization Director-General Dr Tedros Adhanom Ghebreyesus.
To this end, the Recover Better Together Campaign, an initiative organised by the Global Citizen, the European Commission and the WHO, aims to create momentum for global COVID pandemic recovery, with a return to the implementation of global goals.
“To fight the pandemic, we need to pool resources, capabilities, knowledge and intellectual property. That is why we continue to call on world leaders to support the COVAX facility to ensure rapid and equitable access to Covid-19 vaccines for all countries. Another important step is to enable the transfer of medical technology for the duration of the pandemic,” said President Cyril Ramaphosa.
One of key medical resource is oxygen, which is in short supply in many low- and middle-income countries, which have to provide enough for up to half a million COVID patients. WHO data shows that 1.1 million cylinders are needed daily in developing countries, with Africa seeing the biggest surge in demand. Hospitals in Nigeria have reported running out of oxygen, leading to preventable deaths.
According to the WHO, public hospitals across 41 African countries have fewer than 2000 working ventilators. In comparison, the United States has more than 170 000 ventilators. The South African private sector has about 4000 ventilators, and around 2000 in the public sector. The WHO said the launch of the Covid Tools Accelerator Therapeutics pillar, co-led by Unitaid and Wellcome, has improved access to oxygen. On 25 February the Covid-19 Oxygen Emergency Taskforce was also launched by the WHO.
Unitaid Executive Director Dr Philippe Duneton said the Taskforce now needs an additional $90 million US for delivery of oxygen in up to 20 countries including Malawi, Nigeria and Afghanistan.
“This is a global emergency that needs a truly global response, both from international organisations and donors. Many of the countries seeing this demand struggled before the pandemic to meet their daily oxygen needs,” said Duneton. “Now it’s more vital than ever that we come together to build on the work that has already been done, with a firm commitment to helping the worst-affected countries as quickly as possible.”
