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Archive for category: E-News

E-News

covid-19 virus

Researchers identify why Covid-19 patients develop life-threatening blood clots

, 25 June 2021/in Corona News, E-News /by panglobal

covid-19 virus

 

Scientists have identified how and why some Covid-19 patients can develop life-threatening blood clots, which could lead to targeted therapies that prevent this from happening.

The work, led by researchers from RCSI University of Medicine and Health Sciences, is published in the Journal of Thrombosis and Haemostasis.

Previous research has established that blood clotting is a significant cause of death in patients with Covid-19. To understand why that clotting happens, the researchers analysed blood samples that were taken from patients with Covid-19 in the Beaumont Hospital Intensive Care Unit in Dublin.

They found that the balance between a molecule that causes clotting, called von Willebrand Factor (VWF), and its regulator, called ADAMTS13, is severely disrupted in patients with severe Covid-19.

When compared to control groups, the blood of Covid-19 patients had higher levels of the pro-clotting VWF molecules and lower levels of the anti-clotting ADAMTS13. Furthermore, the researchers identified other changes in proteins that caused the reduction of ADAMTS13.

“Our research helps provide insights into the mechanisms that cause severe blood clots in patients with Covid-19, which is critical to developing more effective treatments,” said Dr Jamie O’Sullivan, the study’s corresponding author and research lecturer within the Irish Centre for Vascular Biology at RCSI.

He added: “While more research is needed to determine whether targets aimed at correcting the levels of ADAMTS13 and VWF may be a successful therapeutic intervention, it is important that we continue to develop therapies for patients with Covid-19. Covid-19 vaccines will continue to be unavailable to many people throughout the world, and it is important that we provide effective treatments to them and to those with breakthrough infections.”

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EHA logo

Study presented at EHA21 looks at Pfizer/BioNTech SARS-COV-2 vaccine impairment in immunosuppressed patients

, 22 June 2021/in Corona News, E-News /by panglobal

EHA logo

The European Hematology Association held their virtual congress from 9-17 June – it remains online until 15 August here. Many studies were presented, key among them was one titled: Humoral Response to the Pfizer/BioNTech BNT162b2 Vaccine Is Impaired in Patients Receiving CAR-T or High-Intensity Immunosuppressive Therapy.

In the study the researchers evaluated the efficacy and safety of the Pfizer/BioNTech BNT162b2 vaccine – approved for the prevention of SARS-CoV-2 infection – in patients that underwent hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR)-T therapy. They prospectively followed 79 vaccinated patients who were actively treated at the Tel Aviv Sourasky Medical Center and monitored the safety profile and the humoral immune response to the vaccine.

They note that although the vaccine is recommended for immunosuppressed patients, its efficacy and safety in patients undergoing immunologic cell therapy have not been well-documented.

In their study they found that: “Overall, the vaccine was well-tolerated and all adverse events resolved within a few days except for one secondary graft rejection, which is still under investigation. We observed that only 36% of patients who received CAR-T therapy developed a humoral antibody response compared with 81% of patients who underwent allogeneic HCT. In addition, patients with B cell aplasia and those who received the vaccine shortly after infusion of cells were less likely to develop antibodies. Taken together, these data demonstrate that the humoral response to the BNT162b2 vaccine is significantly impaired in patients receiving CAR-T , as opposed to those after allogeneic HCT who had a good response.”

EHA21 Virtual Congress

This study presentation and others can be accessed at the EHA21 Virtual Congress. The education and scientific program of the congress focuses on clinical practice, recent advances, new data and views from different stakeholders and international organizations. Registration is open until 1 August and the sessions are online until 15 August.

 

 

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doctor

WHO’s Council on the Economics of Health for All issues brief on equitable health innovation

, 9 June 2021/in E-News, Featured Articles /by panglobal

Leading economists and health experts call for a health innovation ecosystem governed by “the common good”

surgery

The WHO Council on the Economics of Health for All, which comprises leading economists and health experts from across the globe, has called on governments, the scientific and medical community and private sector leaders to re-design the health innovation ecosystem toward delivering health technologies for the common good.

In the Council’s first brief, its members called on the public and private sectors to work collaboratively to deliver needed vaccines, therapeutics, diagnostics, and other essential health supplies that are available equitably to those who can benefit.

The Council Brief recommends both immediate and long-term action, urging all stakeholders to work towards creating a health innovation ecosystem characterized by purpose-driven and symbiotic public-private partnerships that put the common good front and centre.

“Mobilizing money to throw at solutions that fail to address the underlying causes of longstanding structural problems will not be sufficient,” according to the Council Brief. “We all must look forward towards re-imagining health innovation as part of a new economic ecosystem that can deliver Health for All.”

Deep change is needed

The Council has made clear that just patching up the existing system will not work. Deep change is needed on how intellectual property rights are governed to drive collective intelligence, how corporate governance is structured, and how the benefits of public investments are shared to avoid the current dynamic of sharing risks but privatizing rewards.

To build an inclusive end-to-end health innovation ecosystem able to deliver the appropriate medical technologies required to achieve Health for All equitably, the following building blocks are critical:

  • Creating purpose-driven innovation through a mission-oriented approach;
  • Reshaping knowledge governance to nurture collective intelligence;
  • Reforming corporate governance to be more long-term and purpose-oriented;
  • Building resilient manufacturing capacity and infrastructure;
  • Introducing conditionalities for public investments to build symbiotic public-private partnerships;
  • Strengthening the capacity of the public sector on both the supply and demand side.

Growing calls for urgent action

In the short-term, the Council, in its brief, adds its voice to the growing calls for urgent action in four areas:

  • Available vaccine doses should be redistributed immediately, not as acts of charity, but as a shared imperative for pandemic control and inclusive, equitable and sustainable access.
  • Technology transfer and building manufacturing capacity must be supported and financed, not as the responsibility or property of any single actor, but as a collective responsibility towards building health greater health security and resilience in all regions, governed as common goods.
  • Knowledge should not be kept as privatized intellectual property under monopoly control but considered collective rewards from a collective value creation process to be openly shared and exchanged.
  • Existing mechanisms set up to address the above aspects, including COVAX, ACT-Accelerator, and the Covid Technology Access Pool, should be utilized and strengthened, not as an approach to fix market failures, but as turning points for creating market-shaping approaches.”

The Council’s brief came ahead of the G7 Leaders’ Summit under the U.K.’s Presidency, which aims to build back better from the COVID-19 pandemic, including by strengthening resilience against future pandemics; and following the Seventy-fourth World Health Assembly and the G20 Global Health Summit co-hosted by Italy and the EU earlier this month.

The Council, which was established by the World Health Organization in November 2020, is chaired by noted economist Professor Mariana Mazzucato, Professor of the Economics of Innovation and Public Value and Founding Director in the Institute for Innovation and Public Purpose at University College London.

Its patron is H.E. Sanna Marin, Prime Minister of Finland.

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Crohns mouse model

Researchers create bioengineered organism that could diagnose Crohn’s disease flareups

Research, 19 May 2021/in E-News /by panglobal
Jeff Tabor, associate professor of bioengineering in Rice’s Brown School of Engineering

Jeff Tabor, associate professor of bioengineering in Rice’s Brown School of Engineering (Credit: Jeff Fitlow/Rice University)

In an important step toward the clinical application of synthetic biology, Rice University researchers have engineered a bacterium with the necessary capabilities for diagnosing a human disease.

The engineered strain of the gut bacteria E. coli senses pH and glows when it encounters acidosis, an acidic condition that often occurs during flareups of inflammatory bowel diseases like colitis, ileitis and Crohn’s disease.

Crohns mouse model

Rice University researchers engineered a strain of the gut bacteria E. coli to detect gastrointestinal acidosis. The organism produces fluorescent molecules that allow researchers to see it with standard optical equipment. Under normal conditions (left) it produces molecules that glow red. When it encounters acidic conditions (right), it glows green, and the brightness of the glow reflects the level of acidity. (Image courtesy of Jeff Tabor/Rice University)

Researchers at the University of Colorado (CU) School of Medicine used the Rice-created organism in a mouse model of Crohn’s disease to show acidosis activates a signature set of genes. The corresponding genetic signature in humans has previously been observed during active inflammation in Crohn’s disease patients. The results are available online in the Proceedings of the National Academy of Sciences.

Colours that show up in the toilet

Study co-author Jeffrey Tabor, whose lab engineered the pH-sensing bacterium, said it could be reprogrammed to make colours that show up in the toilet instead of the fluorescent tags used in the CU School of Medicine experiments.

“We think it could be added to food and programmed to turn toilet water blue to warn patients when a flareup is just beginning,” said Tabor, an associate professor of bioengineering in Rice’s Brown School of Engineering.

Over their 3.5 billion-year history, bacteria have evolved countless specific and sensitive genetic circuits to sense their surroundings. Tabor and colleagues developed a biohacking toolkit that allows them to mix and match the inputs and outputs of these bacterial sensors. The pH-sensing circuit was discovered by Rice Ph.D. student Kathryn Brink in a 2019 demonstration of the plug-and-play toolkit.

pH sensor

PNAS study co-authors Sean Colgan, the director of the CU School of Medicine’s mucosal inflammation program, and Ian Cartwright, a postdoctoral fellow in Colgan’s lab, read about the pH sensor and contacted Tabor to see if it could be adapted for use in a mouse model of Crohn’s disease.

“It turns out that measuring pH within the intestine through noninvasive ways is quite difficult,” said Colgan, the Levine-Kern Professor of Medicine and Immunology in the CU School of Medicine.

So Brink spent a few weeks splicing the necessary sensor circuits into an organism and sent it to Colgan’s lab.

“Normally, the pH in your intestines is around seven, which is neutral, but you get a lot of inflammation in Crohn’s disease, and pH goes to something like three, which is very acidic,” Tabor said.

Colgan and colleagues have studied the genes that are turned on and off under such conditions and “needed a tool to measure pH in the intestine to show that the things they were observing in in vitro experiments were also really happening in a live animal,” Tabor said.

Biological tool

“Colonizing this bacterial strain was the perfect biological tool to monitor acidosis during active inflammation,” Colgan said. “Correlating intestinal gene expression with the bacterial pH sensing bacteria proved to be a useful and valuable set of biomarkers for active inflammation in the intestine.”

Tabor said he believes the pH-sensing bacterium could potentially be advanced for human clinical trials in several years.

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more nurses leads to shorter patient stays

More nurses lead to shorter hospital stays, less readmissions and fewer patient deaths

Research, 19 May 2021/in E-News /by panglobal

Australian study shows that savings made from shorter stays are double the cost of hiring more staff

more nurses lead to fewer patient deaths

 

 

 

 

 

 

 

 

 

 

 

 

 

A study across 55 hospitals in Queensland, Australia suggests that a recent state policy to introduce a minimum ratio of one nurse to four patients for day shifts has successfully improved patient care, with a 7% drop in the chance of death and readmission, and 3% reduction in length of stay for every one less patient a nurse has on their workload.

The study of more than 400,000 patients and 17,000 nurses in 27 hospitals that implemented the policy and 28 comparison hospitals is published in The Lancet. It is the first prospective evaluation of the health policy aimed at boosting nurse numbers in hospitals to ensure a minimum safe standard and suggests that savings made from shorter hospital stays and fewer readmissions were double the cost of hiring more staff.

Despite some evidence that more nurses in hospitals could benefit patient safety, similar policies have not been widely implemented across the globe, partly due to an absence of data on the long-term effects and costs, as well as limited resources. In recent years, Scotland, Wales, and Ireland have mandated numbers of patients per nurse, but strategies to improve nursing levels remains debated worldwide.

Study fills data gap

“Our findings plug a crucial data gap that has delayed a widespread roll-out of nurse staffing mandates. Opponents of these policies often raise concerns that there is no clear evaluation of policy, so we hope that our data convinces people of the need for minimum nurse-to-patient ratios by clearly demonstrating that quality nursing is vital to patient safety and care,” says lead author, Professor Matthew McHugh of the University of Pennsylvania School of Nursing, USA.

In 2016, 27 public hospitals in Queensland were required to instate a minimum of one dedicated nurse for every four patients during day shifts and one for every seven patients for night shifts on medical-surgical wards.

The research team collected data from those 27 Queensland hospitals that instated ratios and from 28 other hospitals in the state that did not, at baseline in 2016 and at follow-up in 2018 (two years after the policy was implemented). Only nurses in direct contact with adult patients in medical-surgical wards were included – data from patients in birthing suites and psychiatric units were not assessed in the study.

Researchers used patient data to assess demographics, diagnoses, and discharge details for patients, as well as length of hospital stay. These data were then linked to death records for 30 days following discharge, and to readmissions within seven days of discharge.

The researchers sent an email survey to nurses in each hospital to ask about the numbers of bedside nurses and patients on their most recent shift. The responses were used to establish the numbers of nurses per patient and then averaged across wards and hospitals. Responses were received from 8,732 nurses (of a possible 26,871) at baseline in 2016, and 8,278 (of a possible 30,658) in 2018.
more nurses leads to shorter patient stays

The study includes baseline data for 231,902 patients (142,986 in hospitals that implemented the policy and 88,916 in comparison hospitals), and for 257,253 patients (160,167 in hospitals that implemented the policy and 97,086 in comparison hospitals) after the policy was brought in.

Comparison hospitals had no change in staffing, with six patients per nurse in 2016 and the same ratio (1:6) in the follow-up period in 2018. Intervention hospitals averaged five patients per nurse at baseline in 2016, with a reduction to four per nurse after the policy implementation.

Patient deaths

To compare the changes in outcomes in the intervention and comparison hospitals over time, the researchers estimated the odds of dying within 30 days of admission and of being readmitted within seven days of discharge, and the additional length of stay, after adjusting for factors such as patient age, sex, existing health conditions and hospital size. They found that the chance of death rose between 2016 and 2018 by 7% in hospitals that did not implement the policy, and fell by 11% in hospitals that did implement the policy.

Readmissions

The chances of being readmitted increased by 6% in the comparison hospitals over time, but stayed the same in hospitals that implemented the policy. Between 2016 and 2018, the length of stay fell by 5% in the hospitals that did not implement the policy, and by 9% in hospitals that did.

Nurse workloads

Further analyses found that when nurse workloads improved by one less patient per nurse, the chance of death and readmissions fell by 7%, and the length of hospital stay dropped by 3%.

Using their modelling to predict figures that would have been expected without the policy in place, the researchers estimated that there could have been 145 more deaths, 255 more readmissions and 29,222 additional days in hospital in the 27 hospitals that implemented the policy between 2016 and 2018.

Financial impact of employing more nurses

To calculate the financial impact of the staffing policy, the researchers used state data to estimate the cost of funding the 167 extra staff needed to reduce workload by one patient per nurse at approximately $33,000,000 (AUD) in the first two years. Based on Australian health economic data, they further estimated that preventing readmissions and reducing lengths of stay resulted in an approximate saving of $69,150,858 in the 27 hospitals across the two years following the mandate.

“Part of the reluctance to bring in a minimum nurse-patient ratio mandate from some policy-makers is the expected rise in costs from increased staffing. Our findings suggest that this is short-sighted and that the savings created by preventing readmissions and reducing length of stay were more than twice the cost of employing the additional nurses needed to meet the required staffing levels – a clear return on investment. Often, policy-makers are concerned about whether they can afford to implement such a policy. We would encourage governments to look at these figures and consider if they can afford not to,” says Professor Patsy Yates of the Queensland University of Technology School of Nursing, Australia.

Study limitations

The authors note that there are a number of limitations associated with the study. Hospitals in the research were not randomly assigned to comparison or intervention groups, as only 27 hospitals in the state were mandated to follow the policy. Furthermore, the hospitals included in both groups were not matched for size or patient demographics and health conditions, although this is accounted for in adjusted analyses.

Access the study: Effects of nurse-to-patient ratio legislation on nurse staffing and patient mortality, readmissions, and length of stay: a prospective study in a panel of hospitals. The Lancet. May 11, 2021. https://doi.org/10.1016/S0140-6736(21)00768-6

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covid-19 vaccination

COVID vaccines: some fully vaccinated people will still get infected – here’s why

, 18 May 2021/in Corona News, E-News /by panglobal

covid-19 vaccination

 

By Tara Hurst  
Lecturer, Biomedical Science, Birmingham City University

 

The development of several COVID vaccines in less than a year has given us all hope of a release from the pandemic. Now the goal has shifted to ensuring widespread vaccine coverage is achieved as quickly as possible around the globe.

However, it is unlikely that any of the vaccines will be 100% effective at stopping transmission or infection. There is a small risk that some fully vaccinated people will get infected. This is known as a “breakthrough infection” – and it’s entirely expected.

It is important to realise the limitations of vaccines. No vaccine offers full protection to everyone who receives it. The measles vaccine has been highly effective at preventing infection, leading to the virus being nearly eradicated in some countries.

Yet there are infections reported even in populations with widespread vaccination. These infections occur not only in the unvaccinated; there are cases of breakthrough infections in fully vaccinated people.

The seasonal flu vaccine offers protection from the circulating viruses. But the circulating flu viruses vary, and vaccinated people may still get ill but have less severe illness.

This is possibly because different arms of the immune response produce different defences, namely antibodies, which are Y-shaped proteins that lock onto germs and neutralise them, and T cells, which find and destroy infected cells. Antibodies are typically raised against the more variable proteins on the surface of the virus, while the more consistent proteins inside the virus are targeted by the T cells. T cells are important for limiting the severity of illness.

For SARS-CoV-2 (the virus that causes COVID-19) there is anecdotal evidence, including from Seychelles, of breakthrough infections, but little has yet been published in scientific journals. A recent report in the New England Journal of Medicine described two COVID-19 cases following vaccination, with both showing mild symptoms that resolved within one week.

And a study from Stanford University, which is yet to be reviewed by other scientists, describes 189 post-vaccination COVID cases out of 22,729 healthcare workers, but attributes at least some of these to partial vaccination. Vaccination will probably make the disease less severe should such breakthroughs occur.

Several explanations

There are several possible explanations for breakthrough infections. The human immune response is encoded in our DNA and varies from person to person. This variability helps us to respond to an array of germs. But the effectiveness of these responses is also variable. This could also be due to several things, including poor health, medication or age.

The ageing immune system does not respond to new antigens (foreign substance that causes your immune system to produce antibodies against it) and vaccines as well as younger immune systems. For one COVID vaccine, there was a measurable difference in the concentration of neutralising antibodies in the elderly compared with younger adults. Some of the elderly participants had no neutralising antibodies at all after both doses of the vaccines.

Another reason for breakthrough infections is due to viral variants that escape immune detection and flourish even in vaccinated people. A virus, especially an “RNA virus” such as SARS-CoV-2, is expected to mutate and give rise to variants, some of which may be more easily transmitted. These variants may also be more or less effectively neutralised by the immune system since the mutations could alter the parts of the virus that are recognised by antibodies and T cells.

A new SARS-CoV-2 variant identified in India (B16172) is thought to make the virus more transmissible and this is a cause for concern in light of the COVID crisis unfolding there. Despite the absence of scientific studies, there are many reports in the media of frequent breakthrough infections and the B16172 variant is blamed, but this has yet to be proved.

In the one study, done on post-vaccine infections with SARS-CoV-2 in California, there was no significantly higher risk of infection due to the variants circulating in that region. Despite the evidence that the vaccines work well against the variants, the rapid increase in the proportion of cases in the UK that are due to B16172 as compared to the dominant Kent strain (B117) has meant that it has been raised to a variant of concern by Public Health England.

While widespread vaccination remains the pandemic end game, it bears mentioning that this is unlikely to prevent all infections. Those who develop COVID after vaccination will probably have a milder illness, and so the risk of breakthrough infections should not deter us from using the current vaccines. Further study into the causes of breakthrough SARS-CoV-2 infections could help scientists to refine COVID vaccines or the schedule of booster doses.

  • This article is republished from The Conversation under a Creative Commons license.
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brain-to-text BCI

Brain-to-text: Researchers develop brain-computer interface that turns neural signals into typed text in real time

Research, 13 May 2021/in E-News /by panglobal
brain-to-text BCI

Thoughts turned into text: Two implanted electrode arrays record the brain activity produced by thinking about writing letters. This information is then collected and processed in real-time by a computer, which converts that data into words on a screen. Courtesy Shenoy lab & Erika Woodrum (artist)

 

Scientists have developed a brain-computer interface (BCI) which for the first time enables neural signals associated with handwriting to be decoded and turned into text in real time.

This breakthrough in BCI technology has the potential to enable paralysed or paraplegic individuals – unable to write or speak – to communicate in writing, at speed, in real time.

The study was published in Nature, May 12.

The researchers developed an intracortical BCI that decodes attempted handwriting movements from neural activity in the motor cortex and translates it to text in real time, using a recurrent neural network decoding system.

They tested the device in a participant with paralysis which in essence enabled him to type without using his hands. By thinking about handwriting letters, the researchers were able to decode the neural signals with an algorithm which turned the letters into typed text on a screen in real time.

The study participant typed 90 characters per minute – more than double the previous record for typing with such a BCI. However, previous studies had not used decoded neural handwriting signals. They had instead used thought-controlled cursor movements on a virtual keyboard.

Neural signals associated with handwriting

Study coauthor Krishna Shenoy, a Howard Hughes Medical Institute (HHMI) investigator at Stanford University and his team have in recent years been studying neural activity associated with speech in an effort to reproduce it. However, they had not considered trying to decode neural signals associated with handwriting, says Frank Willett, an HHMI research specialist and neuroscientist in Shenoy’s group.

First, the participant was asked to copy letters that were displayed on the screen, which included the 26 lower-case letters along with some punctuation: “>” which was used as a space and “~” which was used as a “full stop.” At the same time, implanted electrodes recorded the brain activity from approximately 200 individual neurons associated with handwriting that responded differently while he mentally “wrote” each individual character. After a series of training sessions, the BCI’s computer algorithms learned how to recognize neural patterns corresponding to individual letters, allowing the participant to “write” new sentences that hadn’t been printed out before, with the computer displaying the letters in real time.

“This method is a marked improvement over existing communication BCIs that rely on using the brain to move a cursor to ‘type’ words on a screen,” said Willett, the study’s lead author. “Attempting to write each letter produces a unique pattern of activity in the brain, making it easier for the computer to identify what is being written with much greater accuracy and speed.”

Level of flexibility

This system also provides a level of flexibility that is crucial to restoring communication. Some studies have gone as far as attempting direct thought-to-speech BCIs that, while promising, are currently limited by what is possible through recordings from the surface of the brain which averages responses across thousands of neurons.

“Right now, other investigators can achieve about a 50-word dictionary using machine learning methods when decoding speech,” said Dr. Shenoy. “By using handwriting to record from hundreds of individual neurons, we can write any letter and thus any word which provides a truly ‘open vocabulary’ that can be used in almost any life situation.”

Although it is still relatively early days for this technology, it offers the potential to help those who have completely lost the ability to write and speak.

In the future, Dr. Shenoy’s team intends to test the system on a patient who has lost the ability to speak, such as someone with advanced ALS. In addition, they are looking to increase the number of characters available to the participants (such as capital letters and numbers).

The participant is part of a clinical trial, called BrainGate2, which is being conducted by a collaboration of internationally recognized laboratories, universities, and hospitals working to advance brain-computer interface technologies.

 

Reference

Willett, F.R., Avansino, D.T., Hochberg, L.R. et al. High-performance brain-to-text communication via handwriting. Nature 593, 249–254 (2021). https://doi.org/10.1038/s41586-021-03506-2

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14-year-old becomes youngest patient to receive living donor liver transplant at Cleveland Clinic Abu Dhabi

Surgery, 13 May 2021/in E-News /by panglobal

live liver donor transplant

 

A 14-year-old boy has received a living liver donation from his elder brother at Cleveland Clinic Abu Dhabi, an integral part of Mubadala Health, becoming the youngest patient to undergo the operation in the hospital’s history.

Montasir Elfatih Mohyeldin Taha was diagnosed with biliary atresia in infancy, a condition where the bile ducts outside the liver fail to form during fetal development, not allowing the bile to reach the small intestine where it helps in the digestion of fat. At 10 months, he had to undergo the Kasai procedure, which is done to connect a loop of small bowel directly to the liver so that the bile can drain into it. Montasir’s doctors back home in Sudan knew that it was only a matter of time before he would have to undergo a liver transplant, an inevitable consequence for most children who have this procedure.

Portal hypertension

Earlier this year, Montasir’s symptoms and blood tests revealed that he had started developing liver failure and was suffering from portal hypertension, an increase in the pressure within the vein that carries blood from the digestive organs to the liver, resulting in varicose veins in his esophagus. Seeing the high risk of potential complications, his doctors in Sudan recommended that he undergo a liver transplant at Cleveland Clinic Abu Dhabi.

Dr. Luis Campos, the Director of Liver Transplant and Hepatobiliary at Cleveland Clinic Abu Dhabi, who was part of the interdisciplinary team that cared for Montasir, says this was one of the most complex living donor liver transplant surgeries that they have performed at the hospital.

“There were additional nuances that had to be taken into consideration because of his age, which made it even more challenging. Factors such as height and weight impact the surgery and after-care, and determine the dose of immunosuppressive medication during and after the transplant. There is also a risk of other infectious complications in pediatric liver transplant that do not apply to adult surgeries,” says Dr. Campos.

Multidisciplinary medical team

The multidisciplinary medical team at Cleveland Clinic Abu Dhabi studied the case and evaluated Montasir’s mother and brother for a match in February. After careful discussion with colleagues in the US-based Cleveland Clinic, doctors here decided that his sibling would be a more suitable match.

“My little brother needed me. I was very relieved when I was told that I can help be the cure to his illness. This was one of the easiest decisions that I have had to make,” says Khalifa Elfatih Mohyeldin Taha. “My father passed away six months back and as the eldest son in the family, it was my responsibility to save him.”

Kasai procedure

Dr. Shiva Kumar, the Chair of Gastroenterology and Hepatology in the Digestive Disease Institute at Cleveland Clinic Abu Dhabi, who was also part of the patient’s care team, says one of the biggest challenges during Montasir’s transplant was posed by the young patient’s Kasai procedure.

“While the Kasai procedure is commonly performed to prolong the need for a liver transplant in children, this is a major operation and makes the transplant more challenging to perform,” says Dr. Kumar.

“However, the surgeries of both brothers were successful and without complications. Montasir received a left lobe graft from his brother. This is a smaller portion of the liver than if we were transplanting a right lobe graft. This makes it a safer operation for the donor and helps them recover faster.”

Immunosuppressive regimen

The brothers are on their way to a full recovery. Khalifa is back to his normal life now while the Cleveland Clinic Abu Dhabi care team is monitoring Montasir’s immunosuppressive regimen, which he will be on for the rest of his life.

Khalifa says he could not contain his joy when he was told that the surgery was a success. “The best part of my transplant journey was to see that Montasir’s body had accepted the new organ. My family and I are very grateful to the care team at Cleveland Clinic Abu Dhabi for saving my brother’s life.”

He also hopes that more people consider organ donation. “The feeling of giving a chance to someone to live a normal life is incomparable. Seeing the result of your donation will fill you with contentment.”

https://interhospi.com/wp-content/uploads/sites/3/2021/05/liver_transplant.jpg 473 850 panglobal https://interhospi.com/wp-content/uploads/sites/3/2020/06/Component-6-–-1.png panglobal2021-05-13 11:24:132021-05-13 11:24:1314-year-old becomes youngest patient to receive living donor liver transplant at Cleveland Clinic Abu Dhabi
Lung cells in patients with severe COVID become trapped in a state (indicated by the green color) that prevents the cells from repairing damage caused by the infection. The left image shows cells from a healthy lung; the right image shows lung cells from a patient who died from COVID-19

New Cell Atlas of COVID lungs reveals why SARS-CoV-2 is different and deadly

, 3 May 2021/in Corona News, E-News /by panglobal
Lung cells in patients with severe COVID become trapped in a state (indicated by the green color) that prevents the cells from repairing damage caused by the infection. The left image shows cells from a healthy lung; the right image shows lung cells from a patient who died from COVID-19.

Lung cells in patients with severe COVID become trapped in a state (indicated by the green color) that prevents the cells from repairing damage caused by the infection. The left image shows cells from a healthy lung; the right image shows lung cells from a patient who died from COVID-19. Images: Benjamin Izar / Columbia University Vagelos College of Physicians and Surgeons.

 

A new study published in Nature [1] draws the most detailed picture yet of SARS-CoV-2 infection in the lung, revealing mechanisms that result in lethal COVID-19, and may explain long-term complications and show how COVID-19 differs from other infectious diseases.

Led by researchers at Columbia University Vagelos College of Physicians and Surgeons and Herbert Irving Comprehensive Cancer Center, the study found that in patients who died of the infection, COVID-19 unleashed a detrimental trifecta of runaway inflammation, direct destruction and impaired regeneration of lung cells involved in gas exchange, and accelerated lung scarring.

Though the study looked at lungs from patients who had died of the disease, it provides solid leads as to why survivors of severe COVID may experience long-term respiratory complications due to lung scarring.

“It’s a devastating disease, but the picture we’re getting of the COVID-19 lung is the first step towards identifying potential targets and therapies that disrupt some of the disease’s vicious circuits. In particular, targeting cells responsible for pulmonary fibrosis early on could possibly prevent or ameliorate long-term complications in survivors of severe COVID-19,” says Benjamin Izar, MD, PhD, assistant professor of medicine, who led a group of more than 40 investigators to complete in several months a series of analyses that usually takes years.

This study and a companion paper [2] led by researchers at Harvard/MIT, to which the Columbia investigators also contributed, were published in the journal Nature on April 29.

Study creates atlas of cells in COVID lung

The new study is unique from other investigations in that it directly examines lung tissue (rather than sputum or bronchial washes) using single-cell molecular profiling that can identify each cell in a tissue sample and record each cell’s activity, resulting in an atlas of cells in COVID lung.

“A normal lung will have many of the same cells we find in COVID, but in different proportions and different activation states,” Izar says. “In order to understand how COVID-19 is different compared to both control lungs and other forms of infectious pneumonias, we needed to look at thousands of cells, one by one.”

Izar’s team examined the lungs of 19 individuals who died of COVID-19 and underwent rapid autopsy (within hours of death) – during which lung and other tissues were collected and immediately frozen – and the lungs of non-COVID-19 patients. In collaboration with investigators at Cornell University, the researchers also compared their findings to lungs of patients with other respiratory illnesses.

Drugs targeting IL-1ß may reduce inflammation

Compared to normal lungs, lungs from the COVID patients were filled with immune cells called macrophages, the study found.

Typically during an infection, these cells chew up pathogens but also regulate the intensity of inflammation, which also helps in the fight.

 

The lungs of patients with COVID-19 have more monocytes expressing IL-1beta than lungs from patients with other respiratory conditions.

 

“In COVID-19, we see expansion and uncontrolled activation of macrophages, including alveolar macrophages and monocyte-derived macrophages,” Izar says. “They are completely out of balance and allow inflammation to ramp up unchecked. This results in a vicious cycle where more immune cells come in causing even more inflammation, which ultimately damages the lung tissue.”
One inflammatory cytokine in particular, IL-1ß, is produced at a high rate by these macrophages.
“Unlike other cytokines such as IL-6, which appears to be universally prevalent in various pneumonias, IL-1ß production in macrophages is more pronounced in COVID-19 compared to other viral or bacterial lung infections,” Izar says. “That’s important because drugs exist that tamp down the effects of IL-1ß.”
Some of these drugs are already being tested in clinical trials of COVID patients.

Severe COVID also prevents lung repair

In a typical infection, a virus damages lung cells, the immune system clears the pathogen and the debris, and the lung regenerates.

But in COVID, the new study found that not only does SARS-CoV-2 virus destroy alveolar epithelial cells important for gas exchange, the ensuing inflammation also impairs the ability of the remaining cells to regenerate the damaged lung.

Though the lung still contains cells that can do the repairs, inflammation permanently traps these cells in an intermediate cell state and leaves them unable to complete the last steps of differentiation needed for replacement of mature lung epithelium.

“Among others, IL-1ß appears to be a culprit in inducing and maintaining this intermediate cell state,” says Izar, “thereby linking inflammation and impaired lung regeneration in COVID-19. This suggests that in addition to reducing inflammation, targeting IL-1ß may help take the brakes off cells required for lung repair.”

Preventing accelerated fibrosis

The researchers also found a large number of specific fibroblast cells, called pathological fibroblasts, that create rapid scarring in COVID-19 lungs. When the fibroblast cells fill the lung with scar tissue, a process called fibrosis, the lung has less space for cells involved in gas exchange and is permanently damaged.

Given the importance of pathological fibroblasts in the disease, Izar’s team closely analysed the cells to uncover potential drug targets. An algorithm called VIPER, developed previously by Andrea Califano, Dr, chair of systems biology at Columbia University Vagelos College of Physicians and Surgeons, identified several molecules in the cells that play an important role and could be targeted by existing drugs.

“This analysis predicted that inhibition of STAT signalling could alleviate some of the deleterious effects caused by pathological fibroblasts,” Izar says.

“Our hope is that by sharing this analysis and massive data resource, other researchers and drug companies can begin to test and expand on these ideas and find treatments to not only treat critically ill patients, but also reduce complications in people who survive severe COVID-19.”

References

[1] A molecular single-cell lung atlas of lethal COVID-19. Nature (2021).
https://doi.org/10.1038/s41586-021-03569-1

[2] COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets. Nature (2021).
https://doi.org/10.1038/s41586-021-03570-8

https://interhospi.com/wp-content/uploads/sites/3/2021/05/covid_lungs.jpg 1208 2406 panglobal https://interhospi.com/wp-content/uploads/sites/3/2020/06/Component-6-–-1.png panglobal2021-05-03 09:55:332021-05-03 09:55:33New Cell Atlas of COVID lungs reveals why SARS-CoV-2 is different and deadly
RESPIRE clinical trial

RESPIRE trial of therapeutic for all strains of COVID-19 gets underway in Germany

, 13 April 2021/in Corona News, E-News /by panglobal

RESPIRE clinical trial

 

Investigators hope ATR-002 drug will also be effective against ‘Long-Covid’

 

Tübingen, Germany-based Atriva Therapeutics, a biopharmaceutical company that is pioneering the development of host-targeting antiviral therapies, has enrolled its first patient in its Phase II RESPIRE [1] trial in COVID-19. Prof. Martin Witzenrath, M.D., Vice Director Department of Infectious Diseases and Respiratory Medicine, supervised the first administration of study medication (MEK inhibitor ATR-002 or placebo) at the Charité – Universitätsmedizin Berlin, Germany.

Dr Rainer Lichtenberger, CEO of Atriva Therapeutics, commented: “We are excited to assess the efficacy of ATR-002 in treating COVID-19 and are looking forward to the results of the clinical trial. We can now test our lead candidate against SARS-CoV-2 because our pharmacological target is a common cellular mechanism that RNA viruses use. ATR-002 leaves the virus itself untouched but blocks a cellular factor that the virus needs for its replication and has the potential to reduce the viral load in the infected host.

“Host-directed approaches maintain efficacy also against mutated viruses – a problem that we are commonly seeing in the influenza virus and, unfortunately, in SARS-CoV-2 as well. If we were to see the positive outcomes of the trial we hope for, ATR-002 could provide efficient help against COVID-19 regardless of the given genetic subtype of the underlying viral strain.”

Prof. Gernot Rohde, M.D., Head of Pneumology and Professor for Respiratory Medicine and Allergology at the Goethe University Hospital, Frankfurt am Main, Germany and Global Coordinating Investigator of the RESPIRE trial, said: “While we have been lucky that SARS-CoV-2 vaccines were developed at unprecedented speed, we still are in desperate need for effective therapies against COVID-19. The pandemic situation remains very critical and is far from being under control.

“Being able to contribute to the development of a COVID-19 therapy, I am very much looking forward to the effects that we may see with ATR-002. I am convinced that a medication that can prevent hospitalized patients with a moderate to severe stage of COVID-19 from deteriorating and requiring ICU admission and ventilator support would mean huge progress and could also play a role in impeding the severe long-term effects that are being described as “Long COVID” Syndrome (PASC).”

RESPIRE trial

RESPIRE is a randomized, double-blind, placebo-controlled, international, multi-center Phase II clinical trial in 220 adult patients with moderate to severe COVID-19, requiring hospitalization, but not requiring ICU admission or ventilator support at the time of screening or randomization. On top of standard of care, half of the patients will receive ATR-002 900 mg, administered as tablets once daily on day 1, followed by ATR-002 600 mg once daily on days 2 to 6. Patients in the control group will receive placebo in a matching scheme, on top of standard of care.

The primary objective of the study is to demonstrate the efficacy of ATR-002 versus placebo in addition to standard of care; secondary endpoints include the measurement of changes in clinical signs and symptoms as well as other relevant clinical parameters. Outcomes will be assessed based on the clinical severity status on day 15, using a 7-point ordinal scale as suggested by the WHO COVID-19 Therapeutic Trial Synopsis [2]. All patients will be followed-up for 90 days. The study will also evaluate the pharmacokinetics of ATR-002.

ATR-002’s mode of action

Atriva’s lead product ATR-002 is developed specifically to treat diseases such as influenza and COVID-19, caused by RNA viruses. ATR-002 is a clinical stage MEK inhibitor drug candidate targeting the intracellular Raf/MEK/ERK signaling pathway. This pathway is central for replication of many RNA viruses, such as the influenza virus, hantavirus or respiratory syncytial virus (RSV) and also SARS-CoV-2, the virus that causes COVID-19.

In influenza virus infected cells, the interaction of ATR-002 with MEK (MAPK/ERK kinase) prevents export of the viral genome protein complexes (ribonucleoprotein, RNP) from the nucleus to the cytoplasm, thus blocking the formation of functional new viral particles. This ultimately reduces the viral load in the body. In addition, ATR-002 has the potential to modulate the pro-inflammatory cytokine response of the body, avoiding overshooting cytokine response that can be caused by such viral infections. MEK inhibition can reduce the gene expression of some of the cytokines involved, like TNF-α, IL-1ß, IP-10, IL-8, MCP-1 and MIP-1a, and thus mitigate the overactive inflammatory response in the lungs of patients who are severely ill with influenza or COVID-19.

References

[1] RESPIRE – A Randomized, Double-Blind, Placebo-Controlled, Multi-Centre Clinical Trial to Evaluate the Safety and Efficacy of ATR-002 in Adult Hospitalized Patients with COVID-19.

[2] https://www.who.int/publications/i/item/covid-19-therapeutic-trial-synopsis.

https://interhospi.com/wp-content/uploads/sites/3/2021/04/covid-19-graphic.png 1032 1920 panglobal https://interhospi.com/wp-content/uploads/sites/3/2020/06/Component-6-–-1.png panglobal2021-04-13 08:47:002021-04-13 08:52:34RESPIRE trial of therapeutic for all strains of COVID-19 gets underway in Germany
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