New Gel Stops Brain Tumors

Medication delivered by a novel gel cured 100% of mice with an aggressive brain cancer, a striking result that offers new hope for patients diagnosed with glioblastoma, one of the deadliest and most common brain tumors in humans.

Despite recent technological advancements, there is a dire need for new treatment strategies,” said Honggang Cui, a Johns Hopkins University chemical and biomolecular engineer who led the research. “We think this hydrogel will be the future and will supplement current treatments for brain cancer.”

Cui’s team combined an anticancer drug and an antibody in a solution that self-assembles into a gel to fill the tiny grooves left after a brain tumor is surgically removed. The gel can reach areas that surgery might miss and current drugs struggle to reach to kill lingering cancer cells and suppress tumor growth.

The gel also seems to trigger an immune response that a mouse’s body struggles to activate on its own when fighting glioblastoma. When the researchers rechallenged surviving mice with a new glioblastoma tumor, their immune systems alone beat the cancer without additional medication. The gel appears to not only fend off cancer but help rewire the immune system to discourage recurrence with immunological memory, researchers said.

Still, surgery is essential for this approach, the researchers said. Applying the gel directly in the brain without surgical removal of the tumor resulted in a 50% survival rate.

The surgery likely alleviates some of that pressure and allows more time for the gel to activate the immune system to fight the cancer cells,” Cui said.

The gel solution consists of nano-sized filaments made with paclitaxel, an FDA-approved drug for breast, lung, and other cancers. The filaments provide a vehicle to deliver an antibody called aCD47. By blanketing the tumor cavity evenly, the gel releases medication steadily over several weeks, and its active ingredients remain close to the injection site.

The results are published in Proceedings of the National Academy of Sciences.

Source: https://hub.jhu.edu/

ChatGPT Now Dispenses Advices to Doctors Like a Colleague

Hospitals have begun using “decision support tools” powered by artificial intelligence that can diagnose disease, suggest treatment or predict a surgery’s outcome. But no algorithm is correct all the time, so how do doctors know when to trust the AI’s recommendation? A new study led by Qian Yang, assistant professor of information science in the Cornell Ann S. Bowers College of Computing and Information Science, suggests that if AI tools can counsel the doctor like a colleague – pointing out relevant biomedical research that supports the decision – then doctors can better weigh the merits of the recommendation.

The researchers will present the new study, “Harnessing Biomedical Literature to Calibrate Clinicians’ Trust in AI Decision Support Systems,” in April (23 to 28) at the Association for Computing Machinery CHI Conference on Human Factors in Computing Systems. Previously, most AI researchers have tried to help doctors evaluate suggestions from decision support tools by explaining how the underlying algorithm works, or what data was used to train the AI. But an education in how AI makes its predictions wasn’t sufficient, Yang said. Many doctors wanted to know if the tool had been validated in clinical trials, which typically does not happen with these tools.

A doctor’s primary job is not to learn how AI works,” Yang said. “If we can build systems that help validate AI suggestions based on clinical trial results and journal articles, which are trustworthy information for doctors, then we can help them understand whether the AI is likely to be right or wrong for each specific case.”

To develop this system, the researchers first interviewed nine doctors across a range of specialties, and three clinical librarians. They discovered that when doctors disagree on the right course of action, they track down results from relevant biomedical research and case studies, taking into account the quality of each study and how closely it applies to the case at hand.

Yang and her colleagues built a prototype of their clinical decision tool that mimics this process by presenting biomedical evidence alongside the AI’s recommendation. They used GPT-3 to find and summarize relevant research. (ChatGPT is the better-known offshoot of GPT-3, which is tailored for human dialogue.)

Source: https://news.cornell.edu/

How to Restore Vital Cellular Functions to Pigs one Hour After Death

Within minutes of the final heartbeat, a cascade of biochemical events triggered by a lack of blood flow, oxygen, and nutrients begins to destroy a body’s cells and organs. But a team of Yale scientists has found that massive and permanent cellular failure doesn’t have to happen so quickly.

Using a new technology the team developed that delivers a specially designed cell-protective fluid to organs and tissues, the researchers restored blood circulation and other cellular functions in pigs a full hour after their deaths, they report in the Aug. 3 edition of the journal Nature. The findings may help extend the health of human organs during surgery and expand availability of donor organs, the authors said.

All cells do not die immediately, there is a more protracted series of events,” said David Andrijevic, associate research scientist in neuroscience at Yale School of Medicine and co-lead author of the study. “It is a process in which you can intervene, stop, and restore some cellular function.”The research builds upon an earlier Yale-led project that restored circulation and certain cellular functions in the brain of a dead pig with technology dubbed BrainEx. Published in 2019, that study and the new one were led by the lab of Yale’s Nenad Sestan, Professor of Neuroscience.

If we were able to restore certain cellular functions in the dead brain, an organ known to be most susceptible to ischemia [inadequate blood supply], we hypothesized that something similar could also be achieved in other vital transplantable organs,” Sestan said.

In the new study — which involved senior author Sestan and colleagues Andrijevic, Zvonimir Vrselja, Taras Lysyy, and Shupei Zhang, all from Yale — the researchers applied a modified version of BrainEx called OrganEx to the whole pig. The technology consists of a perfusion device similar to heart-lung machines — which do the work of the heart and lungs during surgery — and an experimental fluid containing compounds that can promote cellular health and suppress inflammation throughout the pig’s body. Cardiac arrest was induced in anesthetized pigs, which were treated with OrganEx an hour after death.

Six hours after treatment with OrganEx, the scientists found that certain key cellular functions were active in many areas of the pigs’ bodies — including in the heart, liver, and kidneys — and that some organ function had been restored. For instance, they found evidence of electrical activity in the heart, which retained the ability to contract.

We were also able to restore circulation throughout the body, which amazed us,” Sestan said.

Normally when the heart stops beating, organs begin to swell, collapsing blood vessels and blocking circulation, he said. Yet circulation was restored and organs in the deceased pigs that received OrganEx treatment appeared functional at the level of cells and tissueUnder the microscope, it was difficult to tell the difference between a healthy organ and one which had been treated with OrganEx technology after death,” Vrselja said.

Source: https://news.yale.edu/

Drug Prevents Breast Cancer Recurrence and Metastasis

Even when detected early, some cancers are more aggressive and more fatal than others. This is the case, for example, with triple negative breast cancer which accounts for 10 to 15% of all breast cancers. This cancer affects 1,000 patients per year in Belgium, while the figure worldwide is 225,000. Around half of the patients will develop local recurrences and metastases, regardless of the treatment they receive. No specific treatment is currently capable of preventing these two events. Patients suffering from pervasive triple negative breast cancer have only a one-in-ten chance of a cure. In 2014, Pierre Sonveaux, a researcher at the University of Louvain (UCLouvain) Institute for experimental and clinical research, succeeded in demonstrating the principle that it was possible to prevent the appearance of melanoma tumour metastases in mice. However, the experimental molecules used at the time were far from being drugs.

Since then, the UCLouvain researcher and his team, including post-doctoral researcher Tania Capeloa, have continued their work thanks in particular to sponsorship obtained by the UCLouvain Foundation. They have now succeeded in establishing that a drug developed for diseases other than cancer, MitoQ, avoids the appearance of metastases in 80% and local recurrences of human breast cancer in 75% of cases in mice. Conversely, most of the mice not treated suffered a recurrence of their cancer, which spread.

To do this, the researchers treated mice affected by human breast cancer. They treated them as hospital patients are treated, i.e. by combining surgery with a carefully dosed cocktail of standard chemotherapies. However, the UCLouvain researchers supplemented this standard treatment with the new molecule, MitoQ. They not only demonstrated that the administration of MitoQ is compatible with standard chemotherapies, but also that this innovative treatment prevents both relapses and metastases of breast cancer in mice. “We expected to be able to block the metastases, says Pierre Sonveaux enthusiastically. But preventing the recurrence of the cancer was totally unexpected. Getting this type of result is a huge motivation for us to carry on.” In short, this is a giant step given that the three main causes of cancer mortality are recurrences, the spread of the cancer caused by metastasis and resistance to treatment. And that there is currently no other known molecule capable of acting like MitoQ.

How does it work? Cancers consist of two types of cancerous cells: those that proliferate and are sensitive to clinical treatments and those that are dormant and that bide their time. Such cells are more harmful. The problem? These cancerous stem cells are resistant to clinical treatments. They result in metastases and if, unfortunately, cancer surgery fails to remove them all, they cause recurrences. These relapses are currently treated using chemotherapy. However, this tends to be relatively ineffective owing to the resistance to treatment developed by the tumorous cells . This is where the important discovery of the UCLouvain scientists comes in: the molecule MitoQ stops cancerous stem cells from awakening.

What next? MitoQ has already come through the first clinical phase successfully. It has been tested on healthy patients, both men and women, and proves to be only slightly toxic (nausea, vomiting). In addition, its behaviour is known. What next? The discovery made by the UCLouvain scientists opens wide the path for the clinical 2 phase, intended to demonstrate the efficacy of the new treatment in cancer patients.

Source: https://uclouvain.be/
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https://www.thebrighterside.news

Tiny Bubbles Destroy Tumours in Seven Minutes

Following her diagnosis with liver cancer last June, 68-year-old Sheila Riley braced herself for painful and gruelling treatmentsSurgery, chemotherapy, radio-therapy and even ablation — where heat is used to destroy tumours — are some of medicine’s most effective tools against cancer, but the potential side-effects can be hard to bear. In fact, Sheila was spared these thanks to a radical new form of therapy that uses tiny bubbles of gas to destroy tumours within minutes and doesn’t leave a mark on the body. She was one of the first patients in the UK to undergo histotripsy, where focused ultrasound waves are directed from outside the body to destroy tumours by generating thousands of exploding gas bubbles. So rapid is the procedure that her tumour was obliterated painlessly — in under seven minutes.

It was amazing,’ says the grandmother of eight, who had the treatment last August at St James’s University Hospital in Leeds. ‘I didn’t need any medication — not even painkillers afterwards,’ adds Sheila, who lives in Bradford with her partner Frank, 70. ‘I was able to go shopping the next day, and two days after my treatment I was out with friends. It didn’t even leave a mark on my skin.

It is now hoped the procedure can help those with tumours in other parts of the bodyHistotripsy was pioneered by researchers at the University of Michigan in the U.S. and relies on a process called cavitation — creating an empty space inside something solid — to eradicate cancer. First, a beam of ultrasound energy is directed through the skin to the tumour site. As the beam hits the targeted spot, it activates thousands of pockets of gas that occur naturally in tissue throughout the body, even tumours, as a result of the respiratory process. These tiny pockets of gas are usually dormant, but when blasted with the sound waves, they expand, vibrate and explode, forming a high-energy cloud of microbubbles in the tumour. As they rapidly expand and collapse, the bubbles break up surrounding cancerous tissue, liquifying it into a solution that then gets passed out of the body as waste.

Unlike existing treatments such as microwave ablation, where a heat-generating probe is used to ‘cook’ tumour cells, there is no heat that might damage surrounding healthy tissue, making cavitation potentially safer. This capacity for ultrasound to destroy tissue has been known about for years but was not previously adopted as a cancer treatment because it was too difficult to control the bubble clouds and avoid damaging healthy tissue.

However, the process has now been fine-tuned and the energy source can be better directed inside the tumour, avoiding the risk of nearby healthy tissue or organs being affected. An international trial is now under way looking at histotripsy for liver cancer. The chief investigator, Professor Tze Min Wah, a senior consultant interventional radiologist at St James’s University Hospital, believes cavitation could transform cancer treatment. ‘Rather than using heat, radiation or surgery to remove the tumour, the bubble cloud created by histotripsy is so powerful that it ruptures the tumour but doesn’t damage the tissue around it,’ she says.

Source: https://www.dailymail.co.uk/

Augmented Reality (AR) Revolutionizes Surgery

Dr Stephen Quinn, a gynaecologist at hospitals in the NHS Trust Imperial College, appears on TV show to help a patient, Hilda, with a condition causing her swollen abdomen. After taking careful scans of Hilda’s body, the team are able to show her the growths, called fibroids, that are behind her pain.

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I’ve spent a lot of my career looking at MRI scans of pelvises, and having these images is extremely helpful in clinic,” said Quinn. “But using augmented reality just took that to a whole different level. It was fantastic being able to to fully visualise exactly what was going on in the pelvis ahead of the surgery to remove the fibroids.”

Unfortunately, the technology is a way off being available on the NHS, but Quinn said AR’s use could be commonplace within the next decade.

For the show, radiologists at Imperial hospitals provided artists with in-depth scans of each patient. Dr Dimitri Amiras, a musculoskeletal consultant radiologist at Imperial, also worked on the experiment.

First, patients would undergo routine scans. “In order to define what the organ is and where the pathology is, that’s all done by radiologists. We are the ones to identify it and look at the imaging techniques work out what is good tissue, what’s bad tissue,” said Amiras. “Then, once we’ve got those images with relevant bits identified, digital artists may draw around them or even use artificial intelligence to make all the pretty pictures and the shiny stuff.”

Once finished, the patients and doctors would wear an AR device to ‘see’ the body part in front of them. Each was 3D, and could be zoomed in or out, rotated, and compared to the same areas on a healthy individual.

Source: https://www.sciencefocus.com/

Robot Performs much Better than Humans at Surgery

For years, the world of medicine has been steadily advancing the art of robot-assisted procedures, enabling doctors to enhance their technique inside the operating theatre. Now US researchers say a robot has successfully performed keyhole surgery on pigs all on its own without the guiding hand of a human. Furthermore, they add, the robot surgeon produced “significantly better” results than humans.

Smart Tissue Autonomous Robot (Star) carried out laparoscopic surgery to connect two ends of an intestine in four pigs. The robot excelled at the procedure, which requires a high level of precision and repetitive movements

Axel Krieger, of Johns Hopkins University, said it marked the first time a robot had performed laparoscopic surgery without human help. “Our findings show that we can automate one of the most intricate and delicate tasks in surgery: the reconnection of two ends of an intestine,” he said. “The Star performed the procedure in four animals and it produced significantly better results than humans performing the same procedure.”

Connecting two ends of an intestine is a challenging procedure in gastrointestinal surgery, requiring a surgeon to apply stitches – or sutures – with high accuracy and consistency. Even a slight hand tremor or misplaced stitch can result in a leak that could result in a patient suffering fatal complications. Krieger, an assistant professor of mechanical engineering at Johns Hopkins, helped create the robot, a vision-guided system designed specifically to suture soft tissue. It improves a 2016 model that repaired a pig’s intestines, but required a large incision to access the intestine and more guidance from humans.
Experts say new features allow for improved surgical precision, including specialised suturing tools and imaging systems that provide more accurate visualisations of the surgical field.
Source: https://www.theguardian.com/

Successful Transplant of Porcine Heart into Adult Human

In a first-of-its-kind surgery, a 57-year-old patient with terminal heart disease received a successful transplant of a genetically-modified pig heart and is still doing well three days later. It was the only currently available option for the patient. The historic surgery was conducted by University of Maryland School of Medicine (UMSOM) faculty at the University of Maryland Medical Center (UMMC), together known as the University of Maryland Medicine.

This organ transplant demonstrated for the first time that a genetically-modified animal heart can function like a human heart without immediate rejection by the body. The patient, David Bennett, a Maryland resident, is being carefully monitored over the next days and weeks to determine whether the transplant provides lifesaving benefits. He had been deemed ineligible for a conventional heart transplant at UMMC as well as at several other leading transplant centers that reviewed his medical records.

 “It was either die or do this transplant. I want to live. I know it’s a shot in the dark, but it’s my last choice,” said Mr. Bennett, the patient, a day before the surgery was conducted. He had been hospitalized and bedridden for the past few months.  I look forward to getting out of bed after I recover.

The U.S. Food and Drug Administration granted emergency authorization for the surgery on New Year’s Eve through its expanded access (compassionate use) provision. It is used when an experimental medical product, in this case the genetically-modified pig’s heart, is the only option available for a patient faced with a serious or life-threatening medical condition. The authorization to proceed was granted in the hope of saving the patient’s life.

“This was a breakthrough surgery and brings us one step closer to solving the organ shortage crisis. There are simply not enough donor human hearts available to meet the long list of potential recipients,” said Bartley P. Griffith, MD, who surgically transplanted the pig heart into the patient. Dr. Griffith is the Thomas E. and Alice Marie Hales Distinguished Professor in Transplant Surgery at UMSOM. “We are proceeding cautiously, but we are also optimistic that this first-in-the-world surgery will provide an important new option for patients in the future.”

Considered one of the world’s foremost experts on transplanting animal organs, known as xenotransplantation, Muhammad M. Mohiuddin, MD, Professor of Surgery at UMSOM, joined the UMSOM faculty five years ago and established the Cardiac Xenotransplantation Program with Dr. Griffith. Dr. Mohiuddin serves as the program’s Scientific/Program Director and Dr. Griffith as its Clinical Director.

“This is the culmination of years of highly complicated research to hone this technique in animals with survival times that have reached beyond nine months. The FDA used our data and data on the experimental pig to authorize the transplant in an end-stage heart disease patient who had no other treatment options,” said Dr. Mohiuddin.The successful procedure provided valuable information to help the medical community improve this potentially life-saving method in future patients.

Source: https://www.medschool.umaryland.edu/

Glue Seals Bleeding Organs in Seconds

Inspired by the sticky substance that barnacles use to cling to rocks, MIT engineers have designed a strong, biocompatible glue that can seal injured tissues and stop bleeding. The new paste can adhere to surfaces even when they are covered with blood, and can form a tight seal within about 15 seconds of application. Such a glue could offer a much more effective way to treat traumatic injuries and to help control bleeding during surgery, the researchers say.

We are solving an adhesion problem in a challenging environment, which is this wet, dynamic environment of human tissues. At the same time, we are trying to translate this fundamental knowledge into real products that can save lives,” says Xuanhe Zhao, a professor of mechanical engineering and civil and environmental engineering at MIT and one of the senior authors of the study. Finding ways to stop bleeding is a longstanding problem that has not been adequately solved, Zhao says. Sutures are commonly used to seal wounds, but putting stitches in place is a time-consuming process that usually isn’t possible for first responders to perform during an emergency situation. Among members of the military, blood loss is the leading cause of death following a traumatic injury, and among the general population, it is the second leading cause of death following a traumatic injury.

In recent years, some materials that can halt bleeding, also called hemostatic agents, have become commercially available. Many of these consist of patches that contain clotting factors, which help blood to clot on its own. However, these require several minutes to form a seal and don’t always work on wounds that are bleeding profusely. Zhao’s lab has been working to address this problem for several years

For their new tissue glue, the researchers once again drew inspiration from the natural world. This time, they focused their attention on the barnacle, a small crustacean that attaches itself to rocks, ship hulls, and even other animals such as whales. These surfaces are wet and often dirty — conditions that make adhesion difficult. “This caught our eye,” Yuk says. “It’s very interesting because to seal bleeding tissues, you have to fight with not only wetness but also the contamination from this outcoming blood. We found that this creature living in a marine environment is doing exactly the same thing that we have to do to deal with complicated bleeding issues.” The researchers’ analysis of barnacle glue revealed that it has a unique composition. The sticky protein molecules that help barnacles attach to surfaces are suspended in an oil that repels water and any contaminants found on the surface, allowing the adhesive proteins to attach firmly to the surface.

The MIT team decided to try to mimic this glue by adapting an adhesive they had previously developed. This sticky material consists of a polymer called poly(acrylic acid) embedded with an organic compound called an NHS ester, which provides adhesion, and chitosan, a sugar that strengthens the material. The researchers froze sheets of this material, ground it into microparticles, and then suspended those particles in medical grade silicone oil.

Christoph Nabzdyk, a cardiac anesthesiologist and critical care physician at the Mayo Clinic in Rochester, Minnesota, is also a senior author of the paper, which appears today in Nature Biomedical Engineering. MIT Research Scientist Hyunwoo Yuk and postdoc Jingjing Wu are the lead authors of the study.

Source: https://news.mit.edu/

Gene Therapy Treats Eye Disease whithout Surgery

A new gene therapy could eventually provide an alternative treatment for Fuchs’ endothelial corneal dystrophy, a genetic eye disease that affects roughly one in 2,000 people globally. Currently, the only treatment is corneal transplant, a major surgery with associated risks and potential complications.

When you do a transplant you make a huge difference for that person, but it’s a big deal for the patient with lots of visits, lots of eye drops, lots of co-pays, and if you had a medical treatment that did not require surgery, that would be great,” says Bala Ambati, a research professor at the University of Oregon who led an eight-year study involving the development of the gene therapy. “Not only could it help patients who need a transplant, but it could also help a lot of other people who could have used that (corneal) tissue.

For the study in the journal eLife, investigators focused on a rare, early-onset version of the disease and carried out the research in mice. They used CRISPR-Cas9, a powerful tool for editing genomes, to knock out a mutant form of a protein that is associated with the disease.

Fuchs’ dystrophy occurs when cells in the corneal layer called the endothelium gradually die off and stressed cells produce structures known as guttae. These cells normally pump fluid from the cornea to keep it clear, but when they die, fluid builds up, the cornea gets swollen, and vision becomes cloudy or hazy.

We were able to stop this toxic protein expression and study it in a mouse model,” says coauthor Hiro Uehara, a senior research associate in the Ambati lab. “We confirmed that (in mice who received it), our treatment was able to rescue loss of corneal endothelial cells, reduce guttata-like structures, and preserve the corneal endothelial cell pump function.

Corneal cells are non-reproducing, meaning you’re born with all of the cells you will ever have, Ambati says. One of the challenges of the study involved using CRISPR gene editing technology on such cells, a process that is technically difficult.

Uehara developed an innovative workaround that increases the utility of the CRISPR technology and could eventually lead to treatments for other diseases involving non-reproducing cells, including some neurologic diseases, immune diseases, and certain genetic disorders affecting the joints. The study marks the first time that researchers have applied the technique, called start codon disruption, to non-reproducing cells.

Source: https://accelerate.uoregon.edu/