Over the last several years, scientists have made great headway in our understanding of how self-sabotaging immune cells play a role in our ability to fight infection. So far, we know that when white blood cells called neutrophils are triggered by bacterial infection, they self-combust and eject their own DNA strands outward like spider webs. Sacrificing themselves, the exploded neutrophils and their outreaching DNA tentacles form sunburst-shaped neutrophil extracellular traps (NETs).
“NET formation is an innate immune response that our body has when it recognizes the presence of pathogens,” says Ben Croker, PhD, a researcher in the Division of Hematology/Oncology at Boston Children’s Hospital. “Once formed, NETs restrict pathogen movement and proliferation and alert the rest of the immune system to the invader’s presence.”
Now, Croker and a team of researchers at Boston Children’s have identified a critical element of NET formation and how it enables the body to fight off infections like methicillin-resistant Staphylococcus aureus (MRSA). Their findings, recently published in Science Signaling, could someday have clinical implications for tough-to-treat infections and even sepsis.…
Cytokines are small proteins produced by the body’s cells that have a big impact on our immune system. Researchers at Boston Children’s Hospital believe that modulating their presence in our bodies could be the key to improving outcomes in life-threatening cases of trauma, hemorrhage and many other conditions including sepsis, which alone impacts nearly one million Americans each year.
The reason? Cells essentially use cytokines to talk to one another. In response to their surroundings, cells release different types of cytokines that encourage inflammatory or anti-inflammatory effects on the body. Infection or trauma causes cells to pump out more cytokines that produce inflammation. Altogether, an escalating chorus of cytokines can sometimes tip a person’s body into overwhelming inflammation that can turn fatal, which is what happens during sepsis.
But what if scientists could remove the problematic cytokines to bring the choir into perfect tune, allowing the immune system to respond with just the right amount of inflammation for healing? …
Sepsis, or blood poisoning, occurs when the body’s response to infection damages its own tissues, leading to organ failure. It is the most common cause of death in people who have been hospitalized, yet no new therapies have been developed in the last 30 years. Many treatments that have prevented death in animal experiments have failed in clinical trials, indicating that a more clinically-relevant sepsis model is needed for therapeutic development.
To bridge this gap, a team of scientists from the Wyss Institute at Harvard University and Boston Children’s Hospital think a better experimental model of sepsis in pigs could help weed out the therapies most likely to succeed in humans. Their method, a scoring criteria to evaluate sepsis in pigs that closely mirrors standard human clinical assessment, is reported in Advances in Critical Care Medicine.…
Bacterial infections that don’t respond to antibiotics are of rising concern. And so is sepsis — the immune system’s last-ditch, failed attack on infection that ends up being lethal itself. Sepsis is the largest killer of newborns and children worldwide and, in the U.S. alone, kills a quarter of a million people each year. Like antibiotic-resistant infections, it has no good treatment.
Sepsis is the most common cause of death in infants and children worldwide, and its incidence is increasing. Damage is caused not only by the bloodstream infection itself but by the systemic inflammatory cascade it triggers — which has been difficult to control without also causing long-lasting immune suppression. During a five-minute Ignite Talk at the 2015 Boston Children’s Hospital Global Pediatric Innovation Summit + Awards, Brian McAlvin, MD, a critical care intensivist at Boston Children’s Hospital, introduced the audience to a filtration technology that could cure systemic inflammatory response syndrome (SIRS).
SIRS, McAlvin noted, is the underlying mechanism for a variety of diseases, not just sepsis. His invention, the Antibody Modified Conduit, is essentially a small tube with antibodies painted on the inner surface that recognize and remove the inflammatory agents. “This technology allows us to choose the inflammatory molecules in the circulation,” says McAlvin, “and take them out of the blood as the condition evolves by changing the antibody that’s present.”
The talk won the pitch competition, earning McAlvin an Apple watch, a one-on-one mentoring session with an influential venture capitalist and a meet-and-greet with Boston Children’s innovation acceleration team, VCs and other stakeholders.
See more posts and videos from the Global Pediatric Innovation Summit.
Some great inventions were on view this week at the second annual Boston Children’s Hospital Innovators Showcase. Hosted by the hospital’s Innovation Acceleration Program and Technology & Innovation Development Office, the event featured everything from virtual reality goggles with gesture control to biomedical technologies. Below are a few new projects that caught Vector’s eye (expect to hear more about them in the coming months), a kid-friendly interview about the SimLab and list of inventions kids themselves would like to see. (Photos by Katherine Cohen except as noted) …
In the tale Goldilocks and the Three Bears, Goldilocks tries all of the bears’ porridge, chairs and beds, finding that only the little bear’s things were just right. Everything else was a little off for her…too hot or too cold, too hard or too soft and so on.
Similarly, for everything to work as it should in the body, things need to be just right. Blood pressure shouldn’t be too high or too low; organs can’t be too big or too small, etc.
Donald Ingber, MD, PhD, and his lab in Boston Children’s Vascular Biology Program take this “just right” approach when thinking about how organs and tissues are structured. Recently, he and a member of his research staff, Akiko Mammoto, MD, PhD, discovered that by changing the stiffness of the surrounding tissues—not too loose and not too tight— they could keep blood vessels from leaking. Their finding could have real consequences for people with sepsis or other diseases featuring leaky vessels. …
Part of the problem is that the methods available for treating sepsis aren’t particularly good. Antibiotics can kill the bacteria, but that still leaves bacterial debris floating in the bloodstream, fueling the already over-excited inflammatory response.
Removing the bacteria altogether—as fast as possible—would be the better solution. At least that’s what Daniel Kohane, MD, PhD, thinks. His lab at Boston Children’s Hospital’s Division of Critical Care Medicine has developed a new approach that combines magnetic nanoparticles, a synthetic molecule (called bis-Zn-DPA) that binds to the bacteria, and magnetized microfluidic devices to pull bacteria from the blood quickly and efficiently. …
Sepsis, or bacterial infection of the bloodstream, is a grave threat to premature infants in the neonatal intensive care unit (NICU) who have catheters and intravenous lines. Even when antibiotics clear the infection itself, the inflammation that it causes can do just as much damage. Not only can sepsis and the resulting inflammation interfere with fragile preemies’ ability to gain weight, but a growing literature suggests that they can impair brain development.
Preventive measures can now avoid many cases of sepsis, but those that slip through can be hard to detect in newborns.
“Newborns can’t speak, and they have unique immune systems, so they tend not to have fevers or show clinical signs,” explains Ofer Levy, MD, PhD, of the Division of Infectious Diseases at Boston Children’s Hospital. “There may be irregular breathing or increased heart rate, or the baby may be acting a little ‘off,’ but these signs are pretty nonspecific. There’s a tremendous need for better diagnostics in this field.”