Stories about: sepsis

When antibiotics fail: A potential new angle on severe bacterial infection and sepsis

bacterial infection sepsisBacterial 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.

Reporting this week in Nature, scientists in Boston Children’s Hospital’s Program in Cellular and Molecular Medicine (PCMM) describe new potential avenues for controlling both sepsis and the runaway bacterial infections that provoke it.

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A filtration technology poised to cure sepsis

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.

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Pediatric innovators showcase highlights inventions

Innovators Showcase Boston Children's HospitalSome 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)

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A biospleen is born

biospleen sepsis Wyss Institute Donald Ingber
The Wyss Institute’s biospleen. (Photos courtesy Wyss Institute)

On a Friday morning a few years ago, a childhood friend of mine walked into his doctor’s office, saying his hip hurt. The pain was pretty severe, and had been getting worse for several days.

By Saturday morning, he was in intensive care, fighting for his life against an overwhelming case of sepsis. He survived, but at a cost: he’s now a quadruple amputee.

It’s people like him—and the other million-plus Americans who develop sepsis every year—that Donald Ingber, MD, PhD, and his team had in mind while developing the biospleen, a device that filters sepsis-causing pathogens from the blood. Announced to the world in September, the biospleen grew out of the organs-on-chips technology that Ingber’s team at the Wyss Institute for Biomedically Inspired Engineering launched commercially this past summer.

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A Goldilocks approach to leaky blood vessels: Not too stiff, but not too loose

Just like Goldilocks wouldn’t eat porridge that was too hot or too cold, blood vessels won't grow properly in tissues that are too stiff or too loose. (Project Gutenberg/Wikimedia Commons)
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.

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Of magnets and bacteria: Filtering the blood of patients with sepsis

(Ryan Somma/Flickr)

There’s no other way to say it: sepsis is a horrible disease. It typically starts with a runaway bacterial infection in the blood, followed by a runaway immune response that severely damages the body it’s trying to save. The results: shock, multiple organ failure and—in between 210,000 and 375,000 people in the United States alone every year—death.

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.

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Modeling sepsis in newborns: toward better detection and treatment

Sepsis, a serious, hard-to-diagnose threat in the NICU, can interfere with a baby's development even when cleared with antibiotics. (Image: Army Medicine/Flickr)

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.”

Levy and colleagues recently described a mouse model that, for the first time, captures the effects of sepsis on the newborn immune system. They and others have begun using it to identify diagnostic markers and better treatments.

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