Sepsis: The Body’s Deadly Response to Infection

Although not as well-known as other medical conditions, sepsis kills more people in the United States than AIDS, breast cancer, or prostate cancer combined. Sepsis is body-wide inflammation, usually triggered by an overwhelming immune response to infection. Though doctors and medical staff are well-aware of the condition—it is involved in 1 in 10 hospital deaths—the condition is notoriously hard to diagnose. In this video, sepsis expert Sarah Dunsmore, a program director with the National Institute of General Medical Sciences (NIGMS), describes what sepsis is and how to recognize it, what kinds of patients are most at risk, and what NIGMS is doing to reduce the impact of this deadly condition.

Quicker Sepsis Treatment Saves Lives: Q & A With Sepsis Researcher Christopher Seymour

Sepsis is a serious medical condition caused by an overwhelming immune response to infection. The body’s infection-fighting chemicals trigger widespread inflammation, which can lead to blood clots and leaky blood vessels. As a result, blood flow is impaired, depriving organs of nutrients and oxygen. In severe cases, one or more organs fail. In the worst cases, blood pressure drops, the heart weakens, and the patient spirals toward septic shock. Once this happens, multiple organs—lungs, kidneys, liver—may quickly fail, and the patient can die.

Because sepsis is traditionally hard to diagnose, doctors do not always recognize the condition in its early stages. In the past, it has been unclear how quickly sepsis needs to be diagnosed and treated to provide patients with the best chance of surviving.

Credit: University of Pittsburgh.

Now we may have an answer: A large-scale clinical study, published recently in the New England Journal of Medicine Exit icon, found that for every hour treatment is delayed, the odds of a patient’s survival are reduced by 4 percent. Christopher Seymour Exit icon, assistant professor of critical care and emergency medicine at the University of Pittsburgh, and his team analyzed the medical records of nearly 50,000 sepsis patients at 149 clinical centers to determine whether administering the standard sepsis treatment—antibiotics and intravenously administered fluids—sooner would save more lives.

I spoke with Seymour about his experience treating sepsis patients and his research on the condition, including the new study.

CP: How big a public health problem is sepsis?

CS: Our recent work with the Centers for Disease Control and Prevention suggests there might be as many as 2 million sepsis cases in the United States each year. I can share personally that sepsis, or septic shock, is far and away the most common life-threatening condition that I treat in the ICU (intensive care unit). It’s quite devastating, particularly among our elders, and it requires prompt care. Although the mortality rate may be decreasing, it’s still quite high. About 1 in 10 patients with sepsis don’t survive their hospital stay. Even young, healthy people can succumb from sepsis. And if you’re fortunate to survive, you can have significant problems with cognitive and physical function for many months to years down the line.

Unfortunately, the incidence of sepsis may even be increasing. More patients are surviving serious illnesses that used to be fatal. They’re alive, but their health is compromised, so they are at higher risk for sepsis. Also—and this is a positive—we are seeing greater recognition and increased reporting of sepsis. Both factors probably contribute to the higher numbers of reported sepsis cases.

CP: What are some of the biggest challenges in fighting sepsis?

CS: The first challenge is public awareness. It’s important that the public knows the word sepsis, that they’re familiar with sepsis being a life-threatening condition that results from an infection, and that they know it can strike anyone—young, old, healthy, or sick. But it’s also important to know that not every infection is septic, nor will every cut or abrasion lead to life-threatening organ dysfunction.

Another part of the problem is that sepsis is not as easy for patients to recognize as, say, myocardial infarction (heart attack). When patients clutch their chest in pain, they intuitively recognize what’s happening. Patients frequently don’t recognize that they’re septic. People should know that when they have an infection or take antibiotics as an outpatient, and they’re starting to feel worse or having other new symptoms Exit icon [PDF, 147KB], they may be at risk of sepsis. They should go to the emergency department or seek medical help.

The second challenge in fighting sepsis is that it’s just hard to diagnose, even for well-trained clinicians. Both issues can lead to delays in care, the most important of which is the delay in treatment with antibiotics.

CP: Tell me about your recent clinical trial. What question did you set out to answer?

CS: There’s been a lot of interest in the early recognition and treatment of sepsis over the past decade. Recently, the National Institutes of Health/National Institute of General Medical Sciences funded a large, multicenter trial called ProCESS, which tested various strategies for treating sepsis. This trial told us that a standardized sepsis protocol among people who had already received antibiotics didn’t necessarily change survival rates. But what it left unanswered was the very important question of when the patient first arrives at the emergency department, how fast do we need to provide antibiotics and fluids for the best possible outcome? Continue reading

Fall 2017 Issue of Findings Magazine

It’s back! Check out the new issue of Findings magazine.

Findings presents cutting-edge research from scientists in diverse biomedical fields. The articles are aimed at high school students with the goal of making science—and the people who do it—interesting and exciting, and to inspire young readers to pursue careers in biomedical research. In addition to putting a face on science, Findings offers activities such as quizzes and crossword puzzles and, in its online version, video interviews with scientists.

The Fall 2017 issue profiles Yale University biologist Enrique De La Cruz, who studies how actin—a protein chain that supports cell structure—breaks so easily. Also profiled is University of California, Berkeley, biologist Rebecca Heald and her study of developmental factors that control an animal’s size.

This issue also features:

  • A virtual reality program designed to help burn patients manage pain
  • The promise of gene therapy for glaucoma
  • The many ways scientists categorize the biological world using “omics”
  • What researchers know—and don’t know—about how general anesthetics work
  • How animation helps researchers visualize interactions between biological molecules
  • How cells use sugary outer coatings to distinguish friend from foe
  • What makes our tissues stiff, squishy, solid, or see-through (hint: its initials are ECM)
  • How super-powerful microscopes are revealing views of biology never possible before

View Findings online, or order a print copy (classroom sets of up to 30 copies are available for educators).

 

Happy Birthday, BioBeat

This month, our blog that highlights NIGMS-funded research turns four years old! For each candle, we thought we’d illuminate an aspect of the blog to offer you, our reader, an insider’s view.

Who are we?

Over the years, the editorial team has included onsite science writers, office interns, staff scientists and guest authors from universities. Kathryn, who’s a regular contributor, writes entirely from her home office. Chris, who has a Ph.D. in neuroscience and now manages the blog, used to do research in a lab. Alisa has worked in NIGMS’ Bethesda-based office the longest: 22 years! She and I remember when we first launched Biomedical Beat as an e-newsletter in 2005. You can read more about each of the writers on the contributors page and if you know someone who’s considering a career in science communications, tell them to drop us a line.

How do we come up with the stories?

We get our story ideas from a range of sources. For instance, newspaper articles about an experimental pest control strategy in Florida and California prompted us to write about NIGMS-funded studies exploring the basic science of the technique. A beautiful visual from a grantee’s institution inspired a short post on tissue regeneration research. And an ongoing conversation with NIGMS scientific staff about the important role of research organisms in biological studies sparked the idea for a playful profile of one such science superstar.

A big change in our storytelling has been shifting the focus from a single finding to broader progress in a lab or field. So instead of reporting on a study just published in a scientific journal, we may write about the scientist’s career path or showcase a collection of recent findings in that particular field. These approaches help us demonstrate that scientific understanding usually progresses through the slow and steady work undertaken by many labs.

What are our favorite posts?

I polled the writers on posts they liked, and the list is really long! Here are the top picks.


Four Ways Inheritance Is More Complex Than Mendel Knew


The Endoplasmic Reticulum: Networking in the Cell


Interview With a Scientist: Janet Iwasa, Molecular Animator


From Basic Research to Bioelectric Medicine


An Insider’s Look at Life: Magnified, an Airport Exhibit of Stunning Microscopy Images

What are your favorite posts?

We regularly review data about the number of times a blog post has been viewed to identify the ones that interest readers the most. That information also helps guide our decisions about other topics to feature on the blog. The Cool Image posts are among the most popular! Below are some other chart-topping posts.


Our Complicated Relationship With Viruses


The Proteasome: The Cells Trash Processor in Action


Demystifying General Anesthetics


Meet Sarkis Mazmanian and the Bacteria That Keep Us Healthy


5 Reasons Biologists Love Math

We always like hearing from readers! If there’s a basic biomedical research topic you’d like us to write about, or if you have feedback on a story or the blog in general, please leave your suggestions in the comment field below or email me.

New Technology May Help Reduce Serious and Costly Post-Surgical Infections—Using Nothing but Air

According to a recent estimate, implant infections following hip and knee replacement surgeries in the U.S. may number 65,000 by 2020, with the associated healthcare costs exceeding $1 billion. A new small, high-tech device could have a significant impact on improving health outcomes and reducing cost for these types of surgeries. The device, Air Barrier System (ABS), attaches on top of the surgical drape and gently emits HEPA-filtered air over the incision site. By creating a “cocoon” of clean air, the device prevents airborne particles—including the bacteria that can cause healthcare-associated infections—from entering the wound.

Air Barrier System
The Air Barrier System creates a “cocoon” of clean air (gray area with size indicated) over a surgical site to remove airborne contaminants and reduce the risk of infection in patients who are receiving an artificial hip, a blood vessel graft, a titanium plate in the spine or other implants.

Scientists recently analyzed the effectiveness of the ABS device in a clinical study Exit icon—funded by NIGMS—involving nearly 300 patients. Each patient needed an implant, such as an artificial hip, a blood vessel graft in the leg or a titanium plate in the spine. Because implant operations involve inserting foreign materials permanently into the body, they present an even higher risk of infection than many other surgeries, and implant infections can cause life-long problems.

The researchers focused on one of the most common causes of implant infections—the air in the operating room. Although operating rooms are much cleaner than almost any other non-hospital setting, it’s nearly impossible to sterilize the entire room. Instead, the scientists focused on reducing contaminants directly over the surgical site. They theorized that if the air around the wound was cleaner, the number of implant infections might go down. Continue reading

A World Without Pain

In an immersive virtual reality environment called “Snow World,” burn patients distract themselves from their pain by tossing snow balls, building snowmen and interacting with penguins. Credit: Ari Hollander and Howard Rose, copyright Hunter Hoffman, UW, www.vrpain.com Exit icon.

You glide across an icy canyon where you meet smiling snowmen, waddling penguins and a glistening river that winds forever. You toss snowballs, hear them smash against igloos, then watch them explode in vibrant colors.

Back in the real world, a dentist digs around your mouth to remove an impacted tooth, a procedure that really, really hurts. Could experiencing a “virtual” world distract you from the pain? NIGMS grantees David Patterson Exit icon and Hunter Hoffman Exit icon show it can.

Patterson, a psychologist at the University of Washington (UW) in Seattle, and Hoffman, a UW cognitive psychologist, helped create the virtual reality program “Snow World” in an effort to reduce excessive pain experienced by burn patients. However, the researchers expect Snow World to help alleviate all kinds of pain, including pain experienced during dental procedures. Continue reading

Visualizing Skin Regeneration in Real Time

Top: Colorful skin cells on a zebrafish . Bottom: Cells from the outer surface of the scale.
More than 70 Skinbow colors distinguish hundreds of live cells from a tiny bit (0.0003348 square inches) of skin on the tail fin of an adult zebrafish. The bottom image shows the cells on the outer surface of a scale. Credit: Chen-Hui Chen, Duke University.

Zebrafish, blue-and-white-striped fish that are about 1.5 inches long, can regrow injured or lost fins. This feature makes the small fish a useful model organism for scientists who study tissue regeneration.

To better understand how zebrafish skin recovers after a scrape or amputation, researchers led by Kenneth Poss of Duke University tracked thousands of skin cells in real time. They found that lifespans of individual skin cells on the surface were 8 to 9 days on average and that the entire skin surface turned over in 20 days.

The scientists used an imaging technique they developed called “Skinbow,” which essentially shows the fish’s outer layer of skin cells in a spectrum of colors when viewed under a microscope. Skinbow is based on a technique created to study nerve cells in mice, another model organism.

The research team’s color-coded experiments revealed several unexpected cellular responses during tissue repair and replacement. The scientists plan to incorporate additional imaging techniques to generate an even more detailed picture of the tissue regeneration process.

The NIH director showcased the Skinbow technique and these images on his blog, writing: “You can see more than 70 detectable Skinbow colors that make individual cells as visually distinct from one another as jellybeans in a jar.”

This work was funded in part by NIH under grant R01GM074057.

Preventing Sepsis in Half the Time

Human digestive system
A new study suggests that an antibiotic regimen half as long as the standard course could be just as effective in treating intra-abdominal infections and preventing sepsis. Credit: Stock image.

When treating infections, the most critical actions are to quash the infection at its site of origin and prevent it from spreading. If allowed to spread to the bloodstream, an infection could result in body-wide inflammation known as sepsis that can cause organ failure and death.

Intra-abdominal infections, most often caused by gut bacteria, can lead to painful inflammation and present a high risk for sepsis. These infections, which include appendicitis, are some of the most common illnesses around the world.

A standard treatment regimen includes surgically removing the original infection and then prescribing antibiotics to keep the infection from coming back and to prevent sepsis. Currently, doctors administer antibiotics until 2 days after the symptoms disappear, for a total of up to 2 weeks.

Like many other researchers, University of Virginia’s Robert Sawyer Exit icon wondered if treating intra-abdominal infections with shorter antibiotic courses could be just as effective as the standard treatment. To find out, he and a team of researchers from around the country designed the Study to Optimize Peritoneal Infection Therapy (STOP-IT). Continue reading

Meet Alfred Atanda Jr.

Alfred Atanda Jr.
Credit: Cynthia Brodoway, Nemours/Alfred I. duPont
Hospital for Children
Alfred Atanda Jr.
Fields: Pediatric orthopedic surgery, sports medicine
Works at: Nemours/Alfred I. duPont Hospital for Children
Blogs: as Philly.com’s Sports Doc at http://bit.ly/sportsdoc Exit icon
Family fact: Youngest of seven children
Musical skills: Piano and trumpet
Kitchen talent: Baking chocolate desserts for his pediatrician wife and their two young children

As a kid, Alfred Atanda loved science, sports and tinkering. He dreamed of being a construction worker or an engineer. Today, he works on one of the most complex construction projects of all: the human body.

As a pediatric orthopedic surgeon, Atanda focuses on sports medicine and injuries to children. He has a special passion for young baseball pitchers who have torn the ulnar collateral ligament (UCL) in the elbow of their throwing arm.

This sort of injury is most often caused by overuse. Many small tears accumulate over a long period, resulting in pain and slower, less accurate pitches. Decades ago, this sort of damage occurred almost exclusively in elite athletes. Now, Atanda sees it in children as young as 12 years old. He aims not only to study and treat these injuries, but also to find ways to prevent them.

His Findings

Atanda was first introduced to research on UCL injuries while working alongside team physicians for the Phillies, the professional baseball team in Philadelphia. The physicians wanted to determine whether ultrasound imaging could detect early warning signs—slight anatomical changes in the ligament—before the damage became severe enough to warrant an operation known as Tommy John surgery.

The research focused on Phillies pitchers who had no pain or other symptoms of injury. The multi-year project showed that the UCL in the throwing elbows of these players got progressively thicker and weaker compared to the same ligament in the players’ nonthrowing elbows. The scientists concluded that these physical changes are caused by prolonged exposure to professional-level pitching.

Alfred Atanda Jr. with Joe Piergrossi
Atanda examines the elbow of a young patient. Courtesy: Cynthia Brodoway, Nemours/Alfred I. duPont Hospital for Children

Atanda wondered whether ultrasound imaging could also detect early signs of UCL damage in young pitchers—those in Little League through high school. There has been a dramatic rise in the number of young pitchers who are experiencing the same injuries and undergoing the same surgery as the pros.

Atanda secured funding for this project from an Institutional Development Award (IDeA). The IDeA program builds research capacities in states like Delaware, where Atanda works, that historically have received low levels of funding from the National Institutes of Health.

Atanda’s project began about a year ago, and has examined 55 young athletes so far.

“We found similar results to what we found with the Phillies,” Atanda says, indicating that the UCL in the throwing elbows of young athletes was noticeably thicker than the UCL in the nonthrowing elbows. And the damage seems progressive, he says: “We saw that these ligaments got thicker as the pitchers got older and had more pitching experience.”

The immediate goal of this project, which he hopes to continue for another 3 years, is prophylaxis. “We’re trying to prevent any kind of overuse elbow injuries and the need for Tommy John surgeries later on,” Atanda says. He also hopes to establish quantitative correlations between pitching behavior and anatomical changes.

Atanda also has longer-term aspirations. “My goal is to change the culture in sports for young athletes in general,” he says. “I want to show there are downsides to pitching so much.”

In addition to championing pitch count limits recommended by the American Sports Medicine Institute, Atanda advises a focus away from excess competition and toward getting exercise, enjoying social inter­action, building self-confidence and having fun.

Atanda’s research is funded by the National Institutes of Health through grant P20GM103464

Content adapted from the NIGMS Findings magazine article Game Changer

Molecules Known to Damage Cells May Also Have Healing Power

Free radicals in an ying-yang symbol
Biology in balance: Molecules called free radicals—like the peroxide molecules illustrated here—have a reputation for being dangerous. Now, they’ve revealed healing powers. In worms, at least. Credit: Stock image

When our health is concerned, some molecules are widely labeled “good,” while others are considered “bad.” Often, the truth is more complicated.

Consider free radical molecules. These highly reactive, oxygen-containing molecules are well known for damaging DNA, proteins and other molecules in our bodies. They are suspected of contributing to premature aging and cancer. But now, new research shows they might also have healing powers Exit icon.

Using the oft-studied laboratory roundworm known as C. elegans, a research group led by Andrew Chisholm Exit icon at the University of California, San Diego, made a surprising discovery. Free radicals, specifically those made in cell structures called mitochondria, appear necessary for skin wounds to heal. In fact, higher (but not dangerously high) levels of the molecules can actually speed wound closure.

If further research shows the same holds true in humans, the work could point to new ways to treat hard-to-heal wounds, like diabetic foot ulcers.

This work was funded in part by NIH under grants R01GM054657 and P40OD010440.