Mouse version of 3q29 deletion: insights into schizophrenia/ASD pathways

Emory researchers see investigating 3q29 deletion as a way of unraveling schizophrenia’s biological and genetic Read more

B cells off the rails early in lupus

Emory scientists could discern that in people with SLE, signals driving expansion and activation are present at an earlier stage of B cell differentiation than previously Read more

Head to head narcolepsy/hypersomnia study

At the sleep research meeting in San Antonio this year, there were signs of an impending pharmaceutical arms race in the realm of narcolepsy. The big fish in a small pond, Jazz Pharmaceuticals, was preparing to market its recently FDA-approved medication: Sunosi/solriamfetol. Startup Harmony Biosciences was close behind with pitolisant, already approved in Europe. On the horizon are experimental drugs designed to more precisely target the neuropeptide deficiency in people with classic narcolepsy type 1 Read more

critical care

Predict the future of critical care in #STATMadness

Emory is participating in STAT Madness, a “March Madness” style bracket competition featuring biomedical research advances instead of basketball teams. Universities or research institutes nominate their champions, research papers that were published the previous year. It’s like “Battle of the Bands.” Whoever gets the loudest — or most numerous — cheers wins.

Please check out all 64 entries, follow the 2019 STAT Madness bracket and vote here:
https://www.statnews.com/feature/stat-madness/bracket/

Emory’s entry for 2019:
It’s like the “precogs” who predict crime in the movie Minority Report, but for sepsis, the deadly response to infection. Shamim Nemati and colleagues have been exploring ways to analyze vital signs in ICU patients and predict sepsis, hours before clinical staff might otherwise notice.

As landmark clinical studies have documented, every hour of delay in giving someone with sepsis antibiotics increases their risk of mortality. So detecting sepsis as early as possible could save thousands of lives. Many hospitals have developed “sniffer” systems that monitor patients for sepsis, but this algorithm tries to spot problems way before they become apparent.

As published in 2018 in Critical Care Medicine, the algorithm can predict sepsis onset—with some false alarms—four, eight, even 12 hours ahead of time. No algorithm is going to be perfect, but it was better than any other previous sepsis predictor. The technology is headed for additional testing and evaluation at several medical centers, as part of a project supported by the federal Biomedical Advanced Research and Development Authority (BARDA).

You can fill out a whole bracket or you can just vote for Emory. The contest will last several rounds. The first round began on Monday, March 4, and lasts until the end of the week. Before 10 am Eastern time Monday morning, there were already more than 5,000 brackets entered!

If Emory advances, then people will be able to continue voting for us starting on Friday. Emory’s first opponent is a regional rival, Vanderbilt University School of Medicine. We are on the upper left side of the bracket.

STAT News is a Boston-based news organization covering biomedical research, pharma and biotech. If you feel like it, please share on social media using the hashtag #statmadness.

Posted on by Quinn Eastman in Uncategorized Leave a comment

2B4: potential immune target for sepsis survival

Emory immunologists have identified a potential target for treatments aimed at reducing mortality in sepsis, an often deadly reaction to infection.

2B4 is an inhibitory molecule found on immune cells. You may have heard of PD1, which cancer immunotherapy drugs block in order to re-energize the immune system. 2B4 appears to be similar; it appears on exhausted T cells after chronic viral infection, and its absence can contribute to autoimmunity.

In their new paper in Journal of Immunology, Mandy Ford, Craig Coopersmith and colleagues show that 2B4 levels are increased on certain types of T cells (CD4+ memory cells) in human sepsis patients and in a mouse model of sepsis called CLP (cecal ligation + puncture). Genetically knocking out 2B4 or blocking it with an antibody both reduce mortality in the CLP model. The effect of the knockout is striking: 82 percent survival vs 13 percent for controls.

How does it work? When fighting sepsis, 2B4 knockout animals don’t have reduced bacterial levels, but they do seem to have CD4+ T cels that survive better. CD4+ T cells, especially memory cells, get killed in large numbers during sepsis, and this is thought to contribute to mortality. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

EHR data superior for studying sepsis

Are there more cases of a given disease because something is causing more, or because doctors have become more aware of that disease? A recent paper in JAMA tackles this question for sepsis, the often deadly response to infection that is the most expensive condition treated in US hospitals.

Researchers from several academic medical centers, including Emory, teamed up to analyze sepsis cases using two methods. The first is based on the ICD (International Classification of Diseases) codes recorded for the patient’s stay in the hospital, which the authors refer to as “claims-based.” The second mines electronic medical record (EHR) data, monitoring the procedures and tests physicians used when treating a patient. The first approach is easier, but might be affected by changing diagnosis and coding practices, while the second is not possible at every hospital.

“This project was undertaken by several large, high quality institutions that have the ability to well characterize their sepsis patients and connect their EHR data,” says Greg Martin, MD, who is a co-author of the JAMA paper along with David Murphy, MD, PhD. The lead author, Chanu Rhee, MD, MPH, is from Brigham and Women’s Hospital, and the entire project was part of a Prevention Epicenter program sponsored by the Centers for Disease Control and Prevention.  Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Pre-hospital recognition of severe sepsis

 

Severe sepsis, a consequence of the body’s response to infection, is a major cause of death in hospitals. The earlier that doctors recognize that a patient has sepsis, the earlier the patient can be treated with antibiotics, fluids and other measures, and the better the chance of survival.

That’s why critical care and emergency medicine researchers have been looking for ways to spot whether someone coming to the hospital might have sepsis, even before arrival.

At Emory, Carmen Polito, Jonathan Sevransky and colleagues recently published a paper in the American Journal of Emergency Medicine on an emergency medical services screening tool for severe sepsis. Polito and Sevransky are in the division of pulmonary, allergy, critical care and sleep medicine in the Department of Medicine. The tool was evaluated based on Grady emergency medical services data from 2011 and 2012.

“Sepsis is largely a face without a name in the EMS setting, “ Polito says. “The goal of our study was to create a tool to assist EMS providers in naming this deadly condition at the point of first medical contact. Similar to other life-threatening, time-sensitive conditions like stroke and heart attack, naming sepsis is the first step in developing coordinated care pathways that focus on delivering rapid, life-saving treatment once the patient arrives at the hospital.”

Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Test of megadose vitamin D in intubated critical care patients

Whether dietary supplementation with vitamin D is beneficial, in terms of preventing disease, has been controversial. However, vitamin D has been reported to increase immune cells’ production of microbe-fighting proteins. That’s why Emory doctors have been testing whether high doses of vitamin D could be helpful for critical care patients, who need to ward off infections.

The results of a small-scale clinical trial, presented in Denver this week at the American Thoracic Society meeting, suggest that high doses of vitamin D could decrease the length of hospital stays in critically ill patients with respiratory failure. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

The age of blood

Nature Medicine has a nice feature from Jeanne Erdmann highlighting the debate over how long donated blood can be stored. It sets the stage for two prospective clinical trials (RECESS and ABLE), which recently concluded but are still being analyzed. The trials were looking at how the age of stored blood affects patients undergoing cardiac surgery or in intensive care, respectively. Erdmann also mentions that the NIH’s Clinical Center already has tightened its standards for blood storage time.

Emory Blood Bank director John Roback and cardiologist Arshed Quyyumi have been participants in this debate, both theoretically and experimentally. In 2011, they proposed that depletion of the messenger molecule nitric oxide limits the benefits donated blood can provide to patients. In addition to nitric oxide depletion, the “storage lesion” is likely to include several changes, such as lysis of red blood cells, mechanical alterations in the remaining cells, and other chemical changes.

Since then, Emory research has shown that transfusion of donated blood more than three weeks old results in impaired blood vessel function in hospitalized patients, but in contrast, not in healthy volunteers. This information could allow doctors to prioritize fresher blood for patients with cardiovascular diseases.

Posted on by Quinn Eastman in Heart Leave a comment

Delivering nutrition to critical care patients

Emory clinical nutrition expert Thomas Ziegler, MD, has a case report article in the Sept. 10 issue of the New England Journal of Medicine.

The case report describes a woman with diabetes who needed surgery because of loss of blood flow to abdominal organs. While she is in intensive care after surgery, it becomes clear that a feeding tube leading from her nose to her stomach is not working. That makes her a good candidate for parenteral nutrition, or bypassing the digestive system and delivering nutrients directly into her blood.

Malnutrition is common in patients who are critically ill and often worsens with prolonged hospitalization. Some patients can’t eat normal food or benefit from a feeding tube into the stomach.

Thomas Ziegler, MD, Director, Center for Clinical and Molecular Nutrition, Department of Medicine

Thomas Ziegler, MD, Director, Center for Clinical and Molecular Nutrition, Department of Medicine

Yet few well-designed clinical trials studying parenteral nutrition have been conducted, Ziegler writes. He also notes that there is considerable debate over when parenteral nutrition is appropriate during critical care and how to administer it.

Ziegler’s own research has shown the beneficial effects of the amino acid glutamine, which must be added fresh to feeding formulas, for some critical care patients.

Several of the questions Ziegler outlines in his article will be issues investigators at Emory’s new Center for Critical Care will tackle. Recently, Timothy Buchman, MD, PhD, joined Emory to lead the critical care team.

Posted on by Quinn Eastman in Uncategorized Leave a comment