Researchers ID blood protein that sheds light on common, post-operative complication

Delirium, a common post-operative complication, is also seen frequently in patients with COVID-19

Newswise — BOSTON – Delirium, a common syndrome among older adults, particularly in those who have recently undergone surgery, critically ill patients in the ICU, and in older patients with multiple health issues, is a form of acute confusion that is characterized by poor attention, disorientation, impaired memory, delusions, and abrupt changes in mood and behavior. Moreover, patients who experience delirium are at increased risk of long term cognitive decline. Recently, clinicians and scientists have recognized that delirium is one of the first signs of COVID-19 infection in older patients and that it occurs frequently in patients with severe COVID-19 disease.

In a new study led by an interdisciplinary team of gerontologists, geriatricians, precision medicine experts, and bioinformaticians at Beth Israel Deaconess Medical Center (BIDMC), researchers identified a single protein present in the blood that is associated with increased risk of post-operative delirium. The finding, published in the Journal of Gerontology: Medical Sciences, sheds light on a potential pathophysiological mechanism underlying delirium and paves the way for a non-invasive, cost-effective test to guide prediction, diagnosis and monitoring of delirium. While further study is needed, pre-operative blood tests for these proteins could help physicians determine which patients are at higher risk for developing delirium.

“Delirium is associated with more complications, longer hospitalizations, increased risk of long-term cognitive decline, dementia and mortality, and costs the U.S. healthcare system an estimated $182 billion each year,” said first author Sarinnapha Vasunilashorn, PhD, Assistant Professor of Medicine at BIDMC and Harvard Medical School (HMS).

“Despite its pervasiveness, delirium remains a clinical diagnosis with no established tests to diagnose the condition,” said co-senior author Towia Libermann, PhD, Director of the BIDMC Genomics, Proteomics, Bioinformatics and Systems Biology Center. “The discovery of a reliable biomarker could change that.”

Vasunilashorn, also a member of the Department of Epidemiology at the Harvard T.H. Chan School of Public Health, and colleagues used a cutting edge proteomics platform, SOMAscan — a large-scale quantitative analysis of the expression levels of proteins — to evaluate proteins present in the blood from a patient cohort called SAGES (Successful Aging after Elective Surgery). Sponsored by the National Institute on Aging, SAGES follows 560 noncardiac surgical patients ages 70 and older with the goal of identifying novel biomarkers of delirium and its associated long-term cognitive outcomes.

“SAGES participants have been very generous with their time, participating in interviews to test their memory and thinking, and also donate small amounts of blood, before and immediately after their major elective surgery,” said co-senior author Edward Marcantonio, MD, Section Chief for Research in the Division of General Medicine at BIDMC and Professor of Medicine at HMS. “We are now analyzing this stored blood with novel techniques, such as SOMAscan, to understand the biological basis of delirium, an incredibly challenging clinical problem.”

The researchers’ analysis of more than 1,300 proteins revealed a single protein (known as chitinase-3-like-protein-1, or CHI3L1/YKL-40) that was present at higher concentrations in the blood both before and after surgery in patients who experienced delirium as compared with patients who did not develop postoperative delirium. This protein — itself linked to aging and age-related conditions including Alzheimer’s disease — plays a critical role in the body’s type 2 immune response.

The team also found that patients who had high pre-operative levels of the protein CHI3L1/YKL-40 combined with high post-operative levels of an immune-related protein called interleukin-6 (or IL-6) were at increased risk of delirium.

“Our study specifically highlights the involvement of this highly specific immune activating protein in postoperative delirium, which may also play a role in COVID-19 associated delirium,” said Libermann, who is also an Associate Professor of Medicine at Harvard Medical School. “In addition to providing a promising candidate for a delirium biomarker, our findings suggest a possible link between delirium, aging and Alzheimer’s disease.”

Co-authors included Simon T. Dillon, PhD, Noel Y. Chan, PhD, Tamarą G. Fong, MD, PhD, Marię Joseph, MS, and Long H. Ngo, PhD, of BIDMC. Sharon Inouye, MD, MPH, of both BIDMC and the Marcus Institute for Aging Research Hebrew SeniorLife; Bridget Tripp, MS, and Hasan H. Otu of the University of Nebraska – Lincoln; Zhongcong Xie, MD, PhD, of Massachusetts General Hospital; Chun Geun Lee, PhD, and Jack A. Elias, MD, of the Warren Alpert School of Medicine at Brown University.

This study was supported by the grants from the National Institute on Aging (R01AG051658, P01AG031720, K01AG057836, R03AG061582, R24AG054259, R21AG057955, R01AG041274, R21AG048600, and K24AG03507) and the Alzheimer’s Association (AARF-18-560786).

The authors have no conflicts of interest to disclose.

 

About Beth Israel Deaconess Medical Center

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.org.

Beth Israel Deaconess Medical Center is a part of Beth Israel Lahey Health, a health care system that brings together academic medical centers and teaching hospitals, community and specialty hospitals, more than 4,000 physicians and 35,000 employees in a shared mission to expand access to great care and advance the science and practice of medicine through groundbreaking research and education.

SEE ORIGINAL STUDY

MEDIA CONTACT
Register for reporter access to contact details
CITATIONS

Journal of Gerontology: Medical Sciences; R01AG051658; P01AG031720; K01AG057836; R03AG061582; R24AG054259; R21AG057955; R01AG041274; R21AG048600; K24AG03507; AARF-18-560786




Filters close

Showing results

110 of 5647
Released: 17-May-2021 9:40 AM EDT
Comprehensive Mount Sinai Study Shows Direct Evidence That COVID-19 Can Infect Cells in Eye
Mount Sinai Health System

Study Has Implications for Preventive Measures to Slow Spread of Virus

Released: 17-May-2021 9:00 AM EDT
How to Win Over Vaccine Skeptics: Live Expert Panel for May 20, 3pm ET
Newswise

How to Win Over Vaccine Skeptics: Live Expert Panel for May 20, 3pm ET

Released: 17-May-2021 9:00 AM EDT
Severe COVID-19 may be linked to long-haul symptoms
University of Michigan

People who experience very severe COVID-19 illness have a higher prevalence of persistent symptoms, according to a new University of Michigan study.

Released: 17-May-2021 8:55 AM EDT
Confused About the Latest Mask Rules? Read This
Michigan Medicine - University of Michigan

A quick guide to navigating life now that the CDC and many states have said that fully vaccinated people do not need to wear masks in many situations.

access_time Embargo lifts in 2 days
Embargo will expire: 19-May-2021 5:00 PM EDT Released to reporters: 17-May-2021 7:15 AM EDT

A reporter's PressPass is required to access this story until the embargo expires on 19-May-2021 5:00 PM EDT The Newswise PressPass gives verified journalists access to embargoed stories. Please log in to complete a presspass application. If you have not yet registered, please Register. When you fill out the registration form, please identify yourself as a reporter in order to advance to the presspass application form.

Newswise: Virtual Awards Ceremony for Alexander Jane Noble Awards Honorees in Tech and Medicine on May 26, 2021
Released: 17-May-2021 7:05 AM EDT
Virtual Awards Ceremony for Alexander Jane Noble Awards Honorees in Tech and Medicine on May 26, 2021
The Novim Group

2021 Alexandra Jane Noble (AJN) Awards ceremony will be virtual, held May 26. ANJ Awards recognizes science innovators

access_time Embargo lifts in 2 days
Embargo will expire: 20-May-2021 2:00 PM EDT Released to reporters: 17-May-2021 7:00 AM EDT

A reporter's PressPass is required to access this story until the embargo expires on 20-May-2021 2:00 PM EDT The Newswise PressPass gives verified journalists access to embargoed stories. Please log in to complete a presspass application. If you have not yet registered, please Register. When you fill out the registration form, please identify yourself as a reporter in order to advance to the presspass application form.

Released: 15-May-2021 8:05 AM EDT
Rutgers Reports First Instance of COVID-19 Triggering Recurrent Blood Clots in Arms
Rutgers University-New Brunswick

Researchers at Rutgers Robert Wood Johnson Medical School are reporting the first instance of COVID-19 triggering a rare recurrence of potentially serious blood clots in people’s arms.

access_time Embargo lifts in 2 days
Embargo will expire: 20-May-2021 10:00 AM EDT Released to reporters: 14-May-2021 2:40 PM EDT

A reporter's PressPass is required to access this story until the embargo expires on 20-May-2021 10:00 AM EDT The Newswise PressPass gives verified journalists access to embargoed stories. Please log in to complete a presspass application. If you have not yet registered, please Register. When you fill out the registration form, please identify yourself as a reporter in order to advance to the presspass application form.


Showing results

110 of 5647

close
2.67647