EXPLOITING BACTERIAL 'SWEET TOOTH' MAY HELP IMAGE AND DIAGNOSE INFECTIONS
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In the movie Mary Poppins, the title character sings that "a spoonful of sugar helps the medicine go down." Now, Johns Hopkins Medicine researchers have shown how a radioactive sugar -- combined with a widely used imaging technology -- could soon help physicians make the medicine work better by enabling them to rapidly detect and monitor infections from the largest group of bacterial pathogens threatening humans.
The new imaging tool uses positron emission tomography -- commonly known as a PET scan -- to noninvasively find and track dangerous infections from the microbial family Enterobacterales, a group that includes the Escherichia coli strains that cause food poisoning; Klebsiella pneumoniae, a cause of pneumonia and a severe threat to patients weakened from COVID-19; and Yersinia pestis, the scourge behind the "Black Death" pandemic of plague in the 14th century that wiped out 75% of the world's population.
Enterobacterales bacteria also have been tagged by the U.S. Centers for Disease Control and Prevention as "urgent and serious antibiotic resistance threats" because of their frequent mutations to drug-resistant strains.
The new diagnostic tool is described in a paper published April 14, 2021, in Science Translational Medicine. It emerged from a creative combination of existing PET scan technology -- a sophisticated 3D visualization system for imaging diseases such as cancer -- with sorbitol, a molecule used in making sugar-free foods. The method capitalizes on the fondness for sorbitol of Gram-negative bacteria (a classification of bacteria based on their resistance to a specific staining procedure) such as Enterobacterales and the fact that other microorganisms, cancers and human cells do not absorb it.
"We converted an already available radioactive imaging tracer into an isotope-tagged sorbitol molecule that would light up clusters of Gram-negative bacteria within the body during a PET scan," says study senior author Sanjay Jain, M.D., professor of pediatrics, and radiology and radiological medicine at the Johns Hopkins University School of Medicine; and professor of international health at the Johns Hopkins Bloomberg School of Public Health.
In a previous study, the researchers demonstrated that PET scans using their novel sugar tracer -- chemically known as 2-deoxy-2 [18F] fluoro-D-sorbitol (18F-FDS) -- successfully detected Enterobacterales infections in mice. This time, the team conducted a clinical study to evaluate the safety and effectiveness of the 18F-FDS PET technique. The work was done in collaboration with scientists from the Fundación Cardiovascular de Colombia-Hospital Internacional de Colombia (Piedecuesta, Colombia).
A total of 71 PET scans were performed in 31 patients, 18 of whom had previously confirmed Enterobacterales infections using traditional blood cultures. The 18F-FDS PET imaging technique was able to detect and localize Enterobacterales infections at multiple body sites, and distinguish them from the patients with infections caused by other bacteria and the ones whose infection-like symptoms were the result of cancer.
The tracer was well tolerated by all of the participants and showed no adverse effects.
Because the 18F-FDS PET imaging technique has shown that it can immediately detect the presence of Enterobacterales bacteria deep inside the body -- compared with laboratory tests which can take two to three days to confirm an infection -- the researchers feel that their method can play an important role in optimizing antibiotic treatments and preventing the rise of dangerous antibiotic-resistant bacteria strains.
"Using broad-spectrum antibiotics to treat a suspected bacterial infection before an infection is confirmed is sometimes like firing a cannonball to kill a fly," says study lead author Alvaro Ordonez, M.D., assistant professor of pediatrics at the Johns Hopkins University School of Medicine. "While such treatment is clinically justified in patients with serious infections of unknown origin, it can promote bacterial resistance to the drugs. Knowing quickly which organism is causing the problem can enable clinicians to target the antibiotic best suited for that bacteria, and that is where our new imaging system could make a difference."
The researchers also say that the 18F-FDS PET imaging technique also can be used to monitor the effectiveness of antibiotic therapy, as they showed for 13 of their clinical trial participants with Enterobacterales infections.
"We scanned the patients before and after their course of treatment," says Ordonez. "In those who did not respond well because of the presence of drug-resistant bacteria, the 18F-FDS signal remained high with the final scans. On the contrary, it decreased in those patients whose infections were significantly treated."
Jain says that larger clinical trials are needed to validate the findings of his team's latest study. "However, we're excited that our data support the role of 18F-FDS PET as a viable diagnostic and treatment monitoring tool," he says.
Jain and Ordonez are available for interviews.
SEEING IS BELIEVING, EVEN FOR THE EARS: VIDEO GOGGLES DIAGNOSE BALANCE AND MOVEMENT LOSS
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Our ears are not just organs for hearing; they also sense head motion, coordinate balance and enable us to move safely in different environments. Now, Johns Hopkins Medicine researchers have found that a test using commercially available, high-speed video goggles can help diagnose vestibular loss -- weakness in the balance mechanism of the inner ear -- more effectively.
In a study published March 25, 2021, in JAMA Otolaryngology-Head & Neck Surgery, Amir Kheradmand, M.D., director of research at the Johns Hopkins Medicine Neuro-Visual and Vestibular Disorders Center, and his team determined that the use of high-speed video goggles and automated analysis software can provide immediate feedback of vestibular loss during a clinical evaluation of patients with dizziness and balance problems.
Their findings show the test can be easily applied with a simple tilt of the head and torso together while the patient is seated and looking straight ahead.
"Imagine watching a video on a cell phone, and when you turn it from vertical to horizontal orientation, the screen adjusts accordingly," says Kheradmand, who also is an associate professor of neurology, and of otolaryngology-head and neck surgery at the Johns Hopkins University School of Medicine, and an adjunct faculty member of the Johns Hopkins University Laboratory for Computational Sensing and Robotics. "That's what our ears do; they sense the movement of our head, so that when you move your head to the right side, your eyes automatically move to the left. This helps keep the world steady in front of you."
"So, what we're measuring with the goggles is the rolling of the eyes relative to the head tilt so that we may do a comprehensive evaluation of the inner ear balance function," Kheradmand explains
Kheradmand says that the oculography (video recording of eye movements) goggles capture moving images of a patient's iris, the colored portion of the eye that controls the amount of light reaching the retina. The goggles also feature sensors that can track head motion and measure the balance function of the ear.
"You don't need complicated laboratory equipment," he says. "We can do the test in seconds to determine any loss of function."
The clinical trial described in the study compared data from the goggles for patients who had lost vestibular ability because of surgery with others who have normal inner ear function. Kheradmand says his team found that the test could accurately detect loss of vestibular function 83% of the time. Future studies, he says, will need to include patients with other causes and varying degrees of vestibular loss to better establish the test's diagnostic ability.
Kheradmand says the test not only uncovers past loss of vestibular function, but also can define if the loss is recent or chronic. However, he adds, the ability to detect loss varies with the length of time a patient has had the condition. In the study, patients who had a long history of loss were harder to identify, while those with very recent loss were easily found.
Kheradmand says that he and his team are excited about the potential use of their test to measure and track recovery from vestibular loss, as well as one day being able to track a patient's response to vestibular physical therapy.
Kheradmand is available for interviews.
GEORGE MASON UNIVERSITY JOINS JOHNS HOPKINS CLINICAL RESEARCH NETWORK
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George Mason University's College of Health and Human Services has joined the Johns Hopkins Clinical Research Network (JHCRN). Developed by the Johns Hopkins Institute for Clinical and Translational Research (ICTR), JHCRN is designed to bring together academic- and community-based clinical researchers to provide new opportunities for research collaborations and accelerate the transfer of new diagnostic, treatment and disease-prevention advances from the research arena to patient care.
George Mason is the first university to join the JHCRN, which was established by Johns Hopkins Medicine in 2009 and includes the clinical health systems of Luminis Health in southern Maryland, TidalHealth in eastern Maryland and Reading Hospital, an affiliate of Tower Health, in Pennsylvania.
The network creates a bridge for research between Johns Hopkins and community-based medical centers by linking physician-scientists and staff members from Johns Hopkins Medicine with various centers in the region. It serves several purposes, the most important of which is making clinical trials available to patients who may not otherwise have access to them.
"The JHCRN is a unique research resource that increases patient access to innovative therapies and outcomes research in their own local communities. It also empowers physicians to design and conduct a broad array of research projects relevant to their communities," says Adrian Dobs, M.D., JHCRN director and professor of medicine and oncology at the Johns Hopkins University School of Medicine. "It is a premier network of affiliated medical institutions which can carry out efficient, collaborative clinical research to achieve high-quality innovative patient care. I am very impressed with the depth and excellence of research being done within the GMU enterprise, and believe our overall network will benefit from this great work."
George Mason is the one of the fastest-growing Research I institutions in the country, and its College of Health and Human Services has more than 1,900 undergraduate students and 1,370 graduate students.
"We are proud to join this highly-respected network of health care delivery organizations to bring research discoveries into clinical practice in a timely manner to improve the health of those we serve," says Germaine Louis, Ph.D., dean of the college. "It is only through partnerships such as these that we can improve health equity and make health visible and accessible for all people."
The JHCRN directly addresses the many complexities of conducting multisite and multi-institutional studies by providing investigators with a larger patient pool and a seamless platform that uses common research protocols. The goal of the network is to speed the approval of new protocols while ensuring careful oversight of patient safety. Rapid startup and timely completion of research studies, aided by widespread access to clinical trials, will make promising therapies available for patient use more quickly.
Initially, the JHCRN focused on expanding cancer-related clinical trials (including medical, surgical and radiation-therapy aspects of cancer treatment), as well as diabetes and surgical studies. Collaborations have facilitated expanded work, including a wide range of research areas, such as pediatrics and intensive care; COVID-19 studies; neuropsychiatric, brain and spine diseases; and radiology and nuclear medicine studies. Present sponsors include federal and industry sources, along with private foundations.
The JHCRN is a program within ICTR, which is a part of a national consortium dedicated to transforming how clinical and translational research is conducted at academic health centers around the country.
For more information about the JHCRN, visit http://ictr.johnshopkins.edu/JHCRN.
Dobs is available for interviews.
Science Translational Medicine