Blood protein changes across lifespan
The bloodstream touches all the tissues in the body. It carries nutrients to tissues and takes waste products away. Tissues also release proteins into the bloodstream that can communicate with other parts of the body, help mount an immune response to disease, and much more.
Because of this constant flow of proteins through the body, some blood tests measure specific proteins to help diagnose diseases. Examples include diabetes, heart disease and kidney and liver problems. Scientists have been curious about whether blood proteins could be used to more broadly assess people’s health and wellness.
To explore this idea further, researchers led by Drs. Benoit Lehallier and Tony Wyss-Coray from Stanford University collected blood plasma samples from more than 4,000 volunteers between the ages of 18 and 95. They compared the levels of nearly 3,000 proteins in blood between people of different ages as well as between men and women within those age groups. The work was funded in part by NIH’s National Institute on Aging (NIA). Results were published in Nature Medicine.
Overall, about two-thirds of the proteins found to change with age differed between men and women. This supports the idea that men and women age differently—and highlights the need to include both sexes in clinical studies for a wide range of diseases.
The researchers identified a subset of 373 proteins that could accurately predict people’s age within a range of a few years in both men and women. Participants who were predicted by their protein signature to be younger than they actually were performed better than their peers on cognitive and physical tests.
Unexpectedly, deeper analyses showed that most protein changes seen with aging did not occur in a linear fashion. Instead, they occurred in waves, with three large peaks of change around the ages of 34, 60 and 78. These waves largely consisted of changes in different proteins and were associated with different biological functions.
Some of the proteins found in these peaks had previously been associated with the development of age-related diseases. For example, proteins associated with cardiovascular disease and Alzheimer’s disease were found in the peaks at 60 and 78 years of age.
“We’ve known for a long time that measuring certain proteins in the blood can give you information about a person’s health status—lipoproteins for cardiovascular health, for example,” says Wyss-Coray. “But it hasn’t been appreciated that so many different proteins’ levels—roughly a third of all the ones we looked at—change markedly with advancing age.”
Vaping-associated lung injury
With research and understanding of electronic cigarettes or vaping product use-associated lung injury (EVALI) still evolving, a new Radiology review looks at the current state of the disease, diagnostics and the need for continued research.
Published online, “Radiologic Pathologic, Clinical, and Physiologic Findings of Electronic Cigarette or Vaping Product Use–associated Lung Injury (EVALI): Evolving Knowledge and Remaining Questions,” is the newest research to tackle EVALI, a rapidly evolving public health crisis that has led to more than 2,500 hospitalizations since August, according to the Centers for Disease Control (CDC).
Recent research shows that most EVALI patients have smoked e-cigarettes that contained some mixture of marijuana and nicotine products, but study authors Seth Kligerman, M.D., and Mark Schiebler, M.D., say part of the problem is lack of regulation of vape pens and their contents.
In cases of EVALI reported to the CDC, 86 percent reported using products containing either nicotine or THC. The lack of regulation, black-market vape products and a young demographic of users all make researching the issue more complicated. The dramatic increase in vaping among middle school and high school students over the past year represents the largest increase in use of any illicit substance tracked by the National Institute of Drug Abuse over the last 44 years, according to the review.
“It all boils down to what is it that they are smoking? What they tell you they are smoking is not necessarily what they have been smoking. We have no idea what’s in these cartridges and sometimes they don’t know either, so there is a lot that’s unknown,” said Dr. Schiebler, professor of radiology at the University of Wisconsin School of Medicine and Public Health, Madison.
Other variabilities including the amount a patient inhales each time, length of inhalation, the volume of substance inside the vape pen and frequency of vaping can all make this research more challenging, said Dr. Kligerman, chief of cardiothoracic imaging and associate professor of radiology at UC San Diego Health.
Both doctors said that while the cases of EVALI seem to have slowed down after reaching a peak last fall, there is still much doctors don’t know about acute and long-term effects.
Originally touted as an alternative to traditional cigarettes, e-cigarettes still contain nicotine and have been marketed primarily to young adults with brightly colored packaging, advertising and flavoring.
Dr. Schiebler said the next phases of research will include epidemiology to trace particular outbreaks back to types of e-cigarettes and their contents, pathology to collect and study cases of EVALI and look for patterns, and research into particle size and how it affects the lungs over time.
The study reports that in most cases, both the imaging and pathologic findings of EVALI are that of organizing pneumonia and diffuse alveolar damage, although the disease can appear differently on scans for some people.
Researchers develop blood test to predict recurrence of gastric cancers
Researchers at the Johns Hopkins Kimmel Cancer Center in Baltimore, working with colleagues in the Netherlands, developed a blood test that can predict recurrence of gastric cancer in patients after surgery. A description of their test, which is still experimental, was published online in the journal Nature Communications.
Investigators analyzed blood samples from 50 patients with gastric cancer who participated in the CRITICS trial, a phase III, randomized controlled study of chemotherapy given at about the time of surgery. They performed deep sequencing of both circulating cell-free DNA (cfDNA) and of white blood cells to look for mutations. Subtracting the white blood cells’ information from cfDNA yielded data investigators could use to predict cancer recurrence within nine weeks following preoperative treatment and surgery.
“We performed this study to see if we could predict whether gastric cancers would recur using noninvasive liquid biopsies. Using a deep sequencing approach of cell-free DNA and white blood cells, we found an outstanding prediction of whether the therapy was successful,” says senior study author Victor Velculescu, M.D., PhD, professor of oncology, pathology and medicine. Velculescu also is co-director of the Kimmel Cancer Center’s cancer genetics and epigenetics program, and associate director for precision medicine.
Alessandro Leal, M.D., PhD, lead author of the paper on the study and former graduate student at the Johns Hopkins University School of Medicine says, “Patients who did not have mutations in the blood after surgery were all cured of cancer, while patients who had mutations in the blood typically recurred. We were able to predict patient outcome about nine months earlier through the blood test than we otherwise could have through clinical evaluation.”
Physicians slow to use new antibiotics against superbugs
New, more effective antibiotics are being prescribed in only about a quarter of infections by carbapenem-resistant Enterobacteriaceae (CRE), a family of the world’s most intractable drug-resistant bacteria, according to an analysis by infectious disease and pharmaceutical scientists at the University of Pittsburgh School of Medicine (UPMC) and published by the journal Open Forum Infectious Diseases.
This sluggish uptake of such high-priority antibiotics prompted the researchers to call for an examination of clinical and pharmaceutical stewardship practices across U.S. hospitals, as well as behavioral and economic factors, to see if the trend can be reversed before lackluster sales lead the pharmaceutical industry to stop developing much-needed antibiotics.
“The infectious diseases community spent the past decade saying, ‘We need new antibiotics, this is a top priority,’ and now we’re at risk of sounding like the boy who cried wolf,” said lead author Cornelius J. Clancy, MD, associate professor of medicine and director of the mycology program and XDR Pathogen Laboratory in Pitt’s Division of Infectious Diseases. “We have a responsibility to learn why it takes so long for antibiotics to be adopted into practice and figure out what we need to do to ensure the best antibiotics quickly reach the patients who desperately need them.”
The CDC has classified CRE as urgent threat pathogens and calls them the “nightmare bacteria.” The WHO and Infectious Disease Society of America have designated CRE as highest priority pathogens for development of new antibiotics. At the time of those declarations, polymyxins were the first-line antibiotics against CRE, even though they failed to work in about half the cases and carried a significant risk of damaging the kidneys.
Since 2015, five antibiotics against CRE have gained FDA approval: ceftazidime-avibactam, meropenem-vaborbactam, plazomicin, eravacycline, and imipenem-relebactam. Studies, including those conducted at UPMC, have shown that the first three of these antibiotics are significantly more effective at fighting CRE and less toxic than polymyxins (eravacycline and imipenem-relebactam are still too new for conclusive data).
Clancy and his colleagues surveyed hospital-based pharmacists in the U.S. to gauge their knowledge of the new antibiotics and their willingness to use them. The drugs were classified as the “first-line” choice against CRE blood infections by 90 percent of the pharmacists, pneumonia by 87 percent, intra-abdominal infections by 83 percent and urinary tract infections by 56 percent.
“Clearly hospital-based pharmacists are aware of these antibiotics and believe they are the best choice for the vast majority of CRE infections,” said Clancy.
But when the team estimated the number of CRE infections nationwide and used national prescription data to calculate the proportions of old vs. new antibiotics used to treat those infections, they found that from February 2018 through January 2019, the new antibiotics were used only about 23 percent of the time. Their use likely started to exceed that of polymyxins only in December 2018, nearly four years after the first of the new antibiotics was approved by the FDA. Even after accounting for CRE infections in which new antibiotics might not be first-choice agents, the team found that use was only about 35 percent of what was expected based on positioning by hospital-based pharmacists.
Allergan and The Medicines Company, developers of two of the new antibiotics, have sought to exit the antimicrobial field since introducing their drugs because of insufficient returns on investment. Achaogen declared bankruptcy months after attaining FDA approval for a third new antibiotic.
The researchers suggest several reasons for the slow uptake of the new antibiotics, starting with cost. A 14-day course of the new antibiotics costs between $13,230 and $15,070, compared to $305 to $784 for the old drugs.
“Cost is a limitation, but I’m not convinced it is the sole cause of our findings,” said Clancy. “Clinicians may not be prescribing the new drugs due to concerns about accelerating antibiotic-resistance or because initial studies on their effectiveness were relatively small. We need to get at the root causes of the disconnect between what the doctors prescribe and what the pharmacists we surveyed believe they should be prescribing, and then find a solution” and that participants remain in the study for follow-up. The report noted there was no significant evidence of either decreased or increased infection rates with vaccination.
