Determining how dogs do this may lead to biomarkers for new clinical laboratory diagnostics tests
Development of new diagnostic olfactory tools for prostate and other cancers is expected to result from research now being conducted by a consortium of researchers at different universities and institutes. To identify new biomarkers, these scientists are studying how dogs can detect the presence of prostate cancer by sniffing urine specimens.
Funded by a grant from the Prostate Cancer Foundation, the pilot study demonstrated that dogs could identify prostate samples containing cancer and discern between cancer positive and cancer negative samples.
Canine Olfactory Combined with Artificial Intelligence Analysis Approach
The part of a canine brain that controls smell is 40 million times greater than that of humans. Some dog breeds have 300 to 350 million sensory receptors, compared to about five million in humans. With their keen sense of smell, dogs are proving to be vital resources in the detection of some diseases.
The pilot study examined how dogs could be trained to detect prostate cancer in human urine samples.
Claire Guest, CEO and Chief Scientific Officer of UK-based Medical Detection Dogs and one of the study authors, is shown above with one of her cancer detecting dogs. In a Prostate Cancer Foundation article, she said, “Prostate cancer is not going to turn out to be a single note. What dogs are really good at discovering is a tune. Think of Beethoven’s Fifth Symphony, those first few notes. We suspect the cancer signature is something like that. It’s a pattern; the dogs are really good at recognizing the pattern. Machines that recognize the notes but can’t read the pattern are not reliable biomarkers,” she noted. The researchers believe the best solution for developing a clinical laboratory diagnostic that detects prostate cancer may be a combined approach using canine olfaction and AI neural networks. (Photo copyright: Janine Warwick/NPR.)
To perform the study, the researchers trained two dogs to sniff urine samples from men with high-grade prostate cancer and from men without the cancer. The two dogs used in the study were a four-year-old female Labrador Retriever named Florin, and a seven-year-old female wirehaired Hungarian Vizsla named Midas. The dogs were trained to respond to cancer-related chemicals, known as volatile organic compounds, or VOCs, the researchers added to the urine samples, and to not respond to the samples without the VOCs.
Both dogs performed well in their cancer detection roles, and both successfully identified five of seven urine samples from men with prostate cancer, correlating to a 71.4% accuracy rate. In addition, Florin correctly identified 16 of 21 non-aggressive or no cancer samples for an accuracy rate of 76.2% and Midas did the same with a 66.7% accuracy rate.
“We wondered if having the dogs detect the chemicals, combined with analysis by GC-MS, bacterial profiling, and an artificial intelligence (AI) neural network trained to emulate the canine cancer detection ability, could significantly improve the diagnosis of high-grade prostate cancer,” said Alan Partin, MD, PhD, Professor of Urology, Pathology and Oncology, Johns Hopkins University School of Medicine and one of the authors of the study, told Futurity.
The researchers determined that canine olfaction was able to distinguish between positive and negative prostate cancer in the samples, and the VOC and microbiota profiling analyses showed a qualitative difference between the two groups. The multisystem approach demonstrated a more sensitive and specific way of detecting the presence of prostate cancer than any of the methods used by themselves.
In their paper, the researchers concluded that “this study demonstrated feasibility and identified the challenges of a multiparametric approach as a first step towards creating a more effective, non-invasive early urine diagnostic method for the highly aggressive histology of prostate cancer.”
Can Man’s Best Friend be Trained to Detect Cancer and Save Lives?
Prostate cancer is the second leading cause of cancer deaths among men in the developed world. And, according to data from the National Cancer Institute, standard clinical laboratory blood tests, such as the prostate-specific antigen (PSA) test for early detection, sometimes miss the presence of cancer.
Establishing an accurate, non-invasive method of sensing the disease could help detect the disease sooner when it is more treatable and save lives.
The American Cancer Society estimates that there will be about 248,530 new cases of prostate cancer diagnosed in 2021 and that there will be approximately 34,130 deaths resulting from the disease during the same year.
Of course, more testing will be needed before Man’s best friend can be put to work detecting cancer in medical environments. But if canines can be trained to detect the disease early, and in a non-invasive way, more timely diagnosis and treatment could result in higher survival rates.
Meanwhile, as researchers identify the elements dogs use to detect cancer and other diseases, this knowledge can result in the creation of new biomarkers than can be used in clinical laboratory tests.
Clinical laboratories and microbiology tests provide key tools for physicians engaged in antibiotic stewardship programs
One important and continuing trend in healthcare is the need for hospitals, nursing homes, and other medical providers to introduce effective antibiotic stewardship programs (ASPs). The findings of a recent study on antibiotic stewardship emphasize the need for improvement and suggest guidelines that will involve and engage clinical laboratories.
In a recent brief of a study The Pew Charitable Trusts (Pew) conducted with the CDC and various public health and medical experts, Pew wrote, “Minimizing inappropriate antibiotic use in hospitals is a vital element in the fight against antibiotic resistance because more than half of patients admitted to hospitals will receive these drugs. Determining how much antibiotic prescribing is inappropriate and setting national targets to reduce such use are necessary steps for guiding clinical efforts and policies that promote improved antibiotic use.”
To do this, and Pew and the CDC are suggesting “widespread adoption of effective antibiotic stewardship programs, which promote responsible antibiotic prescribing, in order to minimize the harmful effects of inappropriate or unnecessary antibiotic use for patients and slow the spread of resistance.”
And because clinical laboratories perform all the in-hospital testing for ASPs, they will be big part of this effort.
Pew/CDC Set New National Targets for Antibiotic Use Improvement
The Pew brief states that in 2018 the researchers began “to evaluate antibiotic use in hospitals and set national targets to improve prescribing.” The brief adds that “Because of the complexity and diversity of illnesses among hospitalized patients, and the limitations on available clinical data for all antibiotic use in hospitals, the panel focused its analysis on four categories of prescribing that account for the most common antibiotic therapies in US hospitals. Using national prescribing data, the experts examined the use of two types of antibiotics—vancomycin and fluoroquinolones—and antibiotic treatments associated with two conditions: community-acquired pneumonia (CAP) and hospital-acquired urinary tract infection (UTI).”
It their paper published in JAMA Network Open, titled, “Assessment of the Appropriateness of Antimicrobial Use in US Hospitals,” the Pew/CDC researchers wrote, “In this cross-sectional study of 1,566 patients at 192 hospitals, antimicrobial use deviated from recommended practices for 55.9% of patients who received antimicrobials for community-acquired pneumonia or urinary tract infection present at admission or who received fluoroquinolone or intravenous vancomycin treatment.”
Infection Control Today reported that the CDC and Pew set the following goals for hospitals, but did not give a deadline for improvement:
Decrease antibiotic inappropriate prescribing in CAP and UTI cases by 90%.
Decrease overprescribing of fluoroquinolones and vancomycin by 95%.
“Meeting these national reduction targets will require widespread adoption of effective antibiotic stewardship programs, which promote responsible antibiotic prescribing in order to minimize the harmful effects of inappropriate or unnecessary antibiotic use for patients and slow the spread of resistance,” noted the Pew brief, which also pointed out that hospitals should provide incentives to report antibiotic use and impact of stewardship programs to the CDC’s National Healthcare Safety Network (NHSN).
‘Ample Room for Improvement’
The Pew/CDC panel of experts analyzed hospitalized patient data from August 2017 through May 2020. Of those patients, the researchers found that:
219 had CAPs,
452 had UTIs,
550 had received fluoroquinolones, and
403 had received vancomycin.
They also found that:
56% of antibiotic prescriptions were wrong in the type of antibiotic, how long it was used, or why it was chosen.
79% of antibiotic prescriptions for CAP were inappropriate.
77% of antibiotic prescriptions did not suit UTI patients.
47% of fluoroquinolone prescriptions were unsupported.
27% of vancomycin prescriptions were amiss.
The researchers concluded that providers have “ample room for improvement,” the Pew brief notes.
“A substantial percentage of CAP, UTI, fluoroquinolone, and vancomycin treatment was unsupported by medical record data collected (55.9% overall and as high as 79.5% for CAP),” the researchers wrote in their published study.
Pew/CDC Researchers Find Many Antibiotic Prescription Errors
According to the Pew/CDC researchers, missteps in antibiotic usage include:
Treating inpatients too long with antibiotics.
Selecting antimicrobials inconsistent with guidelines.
Absence of signs and symptoms of infection.
Lack of clinical laboratory tests or microbiologic evidence of infection.
The study revealed antibiotic duration errors were most prevalent in the CAP patients, some being treated with antibiotics for more than seven days.
“Almost 60% of the inappropriate prescribing is attributed to exceeding the recommended seven days of treatment, and the use of the wrong antibiotic accounts for most of the remaining inappropriate (CAP) cases,” the Pew brief explained.
Antibiotics Prescribed without Evidence of Infection
As medical laboratory professionals know, microbiology tests identify presence and type of bacteria in urine. But the Pew/CDC researchers reported they found UTI cases that lacked evidence of infection.
“In most instances—where antibiotic use was not supported—the antibiotics were prescribed to patients who lacked symptoms or microbiology test results consistent with UTIs,” according to their report.
Antibiotics Overprescribed to COVID-19 Patients
Another study conducted by The Pew Charitable Trusts “assessed the frequency of bacterial infections and antibiotic prescribing patterns in hospitalized patients diagnosed with COVID-19 in the US.” The researchers, according to the Pew brief on that study, titled, “Could Efforts to Fight the Coronavirus Lead to Overuse of Antibiotics?” used “IBM Watson Health’s electronic health records [EHR] database to capture data about approximately 5,000 patients and nearly 6,000 hospital admissions from February through July 2020.”
The researchers of that study found potential antibiotic misuse among COVID-19 patients as well.
52% received at least one antibiotic prescription.
36% had multiple antibiotics.
96% were treated with antibiotics within 48 hours of admission and likely before infection was confirmed.
“Our data shows that there was very likely a significant amount of unnecessary antibiotic prescribing among hospitalized COVID-19 patients,” Rachel Zetts, Officer, Antibiotic Resistance Project at The Pew Charitable Trusts, told Becker’s Hospital Review. “Overprescribing on this scale could negatively impact the progress we’ve made in the fight against antibiotic resistance over the years, so encouraging physicians to reduce inappropriate antibiotic use and equipping them with the tools needed to do so is critical.” Those tools include test results clinical laboratories produce in support of antibiotic stewardship programs. (Photo copyright: The Pew Charitable Trusts.)
Clinical Laboratories are Key Partners
Hospital-based clinical laboratory leaders may want to contact physicians and infection control colleagues and work toward correcting use of antibiotics in patient care. And microbiologists are advised to aggressively communicate available medical laboratory test data about UTI infections, which the Pew/CDC study suggests can be missed.
Medical laboratories provide testing to diagnose infections and to identify strains of infectious agents that may be antibiotic-resistant. Therefore, lab leaders will be key partners in hospitals’ efforts to reduce infections and prevent antibiotic resistance.
Researchers find declining antibody levels in SARS-CoV-2 patients are offset by T cells and B cells that remain behind to fight off reinfection
Questions remain regarding how long antibodies produced by a COVID-19 vaccine or natural infection will provide ongoing protection against SARS-CoV-2. However, a new study showing COVID-19 immunity may be “robust” and “long lasting” may signal important news for clinical laboratories and in vitro diagnostics companies developing serological tests for the coronavirus disease.
The LJI research team analyzed blood samples from 188 COVID-19 patients, 7% of whom had been hospitalized. They measured not only virus-specific antibodies in the blood stream, but also memory B cell infections, T helper cells, and cytotoxic (killer) T cells.
While antibodies eventually disappear from the blood stream, T cells and B cells appear to remain to fight future reinfection.
“As far as we know, this is the largest study ever for any acute infection that has measured all four of those components of immune memory,” Crotty said in a La Jolla Institute news release.
The LJI researchers found that virus-specific antibodies remained in the blood stream months after infection while spike-specific memory B cells—which could trigger an accelerated and robust antibody-mediated immune response in the event of reinfection—actually increased in the body after six months. In addition, COVID-19 survivors had an army of T cells ready to halt reinfection.
“Our data show immune memory in at least three immunological compartments was measurable in ~95% of subjects five to eight months post symptom onset, indicating that durable immunity against secondary COVID-19 disease is a possibility in most individuals,” the study concludes. The small percentage of the population found not to have long-lasting immunity following COVID-19 infection could be vaccinated in an effort to stop reinfection from occurring on the way to achieving herd immunity, the LJI researchers maintained.
Do COVID-19 Vaccines Create Equal Immunity Against Reinfection?
Whether COVID-19 vaccinations will provide the same immune response as an active infection has yet to be determined, but indications are protection may be equally strong.
“It is possible that immune memory will be similarly long lasting similar following vaccination, but we will have to wait until the data come in to be able to tell for sure,”
LJI Research Professor Daniela Weiskopf, PhD, said in the LJI statement. “Several months ago, our studies showed that natural infection induced a strong response, and this study now shows that the response lasts. The vaccine studies are at the initial stages, and so far, have been associated with strong protection. We are hopeful that a similar pattern of responses lasting over time will also emerge for the vaccine-induced responses.”
The study’s authors cautioned that people previously diagnosed with COVID-19 should not assume they have protective immunity from reinfection, the Washington Post noted. In fact, according to the LJI news release, researchers saw a “100-fold range in the magnitude of immune memory.”
Alessandro Sette, Doctor of Biological Sciences (above), an Italian immunologist, Professor at the Center for Autoimmunity and Inflammation/Center for Infectious Disease and Vaccine Research at La Jolla Institute for Immunology, and co-author of the study, told the Washington Post that people should act responsibly. “If I had COVID, I would still not throw away my masks, I would not go to rave parties … It’s like driving a car where you know you have 90% probability that the brakes work.” (Photo copyright: La Jolla Institute for Immunology.)
Previous Studies Found Little Natural Immunity Against SARS-CoV-2 Reinfection
The Scientist reported that several widely publicized previous studies raised concerns that immunity from natural infection was fleeting, perhaps dwindling in weeks or months. And a United Kingdom study published in Nature Microbiology found that COVID-19 generated “only a transient neutralizing antibody response that rapidly wanes” in patients who exhibited milder infection.
Daniel M. Davis, PhD, Professor of Immunology at the University of Manchester, says more research is needed before scientists can know for certain how long COVID-19 immunity lasts after natural infection.
“Overall, these results are interesting and provocative, but more research is needed, following large numbers of people over time. Only then, will we clearly know how many people produce antibodies when infected with coronavirus, and for how long,” Davis told Newsweek.
While additional peer-reviewed studies on the body’s immune response to COVID-19 will be needed, this latest study from the La Jolla Institute for Immunity may help guide clinical laboratories and in vitro diagnostic companies that are developing serological antibody tests for COVID-19 and lead to more definitive answers as to how long antibodies confer protective immunity.
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IBM Research, corporate research laboratory for parent company IBM (NYSE:IBM), has more than 3,000 researchers working in 12 labs on six continents. Each year the lab releases a list of five technologies it forecasts will have the greatest influence on how our bodies, minds, society, and the planet, develop over the next five years. The list is called “5-in-5” and has been released annually for the past 10 years by the tech giant. (more…)
