With FDA clearance already approved, hospital infection control teams and their clinical laboratories may have another diagnostic tool for diagnosing blood infections
Controlling sepsis in hospitals continues to be a major concern in nations around the world, including in the United States. Now, a new 10-minute clinical laboratory blood test that uses artificial intelligence (AI) and digital images to spot biomarkers of the potentially fatal condition may soon be available for use in hospitals. The test, which was approved to be marketed in the US in 2022 by the federal Food and Drug Administration (FDA), may be “one of the most important breakthroughs in modern medical history,” according to US researchers, Good News Network (GNN) reported.
“Early detection of sepsis is an invaluable capability for healthcare professionals. Quickly identifying sepsis is critical to saving lives, but until now, we’ve lacked a reliable tool to either recognize the condition or explore alternate diagnoses,” said O’Neal in an LSU press release.
“IntelliSep is truly a game changer,” said Hollis O’Neal, MD (above), Associate Professor of Medicine at Louisiana State University Health Sciences Center in Baton Rouge. “The test provides hospital staff with information needed to identify and treat septic patients efficiently and reduce the financial and health burdens of overtreatment for hospitals and patients.” Clinical laboratories may have a new blood test for sepsis by the end of the year. (Photo copyright: Louisiana State University.)
How IntelliSep Works
The IntelliSep test analyzes blood samples extracted from emergency room patients who present with sepsis symptoms by squeezing white blood cells through a tiny tube to determine how the cells react and if they change shape. White blood cells in patients with sepsis are softer and spongier and their shape compresses and elongates, increasing the likelihood of developing sepsis.
Images are taken of the cells using an ultra-high-speed camera that can capture up to 500,000 frames per second. The images are the analyzed by an AI-powered computer which calculates the total number of elongated white blood cells to determine if sepsis is present.
IntelliSep then separates patients into three bands of risk for developing sepsis:
Band 1 (low)
Band 2 (medium)
Band 3 (high)
Results of the test are available to emergency room personnel in less than 10 minutes.
“Sepsis is notorious as the ‘silent killer’ because it is so easily missed early on, when a patient’s symptoms can often be mistaken for other less serious illnesses,” Michael Atar, PhD, DDS, Associate Professor, Pediatric Dentistry at New York University told Good News Network. “Rapid diagnosis and treatment is crucial to a good outcome, but there has never been a single, reliable diagnostic test available to doctors, costing precious time and people’s lives.”
Atar is a lead medical technology investor and an advisor to Cytovale.
‘Holy Grail’ of Sepsis Diagnosis
To complete the IntelliSep study, researchers enrolled 1,002 ER patients who presented with signs of sepsis. IntelliSep correctly identified patients who did not have sepsis with an accuracy rate of 97.5%. The technology showed an accuracy rate of 55% for positive sepsis results. Researchers also used IntelliSep to quickly diagnose and assess the severity of a sepsis infection.
There were no sepsis deaths reported in patients with low-risk scores. This indicates the test could help physicians rule out sepsis and seek other diagnoses for those patients.
“Cytovale’s IntelliSep device is, by any objective measure, the ‘holy grail’ that the medical community has been so desperate to find,” Atar told Good News Network. “The technology behind it is genuinely groundbreaking and it has the real-world, tried-and-tested potential to save millions of lives, year on year, across the planet.”
The technology is currently being used in a few hospitals in Louisiana and the inventors hope to have it available in at least 10 other hospitals by the end of the year.
Our Lady of the Lake Regional Medical Center, a not-for-profit Catholic healthcare ministry located in Baton Rouge, was one of the first hospitals to implement IntelliSep.
“Cytovale’s innovative technology will help drastically decrease the number of sepsis-related deaths in hospital settings, and we are honored that, since day one, we have been a part of the research that led to this technology,” said Chuck Spicer, President of Our Lady of the Lake Health in a news release.
Saint Francis Medical Center in Monroe, La., announced on September 3 that it has started using the IntelliSep test in its emergency rooms and staff are impressed by the impact on hospital efficiency.
“If it turns out negative then you don’t have to treat as many patients as you did before, which runs up costs, hospital bills and causes people to be in the hospital for longer periods of time,” said pulmonary disease physician Thomas Gullatt, MD, President, St. Francis Health, told KNOE News.
Patient Expectations for Treatment
Sepsis, also known as septicemia or blood poisoning, is a serious medical condition that occurs when the body improperly reacts to an infection or injury. The dangerous reaction causes extensive inflammation throughout the body and, if not treated early, can lead to organ failure, tissue damage, and even death.
The Centers for Disease Control and Prevention (CDC) reports at least 1.7 million adults develop sepsis annually in the US and at least 350,000 die as a result of the condition. It also states sepsis is one of the main reasons people are readmitted to hospitals.
Clinical laboratories should be aware of developments in the use of this new diagnostic assay and how it is aiding the diagnosis, antibiotic selection, and monitoring of patients with this deadly infection. Patients often learn about new technologies and come to their hospital or provider expecting to be treated with these innovations.
Study findings could lead to new clinical laboratory diagnostics that give pathologists a more detailed understanding about certain types of cancer
New studies proving artificial intelligence (AI) can be used effectively in clinical laboratory diagnostics and personalized healthcare continue to emerge. Scientists in the UK recently trained an AI model using machine learning and deep learning to enable earlier, more accurate detection of 13 different types of cancer.
DNA stores genetic information in sequences of four nucleotide bases: A (adenine), T (thymine), G (guanine) and C (cytosine). These bases can be modified through DNA methylation. There are millions of DNA methylation markers in every single cell, and they change in the early stages of cancer development.
One common characteristic of many cancers is an epigenetic phenomenon called aberrant DNA methylation. Modifications in DNA can influence gene expression and are observable in cancer cells. A methylation profile can differentiate tumor types and subtypes and changes in the process often come before malignancy appears. This renders methylation very useful in catching cancers while in the early stages.
However, deciphering slight changes in methylation patterns can be extremely difficult. According to the scientists, “identifying the specific DNA methylation signatures indicative of different cancer types is akin to searching for a needle in a haystack.”
Nevertheless, the researchers believe identifying these changes could become a useful biomarker for early detection of cancers, which is why they built their AI models.
“Computational methods such as this model, through better training on more varied data and rigorous testing in the clinic, will eventually provide AI models that can help doctors with early detection and screening of cancers,” said Shamith Samarajiwa, PhD (above), Senior Lecturer and Group Leader, Computational Biology and Genomic Data Science, Imperial College London, in a news release. “This will provide better patient outcomes.” With additional research, clinical laboratories and pathologists may soon have new cancer diagnostics based on these AI models. (Photo copyright: University of Cambridge.)
The researchers then used a combination of machine learning and deep learning techniques to train an AI algorithm to examine DNA methylation patterns of the collected data. The algorithm identified and differentiated specific cancer types, including breast, liver, lung and prostate, from non-cancerous tissue with a 98.2% accuracy rate. The team evaluated their AI model by comparing the results to independent research.
In their Biology Methods and Protocols paper, the authors noted that their model does require further training and testing and stressed that “the important aspect of this study was the use of an explainable and interpretable core AI model.” They also claim their model could help medical professionals understand “the underlying mechanisms that contribute to the development of cancer.”
Using AI to Lower Cancer Rates Worldwide
According to the Centers for Disease Control and Prevention (CDC), cancer ranks as the second leading cause of death in the United States with 608,371 deaths reported in 2022. The leading cause of death in the US is heart disease with 702,880 deaths reported in the same year.
Globally cancer diagnoses and death rates are even more alarming. World Health Organization (WHO) data shows an estimated 20 million new cancer cases worldwide in 2022, with 9.7 million persons perishing from various cancers that year.
The UK researchers are hopeful their new AI model will help lower those numbers. They state in their paper that “most cancers are treatable and curable if detected early enough.”
More research and studies are needed to confirm the results of this study, but it appears to be a very promising line of exploration and development of using AI to detect, identify, and diagnose cancer earlier. This type of probing could provide pathologists with improved tools for determining the presence of cancer and lead to better patient outcomes.
Predicted steady increase in the number of new cancer cases globally will stress pathologist and clinical laboratories to process specimens and issue timely cancer diagnoses to referring physicians and patients
In many nations today, it is recognized that the demand for cancer testing services outstrips the capacity of anatomic pathology laboratories to perform cancer testing in a timely manner. Now a new report published in CA, a journal of the American Cancer Society, estimates that the number of new cancers globally will increase substantially during the next few decades.
With today’s cancer diagnostic technologies and standards of practice, it is anatomic pathologists who will typically receive biopsies or patient specimens, perform the tests, and confirm/report whether a patient has cancer. Thus, this new report projecting that the disease will grow 77% to 35 million cases by the year 2050 should be of interest to pathology groups and clinical laboratories worldwide.
The report is a collaboration between the World Health Organization’s International Agency for Research on Cancer (WHO/IARC) and the American Cancer Society (ACS). The report called for “global escalation of cancer control measures” and paying close attention to risk factors such as smoking, obesity, and infections, according to an IARC statement.
Unfortunately, the news about increasing cancer cases comes at a time when worldwide demand for pathologists already far exceeds available supply.
“The impact of this increase will not be felt evenly across countries of different HDI [human development index] levels. Those who have the fewest resources to manage their cancer burdens will bear the brunt of the global cancer burden,” said epidemiology of cancer researcher Freddie Bray, PhD (above), Head of the Cancer Surveillance Branch at the IARC in Lyon, France, in a press release. Bray “specializes in estimating the global cancer burden and predicting future trends,” according to the organization’s website. He also “leads the Global Initiative for Cancer Registry Development (GICR), which is aimed at expanding the coverage and quality of population-based cancer registries in low- and middle-income countries.” Clinical laboratories and anatomic pathologists in the United States and abroad would be wise to keep an eye on the coming cancer burden. (Photo copyright: IARC.)
Top Diagnosed Cancers
To complete their study, the WHO/IARC researchers tapped GLOBOCAN [Global Cancer Observatory] estimates of cancer incidence and mortality, the disease’s geographical variability, and predictions based on global demographic projections.
The 10 most frequently diagnosed cancers for men and women (combined) by percent of cancer sites and number of new cases in 2022 include:
For women, the cancer most often diagnosed was at the breast site. It was also the leading cause of death from cancer, the CA study noted, adding that lung and colorectal cancer cases and deaths in women followed breast cancer.
For men, lung cancer was the top cancer diagnosed in terms of cases and deaths, ahead of prostate and colorectal cancer for new cases.
Geographic HDI Affects Cancer of Citizens
The geographic areas with the highest distribution of new cancer cases and mortality rates in 2022, according to the CA paper, are:
Asia: 49.2% of cases, 56.1% of deaths.
Africa: 5.9% of cases, 7.8% of deaths.
Oceania: 1.4% of cases, 0.8% of deaths.
Euro: 22.4% of cases, 20.4% of deaths.
Americas: 21.2% of cases, 14.9% of deaths.
The WHO/IARC report also associated a country’s human development index (HDI)—a measure of health, longevity, and standard of living—with the likelihood of its residents developing cancer, USA Today reported.
“From a global perspective, the risk of developing cancer tends to increase with increasing HDI level. For example, the cumulative risk of men developing cancer before age of 75 years in 2022 ranged from approximately 10% in low HDI settings to over 30% in very high HDI settings,” the researchers wrote in their CA paper.
This suggests that a lack of resources to diagnose and treat cancer can hinder response and treatment.
In a news release, the WHO pointed out examples of what it termed “striking cancer inequity by HDI.”
“Women in lower HDI countries are 50% less likely to be diagnosed with breast cancer than women in high HDI countries, yet they are at much higher risk of dying of the disease due to late diagnosis and inadequate access to quality treatment,” said medical epidemiologist Isabelle Soerjomataram, MD, PhD, Deputy Head of the Cancer Surveillance Branch, WHO/IARC, in the news release.
Additionally, lung cancer-related resources were four to seven times more likely to be offered in a high-income country than a lower-income country, the WHO noted.
“WHO’s new global survey sheds light on major inequalities and lack of financial protection for cancer around the world, with populations—especially in lower income countries—unable to access the basics of cancer care,” said Bente Mikkelsen, MD, Director of the WHO’s Department of Noncommunicable Diseases, in the news release.
Current State of Pathology Demand
Is the pathology industry prepared for a global cancer burden? Hardly.
In “Examining the Worldwide Pathologist Shortage,” Dark Daily’s sister publication The Dark Report found that demand for pathology services is growing faster than the number of pathologists available to meet that demand. This is true for the United States and most other nations. Consequently, efforts are underway to more accurately measure the number of pathologists practicing in each country. Early data support the claim of an inadequate number of pathologists.
Thus, aligning clinical laboratory and anatomic pathology resources with cancer projections is especially important in light of the WHO/IARC’s recent report which suggests the number of cancer diagnoses and different types of cancer will increase dramatically in coming years.
The data could be helpful to diagnostic leaders seeking evidence to support training of more anatomic pathologists and expansion of AP laboratories, where cancer is most often confirmed and reported.
Shortage could disrupt the ability of clinical laboratories in hospitals and health systems to run certain tests for bloodstream infections
US clinical laboratories may soon experience a “disruption of availability” of BACTEC blood culture media bottles distributed by Becton Dickinson (BD). That’s according to the federal Centers for Disease Control and Prevention (CDC) which issued a Health Alert Network (HAN) Health Advisory to all clinical laboratory professionals, healthcare providers and facility administrators, and other stakeholders warning of the potential shortfall of critical testing supplies.
“This shortage has the potential to disrupt patient care by leading to delays in diagnosis, misdiagnosis, or other challenges in the clinical management of patients with certain infectious diseases,” the CDC stated in the health advisory.
The CDC advises healthcare providers and health departments that use the bottles to “immediately begin to assess their situations and develop plans and options to mitigate the potential impact of the shortage on patient care.”
The advisory notes that the bottles are a key component in continuous-monitoring blood culture systems used to diagnose bloodstream infections and related conditions, such as endocarditis, sepsis, and catheter-related infections. About half of all US laboratories use the BD blood culture system, which is compatible only with the BACTEC bottles, the CDC advisory states.
Infectious disease specialist Krutika Kuppalli, MD (above), Chair of the Infectious Diseases Society of America (IDSA) and a Medical Officer for COVID-19 Health Operations at the World Health Organization, outlined the potential impact of the shortage on healthcare providers and clinical laboratories. “Without the ability to identify pathogens or [their susceptibility to specific antibiotics], patients may remain on broad antibiotics, increasing the risk of antibiotic resistance and Clostridium difficile-associated diarrhea,” she told STAT. “Shortages may also discourage ordering blood cultures, leading to missed infections that need treatment.” (Photo copyright: Loyola University Health System.)
FDA Advises Conservation of Existing BACTEC Supplies
The CDC advisory followed a July 10 notice from the US Food and Drug Administration (FDA) that also warned healthcare providers of “interruptions in the supply” of the bottles. The supply disruption “is expected to impact patient diagnosis, follow up patient management, and antimicrobial stewardship efforts,” the FDA’s letter states. “The FDA recommends laboratories and healthcare providers consider conservation strategies to prioritize the use of blood culture media bottles, preserving the supply for patients at highest risk.”
Hospitals have been warned that the bottle shortage could last until September, STAT reported.
BD issued a press release in which BD Worldwide Diagnostic Solutions President Nikos Pavlidis cast blame for the shortage on an unnamed supplier.
“We understand the critical role that blood culture testing plays in diagnosing and treating infections and are taking all available measures to address this important issue, including providing the supplier our manufacturing expertise, using air shipments, modifying BD manufacturing schedules for rapid production, and collaborating with the US Food and Drug Administration to review all potential options to mitigate delays in supply,” Pavlidis said. “As an additional stopgap measure, our former supplier of glass vials will restart production to help fill the intermittent gap in supply.”
Steps Clinical Laboratories Can Take
The CDC and FDA both suggested steps that clinical laboratories and other providers can take to conserve their supplies of the bottles.
Laboratories should strive to prevent contamination of blood cultures, which “can negatively affect patient care and may require the collection of more blood cultures to help determine whether contamination has occurred,” the CDC advised.
In addition, providers should “ensure that the appropriate volume is collected when collecting blood for culture,” the advisory states. “Underfilling bottles decreases the sensitivity to detect bacteremia/fungemia and may require additional blood cultures to be drawn to diagnose an infection.”
Laboratories should also explore alternative options, such as “sending samples out to a laboratory not affected by the shortage.”
The FDA advised providers to collect blood cultures “when medically necessary” in compliance with clinical guidelines, giving priority to patients exhibiting signs of a bloodstream infection.
In an email to STAT, Andrew T. Pavia, MD, Professor of Internal Medicine and Pediatrics at the University of Utah, offered examples of situations where blood culture tests are unnecessary according to clinical guidelines.
“There are conditions like uncomplicated community acquired pneumonia or skin infections where blood cultures are often obtained but add very little,” he told STAT. “It will be critical though that blood cultures are obtained from patients with sepsis, those likely to have bloodstream infections, and very vulnerable patients.”
Hospitals Already Addressing Shortage
STAT reported that some hospitals have already taken measures to reduce the number of tests they run. And some are looking into whether they can safely use bottles past their expiration dates.
Sarah Turbett, MD, Associate Director of Clinical Microbiology Laboratories at Massachusetts General Hospital in Boston, told STAT that her team tested bottles “that were about 100 days past their expiration date to see if they were still able to detect pathogens with the same efficacy as bottles that had not yet expired. They saw no difference in the time to bacterial growth—needed to detect the cause of an infection—in the expired bottles when compared to bottles that had not expired.”
Turbett pointed to a letter in the Journal of Clinical Microbiology and Infection in which European researchers found that bottles from a different brand “were stable for between four and seven months after their expiration dates,” STAT reported.
During a Zoom call hosted by the CDC and the IDSA, hospital representatives asked if the FDA would permit use of expired bottles. However, “a representative of the agency was not able to provide an immediate answer,” STAT reported.
With sepsis being the leading cause of death in hospitals, these specimen bottles for blood culture testing are essential in diagnosing patients with relevant symptoms. This is a new example of how the supply chain for clinical laboratory instruments, tests, and consumables—which was a problem during the SARS-CoV-2 pandemic—continues to be problematic in unexpected ways.
Taking a wider view of supply chain issues that can be disruptive to normal operations of clinical laboratories and anatomic pathology groups, the market concentration of in vitro diagnostics (IVD) manufacturers means fewer vendors offering the same types of products. Consequently, if a lab’s prime vendor has a supply chain issue, there are few options available to swiftly purchase comparable products.
A separate but related issue in the supply chain involves “just in time” (JIT) inventory management—made famous by Taiichi Ohno of Toyota back in the 1980s. This management approach was designed to deliver components and products to the user hourly, daily, and weekly, as appropriate. The goal was to eliminate the cost of carrying large amounts of inventory. This concept evolved into what today is called the “Lean Manufacturing” method.
However, as was demonstrated during the SARS-CoV-2 pandemic, manufacturers and medical laboratories that had adopted JIT found themselves with inadequate numbers of components and finished products.
In the case of the current shortage of BD blood culture media bottles, this is a real-world example of how market concentration limited the number of vendors offering comparable products. At the same time, if this particular manufacturer was operating with the JIT inventory management approach, it found itself with minimal inventories of these media bottles to ship to lab clients while it addressed the manufacturing problems that caused this shortage.
Study results from Switzerland come as clinical laboratory scientists seek new ways to tackle the problem of antimicrobial resistance in hospitals
Microbiologists and clinical laboratory scientists engaged in the fight against antibiotic-resistant (aka, antimicrobial resistant) bacteria will be interested in a recent study conducted at the University of Basel and University Hospital Basel in Switzerland. The epidemiologists involved in the study discovered that some of these so-called “superbugs” can remain in the body for as long as nine years continuing to infect the host and others.
The researchers wanted to see how two species of drug-resistant bacteria—K. pneumoniae and E. coli—changed over time in the body, according to a press release from the university. They analyzed samples of the bacteria collected from patients who were admitted to the hospital over a 10-year period, focusing on older individuals with pre-existing conditions. They found that K. pneumoniae persisted for up to 4.5 years (1,704 days) and E. coli persisted for up to nine years (3,376 days).
“These patients not only repeatedly become ill themselves, but they also act as a source of infection for other people—a reservoir for these pathogens,” said Lisandra Aguilar-Bultet, PhD, the study’s lead author, in the press release.
“This is crucial information for choosing a treatment,” explained Sarah Tschudin Sutter, MD, Head of the Division of Infectious Diseases and Hospital Epidemiology, and of the Division of Hospital Epidemiology, who specializes in hospital-acquired infections and drug-resistant pathogens. Sutter led the Basel University study.
“The issue is that when patients have infections with these drug-resistant bacteria, they can still carry that organism in or on their bodies even after treatment,” said epidemiologist Maroya Spalding Walters, MD (above), who leads the Antimicrobial Resistance Team in the Division of Healthcare Quality Promotion at the federal Centers for Disease Control and Prevention (CDC). “They don’t show any signs or symptoms of illness, but they can get infections again, and they can also transmit the bacteria to other people.” Clinical laboratories working with microbiologists on antibiotic resistance will want to follow the research conducted into these deadly pathogens. (Photo copyright: Centers for Disease Control and Prevention.)
COVID-19 Pandemic Increased Antibiotic Resistance
The Basel researchers looked at 76 K. pneumoniae isolates recovered from 19 patients and 284 E. coli isolates taken from 61 patients, all between 2008 and 2018. The study was limited to patients in which the bacterial strains were detected from at least two consecutive screenings on admission to the hospital.
“DNA analysis indicates that the bacteria initially adapt quite quickly to the conditions in the colonized parts of the body, but undergo few genetic changes thereafter,” the Basel University press release states.
The researchers also discovered that some of the samples, including those from different species, had identical mechanisms of drug resistance, suggesting that the bacteria transmitted mobile genetic elements such as plasmids to each other.
One limitation of the study, the authors acknowledged, was that they could not assess the patients’ exposure to antibiotics.
Meanwhile, recent data from the World Health Organization (WHO) suggests that the COVID-19 pandemic might have exacerbated the challenges of antibiotic resistance. Even though COVID-19 is a viral infection, WHO scientists found that high percentages of patients hospitalized with the disease between 2020 and 2023 received antibiotics.
“While only 8% of hospitalized patients with COVID-19 had bacterial co-infections requiring antibiotics, three out of four or some 75% of patients have been treated with antibiotics ‘just in case’ they help,” the WHO stated in a press release.
WHO uses an antibiotic categorization system known as AWaRe (Access, Watch, Reserve) to classify antibiotics based on risk of resistance. The most frequently prescribed antibiotics were in the “Watch” group, indicating that they are “more prone to be a target of antibiotic resistance and thus prioritized as targets of stewardship programs and monitoring.”
“When a patient requires antibiotics, the benefits often outweigh the risks associated with side effects or antibiotic resistance,” said Silvia Bertagnolio, MD, Unit Head in the Antimicrobial resistance (AMR) Division at the WHO in the press release. “However, when they are unnecessary, they offer no benefit while posing risks, and their use contributes to the emergence and spread of antimicrobial resistance.”
Citing research from the National Institutes of Health (NIH), NPR reported that in the US, hospital-acquired antibiotic-resistant infections increased 32% during the pandemic compared with data from just before the outbreak.
“While that number has dropped, it still hasn’t returned to pre-pandemic levels,” NPR noted.
The UPenn researchers have already developed an antimicrobial treatment derived from guava plants that has proved effective in mice, Vox reported. They’ve also trained an AI model to scan the proteomes of extinct organisms.
“The AI identified peptides from the woolly mammoth and the ancient sea cow, among other ancient animals, as promising candidates,” Vox noted. These, too, showed antimicrobial properties in tests on mice.
These findings can be used by clinical laboratories and microbiologists in their work with hospital infection control teams to better identify patients with antibiotic resistant strains of bacteria who, after discharge, may show up at the hospital months or years later.
