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Washington University Researchers Uses Medical Laboratory Test Results and Big Data to Find Accelerated Aging and Risk of Early Cancer in Young Adults

Study shows that computer analysis of clinical laboratory test results has improved greatly in recent years

Studies using “big data” continue to show how combining different types of healthcare information can generate insights not available with smaller datasets. In this case, researchers at Washington University School of Medicine (WashU Medicine), St. Louis, Mo., determined that—by using the results from nine different types of clinical laboratory tests—they could correlate those test results to younger people who had “aged faster” and had developed cancer earlier than usual, according to CNN.

“Accumulating evidence suggests that the younger generations may be aging more swiftly than anticipated, likely due to earlier exposure to various risk factors and environmental insults. However, the impact of accelerated aging on early-onset cancer development remains unclear,” said Ruiyi Tian, PhD candidate at WashU Medicine’s Yin Cao Lab in an American Association for Cancer Research (AACR) news release.

The scientists presented their findings, which have not yet been published, at the AACR’s annual meeting held in April. Tian and the other researchers “hypothesized that increased biological age, indicative of accelerated aging, may contribute to the development of early-onset cancers, often defined as cancers diagnosed in adults younger than 55 years. In contrast to chronological age—which measures how long a person has been alive—biological age refers to the condition of a person’s body and physiological processes and is considered modifiable,” AACR noted in a news release.

“We all know cancer is an aging disease. However, it is really coming to a younger population. So, whether we can use the well-developed concept of biological aging to apply that to the younger generation is a really untouched area,” Yin Cao, ScD MPH (above), associate professor of surgery and associate professor of medicine at Washington University School of Medicine in St. Louis, and senior author of the study, told CNN. Analysis of clinical laboratory test results using computer algorithms continues to show value for new research into deadly diseases. (Photo copyright: Washington University.)

Lab Tests Share Insights about Aging

To acquire the data they needed for their research, the WashU Medicine scientists turned to the UK Biobank, a biomedical and research resource with genetic and health information on half a million UK residents.

The researchers reviewed the medical records of 148,724 biobank participants, age 37 to 54, focusing on nine blood-based biomarkers that “have been shown to correlate with biological age,” CNN reported. Those biomarkers are:

According to CNN, the researchers “plugged” the nine values into an algorithm called PhenoAge. Using the algorithm they compared the biological ages with each person’s actual chronological age to determine “accelerated aging.” They then consulted cancer registries to capture data on those in the study who were diagnosed with cancer before age 55. They found 3,200 cases.

Young Adults Aging Faster than Earlier Generations

According to the AACR news release, the WashU Medicine study found that:

  • “Individuals born in or after 1965 had a 17% higher likelihood of accelerated aging than those born between 1950 and 1954.
  • “Each standard deviation increase in accelerated aging was associated with a 42% increased risk of early-onset lung cancer, a 22% increased risk of early-onset gastrointestinal cancer, and a 36% increased risk of early-onset uterine cancer.
  • “Accelerated aging did not significantly impact the risk of late-onset lung cancer (defined here as cancer diagnosed after age 55), but it was associated with a 16% and 23% increased risk of late-onset gastrointestinal and uterine cancers, respectively.”

“We speculate that common pathways, such as chronic inflammation and cellular senescence, may link accelerated aging to the development of early-onset cancers,” the study’s principal investigator Yin Cao, ScD, MPH, associate professor of surgery and associate professor of medicine at WashU Medicine, told The Hill.

“Historically, both cancer and aging have been viewed primarily as concerns for older populations. The realization that cancer, and now aging, are becoming significant issues for younger demographics over the past decades was unexpected,” Tian told Fox News.

More Screenings, Further Analysis

The study’s results may suggest a change in clinical laboratory screenings for younger people.

“We see cancers earlier all the time now, and nobody knows why. The subset in the population that has accelerated aging may need screening more often or earlier,” Emanuela Taioli, MD, PhD, professor of population health and science and of thoracic surgery, and director of the Institute for Translational Epidemiology, Icahn School of Medicine at Mount Sinai, told Health.

In future studies, WashU Medicine scientists may aim to include groups of greater diversity and explore why people are aging faster and have risk of early-onset cancers. 

“There is room to improve using better technologies. Looking at the bigger picture, the aging concept can be applied to younger people to include cancers, cardiovascular disease, and diabetes,” Cao told Discover Magazine.

While more research is needed, use of the UK’s Biobank of healthcare data—including clinical laboratory test results—enabled the WashU Medicine researchers to determine that accelerated aging among young adults is happening with some regularity. This shows that capabilities in computer analysis are gaining more refined capabilities and are able to tease out insights impossible to achieve with earlier generations of analytical software.

These findings should inspire clinical laboratory professionals and pathologists to look for opportunities to collaborate in healthcare big data projects involving their patients and the communities they serve.

—Donna Marie Pocius

Related Information:

Accelerated Aging May Increase the Risk of Early-onset Cancers in Younger Generations

Accelerated Aging Linked to Cancer Risk in Younger Adults, Research Shows

An Epigenetic Biomarker of Aging for Lifespan and Health Span in Aging

Accelerated Aging May be a Cause of Increased Cancers in People under 55

Cancer Rates Rising in Young People Due to “Accelerated Aging,” New Study Finds

Research Shows Accelerated Aging Linked to Increased Cancer Risk in Younger Adults

Rate of Biological Aging is Accelerating in Young People, Leading to Medical Issues

Scathing Report from Former Health Minister Finds England’s NHS Plagued by Long Wait Times, Crumbling Infrastructure

Declining health of UK’s population also affecting performance of the country’s national health service, report notes

England’s National Health Service (NHS) is “in serious trouble” due to long waiting times, outdated technology, misallocated resources, and numerous other problems, with dire consequences for the country’s populace. That’s according to a new report by NHS surgeon and former Health Minister Lord Ara Darzi, OM KBE FRS FMedSci HonFREng, who was tasked by the United Kingdom’s new Labor government to investigate the ailing healthcare system. His report may contain lessons for US healthcare—including clinical laboratories—as well.

“Although I have worked in the NHS for more than 30 years, I have been shocked by what I have found during this investigation—not just in the health service but in the state of the nation’s health,” Darzi stated in a UK government press release. “We want to deliver high quality care for all but far too many people are waiting for too long and in too many clinical areas, quality of care has gone backwards.”

Many of the problems he identified relate to wait times.

“From access to GPs (general practitioners) and to community and mental health services, on to accident and emergency, and then to waits not just for more routine surgery and treatment but for cancer and cardiac services, waiting time targets are being missed,” he wrote in his report.

For example, “as of June 2024, more than one million people were waiting for community services, including more than 50,000 people who had been waiting for over a year, 80% of whom are children and young people,” he wrote.

Accident and emergency care (A/E) “is in an awful state,” the report noted, “with A/E queues more than doubling from an average of just under 40 people on a typical evening in April 2009 to over 100 in April 2024. One in 10 patients are now waiting for 12 hours or more.”

“In the last 15 years, the NHS was hit by three shocks—austerity and starvation of investment, confusion caused by top-down reorganization, and then the pandemic which came with resilience at an all-time low. Two out of three of those shocks were choices made in Westminster,” said NHS surgeon and former Health Minister Lord Ara Darzi in a government press release. “It took more than a decade for the NHS to fall into disrepair so it’s going to take time to fix it. But we in the NHS have turned things around before, and I’m confident we will do it again.” (Photo copyright: Health Data Research UK.)

Delays in Other Critical Tests

Genetic test results are lagging as well. “In 2024, more than 35,000 genomic tests are being completed each month but only around 60% on time,” Darzi wrote.

He also noted that “only around 5% of eligible patients with brain cancer are able to access whole genome sequencing (WGS), which is important for treatment selection.” Just two-thirds (65.8%) get their first treatment within 62 days, and more than 30% wait more than 31 days for radical radiotherapy, according to the report.

Overall, “the UK has appreciably higher cancer mortality rates than other countries, with no progress whatsoever made in diagnosing cancer at stage one and two between 2013 and 2021,” he wrote.

Patients have also experienced delays in access to cardiovascular treatment. For example, in 2013-2014, high-risk heart attack patients waited an average of 114 minutes for intervention to unblock an artery, Darzi noted in his report. However, in 2022-2023, the average time was 146 minutes, a 28% increase.

“For the most part, once people are in the system, they receive high quality care,” he wrote. “But there are some important areas of concerns, such as maternity care, where there have been a succession of scandals and inquiries.”

Key Factors Leading to Delays

Darzi pointed to four key factors that have led to the problems.

Lack of funding. “The 2010s was the most austere decade since the NHS was founded, with spending growing at around 1% in real terms,” Darzi wrote, compared with a long-term average of 3.4%.

One result was that administrators took funds from the capital budget to cover day-to-day needs, leading to “crumbling buildings that hit productivity,” he noted.

“The backlog maintenance bill now stands at more than £11.6 billion and a lack of capital means that there are too many outdated scanners, too little automation, and parts of the NHS are yet to enter the digital era,” he wrote.

The COVID-19 pandemic. Given the preceding “decade of austerity,” NHS had fewer resources to deal with the crisis than most other high-income health systems, he wrote. As a result, NHS “delayed, cancelled, or postponed far more routine care during the pandemic than any comparable health system.” This led to “a bigger backlog than other health systems.”

Lack of patient and staff engagement. Patient satisfaction “has declined and the number of complaints has increased, while patients are less empowered to make choices about their care,” he wrote. In addition, “too many staff have become disengaged, and there are distressingly high-levels of sickness absence—as much as one working month a year for each nurse and each midwife working in the NHS.”

Management structures and systems. Darzi laid considerable blame on the UK’s Health and Social Care Act of 2012, which led to what he described as “a costly and distracting process of almost constant reorganization of the ‘headquarters’ and ‘regulatory’ functions of the NHS.”

One consequence, he wrote, is that too many clinicians have been deployed in hospitals instead of community-based care, despite years of promises by successive governments to put more emphasis on the latter.

National Health in Decline

Along with issues within the NHS, “the health of the nation has deteriorated and that impacts its performance,” Darzi wrote. “There has been a surge in multiple long-term conditions, and, particularly among children and young people, in mental health needs. Fewer children are getting the immunizations they need to protect their health, and fewer adults are participating in some of the key screening programs, such as for breast cancer.”

Darzi’s investigation included frontline visits to NHS facilities as well as focus groups with NHS staff and patients, the press release states. He also consulted an expert reference group consisting of more than 70 organizations and examined analyses from NHS England, the UK’s Department of Health and Social Care, and external groups.

It is interesting that there is no mention of anatomic pathology and medical laboratory testing services in Lord Darzi’s report. As reported in recent years by new outlets in the United Kingdom, delays in cancer diagnoses—often as long as six months—were severe enough that, in 2018, the NHS announced funding for a program to create a national digital pathology network to improve productivity of pathologists and shorten wait times for the results of cancer tests.

—Stephen Beale

Related Information:

The NHS Is in ‘Serious Trouble’ and Needs Major Reform – Here Are the Pitfalls the Government Must Avoid

‘Major Surgery, Not Sticking Plaster Solutions’ Needed to Rebuild NHS

Independent Investigation of the National Health Service in England

No Extra NHS Funding without Reform, Says PM

No More Money for NHS Without Reform, Says Starmer As He Outlines Vision for Health Service

Long NHS Delays in England Leading to Thousands of Unnecessary Deaths, Inquiry Finds

NHS Is Broken but No Extra Funding without Reform, Starmer Says

The Left Must Accept NHS Reform or It Will Die, Says Streeting

Welsh and UK Government to Co-Operate on NHS Reform

Keir Starmer Says UK’s NHS Needs to ‘Reform or Die’

Welsh NHS Needs Reform, Keir Starmer Says

National Institutes of Health Study Finds No Reliable Biomarkers Exist for Long COVID

Study is another example of how important clinical laboratory testing is when government officials attack a new public health issue

Long COVID—aka SARS-CoV-2 infection’s post-acute sequelae (PASC)—continues to confound researchers seeking one or more clinical laboratory biomarkers for diagnosing the condition. A new study led by the National Institutes of Health’s (NIH) RECOVER Initiative and supported by NYU Langone Health recently revealed that “routine clinical laboratory tests were unable to provide a reliable biomarker of … long COVID,” Inside Precision Medicine reported.

The NIH’s Researching COVID to Enhance Recovery (RECOVER) Initiative used a cohort study of more than 10,000 individuals with and without previous COVID-19 diagnoses and compared samples using 25 common laboratory tests in hopes a useful biomarker could be identified. They were unsuccessful.

Leora Horwitz, MD, director of the Center for Healthcare Innovation and Delivery Science and co-principal investigator for the RECOVER CSC (Clinical Science Core) at NYU Langone; Andrea S. Foulkes, ScD, director of biostatistics at Massachusetts General Hospital, Boston; and Grace A. McComsey, MD, VP of research and associate chief scientific officer at University Hospitals Health System, and professor of pediatrics and medicine at Case Western Reserve University, led the study.

Long COVID—or PASC—is an umbrella term for those with persistent post-COVID infection symptoms that negatively impact quality of life. Though it affects millions worldwide and has been called a major public health burden, the NIH/Langone study scientists noted one glaring problem: PASC is defined differently in the major tests they studied. This makes consistent diagnoses difficult.

The study brought to light possible roadblocks that prevented biomarker identification.

“Although potential models of pathogenesis have been postulated, including immune dysregulation, viral persistence, organ injury, endothelial dysfunction, and gut dysbiosis, there are currently no validated clinical biomarkers of PASC,” the study authors wrote in their study, “Differentiation of Prior SARS-CoV-2 Infection and Postacute Sequelae by Standard Clinical Laboratory Measurements in the RECOVER Cohort,” published in the journal Annals of Internal Medicine.

“This study is an important step toward defining long COVID beyond any one individual symptom,” said study author Leora Horwitz, MD (above), director of the Center for Healthcare Innovation and Delivery Science and co-principal investigator for the RECOVER CSC at NYU Langone, in a Langone Health news release. “This definition—which may evolve over time—will serve as a critical foundation for scientific discovery and treatment design.” In the future, clinical laboratories may be tasked with finding combinations of routine and reference tests that, together, enable a more precise and earlier diagnosis of long COVID.  (Photo copyright: Yale School of Medicine.)

NIH/Langone Study Details

“The study … examined 25 routinely used and standardized laboratory tests chosen based on availability across institutions, prior literature, and clinical experience. These tests were conducted prospectively in laboratories that are certified by the Clinical Laboratory Improvement Amendments (CLIA). The samples were collected from 10,094 RECOVER-Adult participants, representing a diverse cohort from all over the US,” Inside Precision Medicine reported.

However, the scientists found no clinical laboratory “value” among the 25 tests examined that “reliably indicate previous infection, PASC, or the particular cluster type of PASC,” Inside Precision Medicine noted, adding that “Although some minor differences in the results of specific laboratory tests attempted to differentiate between individuals with and without a history of infection, these findings were generally clinically meaningless.”

“In a cohort study of more than 10,000 participants with and without prior SARS-CoV-2 infection, we found no evidence that any of 25 routine clinical laboratory values provide a reliable biomarker of prior infection, PASC, or the specific type of PASC cluster. … Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC,” the study authors wrote in Annals of Internal Medicine.

In addition to a vague definition of PASC, the NIH/Langone researchers noted a few other potential problems identifying a biomarker from the research.

“Use of only selected biomarkers, choice of comparison groups, if any (people who have recovered from PASC or healthy control participants); duration of symptoms; types of symptoms or phenotypes; and patient population features, such as sex, age, race, vaccination status, comorbidities, and severity of initial infection,” could be a cause for ambiguous results, the scientists wrote.

Future Research

“Understanding the basic biological underpinnings of persistent symptoms after SARS-CoV-2 infection will likely require a rigorous focus on investigations beyond routine clinical laboratory studies (for example, transcriptomics, proteomics, metabolomics) to identify novel biomarkers,” the study authors wrote in Annals of Internal Medicine.

“Our challenge is to discover biomarkers that can help us quickly and accurately diagnose long COVID to ensure people struggling with this disease receive the most appropriate care as soon as possible,” said David Goff, MD, PhD, director of the division of cardiovascular sciences at the NIH’s National Heart, Lung, and Blood Institute, in an NHLBI news release. “Long COVID symptoms can prevent someone from returning to work or school, and may even make everyday tasks a burden, so the ability for rapid diagnosis is key.”

“Approximately one in 20 US adults reported persisting symptoms after COVID-19 in June 2024, with 1.4% reporting significant limitations,” the NIH/Langone scientists wrote in their published study.

Astute clinical laboratory scientists will recognize this as possible future diagnostic testing. There is no shortage of need.

—Kristin Althea O’Connor

Related Information:

“Long COVID” Evades Common SARS-CoV-2 Clinical Lab Tests

Differentiation of Prior SARS-CoV-2 Infection and Postacute Sequelae by Standard Clinical Laboratory Measurements in the RECOVER Cohort

Long COVID Diagnostics: An Unconquered Challenge

RECOVER Study Offers Expanded Working Definition of Long COVID

Routine Lab Tests Are Not a Reliable Way to Diagnose Long COVID

Broad Institute of MIT and Harvard Studies Use of Polygenic Risk Scores to Evaluate Genetic Risk for 10 Diseases

Though not biomarkers per se, these scores for certain genetic traits may someday be used by clinical laboratories to identify individuals’ risk for specific diseases

Can polygenic risk scores (a number that denotes a person’s genetic predisposition for certain traits) do a better job at predicting the likelihood of developing specific diseases, perhaps even before the onset of symptoms? Researchers at the Broad Institute of MIT and Harvard (Broad Institute) believe so, and their study could have implications for clinical laboratories nationwide.

In cooperation with medical centers across the US, the scientists “optimized 10 polygenic scores for use in clinical research as part of a study on how to implement genetic risk prediction for patients,” according to a Broad Institute news release.

The research team “selected, optimized, and validated the tests for 10 common diseases [selected from a total of 23 conditions], including heart disease, breast cancer, and type 2 diabetes. They also calibrated the tests for use in people with non-European ancestries,” the news release notes.

As these markers for genetic risk become better understood they may work their way into clinical practice. This could mean clinical laboratories will have a role in sequencing patients’ DNA to provide physicians with information about the probability of a patient’s elevated genetic risk for certain conditions.

However, the effectiveness of polygenic risk scores has faced challenges among diverse populations, according to the news release, which also noted a need to appropriately guide clinicians in use of the scores.

The researchers published their study, “Selection, Optimization and Validation of 10 Chronic Disease Polygenic Risk Scores for Clinical Implementation in Diverse US Populations,” in Nature Medicine.

“With this work, we’ve taken the first steps toward showing the potential strength and power of these scores across a diverse population,” said Niall Lennon, PhD (above), Chief Scientific Officer of Broad Clinical Labs.  “We hope in the future this kind of information can be used in preventive medicine to help people take actions that lower their risk of disease.” Clinical laboratories may eventually be tasked with performing DNA sequencing to determine potential genetic risk for certain diseases. (Photo copyright: Broad Institute.)

Polygenic Scores Need to Reflect Diversity

“There have been a lot of ongoing conversations and debates about polygenic risk scores and their utility and applicability in the clinical setting,” said Niall Lennon, PhD, Chair and Chief Scientific Officer of Broad Clinical Labs and first author of the study, in the news release. However, he added, “It was important that we weren’t giving people results that they couldn’t do anything about.”

In the paper, Lennon and colleagues explained polygenic risk scores “aggregate the effects of many genetic risk variants” to identify a person’s genetic predisposition for a certain disease or phenotype.

“But their development and application to clinical care, particularly among ancestrally diverse individuals, present substantial challenges,” they noted. “Clinical use of polygenic risk scores may ultimately prevent disease or enable its detection at earlier, more treatable stages.” 

The scientists set a research goal to “optimize polygenic risk scores for a diversity of people.”

They collaborated with the Electronic Medical Records and Genomics network (eMERGE) and 10 academic medical centers that enrolled 25,000 participants in the eMERGE study. Funded by the National Human Genome Research Institute of the National Institutes of Health (NIH), the eMERGE network conducts genetic research in support of genetic medicine. 

While performing the polygenic risk score testing on participants, Broad Clinical Labs focused on 10 conditions—including cardiometabolic diseases and cancer—selected by the research team based on “polygenic risk score performance, medical actionability, and clinical utility,” the Nature Medicine paper explained. 

For each condition, the researchers:

  • Identified “exact spots in the genome that they would analyze to calculate the risk score.”
  • Verified accurate genotyping of the spots by comparing results of tests with whole genome sequences from patient blood samples.
  • Used information from the NIH’s All of Us Research Program to “create a model to calibrate a person’s polygenic risk score according to that individual’s genetic ancestry.”

The All of Us program, which aims to collect health information from one million US residents, has three times more people of non-European ancestry than other data sources developing genetic risk scores, HealthDay News reported.

20% of Study Participants Showed High Risk for Disease

To complete their studies, Broad Institute researchers processed a diverse group of eMERGE participants to determine their clinical polygenic risk scores for each of the 10 diseases between July 2022 and August 2023.

Listed below are all conditions studied, as well as the number of participants involved in each study and the number of people with scores indicating high risk of the disease, according to their published paper:

Over 500 people (about 20%) of the 2,500 participants, had high risk for at least one of the 10 targeted diseases, the study found. 

Participants in the study self-reported their race/ancestry as follows, according to the paper:

  • White: 32.8%
  • Black: 32.8%
  • Hispanic: 25.4%
  • Asian: 5%
  • American Indian: 1.5%
  • Middle Eastern: 0.9%
  • No selection: 0.8%

“We can’t fix all biases in the risk scores, but we can make sure that if a person is in a high-risk group for a disease, they’ll get identified as high risk regardless of what their genetic ancestry is,” Lennon said.

Further Studies, Scoring Implications

With 10 tests in hand, Broad Clinical Labs plans to calculate risk scores for all 25,000 people in the eMERGE network. The researchers also aim to conduct follow-up studies to discover what role polygenic risk scores may play in patients’ overall healthcare.

“Ultimately, the network wants to know what it means for a person to receive information that says they’re at high risk for one of these diseases,” Lennon said.

The researchers’ findings about disease risk are likely also relevant to healthcare systems, which want care teams to make earlier, pre-symptomatic diagnosis to keep patients healthy.

Clinical laboratory leaders may want to follow Broad Clinical Labs’ studies as they perform the 10 genetic tests and capture information about what participants may be willing to do—based on risk scores—to lower their risk for deadly diseases.

—Donna Marie Pocius

Related Information:

Genetic Risk Prediction for 10 Chronic Diseases Moves Closer to the Clinic

Selection, Optimization, and Validation of 10 Chronic Disease Polygenic Risk Scores for Clinical Implementation in Diverse US Populations

Gene-Based Tests Could Predict Your Odds for Common Illnesses

ECRI Study Finds Errors During Testing Processes Are Responsible for Most Diagnostic Errors

Researchers note that many sources of errors associated with diagnostic testing involve how providers order tests and how specimens are handled

ECRI (Emergency Care Research Institute), a non-profit organization that focuses on healthcare quality and patient safety, has released results from a study which lays blame for most diagnostic errors on systemic issues that arise during clinical laboratory, radiology, and other diagnostic testing processes. These issues relate to “ordering, collecting, processing, obtaining results, or communicating results,” the organization stated in a news release.

“It’s a common misconception that if a patient has a missed or incorrect diagnosis, their doctor came up with the wrong hypothesis after having all the facts,” said ECRI President and CEO Marcus Schabacker MD, PhD, in the news release. “That does happen occasionally, but we found that was tied to less than 3% of diagnostic errors. What’s more likely to break the diagnostic process are technical, administrative, and communication-related issues. These represent system failures, where many small mistakes lead to one big mistake.”

The researchers based their analysis on reports of adverse patient safety events and “near-misses” submitted to ECRI and the Institute for Safe Medication Practices (ISMP) in 2023. Healthcare providers submitted the data from across the US, ECRI noted.

From a total of 3,014 patient safety events, ECRI determined that 1,011 were related to diagnostic errors. Then, it sorted the events based on “the appropriate step in the diagnostic process where the breakdown occurred,” according to the news release.

ECRI did not reveal how many errors were related to clinical laboratory testing as opposed to radiological or ultrasound imaging.

“The problem of diagnostic safety comes down to the lack of a systems-based approach,” said ECRI President and CEO Marcus Schabacker MD, PhD (above), in a news release. “Since there are multiple potential failure points, a single intervention is insufficient.” Diagnostic errors can also include imaging/radiology and other types of diagnostic procedures—not just clinical laboratory tests. (Photo copyright: ECRI.)

Where Errors Occur

According to ECRI’s analysis, the largest number of errors by far (nearly 70%) happened during the clinical laboratory testing process. Among these, “more than 23% were a result of a technical or processing error, like the misuse of testing equipment, a poorly processed specimen, or a clinician lacking the proper skill to conduct the test,” ECRI stated. “Another 20% of testing errors were a result of mixed-up samples, mislabeled specimens, and tests performed on the wrong patient.”

Outside the testing process, other errors occurred during monitoring and follow-up (12%) and during referral and consultation (9%).

One major factor behind diagnostic errors, ECRI noted, was miscommunication among providers and between providers and patients.

The organization also cited “productivity pressures that prevent providers from exploring all investigative options or from consulting other providers” as leading to diagnostic errors.

In some cases, providers who ordered lab tests delayed reviewing the results or the patients were not notified of the results.

“Referrals to specialists or requests for additional consultations can complicate the process, presenting more potential failure points,” ECRI noted.

Troubling Imaging Anecdotes, Previous Studies

The ECRI news release cites two de-identified patient stories, both related to imaging. One case involved a woman who “experienced abdominal pain and abnormal vaginal bleeding,” but a diagnosis of uterine cancer was delayed nearly a year. “MRIs were ordered, but not all the results were reviewed, as her symptoms worsened. Despite masses being detected on an ultrasound, a missed appointment and communication barriers delayed her diagnosis. She was finally diagnosed after severe pain led to hospitalization.”

In one “near-miss” incident, a patient did not receive an essential carotid ultrasound procedure prior to being scheduled for open-heart surgery. Staff caught the omission and canceled the surgery. A later ultrasound “revealed he would have had a catastrophic surgical outcome if the surgery had proceeded as scheduled,” ECRI stated.

Two earlier studies noted in the news release highlight the impact of diagnostic errors.

A 2017 study, published in the journal BMJ Quality Safety, estimated that diagnostic errors affect approximately 5% of US adults—a total of 12 million—each year. In that paper, the authors combined estimates from three observational studies that defined diagnostic error in similar ways.

“Based upon previous work, we estimate that about half of these errors could potentially be harmful,” the authors wrote.

And a 2024 study published in the same journal estimated that 795,000 Americans die or become permanently disabled each year due to misdiagnosis of dangerous diseases. “Just 15 diseases account for about half of all serious harms, so the problem may be more tractable than previously imagined,” the authors wrote.

Recommendations for Providers, Labs

ECRI advised that healthcare providers should adopt a “total systems safety approach and human-factors engineering” to reduce diagnostic errors. This is good advice for clinical laboratories as well.

Specific steps should include “integrating EHR workflows, optimizing testing processes, tracking results, and establishing multidisciplinary diagnostic management teams to analyze safety events,” the news release states.

Schabacker also advised patients to “ask questions to understand why their doctor is ordering tests, and are those tests urgent,” he said. “Schedule your appointments and tests quickly and follow up with your provider if you’re awaiting results. If possible, ask a family member or friend to join you in important appointments, to help ask questions and take notes.”

Clinical laboratory managers have been alerted to the involvement of lab testing in incidents of medical errors. This report by ECRI is more evidence of the gaps in care delivery that often contribute to medical error. Medical lab professionals may want to review the ECRI report to learn more about what the authors identify as the specific breakdowns in care processes that contribute to medical errors.

—Stephen Beale

Related Information:

Data Analysis Reveals Common Errors That Prevent Patients from Getting Timely, Accurate Diagnoses

Nearly 70% of Diagnostic Errors Occur During Testing: ECRI

Errors within the Total Laboratory Testing Process, from Test Selection to Medical Decision-Making – A Review of Causes, Consequences, Surveillance and Solutions

Burden of Serious Harms from Diagnostic Error in the USA

South Korean Study Finds Fecal Microbiota Transplants May Help Patients with Gastrointestinal Cancers That are Resistant to Immunotherapies

Study findings could lead to improved treatments for broad range of cancers and the need for microbiome testing by clinical laboratories to guide clinicians

Is it possible that there is a connection between an individual’s gut microbiota and the ability to fight off gastrointestinal (GI) cancer? Findings from a preliminary research study performed by researchers in South Korea suggest that a link between the two may exist and that fecal microbiota transplants (FMTs) may enhance the efficacy of immunotherapies for GI cancer patients. 

The proof-of-concept clinical trial, conducted at the Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Republic of Korea, analyzed how an FMT could help 13 patients with metastatic solid tumors that were resistant to the anti-PD-1 antibody drug known as nivolumab (Opdivo). Anti-PD-1 drugs are immunotherapies that help treat cancer by improving an individual’s immune response against cancer cells. 

Four of the trial participants had gastric cancer, five had esophageal cancer, and the remaining four had hepatocellular carcinoma. The patients were given a colonoscopy to implant the FMTs. The recipients also received antibiotics to reduce the response of their existing microbiotas.

The FMT donors also had gastric cancer, esophageal cancer, or hepatocellular carcinoma. Prior to donating their fecal matter, the donors experienced complete or partial response to the anti-PD-1 drugs nivolumab or pembrolizumab (Keytruda) for at least six months after receiving initial treatments. 

The researchers published their study, titled, “Fecal Microbiota Transplantation Improves Anti-PD-1 Inhibitor Efficacy in Unresectable or Metastatic Solid Cancers Refractory to Anti-PD-1 Inhibitor,” in the journal Cell Host and Microbe.

“This research highlights the complex interplay between beneficial and detrimental bacteria within the gut microbiota in determining treatment outcomes,” co-senior study author Hansoo Park, MD, PhD, Assistant Professor, Biomedical Science and Engineering, Gwangju Institute of Science and Technology, told The ASCO Post. “While the connection between gut microbiota and immune response to cancer therapy has been a growing area of interest, our study provides concrete evidence and new avenues for improving treatment outcomes in a broader range of cancers,” he added. Further studies may confirm the need for microbiome testing by clinical laboratories to guide clinicians treating patients with colon cancers. (Photo copyright: Gwangju Institute of Science and Technology.)

Surprising Results

Fecal material for an FMT procedure combines donated fecal matter with a sterile saline solution which is then filtered to produce a liquid solution. That solution is then administered to the recipient via colonoscopy, upper GI endoscopy, enema, or an oral capsule. The solution may also be frozen for later use.

Upon analyzing the recipients, the scientists found that six of the patients (46.2%) who had experienced resistance to immunotherapies for their cancers, benefitted from the FMTs.

“One of the most surprising results was from a [patient with] hepatocellular carcinoma who initially showed no response to the first [FMT] and continued to experience cancer progression. However, after switching the donor for the second [transplant], the patient exhibited remarkable tumor shrinkage,” co-senior study author Sook Ryun Park, MD, PhD, Assistant Professor, Asan Medical Center at the University of Ulsan College of Medicine in Seoul, told The ASCO Post, a journal of the American Society of Clinical Oncology.

“Both donors were long-lasting, good responders to anti-PD-1 inhibitors, but because we did not yet know the causative bacteria responsible for the [FMT] response, we could not predict whether the treatment would be effective,” she added.

The researchers also determined that the presence of a bacterial strain known as Prevotella merdae helped to improve the effectiveness of the FMTs, while two strains of bacteria—Lactobacillus salivarius and Bacteroides plebeius (aka, Phocaeicola plebeius)—had a detrimental impact on the transplants. 

Challenges to Widespread Adoption of FMTs

The researchers acknowledge there are challenges in widespread acceptance and use of FMTs in treating cancers but remain optimistic about the possibilities.

“Developing efficient and cost-effective methods for production and distribution is necessary for widespread adoption,” Sook Ryun Park told The ASCO Post. “Addressing these challenges through comprehensive research and careful planning will be essential for integrating FMT into the standard of care for cancer treatment.”

The research for this study was supported by grants from the Asan Institute for Life Sciences, Asan Medical Center, National Cancer Centre in Korea, the GIST Research Institute, the Bio and Medical Technology Development Program from Ministry of Science, and the Ministry of Science and ICT of the South Korean Government.

More research and clinical trials are needed before this use of FMTs can be utilized in clinical settings. However, the study does demonstrate that the potential benefits of FMTs may improve outcomes in patients with certain cancers. As this happens, microbiologists may gain a new role in analyzing the microbiomes of patients with gastrointestinal cancers.

“By examining the complex interactions within the microbiome, we hope to identify optimal microbial communities that can be used to enhance cancer treatment outcomes,” Hansoo Park told The ASCO Post. “This comprehensive approach will help us understand how the microbial ecosystem as a whole contributes to therapeutic success.”

—JP Schlingman

Related Information:

Fecal Microbiota Transplant May Help Patients with Gastrointestinal Cancers Overcome Immunotherapy Resistance

Fecal Microbiota Transplantation Improves Anti-PD-1 Inhibitor Efficacy in Unresectable or Metastatic Solid Cancers Refractory to Anti-PD-1 Inhibitor

Fecal Microbiota Transplants Can Boost the Effectiveness of Immunotherapy in Gastrointestinal Cancers

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