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Endocrine Society Releases New Guidelines Advising Physicians to Not Screen for Vitamin D, which Could Affect Test Referrals to Clinical Laboratories

New guidelines also advise people to limit their vitamin D supplementation to recommended daily doses

Clinical laboratories may eventually receive fewer doctors’ orders for vitamin D testing thanks to new guidelines released by the Endocrine Society. The new Clinical Practice Guideline advises against “unnecessary testing for vitamin D levels.” It also urges healthy people, and those 75-years of age or younger, to avoid taking the vitamin at levels above the daily recommended amounts, according to a news release.

The Society shared its recommendations at its annual meeting and in the Journal of Clinical Endocrinology and Metabolism titled, “Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline.”

Even though the Endocrine Society does recommend vitamin D supplements for certain groups, it advises individuals to hold off on routine testing. That’s because there appears to be uncertainty among ordering clinicians about what to do for patients based on their vitamin D test results.

“When clinicians measure vitamin D, they’re forced to decide what to do about it. That’s where questions about the levels come in. And that’s a big problem. So, what this panel is saying is ‘Don’t screen,’” Clifford Rosen, MD, Director of Clinical and Translational Research and Senior Scientist, Maine Medical Center Research Institute at the University of Maine, told Medscape Medical News.

“We have no data that there’s anything about screening that allows us to improve quality of life. Screening is probably not worthwhile in any age group,” he added.

“This guideline refers to people who are otherwise healthy, and there’s no clear indication for vitamin D, such as people with already established osteoporosis. This guideline is not relevant to them,” the author of the Endocrine Society guideline, Anastassios G. Pittas, MD (above), Professor of Medicine at Tufts University School of Medicine in Boston, told Medscape Medical News. This new guideline could result in doctors ordering fewer vitamin D tests from clinical laboratories. (Photo copyright: Tufts University.)

Vitamin D Screening Not Recommended for Certain Groups

The Endocrine Society’s new clinical guidelines advise healthy adults under 75 years of age to refrain from taking vitamin D supplements that exceed US Institute of Medicine—now the National Academy of Medicine (NAM)—recommendations.

Additionally, these updated guidelines:

  • Recommend vitamin D supplements at levels above NAM recommendations to help lower risks faced by children 18 years and younger, adults 75 and older, pregnant women, and people with prediabetes.
  • Suggest daily, lower-dose vitamin D (instead of non-daily, higher-dose of the vitamin) for people 50 years and older who have “indications for vitamin D supplementation or treatment.”
  • Advise “against routine testing for 25-hydroxyvitamin D [aka, calcifediol] levels” in all the above groups “since outcome-specific benefits based on these levels have not been identified. This includes 25-hyrdoxyvitamin D screening in people with dark complexion or obesity.”

One exception to the guideline applies to people with already established osteoporosis, according to the guideline’s author endocrinologist Anastassios G. Pittas, MD, Chief of Endocrinology, Diabetes and Metabolism; Co-Director, Tuft’s Diabetes and Lipid Center; and Professor of Medicine at Tufts University School of Medicine in Boston.

Vitamin D’s Link to Disease Studied

During a panel discussion at the Endocrine Society’s annual meeting, members acknowledged that many studies have shown relationships between serum concentrations of 25-hydroxy vitamin D (25(OH)D) and physical disorders including those of musculoskeletal, metabolic, and cardiovascular systems. Still, they questioned the link of vitamin D supplementation and testing with disease prevention.

“There is paucity of data regarding definition of optimal levels and optimal intake of vitamin D for preventing specific diseases. … What we really need are large-scale clinical trials and biomarkers so we can predict disease outcome before it happens,” said Panel Chair Marie Demay, MD, Endocrinologist, Massachusetts General Hospital, and Professor of Medicine, Harvard Medical School, Boston, Medscape Medical News reported.

Meanwhile, in their Journal of Clinical Endocrinology and Metabolism paper, the researchers note that use of supplements (1,000 IU or more per day) increased from 0.3% to 18.2%, according to the National Health and Nutrition Examination Survey (NHANES) conducted by the National Center for Health Statistics (NCHS), CDC, for the years 1999-2000 and 2013-2014.

“The use of 25(OH)D testing in clinical practice has also been increasing; however, the cost effectiveness of widespread testing has been questioned, especially given the uncertainty surrounding the optimal level of 25(OH)D required to prevent disease,” the authors wrote.

“Thus, the panel suggests against routine 25(OH)D testing in all populations considered,” the researchers stated at the Endocrine Society annual meeting.

Other Groups Weigh-in on Vitamin D Testing

Pathologists and medical laboratory leaders may recall the explosion in vitamin D testing starting about 20 years ago. Vitamin D testing reimbursed by Medicare Part B “increased 83-fold” during the years 2000 to 2010, according to data cited in an analysis by the American Academy of Family Physicians (AAFP).

“Screening for vitamin D deficiency leads to hundreds of millions of dollars of waste in testing costs annually,” the AAFP noted in an editorial on the organization’s website titled, “Vitamin D Screening and Supplementation in Primary Care: Time to Curb Our Enthusiasm.”

Also, the US Preventive Services Task Force (USPSTF) said in a statement that there is not enough information to “recommend for or against” testing for vitamin D deficiency.

“No organization recommends population-based screening for vitamin D deficiency, and the American Society for Clinical Pathology recommends against it,” the USPSTF noted.

Clinical Laboratories Can Get the Word Out

The vitamin D debate has been going on for a while. And the latest guidance from the Endocrine Society may cause physicians and patients to stop ordering vitamin D tests as part of annual physicals or in routine screenings.

Medical laboratories can provide value by ensuring physicians and patients have the latest information about vitamin D test orders, reports, and interpretation.

—Donna Marie Pocius

Related Information:

Endocrine Society Recommends Healthy Adults Take the Recommended Daily Allowance of Vitamin D

Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline

Don’t Screen for Vitamin D: New Endo Society Guideline

Institute of Medicine Recommendations Vitamin D

Vitamin D Screening and Supplementation in Primary Care: Time to Curb Our Enthusiasm

US Preventive Services Task Force Recommendation Vitamin D Deficiency Screening

FDA Grants Marketing Authorization to First Ever AI-Powered SaMD Diagnostic Tool for Sepsis That Shares Patient’s Risk within 24 Hours and Works with EHRs

Infection control teams and clinical laboratory managers may want to look at this new product designed to improve the diagnosis and treatment of sepsis

Accurate and fast diagnosis of sepsis for patients arriving in emergency departments is the goal of a new product that was just cleared by the federal Food and Drug Administration (FDA). It is also the newest example of how artificial intelligence (AI) continues to find its way into pathology and clinical laboratory medicine.

Sepsis is one of the deadliest killers in US hospitals. That is why there is interest in the recent action by the FDA to grant marketing authorization for an AI-powered sepsis detection software through the agency’s De Novo Classification Request. The DNCR “provides a marketing pathway to classify novel medical devices for which general controls alone, or general and special controls, provide reasonable assurance of safety and effectiveness for the intended use, but for which there is no legally marketed predicate device,” the FDA’s website states.

Developed by Chicago-based Prenosis, the Sepsis ImmunoScore is an AI and machine learning (ML) Software as a Medical Device (SaMD) used to “guide rapid diagnosis and prediction of sepsis” within 24 hours of the patient’s presentation in an emergency department or hospital, according to a company news release.

In a separate statement, Prenosis announced a commercial distribution deal with Roche, Basel, Switzerland, as well as the SaMD’s availability on Roche’s navify Algorithm Suite (a digital library of medical algorithms).

Unlike a single analyte assay that is run in a clinical laboratory, Prenosis’ AI/ML software uses 22 diagnostic and predictive parameters, along with ML algorithms, to analyze data and produce a clinically actionable answer on sepsis.

It is important for clinical laboratory managers and pathologists to recognize that this diagnostic approach to sepsis brings together a number of data points commonly found in a patient’s electronic health record (EHR), some of which the lab generated and others the lab did not generate.

“Sepsis is a serious and sometimes deadly complication. Technologies developed to help prevent this condition have the potential to provide a significant benefit to patients,” said Jeff Shuren, MD, JD, Director of the FDA’s Center for Devices and Radiological Health, in a statement. “The FDA’s authorization of the Prenosis Sepsis ImmunoScore software establishes specific premarket and post-market requirements for this device type.” Clinical laboratory EHRs contain some of the data points Prenosis’ diagnostic software uses. (Photo copyright: US Food and Drug Administration.)  

How it Works

To assist doctors diagnose sepsis, the ImmunoScore software is first integrated into the patient’s hospital EHR. From there, it leverages 22 parameters including:

Instead of requiring a doctor or nurse to look at each parameter separately, the SaMD tool uses AI “to evaluate all those markers at once”, CNBC noted. It then produces a risk score and four discrete risk stratification categories (low, medium, high, and very high) which correlate to “a patient’s risk of deterioration” represented by:

  • Hospital length of stay.
  • In-hospital mortality.
  • Intensive care unit transfer within 24 hours.
  • Vasopressor use within 24 hours.
  • Need for mechanical ventilation within 24 hours.

By sharing these details—a number from one to 100 for each of the 22 diagnostic and predictive parameters—Sepsis ImmunoScore helps doctors determine which will likely contribute most to the patient’s risk for developing sepsis, MedTech Dive reported.

“A lot of clinicians don’t trust AI products for multiple reasons. We are trying very hard to counter that skepticism by making a tool that was validated by the FDA first, and then the second piece is we’re not trying to replace the clinician,” Bobby Reddy Jr., PhD, Prenosis co-founder and CEO, told MedTech Dive.

Big Biobank and Blood Sample Data

Prenosis, which says its goal is the “enabling [of] precision medicine in acute care” developed Sepsis ImmunoScore using the company’s own biobank and a dataset of more than 100,000 blood samples from more than 25,000 patients.

AI algorithms drew on this biological/clinical dataset—the largest in the world for acute care patients suspected of having serious infections, according to Prenosis—to “elucidate patterns in rapid immune response.”

Carle Foundation Hospital, Urbana, Ill., is one of three Illinois hospitals that helped build the biobank and dataset used by Prenosis, according to a Carle news release.

“It does not work without data, and the data started at Carle,” said critical care specialist Karen White, MD, PhD, Carle Foundation Hospital, St. Louis, MO, in the news release.  “The project involved a large number of physicians, research staff, and internal medicine residents at Carle who helped recruit patients, collect data, and samples,” she said.

Opportunity for Clinical Laboratories

Sepsis is a life-threatening condition based on an “extreme response to an infection” that affects nearly 1.7 million adults in the US each year and is responsible for 350,000 deaths, according to US Centers for Disease Control and Prevention (CDC) data. 

A non-invasive diagnostic tool like Sepsis ImmunoScore will be a boon to emergency physicians and the patients they treat. Now that the FDA has authorized the SaMD diagnostic tool to go to market, it may not be long before physicians can use the information it produces to save lives.

Clinical laboratory managers inspired by the development of Sepsis ImmunoScore may want to look for similar ways they can take certain lab test results and combine them with other data in an EHR to create intelligence that physicians can use to better treat their patients. The way forward in laboratory medicine will be combining lab test results with other relevant sets of data to create clinically actionable intelligence for physicians, patients, and payers.

—Donna Marie Pocius

Related Information:

Prenosis Announces FDA De Novo Marketing Authorization of the Sepsis ImmunoScore  

Prenosis Announces Commercial Distribution Collaboration with Roche for Sepsis ImmunoScore

FDA Authorizes Prenosis Software as First AI Tool That Can Diagnose Sepsis

FDA Round-Up April 5, 2024

FDA Grants De Novo Clearance to AI Tool for Detecting Sepsis

New AI Tool for Sepsis Diagnosis Gets its Start to Research at Carle

An AI Tool to Stop Sepsis

Johns Hopkins Research Team Uses Machine Learning on DNA “Dark Matter” in Blood to Identify Cancer

Findings could lead to new biomarkers clinical laboratories would use for identifying cancer in patients and monitoring treatments

As DNA “dark matter” (the DNA sequences between genes) continues to be studied, researchers are learning that so-called “junk DNA” (non-functional DNA) may influence multiple health conditions and diseases including cancer. This will be of interest to pathologists and clinical laboratories engaged in cancer diagnosis and may lead to new non-invasive liquid biopsy methods for identifying cancer in blood draws.

Researchers at Johns Hopkins Kimmel Cancer Center in Baltimore, Md., developed a technique to identify changes in repeat elements of genetic code in cancerous tissue as well as in cell-free DNA (cf-DNA) that are shed in blood, according to a Johns Hopkins news release.

The Hopkins researchers described their machine learning approach—called ARTEMIS (Analysis of RepeaT EleMents in dISease)—in the journal Science Translational Medicine titled, “Genomewide Repeat Landscapes in Cancer and Cell-Free DNA.”

ARTEMIS “shows potential to predict cases of early-stage lung cancer or liver cancer in humans by detecting repetitive genetic sequences,” Genetic Engineering and Biotechnology News (GEN) reported.

This technique could enable non-invasive monitoring of cancer treatment and cancer diagnosis, Technology Networks noted.

“Our study shows that ARTEMIS can reveal genomewide repeat landscapes that reflect dramatic underlying changes in human cancers,” said study co-leader Akshaya Annapragada (above), an MD/PhD student at the Johns Hopkins University School of Medicine, in a news release. “By illuminating the so-called ‘dark genome,’ the work offers unique insights into the cancer genome and provides a proof-of-concept for the utility of genomewide repeat landscapes as tissue and blood-based biomarkers for cancer detection, characterization, and monitoring.” Clinical laboratories may soon have new biomarkers for the detection of cancer. (Photo copyright: Johns Hopkins University.)

Detecting Early Lung, Liver Cancer

Artemis is a Greek word meaning “hunting goddess.” For the Johns Hopkins researchers, ARTEMIS also describes a technique “to analyze junk DNA found in tumors” and which float in the bloodstream, Financial Times explained.

“It’s like a grand unveiling of what’s behind the curtain,” said geneticist Victor Velculescu, MD, PhD, Professor of Oncology and co-director of the Cancer Genetics and Epigenetics Program at Johns Hopkins Kimmel Cancer Center, in the news release.

“Until ARTEMIS, this dark matter of the genome was essentially ignored, but now we’re seeing that these repeats are not occurring randomly,” he added. “They end up being clustered around genes that are altered in cancer in a variety of different ways, providing the first glimpse that these sequences may be key to tumor development.”

ARTEMIS could “lead to new therapies, new diagnostics, and new screening approaches for cancer,” Velculescu noted.

Repeats of DNA Sequences Tough to Study

For some time technical limitations have hindered analysis of repetitive genomic sequences by scientists. 

“Genetic changes in repetitive sequences are a hallmark of cancer and other diseases, but characterizing these has been challenging using standard sequencing approaches,” the study authors wrote in their Science Translational Medicine paper.

“We developed a de novo k-mer (short sequences of DNA)-finding approach called ARTEMIS to identify repeat elements from whole-genome sequencing,” the researchers wrote.

The scientists put ARTEMIS to the test in laboratory experiments.

The first analysis involved 1,280 types of repeating genetic elements “in both normal and tumor tissues from 525 cancer patients” who participated in the Pan-Cancer Analysis of Whole Genomes (PCAWG), according to Technology Networks, which noted these findings:

  • A median of 807 altered elements were found in each tumor.
  • About two-thirds (820) had not “previously been found altered in human cancer.”

Second, the researchers explored “genomewide repeat element changes that were predictive of cancer,” by using machine learning to give each sample an ARTEMIS score, according to the Johns Hopkins news release. 

The scoring detected “525 PCAWG participants’ tumors from the healthy tissues with a high performance” overall Area Under the Curve (AUC) score of 0.96 (perfect score being 1.0) “across all cancer types analyzed,” the Johns Hopkins’ release states.

Liquid Biopsy Deployed

The scientists then used liquid biopsies to determine ARTEMIS’ ability to noninvasively diagnose cancer. Researchers used blood samples from:

Results, according to Johns Hopkins:

  • ARTEMIS classified patients with lung cancer with an AUC of 0.82.
  • ARTEMIS detected people with liver cancer, as compared to others with cirrhosis or viral hepatitis, with a score of AUC 0.87.

Finally, the scientists used their “ARTEMIS blood test” to find the origin of tumors in patients with cancer. They reported their technique was 78% accurate in discovering tumor tissue sources among 12 tumor types.

“These analyses reveal widespread changes in repeat landscapes of human cancers and provide an approach for their detection and characterization that could benefit early detection and disease monitoring of patients with cancer,” the researchers wrote in Science Translational Medicine.

Large Clinical Trials Planned

Velculescu said more research is planned, including larger clinical trials.

“While still at an early stage, this research demonstrates how some cancers could be diagnosed earlier by detecting tumor-specific changes in cells collected from blood samples,” Hattie Brooks, PhD, Research Information Manager, Cancer Research UK (CRUK), told Financial Times.

Should ARTEMIS prove to be a viable, non-invasive blood test for cancer, it could provide pathologists and clinical laboratories with new biomarkers and the opportunity to work with oncologists to promptly diagnosis cancer and monitor patients’ response to treatment.

—Donna Marie Pocius

Related Information:

“Junk DNA” No More: Johns Hopkins Investigators Develop Method of Identifying Cancers from Repeat Elements of Genetic Code

Genomewide Repeat Landscapes in Cancer and Cell-Free DNA

AI Detects Cancer VIA DNA Repeats in Liquid Biopsies

Genetic “Dark Matter” Could Help Monitor Cancer

AI Explores “Dark Genome” to Shed Light on Cancer Growth

University of Ghent Belgium Research Team Finds Stool Transplants Improve Motor Symptoms in Early-stage Parkinson’s Disease Patients

Findings could lead to clinical laboratory tests that help physicians identify microbes lacking in the microbiomes of their Parkinson patients

Microbiologists and clinical laboratory scientists know that gut microbiome can be involved in the development of Parkinson’s disease, a progressive neurological disorder that affects the nervous system due to damage caused to nerve cells in the brain. There is no cure for the illness. But a new treatment developed by researchers at the VIB Center for Inflammation Research at the University of Ghent in Belgium, may help to alleviate the symptoms.

During a clinical trial, VIB Center for Inflammation Research (VIB-IRC) scientists discovered that fecal microbiota transplantation (FMT), also known as a stool transplant, can improve motor skills in some Parkinson’s patients, according to Neuroscience News.

Parkinson’s disease (PD) develops when a protein called alpha-synuclein misfolds and forms into bundled clusters damaging nerve cells in the brain that produce dopamine. These formations, which are believed to appear in the gastrointestinal wall in the early stages of PD, then reach the brain via the vagus nerve leading to typical PD symptoms in patients.

Dopaminergic medication, deep brain stimulation, and speech and occupational therapy are some of the treatments currently available to people with Parkinson’s disease, but researchers are constantly on the lookout for more and better treatments,” Medical News Today reported.

The scientists published their findings in eClinicalMedicine titled, “Safety and Efficacy of Fecal Microbiota Transplantation in Patients with Mild to Moderate Parkinson’s Disease (GUT-PARFECT): A Double-Blind, Placebo-Controlled, Randomized, Phase 2 Trial.”

“Our study provides promising hints that FMT can be a valuable new treatment for Parkinson’s disease,” Roosmarijn Vandenbroucke, PhD (above), Principal Investigator, VIB-UGent Center for Inflammation Research and full professor, UGent Department of Biomedical molecular biology, Faculty of Sciences, told Neuroscience News. “More research is needed, but it offers a potentially safe, effective, and cost-effective way to improve symptoms and quality of life for millions of people with Parkinson’s disease worldwide.” Clinical laboratories will likely be involved in identifying the best microbes for the FMT treatments. (Photo copyright: University of Ghent.)

Correlation between Gut Microbiome and Neurogenerative Disease

To perform their clinical study—referred to as GUT-PARFECT—the IRC researchers first recruited patients with early-stage PD and healthy donors who provided stool samples to the Ghent Stool Bank. The PD patients received the healthy stool via a tube inserted into the nose which led directly into the small intestine.

The FMT procedures were performed on 46 patients with PD between December 2020 and December 2021. The participants in this group ranged in ages from 50 to 65. There were 24 PD patients in the placebo group, and a total of 22 donors provided the healthy stool. Clinical evaluations were performed at baseline, three, six, and 12 months.

After 12 months, the group that received the transplants showed a reduction in symptoms compared to the placebo group. Their motor score on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) improved by a mean of 5.8 points. The improvement registered on the same scale for the placebo group was 2.7 points.

Developed in the 1980s, the MDS-UPDRS is a scale utilized to evaluate various aspects of PD by measuring patient responses via a questionnaire rating several issues (such as cognitive impairment, apathy, depression, and anxiousness) common in PD patients from normal to severe. It is divided into four parts:

  • Part I: Non-motor experiences of daily living.
  • Part II: Motor experiences of daily living.
  • Part III: Motor examination.
  • Part IV: Motor complications.

During the final six months of the research, the improvement in motor symptoms became even greater. To the VIB-IRC researchers this implied that an FMT may have long-lasting effects on PD patients. The FMT study group also experienced less constipation, a condition that can be bothersome for some PD patients.

“Our results are really encouraging!” said the study’s first author, Arnout Bruggeman, MD, PhD student, VIB-UGent Center for Inflammation Research, in a UGent News release. “After twelve months, participants who received the healthy donor stool transplant showed a significant improvement in their motor score, the most important measure for Parkinson’s symptoms.”

Findings Could Lead to Other Targeted Therapies for PD

The VIB-IRC researchers believe there is a correlation between the gut microbiome and Parkinson’s disease.

“Our findings suggested a single FMT induced mild, but long-lasting beneficial effects on motor symptoms in patients with early-stage PD. These findings highlight the potential of modulating the gut microbiome as a therapeutic approach and warrant a further exploration of FMT in larger cohorts of patients with PD in various disease stages,” the IRC researchers wrote in eClinicalMedicine.  

“Our next step is to obtain funding to determine which bacteria have a positive influence. This could lead to the development of a ‘bacterial pill’ or other targeted therapy that could replace FMT in the future,” Debby Laukens, PhD, Associate Professor, Ghent University, told Neuroscience News.

According to the Parkinson’s Foundation website, nearly one million people in the US live with PD. It is second only to Alzheimer’s disease in the category of neurodegenerative diseases.

More research and studies are needed before the VIB-IRC’s stool transplant treatment can be used in clinical care. As researchers learn more about which specific strains of bacteria are doing the beneficial work in PD patients, that data could eventually lead to clinical laboratory tests performed to help physicians identify which microbes are lacking in the microbiomes of their PD patients, and if fecal transplants could help those patients.

—JP Schlingman

Related Information:

Fecal Bacteria Transplant May Improve Parkinson’s Symptoms

Safety and Efficacy of Fecal Microbiota Transplantation in Patients with Mild to Moderate Parkinson’s Disease (GUT-PARFECT): A Double-Blind, Placebo-Controlled, Randomized, Phase 2 Trial

Stool Transplantation Shows Promise For Parkinson’s Disease

Fecal Microbiota Transplant Eases Parkinson’s Symptoms in Trial

Stool Transplant Could Improve Motor Symptoms in Parkinson’s Disease

In Conversation: Why Parkinson’s Research is Zooming in on the Gut

Clinical Trial Shows New Laboratory Developed Blood Test 83% Effective at Detecting Colorectal Cancer

Accurate blood-based clinical laboratory testing for cancer promises to encourage more people to undergo early screening for deadly diseases

One holy grail in diagnostics is to develop less-invasive specimen types when screening or testing for different cancers. This is the motivation behind the creation of a new assay for colorectal (colon) cancer that uses a blood sample and that could be offered by clinical laboratories. The data on this assay and its performance was featured in a recent issue of the New England Journal of Medicine(NEJM).

The company developing this new test recognized that more than 50,000 people will die in 2024 from colon cancer, according to the American Cancer Society. That’s primarily because people do not like colonoscopies even though the procedure can detect cancer in its early stages. Similarly, patients tend to find collecting their own fecal samples for colon cancer screening tests to be unpleasant.

But the clinical laboratory blood test for cancer screening developed by Guardant Health may make diagnosing the deadly disease less invasive and save lives. The test “detects 83% of people with colorectal cancer with specificity of 90%,” a company press release noted.

“Early detection could prevent more than 90% of colorectal cancer-related deaths, yet more than one third of the screening-eligible population is not up to date with screening despite multiple available tests. A blood-based test has the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer-related mortality,” the study authors wrote in the NEJM.

As noted above, this is the latest example of test developers working to develop clinical laboratory tests that are less invasive for patients, while equaling or exceeding the sensitivity and specificity of existing diagnostic assays for certain health conditions.

“I do think having a blood draw versus undergoing an invasive test will reach more people, My hope is that with more tools we can reach more people,” Barbara H. Jung, MD (above), President of the American Gastroenterological Association, told NPR. Clinical laboratory blood tests for cancer may encourage people who do not like colonoscopies to get regular screening. (Photo copyright: American Gastroenterology Association.)

Developing the Shield Blood Test

Colorectal cancer is the “third most common cancer among men and women in the US,” according to the American Gastrological Association (AGA). And yet, millions of people do not get regular screening for the disease.

To prove their Shield blood test, Guardant Health, a precision oncology company based in Redwood City, Calif., enrolled more than 20,000 patients between the ages of 45-84 from across the US in a prospective, multi-site registrational study called ECLIPSE (Evaluation of ctDNA LUNAR Assay In an Average Patient Screening Episode).

“We assessed the performance characteristics of a cell-free DNA (cfDNA) blood-based test in a population eligible for colorectal cancer screening. The coprimary outcomes were sensitivity for colorectal cancer and specificity for advanced neoplasia (colorectal cancer or advanced precancerous lesions) relative to screening colonoscopy. The secondary outcome was sensitivity to detect advanced precancerous lesions,” the study authors wrote in the NEJM.

In March, Guardant completed clinical trials of its Shield blood test for detecting colorectal cancer (CRC) in men and women. According to the company press release, the test demonstrated:

  • 83% sensitivity in detecting individuals with CRC.
  • 88% sensitivity in detecting pathology-confirmed Stages I-III.

Additionally, the Shield test showed sensitivity by stage of:

  • 65% for pathology-confirmed Stage I,
  • 55% for clinical Stage I,
  • 100% for Stage II, and
  • 100% for Stage III.

“The results of the study are a promising step toward developing more convenient tools to detect colorectal cancer early while it is more easily treated,” said molecular biologist and gastroenterologist William M. Grady, MD, Medical Director, Gastrointestinal Cancer Prevention Program at Fred Hutchinson Cancer Center and corresponding author of the ECLIPSE study in the press release. “The test, which has an accuracy rate for colon cancer detection similar to stool tests used for early detection of cancer, could offer an alternative for patients who may otherwise decline current screening options.”

Are Colonoscopies Still Needed?

“More than three out of four Americans who die from colorectal cancer are not up to date with their recommended screening, highlighting the need for a more convenient and less invasive screening method that can overcome barriers associated with traditional options,” Daniel Chung, MD, gastroenterologist at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School, said in the Guardant press release.

Barbara H. Jung, MD, President of the American Gastroenterological Association, says that even if Guardant’s Shield test makes it to the public the “dreaded colonoscopy” will still be needed because the procedure is used to locate and test polyps. “And when you find those you can also remove them, which in turn prevents the cancer from forming,” she told NPR.

There is hope that less invasive clinical laboratory testing will encourage more individuals to get screened for cancer earlier and regularly, and that the shift will result in a reduction in cancer rates.

“Colorectal cancer is highly treatable if caught in the early stages,” said Chris Evans, President of the Colon Cancer Coalition, in the Guardant press release.

Guardant Health’s ECLIPSE study is a prime example of the push clinical laboratory test developers are making to create user-friendly test options that make it easier for patients to follow through with regular screening for early detection of diseases. It echoes a larger effort in the medical community to think outside the box and come up with creative solutions to reach wider audiences in the name of prevention.

—Kristin Althea O’Connor

Related Information:

Guardant Health ECLIPSE Study Data Demonstrating Efficacy of Shield Blood-based Test for Colorectal Cancer Screening to be Published in The New England Journal of Medicine

A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening

Guardant Health Announces Positive Results from Pivotal ECLIPSE Study Evaluating a Blood Test for the Detection of Colorectal Cancer

A Simple Blood Test Can Detect Colorectal Cancer Early, Study Finds

Key Statistics for Colorectal Cancer

Colorectal Cancer Facts and Statistics

Cancer Stat Facts: Colorectal Cancer

University of Warwick Researchers Identity Blood Protein Biomarkers That Can Predict Dementia Onset Years in Advance

With further study, this research may provide clinical laboratories with a new proteomic biomarker for dementia screenings that identifies risk more than 10 years before symptoms appear

Researchers at the University of Warwick in the UK and Fudan University in Shanghai, China, identified four protein biomarkers in blood that they say can predict dementia up to 15 years before diagnosis. They say these biomarkers may lead to clinical laboratory blood tests that offer alternatives to costly brain scans and lumbar punctures for diagnosis of dementia.

The scientists “used the largest cohort of blood proteomics and dementia to date,” according to a University of Warwick news release. This included taking blood from 52,645 “healthy” people without dementia who participated in the UK Biobank—a population-based study cohort, the new release noted.

“The proteomic biomarkers are [easy] to access and non-invasive, and they can substantially facilitate the application of large-scale population screening,” said neurovegetative disease specialist Jin-tai Yu, MD, PhD, a professor at Fudan University and co-author of the study, in the news release.

The scientists published their findings in the journal Nature Aging titled, “Plasma Proteomic Profiles Predict Future Dementia in Healthy Adults.”

“The advent of proteomics offers an unprecedented opportunity to predict dementia onset,” the researchers wrote.

“This is a well-conducted study that adds to what we know about changes in blood that occur very early in diseases that cause dementia, which will be important for early diagnosis in the future,” said Tara Spires-Jones, PhD, in a post from the Science Media Center in the UK. “However,” she added, “it is important to note that these are still scientific research studies and that there are currently no blood tests available for routine use that can diagnose dementia with certainty.

Jones, who was not involved in the study, is President of the British Neuroscience Association (BNA) and group leader of the UK Dementia Research Institute at the University of Edinburgh.

“Based on this study, it does seem likely that blood tests will be developed that can predict risk for developing dementia over the next 10 years, although individuals at higher risk often have difficulty knowing how to respond,” Suzanne Schindler, MD, PhD (above), told Reuters. Schindler, an Associate Professor of Neurology at Washington University in St. Louis, was not involved in the research. Clinical laboratories may soon have a new blood test for dementia. (Photo copyright: VJDementia.)

Predicting Onset of Dementia with 90% Accuracy

The researchers analyzed 52,645 blood samples from the UK Biobank (UKBB). The samples were collected between 2006 and 2010 from healthy individuals who at that time were without dementia.

By March 2023, 1,417 of the study participants had developed Alzheimer’s disease or some other form of dementia. The researchers looked at 1,463 proteins and identified four that were present in high levels among those people:

“Individuals with higher GFAP levels were 2.32 times more likely to develop dementia,” the researchers wrote in Nature Aging. “Notably, GFAP and LTBP2 were highly specific for dementia prediction. GFAP and NEFL began to change at least 10 years before dementia diagnosis.”

When adding known risk factors such as age, sex, and genetics, the researchers said they could predict onset of dementia with 90% accuracy, according to the University of Warwick news release.

“Our findings strongly highlight GFAP as an optimal biomarker for dementia prediction, even more than 10 years before the diagnosis, with implications for screening people at high risk for dementia and for early intervention,” the researchers wrote.

The news release also noted that smaller studies had already identified some of the proteins as potential biomarkers, “but this new research was much larger and conducted over several years.”

Further Validation Needed

Amanda Heslegrave, PhD, of the UK Dementia Research Institute, University College London described the UKBB as “an excellent resource” in the Science Media Center (SMC) post. However, she noted, it’s “a highly curated biobank and may not capture all populations that we need to know the risk for. The new biomarkers identified will need further validation before being used as screening tools.”

Another expert raised additional questions about the University of Warwick/Fudan University study in the SMC post.

“These results may help researchers understand the biological systems involved in the development of dementia,” said David Curtis, MD, PhD, of the UCL Genetics Institute at University College London. “However in my view the strengths of the reported associations are not really strong enough to say that these would form a useful test for predicting who will get dementia in the future.”

Conversely, Curtis pointed to other studies suggesting that phosphorylated tau (p-tau) proteins are better candidates for developing a simple blood test.

P-tau “provides a very good indicator of whether the pathological processes leading to Alzheimer’s disease are present in the brain,” he said. “When effective treatments for Alzheimer’s disease are developed it will be very helpful indeed to have simple blood tests—such as measuring phosphorylated tau—available in order to identify who could benefit.”

At least two blood tests based on the p-tau217 variant—from ALZpath and C2N—are currently available to US clinicians as laboratory developed tests (LDT).

In “University of Gothenburg Study Findings Affirm Accuracy of Clinical Laboratory Blood Test to Diagnose Alzheimer’s Disease,” Dark Daily reported on a study from the University of Gothenburg in Sweden which found that the ALZpath test was as good or better than lumbar punctures and brain scans as a diagnostic tool for Alzheimer’s.

UK Biobank

The UK Biobank continues to be used by researchers both in the UK and abroad because of the full sets of data on large numbers of patients over many years. There are few other sources of such data elsewhere in the world. The UK Biobank is a large-scale biomedical database and research resource. It contains de-identified genetic, lifestyle and health information, and biological samples from 500,000 UK participants.

On its website, the UK Biobank states, “It is the most comprehensive and widely-used dataset of its kind and is globally accessible to approved researchers who are undertaking health-related research that is in the public interest, whether they are from academic, commercial, government or charitable settings.”

Thus, clinical laboratory managers and pathologists can expect a continuing stream of published studies that identify biomarkers associated with different health conditions and to see where the data used in these analyses came from the UK’s biobank.

—Stephen Beale

Related Information:

Protein Biomarkers Predict Dementia 15 Years Before Diagnosis, According to New Study

Plasma Proteomic Profiles Predict Future Dementia in Healthy Adults

Proteins May Predict Who Will Get Dementia 10 Years Later, Study Finds

Expert Reaction to Study of Potential Protein Biomarkers for Dementia Risk

Two New p-Tau217 Blood Tests Join a Crowded Field

Plasma p-Tau-217 Assays Work Well, But No Home Run for Diagnosis

Dementia Can Be Predicted More than a Decade Before Diagnosis with These Blood Proteins

Dementia Predicted 10 Years Before Diagnosis

Early Blood Test to Predict Dementia Is Step Closer as Biological Markers Identified

Validating Blood Tests as A Possible Routine Diagnostic Assay of Alzheimer’s Disease

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