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UK Researchers Create Analytical Algorithm That Identifies Patients with Advanced Liver Disease by Analyzing Routine Clinical Laboratory Blood Test Results

By mining results of unrelated blood tests, the CIRRUS algorithm can inform doctors and patients earlier than usual of liver disease

For years Dark Daily and its sister publication The Dark Report have predicted that the same type of analytical software used on Wall Street to analyze bundles of debt, such as car loans, mortgages, and installment loans, would eventually find application in healthcare and clinical laboratory medicine. Now, researchers at the University of Southampton in England have developed just such an analytical tool.

The UK researchers call their algorithm CIRRUS, which stands for CIRRhosis Using Standard tests. It can, they say, accurately predict if a patient has cirrhosis of the liver at a much earlier stage than usual and produce information that is clinically actionable, using results from several common, routinely-ordered medical laboratory tests.

The University of Southampton scientists published their findings in BMJ Open.

Currently, the leading edge for this in clinical laboratory medicine is analysis of digital pathology images using image analysis tools and artificial intelligence (AI). However, CIRRUS is an example that analytical software is advancing in its ability to mine data from a number of clinically-unrelated lab tests on a patient and identify a health condition that might otherwise remain unknown.

The UK researchers designed the CIRRUS algorithm using routine clinical laboratory blood tests often requested in general practice to identify individuals at risk of advanced liver disease. These tests include:

Reversing Liver Disease through Lifestyle Changes

“More than 80% of liver cirrhosis deaths are linked to alcohol or obesity and are potentially preventable,” noted Nick Sheron, MD, FRCP, Head of Population Hepatology at University of Southampton, and lead author of the study, in a press release. “However, the process of developing liver cirrhosis is silent and often completely unsuspected by GPs [general practitioners]. In 90% of these patients, the liver blood test that is performed is normal, and so liver disease is often excluded.

“This new CIRRUS algorithm can find a fingerprint for cirrhosis in the common blood tests done routinely by GPs,” he continued. “In most cases the data needed to find these patients already exists and we could give patients the information they need to change their lifestyle. Even at this late stage, if people address the cause by stopping drinking alcohol or reducing their weight, the liver can still recover.”

Mining Clinical Laboratory Blood Test Results

To perform the study, the research team analyzed data on blood test results for nearly 600,000 patients. Unlike most diagnostic liver algorithms, the CIRRUS model was created using a dataset comprised of patients from both primary and secondary care without the main intent of preselecting for liver disease. This renders it better suited for detecting liver disease outside a secondary care hepatology environment.

“Whilst we are all preoccupied with the coronavirus pandemic we must not lose sight of other potentially preventable causes of death and serious illness,” said Michael Moore, BM, BS, MRCP, FRCGP, Professor of Primary Health Care Research and Head of Academic Unit Primary Care and Population Sciences at University of Southampton, in the press release. Professor Moore co-authored the CIRRUS study.

“This test using routine blood test data available, gives us the opportunity to pick up serious liver disease earlier, which might prevent future emergency admission to hospital and serious ill health,” he said.

Cirrhosis micrograph showing scaring of liver tissue
Cirrhosis (shown above in a trichrome stained micrograph) is a condition in which the liver is scarred and permanently damaged. As the condition progresses, more scar tissue replaces healthy liver tissue. This accumulated scar tissue prevents the liver from doing its primary job of regulating chemical levels in the blood and excreting bile, a substance which helps eliminate toxins from the body and breaks down fats during digestion. As cirrhosis worsens, the liver begins to fail. (Photo copyright: Wikipedia.)

According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), cirrhosis is most common in adults ages 45 to 54 and about 1 in 400 adults in the US live with the disease. However, the actual number may be much higher as many people are not aware they have cirrhosis, because they do not experience symptoms until the liver is badly damaged. 

The NIDDK reports complications from cirrhosis include:

  • Portal Hypertension, a condition where scar tissue partially blocks the normal flow of blood through the liver,
  • Infections,
  • Liver Cancer,
  • Liver Failure,
  • Bone diseases, such as osteoporosis,
  • Gallstones,
  • Bile duct issues,
  • Malabsorption and malnutrition,
  • Bruising and bleeding easily,
  • Sensitivity to medicines,
  • Insulin resistance, and
  • Type 2 diabetes.

“Liver cirrhosis is a silent killer. The tests used most by GPs are not picking up the right people and too many people are dying preventable deaths. We looked at half a million anonymous records and the data we needed to run CIRRUS was already there in 96% of the people who went on to have a first liver admission,” stated Sheron in the press release. “With just a small change in the way we handle this data it should be possible to intervene in time to prevent many of these unnecessary deaths.”

“Alcohol-related liver diseases are far and away the most significant cause of alcohol-specific deaths, yet currently the vast majority of people find out that their liver is diseased way too late,” said Richard Piper, PhD, Chief Executive of Alcohol Change UK, a British charity and campaign group dedicated to reducing harm caused by alcohol abuse. “What is needed is a reliable means of alerting doctors and their patients to potential liver disease as early as possible. The CIRRUS process shows real promise, and we want to see it further developed, tested and implemented, to help save hundreds of thousands, if not millions, of lives.”

CIRRUS is a true milestone in the development of computer-assisted healthcare diagnostics. It will need more research, but the University of Southampton study shows that analytical software tools can mine clinical laboratory test results that were ordered for unrelated diagnostics and identify existing health conditions that might otherwise remain hidden to the patient’s physicians.

—JP Schlingman

Related Information:

Routine Blood Tests Could Be Key to Stopping the Silent Killer of Liver Disease

Can Routine Blood Tests be Modelled to Detect Advanced Liver Disease in the Community: Model Derivation and Validation Using UK Primary and Secondary Care Data

New Algorithm Can Predict Advanced Liver Disease

Routine Blood Tests Contain ‘Hidden Fingerprint’ Indicating Liver Cirrhosis

Common DNA Testing Method Using SNP Chips Struggles to Find Rare Variants Associated with BRCA Test, UK Researchers Find

Results of the UK study confirm for clinical laboratory professionals the importance of fully understanding the design and function of SNP chips they may be using in their labs

Here is another example of a long-established clinical laboratory test that—upon new evidence—turns out to be not as accurate as once thought. According to research conducted at the University of Exeter in Devon, UK, Single-nucleotide polymorphism (SNP) chips (aka, SNP microarrays)—technology commonly used in commercial genetic testing—is inadequate at detecting rare gene variants that can increase breast cancer risk.  

A news release announcing the results of the large-scale study states, “A technology that is widely used by commercial genetic testing companies is ‘extremely unreliable’ in detecting very rare variants, meaning results suggesting individuals carry rare disease-causing genetic variants are usually wrong.”

Why is this a significant finding for clinical laboratories? Because medical laboratories performing genetic tests that use SNP chips should be aware that rare genetic variants—which are clinically relevant to a patient’s case—may not be detected and/or reported by the tests they are running.

UK Researchers Find ‘Shockingly High False Positives’

The objective of the Exeter study published in British Medical Journal (BMJ), titled, “Use of SNP Chips to Detect Rare Pathogenic Variants: Retrospective, Population Based Diagnostic Evaluation,” was “To determine whether the sensitivity and specificity of SNP chips are adequate for detecting rare pathogenic variants in a clinically unselected population.”

The conclusion reached by the Exeter researchers, the BMJ study states, is that “SNP chips are extremely unreliable for genotyping very rare pathogenic variants and should not be used to guide health decisions without validation.”  

Leigh Jackson, PhD, Lecturer in Genomic Medicine at University of Exeter and co-author of the BMJ study, said in the news release, “The number of false positives on rare genetic variants produced by SNP chips was shockingly high. To be clear: a very rare, disease-causing variant detected using [an] SNP chip is more likely to be wrong than right.” 

Caroline Wright, PhD, Professor in Genomic Medicine at the University of Exeter Medical School
In the news release, Caroline Wright, PhD (above), Professor in Genomic Medicine at the University of Exeter Medical School and senior author of the BMJ study, said, “SNP chips are fantastic at detecting common genetic variants, yet we have to recognize that tests that perform well in one scenario are not necessarily applicable to others.” She added, “We’ve confirmed that SNP chips are extremely poor at detecting very rare disease-causing genetic variants, often giving false positive results that can have profound clinical impact. These false results had been used to schedule invasive medical procedures that were both unnecessary and unwarranted.” (Photo copyright: University of Exeter.)

Large-Scale Study Taps UK Biobank Data

The Exeter researchers were concerned about cases of unnecessary invasive medical procedures being scheduled by women after learning of rare genetic variations in BRCA1 (breast cancer type 1) and BRCA2 (breast cancer 2) tests.

“The inherent technical limitation of SNP chips for correctly detecting rare genetic variants is further exacerbated when the variants themselves are linked to very rare diseases. As with any diagnostic test, the positive predictive value for low prevalence conditions will necessarily be low in most individuals. For pathogenic BRCA variants in the UK Biobank, the SNP chips had an extremely low positive predictive value (1-17%) when compared with sequencing. Were these results to be fed back to individuals, the clinical implications would be profound. Women with a positive BRCA result face a lifetime of additional screening and potentially prophylactic surgery that is unwarranted in the case of a false positive result,” they wrote.

Using UK Biobank data from 49,908 participants (55% were female), the researchers compared next-generation sequencing (NGS) to SNP chip genotyping. They found that SNP chips—which test genetic variation at hundreds-of-thousands of specific locations across the genome—performed well when compared to NGS for common variants, such as those related to type 2 diabetes and ancestry assessment, the study noted.

“Because SNP chips are such a widely used and high-performing assay for common genetic variants, we were also surprised that the differing performance of SNP chips for detecting rare variants was not well appreciated in the wider research or medical communities. Luckily, we had recently received both SNP chip and genome-wide DNA sequencing data on 50,000 individuals through the UK Biobank—a population cohort of adult volunteers from across the UK. This large dataset allowed us to systematically investigate the performance of SNP chips across millions of genetic variants with a wide range of frequencies, down to those present in fewer than 1 in 50,000 individuals,” wrote Wright and Associate Professor of Bioinformatics and Human Genetics at Exeter, Michael Weedon, PhD, in a BMJ blog post.

The Exeter researchers also analyzed data from a small group of people in the Personal Genome Project who had both SNP genotyping and sequencing information available. They focused their analysis on rare pathogenic variants in BRCA1 and BRCA2 genes.

The researchers found:

  • The rarer the variant, the less reliable the test result. For example, for “very rare variants” in less than one in 100,000 people, 84% found by SNP chips were false positives.
  • Low positive predictive values of about 16% for very rare variants in the UK Biobank.
  • Nearly all (20 of 21) customers of commercial genetic testing had at least one false positive rare disease-causing variant incorrectly genotyped.
  • SNP chips detect common genetic variants “extremely well.”

Advantages and Capabilities of SNP Chips

Compared to next-gen genetic sequencing, SNP chips are less costly. The chips use “grids of hundreds of thousands of beads that react to specific gene variants by glowing in different colors,” New Scientist explained.

Common variants of BRCA1 and BRCA2 can be found using SNP chips with 99% accuracy, New Scientist reported based on study data.

However, when the task is to find thousands of rare variants in BRCA1 and BRCA2 genes, SNP chips do not fare so well.

“It is just not the right technology for the job when it comes to rare variants. They’re excellent for the common variants that are present in lots of people. But the rarer the variant is, the less likely they are to be able to correctly detect it,” Wright told CNN.

SNP chips can’t detect all variants because they struggle to cluster needed data, the Exeter researchers explained.

“SNP chips perform poorly for genotyping rare genetic variants owing to their reliance on data clustering. Clustering data from multiple individuals with similar genotypes works very well when variants are common,” the researchers wrote. “Clustering becomes more difficult as the number of people with a particular genotype decreases.”

Clinical laboratories Using SNP Chips

The researchers at Exeter unveiled important information that pathologists and medical laboratory professionals will want to understand and monitor. Cancer patients with rare genetic variants may not be diagnosed accurately because SNP chips were not designed to identify specific genetic variants. Those patients may need additional testing to validate diagnoses and prevent harm.

—Donna Marie Pocius

Related Information:

Large-scale Study Finds Genetic Testing Technology Falsely Detects Very Rare Variants

Use of SNP Chips to Detect Rare Pathogenic Variants: Retrospective, Population-Based Diagnostic Evaluation

The Home DNA Kits “Falsely Warning of High Risk of Cancer”: DIY Genetic Tests are “Extremely Unreliable” at Detecting Rare Genetic Variants, Major New Study Warns

SNP Chips Perform Poorly for Detecting Rare Genetic Variants

Chip-based DNA Testing Wrong More than Right for Very Rare Variants

Common Genetic Tests Often Wrong When Identifying Rare Disease-Causing Variants Such as BRCA1and BRCA2, Study Says

UK’s NHS Will Use Amazon Alexa to Deliver Official Health Advice to Patients in the United Kingdom

Since Alexa is now programed to be compliant with HIPAA privacy rules, it’s likely similar voice assistance technologies will soon become available in US healthcare as well

Shortages of physicians and other types of caregivers—including histopathologists and pathology laboratory workers—in the United Kingdom (UK) has the UK’s National Health Service (NHS) seeking alternate ways to get patients needed health and medical information. This has prompted a partnership with Amazon to use the Alexa virtual assistant to answer patients healthcare inquiries.

Here in the United States, pathologists and clinical laboratory executives should take the time to understand this development. The fact that the NHS is willing to use a device like Alexa to help it maintain access to services expected by patients in the United Kingdom shows how rapidly the concept of “virtual clinical care” is moving to become mainstream.

If the NHS can make it work in a health system serving 66-million people, it can be expected that health insurers, hospitals, and physicians in the United States will follow that example and deploy similar virtual health services to their patients.

For these reasons, all clinical laboratories and anatomic pathology groups will want to develop a strategy as to how their organizations will interact with virtual health services and how their labs will want to deploy similar virtual patient information services.

Critical Shortages in Healthcare Services

While virtual assistants have been answering commonly-asked health questions by mining popular responses on the Internet for some time, this new agreement allows Alexa to provide government-endorsed medical advice drawn from the NHS website.

By doing this, the NHS hopes to reduce the burden on healthcare workers by making it easier for UK patients to access health information and receive answers to commonly-asked health questions directly from their homes, GeekWire reported. 

“The public needs to be able to get reliable information about their health easily and in ways they actually use. By working closely with Amazon and other tech companies, big and small, we can ensure that the millions of users looking for health information every day can get simple, validated advice at the touch of a button or voice command,” Matthew Gould, CEO of NHSX, a division of the NHS that focuses on digital initiatives, told GeekWire

The Verge reported that when the British government officially announced the partnership in a July press release, the sample questions that Alexa could answer included:

  • Alexa, how do I treat a migraine?
  • Alexa, what are the symptoms of the flu?
  • Alexa, what are the symptoms of chickenpox?

“We want to empower every patient to take better control of their healthcare and technology like this is a great example of how people can access reliable, world-leading NHS advice from the comfort of their home, reducing the pressure on our hardworking GPs (General Practitioners) and pharmacists,” said Matt Hancock, Secretary of State for Health and Social Care, in the press release.

MD Connect notes that the NHS provides healthcare services free of charge to more than 66-million individuals residing in the UK. With 1.2 million employees, the NHS is the largest employer in Europe, according to The Economist. That article also stated that the biggest problem facing the NHS is a staff shortage, citing research conducted by three independent organizations:

Their findings indicate “that NHS hospitals, mental-health providers, and community services have 100,000 vacancies, and that there are another 110,000 gaps in adult social care. If things stay on their current trajectory, the think-tanks predict that there will be 250,000 NHS vacancies in a decade,” The Economist reported.

UK’s Matt Hancock, Secretary of State for Health and Social Care (above), defends the NHS’ partnership with Amazon Alexa, saying millions already use the smart speaker for medical advice and it’s important the health service uses the “best of modern technology.” Click here to watch the video. (Video and caption copyright: Sky News.)

“This idea is certainly interesting and it has the potential to help some patients work out what kind of care they need before considering whether to seek face-to-face medical help, especially for minor ailments that rarely need a GP appointment, such as coughs and colds that can be safely treated at home,” Professor Helen Stokes-Lampard, Chairman at the Royal College of General Practitioners, and Chair of the Board Of Directors/Trustees at National Academy of Social Prescribing, told Sky News.

“However,” she continued, “it is vital that independent research is done to ensure that the advice given is safe, otherwise it could prevent people seeking proper medical help and create even more pressure on our overstretched GP service.”

Amazon has assured consumers that all data obtained by Alexa through the NHS partnership will be encrypted to ensure privacy and security, MD Connect notes. Amazon also promised that the personal information will not be shared or sold to third parties.

Alexa Now HIPAA Compliant in the US

This new agreement with the UK follows the announcement in April of a new Alexa Skills Kit that “enables select Covered Entities and their Business Associates, subject to the US Health Insurance Portability and Accountability Act of 1996 (HIPAA), to build Alexa skills that transmit and receive protected health information (PHI) as part of an invite-only program. Six new Alexa healthcare skills from industry-leading healthcare providers, payors, pharmacy benefit managers, and digital health coaching companies are now operating in our HIPAA-eligible environment.”

Developers of voice assistance technologies can freely use these Alexa skills, which are “designed to help customers manage a variety of healthcare needs at home simply using voice—whether it’s booking a medical appointment, accessing hospital post-discharge instructions, checking on the status of a prescription delivery, and more,” an Amazon Developer Alexa blog states.

The blog lists the HIPAA-compliant Alexa skills as:

  • Express Scripts: Members can check the status of a home delivery prescription and can request Alexa notifications when their prescription orders are shipped.
  • Cigna Health Today by Cigna (NYSE:CI): Eligible employees with one of Cigna’s large national accounts can now manage their health improvement goals and increase opportunities for earning personalized wellness incentives.
  • My Children’s Enhanced Recovery After Surgery (ERAS) (by Boston Children’s Hospital: Parents and caregivers of children in the ERAS program can provide their care teams updates on recovery progress and receive information regarding their post-op appointments.
  • Swedish Health Connect by Providence St. Joseph Health, a healthcare system with 51 hospitals across seven states and 829 clinics: Customers can find an urgent care center near them and schedule a same-day appointment.
  • Atrium Health, a healthcare system with more than 40 hospitals and 900 care locations throughout North and South Carolina and Georgia: Customers in North and South Carolina can find an urgent care location near them and schedule a same-day appointment.
  • Livongo, a digital health company that creates new and different experiences for people with chronic conditions: Members can query their last blood sugar reading, blood sugar measurement trends, and receive insights and Health Nudges that are personalized to them.

HIPAA Journal notes: “This is not the first time that Alexa skills have been developed, but a stumbling block has been the requirements of HIPAA Privacy Rules, which limit the use of voice technology with protected health information. Now, thanks to HIPAA compliant data transfers, the voice assistant can be used by a select group of healthcare organizations to communicate PHI without violating the HIPAA Privacy Rule.”

Steady increases associated with the costs of medical care combined with a shortage of healthcare professionals on both continents are driving trends that motivate government health programs and providers to experiment with non-traditional ways to interact with patients.

New digital and Artificial Intelligence (AI) tools like Alexa may continue to emerge as methods for providing care—including clinical laboratory and pathology advice—to healthcare consumers.

—JP Schlingman

Related Information:

“Alexa, How Do I Treat a Migraine?” Amazon and NHS Unveil Partnership

Amazon’s Alexa Will Deliver NHS Medical Advice in the UK

NHS Health Information Available Through Amazon’s Alexa

UK’s National Health Service Taps Amazon’s Alexa to Field Common Medical Questions

What Happens When Amazon Alexa Gives Health Advice?

Alexa, Where Are the Legal Limits on What Amazon Can Do with My Health Data?

Amazon Alexa Offering NHS Health Advice

A Shortage of Staff Is the Biggest Problem Facing the NHS

Need Quick Medical Advice in Britain? Ask Alexa

Alexa Blogs: Introducing New Alexa Healthcare Skills

Amazon Announces 6 New HIPAA Compliant Alexa Skills

Amazon Alexa Is Now HIPAA-Compliant: Tech Giant Says Health Data Can Now Be Accessed Securely

Can Artificial Intelligence Diagnose Skin Cancers More Accurately than Anatomic Pathologists? Heidelberg University Researchers Say “Yes”

Apple Updates Its Mobile Health Apps, While Microsoft Shifts Its Focus to Artificial Intelligence. Both Will Transform Healthcare, But Which Will Impact Clinical Laboratories the Most?

As Primary Care Providers and Health Insurers Embrace Telehealth, How Will Clinical Laboratories Provide Medical Lab Testing Services?

VA Engages Private Sector Companies in Major Telehealth Initiative to Bring Critical Healthcare Services to Thousands of Veterans Living in Remote Areas

UK’s NHS to Distribute New Clinical Laboratory Test for Women Suspected of Having Pre-Eclampsia

Based on clinical trials of the medical laboratory test, pregnant women can expect a reduced risk for experiencing complications associated with the dangerous blood disorder

Clinical pathology laboratories and obstetricians in the UK may soon have a new blood test that can help provide earlier diagnoses of pre-eclampsia, a hypertensive disorder of pregnancy that can cause liver and kidney disfunctions and, if untreated, can lead to eclampsia and deadly seizures.

Following a clinical trial conducted by scientists at King’s College London (King’s College), the National Health Service (NHS) in the United Kingdom (UK) announced it would be making the new test widely available.

The researchers published their findings in The Lancet medical journal. Their paper explains that the clinical trial took place in 11 maternity units in the UK from June 2016 through October 2017. And that 1,023 women were divided into two groups:

  • 576 (56%) were in the “intervention group,” meaning they had PGF test results made available to their maternity teams;
  • 447 (44%) did not have PGF test results made available.

The researchers, the Independent reported, wanted to determine the impact, if any, the new test’s results would have on diagnoses.

Significantly Reduced Time to Diagnosis

Trial results indicated that measuring the placental growth factor (PGF) in women who are suspected of having pre-eclampsia can increase speed to diagnosis. “PGF testing was shown to reduce the average time to pre-eclampsia diagnosis from 4.1 days to 1.9 days, and serious complications before birth (such as eclampsia, stroke, and maternal death) [dropped] from 5% to 4%,” a King’s College press release stated.

“Complications like stroke, seizures and maternal death fell by 20% when doctors had access to PGF testing,” the Independent reported.

The researchers stated in their study, “Our trial has shown that, in women presenting with suspected pre-eclampsia, PGF measurement, incorporated into a management algorithm based on national guidelines, significantly reduces the time taken for treating clinicians to diagnose pre-eclampsia. This improvement was associated with a significant reduction in maternal adverse outcomes, with no detected difference in gestational age at delivery or adverse perinatal outcomes.”

The King’s College press release states, “Pre-eclampsia is suspected in around 10% of UK pregnancies, affecting approximately 80,000 women annually. If untreated, it can progress to cause complications in the woman, including damage to vital organs, fits, and can be fatal for the woman and baby. Globally, 100 women die as a result of the condition every day.”

The release also noted that “doctors were able to diagnose pre-eclampsia on average two days sooner. This was associated with significant improvements in outcomes for women without causing health problems for babies.”

Tony Young, PhD (above), National Clinical Lead for Innovation at NHS, stated in the King’s College press release that “This innovative blood test helps determine the risks of pre-eclampsia in pregnancy, enabling women to be directed to appropriate care or reduce unnecessary worry more quickly.” (Photo copyright: LinkedIn.)

Measuring PGF in Clinical Laboratory Study

PGF is a molecular marker for inflammation associated mostly with the mother’s placenta. The King’s College researchers wanted to find out if a quicker diagnosis of pre-eclampsia was possible. And, if so, could it reduce adverse outcomes in the mother and baby?

“For the last hundred years, we have diagnosed pre-eclampsia through measuring blood pressure and checking for protein in a woman’s urine. These are relatively imprecise and often quite subjective,” said Lucy Chappell, PhD, NIHR Research Professor in Obstetrics at King’s College, and lead author of the study, in the news release.

“We knew that monitoring PGF was an accurate way to help detect the condition, but [we] were unsure whether making this tool available to clinicians would lead to better care for women. Now we know that it does,” she concluded.

Pre-eclampsia can lead to stroke, seizures, and even death of expectant mothers and unborn children. It is usually diagnosed after 20 weeks of gestation through blood pressure tests and urine tests that show hypertension and elevated protein levels.

“We found that the availability of PGF test results substantially reduced the time to clinical confirmation of pre-eclampsia. Where PGF was implemented, we found a lower incidence of maternal adverse outcomes,” the researchers wrote in their study.

Similar Study in the US

In the UK, pre-eclampsia affects about one in 20 pregnancies or 80,000 women each year, New Scientist explained. While in the US, data compiled from the Centers for Disease Control and Prevention (CDC) indicate that pre-eclampsia affects one in 25 pregnancies or about 154,220 women annually.

Researchers in Ohio also recently reported on a test and a piloted clinical study for rapid diagnosis of pre-eclampsia.

Scientists at Ohio State University’s College of Medicine and Wexner Medical Center (OSU), and at Nationwide Children’s Hospital, have developed a non-invasive red-dye-on-paper urine test to identify pre-eclampsia at the point-of-care, a Wexner press release announced.

“This is the first clinical study using the point-of-care, paper-based Congo Red Dot (CRD) diagnostic test, and the mechanism proved superior in establishing or ruling out a diagnosis of pre-eclampsia,” Kara Rood, MD, a maternal-fetal medicine physician at Wexner Medical Center and first author of the study said in the Wexner press release. “Our findings will have a huge impact on the health of women and children.”

The researchers published their findings in EClinicalMedicine, a Lancet Journal.

“Pre-eclampsia is often described as ‘mysterious’ because it’s difficult to diagnose. Our researchers show that there’s an easy, non-invasive test that will help diagnose this condition and maintain the health of pregnant women and their babies,” K. Craig Kent, MD, OSU Dean of the College of Medicine, said in the press release.

Clinical laboratory tests such as these being developed in the US and abroad could help pregnant women worldwide experience happy pregnancies and give birth to healthy babies. Medical laboratory leaders in this country may want to stay abreast of the development of these simple blood and urine tests.

                                                                        —Donna Marie Pocius

Related Information:

Pre-Eclampsia: NHS to Roll Out Breakthrough Test Which Speeds Up Diagnosis and Can Save Lives

Blood Test Helps Accurate, Rapid Diagnosis for Pre-eclampsia

Blood Pressure in Pregnancy

Placental Growth Factor Testing to Assess Women with Suspected Pre-eclampsia: a Multi-Centre, Pragmatic, Stepped-wedge Cluster Randomized Controlled Trial

Pre-Eclampsia Blood Test Could Help Diagnose the Condition Earlier

Research Finds Simple Urine Test Allows for Rapid Diagnosis of Pre-eclampsia

UTSA Researchers Create Leukemia Proteome Atlases to Assist in Leukemia Research and Personalized Medicine Treatments

This new atlas of leukemia proteomes may prove useful for medical laboratories and pathologists providing diagnostic and prognostic services to physicians treating leukemia patients

Clinical pathology laboratories, hematopathologists, and medical technologists (aka, medical laboratory scientists) have a new tool that aids in leukemia research and helps hematologists and other medical practitioners treat patients with acute myelogenous leukemia (aka, acute myeloid leukemia or AML).

Researchers at the University of Texas at San Antonio (UTSA) and the University of Texas MD Anderson Cancer Center created the online atlases—categorized into adult and pediatric datasets—to “provide quantitative, molecular hallmarks of leukemia; a broadly applicable computational approach to quantifying heterogeneity and similarity in molecular data; and a guide to new therapeutic targets for leukemias,” according to the Leukemia Atlases website.

In building the Leukemia Proteome Atlases, the researchers identified and classified protein signatures that are present when patients are diagnosed with AML. Their goal is to improve survival rates and aid scientific research for this deadly disease, as well as develop personalized, effective precision medicine treatments for patients.  

The researchers published their findings in Nature Biomedical Engineering, titled, “A Quantitative Analysis of Heterogeneities and Hallmarks in Acute Myelogenous Leukaemia.” A link to a downloadable PDF of the entire published study is below.

 Leukemia: One or Many Diseases?

To perform the study, the scientists looked at the proteomic screens of 205 biopsies of patients with AML and analyzed the genetic, epigenetic, and environmental diversity in the cancer cells. Their analysis “revealed 154 functional patterns based on common molecular pathways, 11 constellations of correlated functional patterns, and 13 signatures that stratify the outcomes of patients.”

Amina Qutub, PhD, Associate Professor at UTSA and one of the authors of the research, told UTSA Today, “Acute myelogenous leukemia presents as a cancer so heterogeneous that it is often described as not one, but a collection of diseases.”

“To decipher the clues found in proteins from blood and bone marrow of leukemia patients, we developed a new computer analysis—MetaGalaxy—that identifies molecular hallmarks of leukemia,” noted Amina Qutub, PhD (above), UTSA Professor of Biomedical Engineering and one of the UTSA study’s authors. “These hallmarks are analogous to the way constellations guide navigation of the stars: they provide a map to protein changes for leukemia,” she concluded. (Photo copyright: UTSA.)

To better understand the proteomic levels associated with AML, and share their work globally with other scientists, the researchers created the Leukemia Proteome Atlases web portal. The information is displayed in an interactive format and divided into adult and pediatric databases. The atlases provide quantitative, molecular hallmarks of AML and a guide to new therapeutic targets for the disease. 

Fighting an Aggressive and Lethal Cancer

AML is a type of cancer where the bone marrow makes an abnormal type of white blood cells called myeloblasts, red blood cells, or platelets. It is one of the most lethal forms of leukemia and only about one in four patients (28.3%) diagnosed with the disease will survive five years after their initial diagnosis, according to Cancer Stat Facts on Leukemia posted by the National Cancer Institute (NCI) at the National Institutes of Health (NIH).

The NCI predicts there will be approximately 21,540 new cases of AML diagnosed this year. They will account for about 1.2% of all new cancer cases. The disease will be responsible for approximately 10,920 deaths in 2019, or 1.8% of all cancer deaths. In 2016, there were an estimated 61,048 people living with AML in the US. 

“Our ‘hallmark’ predictions are being experimentally tested through drug screens and can be ‘programmed’ into cells through synthetic manipulation of proteins,” Qutub continued. “A next step to bring this work to the clinic and impact patient care is testing whether these signatures lead to the aggressive growth or resistance to chemotherapy observed in leukemia patients.

“At the same time, to rapidly accelerate research in leukemia and advance the hunt for treatments, we provide the hallmarks in an online compendium [LeukemiaAtlas.org] where fellow researchers and oncologists worldwide can build from the resource, tools, and findings.”

By mapping AML patients from the proteins present in their blood and bone marrow, the researchers hope that healthcare professionals will be able to better categorize patients into risk groups and improve treatment outcomes and survival rates for this aggressive form of cancer.  

The Leukemia Proteome Atlases are another example of the trend where researchers work together to compile data from patients and share that information with other scientists and medical professionals. Hopefully, having this type of data readily available in a searchable database will enable researchers—as well as clinical laboratory scientists and pathologists—to gain a better understanding of AML and benefit cancer patients through improved diagnosis, treatment, and monitoring. 

—JP Schlingman

Related Information:

Computational Researchers and Oncologists Develop Protein Cancer Atlas to Accelerate Personalized Medicine for Leukemia Patients

Leukemia Protein Atlas Holds Power to Accelerate Precision Medicine

A Quantitative Analysis of Heterogeneities and Hallmarks in Acute Myelogenous Leukaemia

Downloadable PDF: A quantitative analysis of heterogeneities and hallmarks in acute myelogenous leukaemia

Cancer Stat Facts: Leukemia – Acute Myeloid Leukemia (AML)

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