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Clinical Laboratories and Pathology Groups

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News, Analysis, Trends, Management Innovations for
Clinical Laboratories and Pathology Groups

Hosted by Robert Michel
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Virginia Commonwealth University Study Determines 40% of Americans Have Liver Disease

Clinical laboratories and anatomic pathology groups should prepare for a marked increase in orders for liver disease testing

New research from Virginia Commonwealth University’s Institute for Liver Disease and Metabolic Health in Richmond shows that four out of every 10 Americans has fatty liver disease of some type, according to a news release. Forty percent of Americans is an astonishing number! The study’s findings will almost certainly lead to clinical laboratories performing more testing in support of diagnosis, treatment decision making, and patient monitoring for liver disease than currently ordered by physicians.

Hepatologist Juan Pablo Arab, MD, director of alcohol sciences at Virginia Commonwealth University (VCU), led the team that conducted the research. He noted that the driving force behind the numbers is obesity and type two diabetes.

The researchers based their study on data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey, which recorded the health of more than 5,000 individuals from 2017 to 2018, Newsmax reported.

“By 2018, federal data showed that 42% of adults had some form of fatty liver disease—higher than prior estimates,” Arab’s team told Newsmax, adding that “Hispanic adults were at especially high risk … with nearly half (47%) affected.”

The scientists published their findings in Nature Communications Medicine titled, “Disparities in Steatosis Prevalence in the United States by Race or Ethnicity according to the 2023 Criteria.”

“This study highlights a significant health issue that affects a large portion of the US population, and it shows that certain groups are at a higher risk. We hope these findings will guide more targeted health interventions to reduce the burden of liver disease, especially in high-risk communities,” said Juan Pablo Arab, MD (above), hepatologist with VCU’s Institute for Liver Disease and Metabolic Health, director of alcohol sciences, and lead researcher in the VCU study, in a VCU news release. These insights can be expected to lead to guidelines calling for more clinical laboratory testing associated with the diagnosis of fatty liver disease. (Photo copyright: Virginia Commonwealth University.)

Clinical Laboratory Testing

The VCU researchers found that metabolic dysfunction-associated steatotic liver disease (MASLD), also known as nonalcoholic fatty liver disease (NAFLD), was primarily brought on by obesity and type 2 diabetes.

“Groups at greater risk for MASLD include men, adults older than 40, individuals with health insurance, those with higher body mass index, and people with other health issues like diabetes, high blood pressure, high triglycerides, and low levels of good cholesterol. Interestingly, the study found that black individuals had the lowest risk of developing MASLD compared with other groups,” the VCU news release notes.

Fatty liver disease can also be caused by excessive alcohol consumption (called alcohol-associated liver disease or ALD) or a combination of both metabolic dysfunction and moderate-to-high alcohol intake, which is called MetALD, Newsmax reported.

“Although MASLD was the most common type of liver disease found in this study, the researchers also uncovered substantial rates of MetALD and alcohol-associated liver disease. For MetALD, the study showed that men and individuals with a higher BMI [body mass index] were at a greater risk, and Asians were at lower risk. Surprisingly, the only factor that appeared to lower the risk of ALD was having health insurance, though the reasons for this are not clear,” according to the VCU news release.

On its website, Mayo Clinic notes that NAFLD is often symptomless, and that doctors typically depend on routine clinical laboratory blood test results to reach a diagnosis. Additional testing helps determine whether higher than normal liver enzymes are actually from fatty liver disease or some other condition.

Medical laboratories play a key role in facilitating the final diagnoses. According to Mayo Clinic, blood tests to identify liver disease include:

Medical imaging could also be required to reach a diagnosis, beginning with an abdominal ultrasound, Mayo Clinic added. Additionally, more precise tests may be ordered to determine the stiffness of the liver and likelihood of scarring or fibrosis. Those modalities include:

Labs will often perform these tests on the same patient multiple times as the patient’s lifestyle changes. A liver biopsy may also be required to determine severity of damage, Mayo Clinic added.

Increase in Testing

Fatty liver disease at its most severe can lead to acute liver failure and fatal kidney complications, the American Liver Foundation (ALF) reported. If symptoms appear, a patient may experience “fatigue, weakness, weight loss, loss of appetite, nausea,

abdominal pain, spider-like blood vessels, yellowing of the skin and eyes (jaundice), itching, fluid buildup and swelling of the legs (edema) and abdomen (ascites), and mental confusion,” the ALF added.

As more healthcare providers focus their attention on diagnosing and treating this potentially deadly disease, clinical laboratories and anatomical pathology groups will likely see an uptick in tests ordered by doctors moving from initial diagnoses to more detailed testing and eventually to treatment follow ups.

—Kristin Althea O’Connor

Related Information:

Fatty Liver Disease Now Affects Four in 10 US Adults

More than 40% of US Adults Have Liver Disease, with Higher Risk among Hispanics, New Study Finds

Disparities in Steatosis Prevalence in the United States by Race or Ethnicity According to the 2023 Criteria

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Nonalcoholic Fatty Liver Disease

Non-Alcoholic Fatty Liver Disease (NAFLD)

Virginia Commonwealth University Scientists Combine dPCR and High-Speed Microscopic Imaging to Reduce Cost of Diagnosing Cancers

VCU scientists used the technique to measure mutations associated with acute myeloid leukemia, potentially offering an attractive alternative to DNA sequencing

More accurate but less-costly cancer diagnostics are the Holy Grail of cancer research. Now, research scientists at Virginia Commonwealth University (VCU) say they have developed a clinical laboratory diagnostic technique that could be far cheaper and more capable than standard DNA sequencing in diagnosing some diseases. Their method combines digital polymerase chain reaction (dPCR) technology with high-speed atomic force microscopy (HS-AFM) to generate nanoscale-resolution images of DNA.

The technique allows the researchers to measure polymorphisms—variations in gene lengths—that are associated with many cancers and neurological diseases. The VCU scientists say the new technique costs less than $1 to scan each dPCR reaction.

The researchers used the technique to measure and quantify polymorphisms associated with mutations in the FLT3 gene. Cancer researchers have linked these mutations, known as internal tandem duplications (ITDs), to a poor prognosis of acute myeloid leukemia (AML) and a more aggressive form of the disease, Nature Leukemia noted in “Targeting FLT3 Mutations in AML: Review of Current Knowledge and Evidence.”

“We chose to focus on FLT3 mutations because they are difficult to [diagnose], and the standard assay is limited in capability,” said physicist Jason Reed, PhD, Assistant Professor in the Virginia Commonwealth University Department of Physics, in a VCU press release.

Reed is an expert in nanotechnology as it relates to biology and medicine. He led a team that included other researchers in VCU’s physics department as well as physicians from VCU Massey Cancer Center and the Department of Internal Medicine at VCU School of Medicine.

Jason Reed, PhD with Andrey Mikheikin, PhD, on left and Sean Koebley, PhD, on right in a press release from Virginia Commonwealth University (VCU)
“The technology needed to detect DNA sequence rearrangements is expensive and limited in availability, yet medicine increasingly relies on the information it provides to accurately diagnose and treat cancers and many other diseases,” said Jason Reed, PhD (above center, with Andrey Mikheikin, PhD, on left and Sean Koebley, PhD, on right), in a press release from Virginia Commonwealth University (VCU). “We’ve developed a system that combines a routine laboratory process with an inexpensive yet powerful atomic microscope that provides many benefits over standard DNA sequencing for this application, at a fraction of the cost.” (Photo copyright: Virginia Commonwealth University.)

Validating the Clinical Laboratory Test

The physicists worked with two VCU physicians—hematologist/oncologist Amir Toor, MD, and hematopathologist Alden Chesney, MD—to compare the imaging technique to the LeukoStrat CDx FLT3 Mutation Assay, which they described as the “current gold standard test” for diagnosing FLT3 gene mutations.

The researchers said their technique matched the results of the LeukoStrat test in diagnosing the mutations. But unlike that test, the new technique also can measure variant allele frequency (VAL). This “can show whether the mutation is inherited and allows the detection of mutations that could potentially be missed by the current test,” states the VCU press release.

The VCU researchers published their findings in ACS Nano, a journal of the American Chemical Society (ACS), titled, “Digital Polymerase Chain Reaction Paired with High-Speed Atomic Force Microscopy for Quantitation and Length Analysis of DNA Length Polymorphisms.” They also presented their findings at the annual meetings of the Association of Molecular Pathology (AMP) and American Society of Hematology (ASH).

“We plan to continue developing and testing this technology in other diseases involving DNA structural mutations,” Reed said. “We hope it can be a powerful and cost-effective tool for doctors around the world treating cancer and other devastating diseases driven by DNA mutations.”

How the New Diagnostic Technique Works

Sean Koebley, PhD, Postdoctoral Fellow at Virginia Commonwealth University and another member of the VCU research team, described the new diagnostic technique in a video produced for the ASH and AMP meetings.

“In our approach we first used digital PCR, in which a mixed sample is diluted to less than one target molecule per aliquot and the aliquots are amplified to yield homogeneous populations of amplicons,” he said. “Then, we deposited each population onto an atomically-flat partitioned surface.”

The VCU researchers “scanned each partition with high-speed atomic force microscopy, in which an extremely sharp tip is rastered across the surface, returning a 3D map of the surface with nanoscale resolution,” he said. “We wrote code that traced the length of each imaged DNA molecule, and the distribution of lengths was used to determine whether the aliquot was a wild type [unmutated] or variant.”

In Diagnostics World, Reed said the method “doesn’t really have any more complexity than a PCR assay itself. It can easily be done by most lab technicians.”

Earlier Research

A VCU press release from 2017 noted that Reed’s research team had developed technology that uses optical lasers (similar to those in a DVD player) to accelerate the scanning. The researchers previously published a study about the technique in Nature Communications, and a patent is currently pending.

“DNA sequencing is a powerful tool, but it is still quite expensive and has several technological and functional limitations that make it difficult to map large areas of the genome efficiently and accurately,” Reed said in the 2017 VCU press release. “Our approach bridges the gap between DNA sequencing and other physical mapping techniques that lack resolution. It can be used as a stand-alone method or it can complement DNA sequencing by reducing complexity and error when piecing together the small bits of genome analyzed during the sequencing process.”

Using CRISPR technology, the team also developed what they described as a “chemical barcoding solution,” placing markers on DNA molecules to identify genetic mutations.

New DNA Clinical Laboratory Testing?

Cancer diagnostics are constantly evolving and improving. It is not clear how long it will be before VCU’s new technique will reach clinical laboratories that perform DNA testing, if at all. But VCU’s new technique is intriguing, and should it prove viable for clinical diagnostic use it could revolutionize cancer diagnosis. It is a development worth watching.

—Stephen Beale

Related Information:

VCU Technology Could Upend DNA Sequencing for Diagnosing Certain DNA Mutations

A Team Led by a VCU Physicist Has Developed a Revolutionary Imaging Technique to Map DNA Mutations

Low-Cost Approach to Detecting DNA Rearrangement Mutations

Targeting FLT3 Mutations in AML: Review of Current Knowledge and Evidence

System, Method, Computer-Accessible Medium and Apparatus for DNA Mapping

Digital Polymerase Chain Reaction Paired with High-Speed Atomic Force Microscopy for Quantitation and Length Analysis of DNA Length Polymorphisms

Internal Tandem Duplications of the FLT3 Gene Are Present in Leukemia Stem Cells

Clinical Laboratory Leaders Agree: Showing Value Is More Important than Ever as Healthcare Transitions Away from Fee-for Service Reimbursement

How medical laboratories can show value through process improvement methods and analytics will be among many key topics presented at the upcoming Lab Quality Confab conference

Quality management is the clinical laboratory’s best strategy for surviving and thriving in this era of shrinking lab budgets, PAMA price cuts, and value-based payment. In fact, the actions laboratories take in the next few months will set the course for their path to clinical success and financial sustainability in 2020 and beyond.

But how do medical laboratory managers and pathologists address these challenges while demonstrating their lab’s value? One way is through process improvement methods and another is through the use of analytics.

Clinical pathologists, hospital lab leaders, and independent lab executives have told Dark Daily that the trends demanding their focus include:

  • Ensuring needed resources and appropriate tests, while the lab is scrutinized by insurance companies and internally by hospital administration;
  • PAMA’s (Protecting Access to Medicare Act of 2014) effects on reimbursement;
  • Consumers’ demand for lower cost and better access to quality healthcare;
  • Serving patients in a wider continuum of care; and
  • Collaborating instead of competing with other labs in the market.

“The laboratory and resources we are given are being scrutinized in a different way than they have been historically,” said Christopher Doern, PhD, Director of Microbiology and Associate Professor of Pathology, Virginia Commonwealth University Health System (VCU Health) Medical College of Virginia, Richmond, in an exclusive interview with Dark Daily.

“Our impact on patient care, in many cases, is very indirect. So, it is difficult to point to outcomes that occur. We know things we do matter and change patient care, but objectively showing that is a real struggle. And we are being asked to do more than we ever had before, and those are the two big things that keep me up at night these days,” he added.

This is where process improvement methods and analytics are helping clinical laboratories understand critical issues and find opportunities for positive change.

“You need to have a strategy that you can adapt to a changing landscape in healthcare. You have to use analytics to guide your progress and measure your success,” Patricia Nortmann, System Director of Laboratory Services at St. Elizabeth Healthcare, Erlanger, Ky., told Dark Daily.

Clinical Laboratories Can Collaborate Instead of Compete

Prior to a joint venture with TriHealth in Cincinnati, St. Elizabeth lab leaders used data to inform their decision-making. Over about 12 years preceding the consolidation of labs they:

  • Centralized the outreach core lab;
  • Installed front-end automation in chemistry;
  • Standardized the laboratory information system (LIS) and analyzer platforms across five affiliate hospitals; and
  • Implemented front-end automation outside the core area and in the microbiology lab.

“We are now considered a regional reference lab in the state of Kentucky for two healthcare organizations—St. Elizabeth and TriHealth,” Nortmann said. 

Thanks to these changes, the lab more than doubled its workload, growing from 2.1 million to 4.3 million outreach tests in the core laboratory, she added.

Christopher Doern, PhD (left), Director of Microbiology and Associate Professor of Pathology at Virginia Commonwealth University Health System; Patricia Nortmann (center), System Director of Laboratory Services at St. Elizabeth Healthcare; and Joseph Cugini (right), Manager Client Solutions at Health Network Laboratories, will present practical solutions and case studies in quality improvement and analytics for clinical laboratory professionals at the 13th Annual Lab Quality Confab, October 15-16, 2019, at the Hyatt Regency in Atlanta, Ga. (Photo copyright: The Dark Report.)

Using Analytics to Test the Tests

Clinical laboratories also are using analytics and information technology (IT) to improve test utilization.

At VCH Health, Doern said an analytics solution interfaces with their LIS, providing insights into test orders and informing decisions about workflow. “I use this analytics system in different ways to answer different questions, such as:

  • How are clinicians using our tests?
  • When do things come to the lab?
  • When should we be working on them? 

“This is important for microbiology, which is a very delayed discipline because of the incubation and growth required for the tests we do,” he said.

Using analytics, the lab solved an issue with Clostridium difficile (C diff) testing turnaround-time (TAT) after associating it with specimen transportation.

Inappropriate or duplicate testing also can be revealed through analytics. A physician may reconsider a test after discovering another doctor recently ordered the same test. And the technology can guide doctors in choosing tests in areas where the related diseases are obscure, such as serology.  

Avoiding Duplicate Records While Improving Payment

Another example of process improvement is Health Network Laboratories (HNL) in Allentown, Pa. A team there established an enterprise master patient index (EMPI) and implemented digital tools to find and eliminate duplicate patient information and improve lab financial indicators.

“The system uses trusted sources of data to make sure data is clean and the lab has what it needs to send out a proper bill. That is necessary on the reimbursement side—from private insurance companies especially—to prevent denials,” Joseph Cugini, HNL’s Manager Client Solutions, told Dark Daily

HNL reduced duplicate records in its database from 23% to under one percent. “When you are talking about several million records, that is quite a significant improvement,” he said.

Processes have improved not only on the billing side, but in HNL’s patient service centers as well, he added. Staff there easily find patients’ electronic test orders, and the flow of consumers through their visits is enhanced.

Learn More at Lab Quality Confab Conference

Cugini, Doern, and Nortmann will speak on these topics and more during the 13th Annual Lab Quality Confab (LQC), October 15-16, 2019, at the Hyatt Regency in Atlanta, Ga. They will offer insights, practical knowledge, and case studies involving Lean, Six Sigma, and other process improvement methods during this important 2-day conference, a Dark Daily news release notes.

Register for LQC, which is produced by Dark Daily’s sister publication The Dark Report, online at https://www.labqualityconfab.com/register, or by calling 512-264-7103.   

—Donna Marie Pocius

Related Information:

13th Annual Lab Quality Confab October 15-16, 2019. Hyatt Regency, Atlanta, Ga.

Clinical Laboratory Innovators in Lean, Six Sigma, and Process Improvement to Gather in Atlanta October 15-16, 2019

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