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Researchers Use Machine Learning to Identify Thousands of New Marine RNA Viruses in Study of Interest to Microbiologists and Clinical Laboratory Scientists

Screening and analysis of ocean samples also identified a possible missing link in how the RNA viruses evolved

An international team of scientists has used genetic screening and machine learning techniques to identify more than 5,500 previously unknown species of marine RNA viruses and is proposing five new phyla (biological groups) of viruses. The latter would double the number of RNA virus phyla to 10, one of which may be a missing link in the early evolution of the microbes.

Though the newly-discovered viruses are not currently associated with human disease—and therefore do not drive any current medical laboratory testing—for virologists and other microbiologists, “a fuller catalog of these organisms is now available to advance scientific understanding of how viruses evolve,” said Dark Daily Editor-in-Chief Robert Michel.

“While scientists have cataloged hundreds of thousands of DNA viruses in their natural ecosystems, RNA viruses have been relatively unstudied,” wrote four microbiologists from Ohio State University (OSU) who participated in the study in an article they penned for The Conversation.

The OSU study authors included:

Zayed was lead author of the study and Sullivan led the OSU research team.

The researchers published their findings in the journal Science, titled, “Cryptic and Abundant Marine Viruses at the Evolutionary Origins of Earth’s RNA Virome.”

Matthew Sullivan, PhD
“RNA viruses are clearly important in our world, but we usually only study a tiny slice of them—the few hundred that harm humans, plants and animals,” explained Matthew Sullivan, PhD (above), Director, Center of Microbiome Science, in an OSU news story. Sullivan led the OSU research team. “We wanted to systematically study them on a very big scale and explore an environment no one had looked at deeply, and we got lucky because virtually every species was new, and many were really new,” he added. (Photo copyright: University of Ohio.)

RNA versus DNA Viruses

In contrast to the better-understood DNA virus, an RNA virus contains RNA instead of DNA as its genetic material, according to Samanthi Udayangani, PhD, in an article she penned for Difference Between. Examples of RNA viruses include:

One major difference, she explains, is that RNA viruses mutate at a higher rate than do DNA viruses.

The OSU scientists identified the new species by analyzing a database of RNA sequences from plankton collected during a series of ocean expeditions aboard a French schooner owned by the Tara Ocean Foundation.

“Plankton are any aquatic organisms that are too small to swim against the current,” the authors explained in The Conversation. “They’re a vital part of ocean food webs and are common hosts for RNA viruses.”

The team’s screening process focused on the RNA-dependent RNA polymerase (RdRp) gene, “which has evolved for billions of years in RNA viruses, and is absent from other viruses or cells,” according to the OSU news story.

“RdRp is supposed to be one of the most ancient genes—it existed before there was a need for DNA,” Zayed said.

The RdRp gene “codes for a particular protein that allows a virus to replicate its genetic material. It is the only protein that all RNA viruses share because it plays an essential role in how they propagate themselves. Each RNA virus, however, has small differences in the gene that codes for the protein that can help distinguish one type of virus from another,” the study authors explained.

The screening “ultimately identified over 44,000 genes that code for the virus protein,” they wrote.

Identifying Five New Phyla

The researchers then turned to machine learning to organize the sequences and identify their evolutionary connections based on similarities in the RdRp genes.

“The more similar two genes were, the more likely viruses with those genes were closely related,” they wrote.

The technique classified many of the sequences within the five previously known phyla of RNA viruses:

But the researchers also identified five new phyla—including two dubbed “Taraviricota” and “Arctiviricota”—that “were particularly abundant across vast oceanic regions,” they wrote. Taraviricota is named after the Tara expeditions and Arctiviricota gets its name from the Arctic Ocean.

They speculated that Taraviricota “might be the missing link in the evolution of RNA viruses that researchers have long sought, connecting two different known branches of RNA viruses that diverged in how they replicate.”

In addition to the five new phyla, the researchers are proposing at least 11 new classes of RNA viruses, according to the OSU story. The scientists plan to issue a formal proposal to the International Committee on Taxonomy of Viruses (ICTV), the body responsible for classification and naming of viruses. 

Studying RNA Viruses Outside of Disease Environments

“As the COVID-19 pandemic has shown, RNA viruses can cause deadly diseases. But RNA viruses also play a vital role in ecosystems because they can infect a wide array of organisms, including microbes that influence environments and food webs at the chemical level,” wrote the four study authors in The Conversation. “Mapping out where in the world these RNA viruses live can help clarify how they affect the organisms driving many of the ecological processes that run our planet. Our study also provides improved tools that can help researchers catalog new viruses as genetic databases grow.”

This remarkable study, which was partially funded by the US National Science Foundation, will be most intriguing to virologists and microbiologists. However, clinical laboratories also should be interested in the fact that the catalog of known viruses has just expanded by 5,500 types of RNA viruses.

Stephen Beale

Related Information:

Researchers Identified Over 5,500 New Viruses in the Ocean, Including a Missing Link in Viral Evolution

Cryptic and Abundant Marine Viruses at the Evolutionary Origins of Earth’s RNA Virome

There’s More to RNA Viruses than Diseases

Differences Between DNA and RNA Viruses

Ocean Water Samples Yield Treasure Trove of RNA Virus Data

Global Survey of Marine RNA Viruses Sheds Light on Origins and Abundance of Earth’s RNA Virome

Scientists Find Trove of over 5,000 New Viruses Hidden in Oceans

Virologists Identify More than 5,000 New Viruses in the Ocean

Scientists Use Thousands of Genetic Markers to Develop Risk Scores for Six Common Diseases: Findings May Have Implications for Clinical Laboratories

Study demonstrates how precision medicine is advancing because of new insights from the use and interpretation of whole-genome sequencing

As part of the Genomic Medicine at Veterans Affairs Study (GenoVA), researchers from Harvard Medical School, Veterans Affairs Boston Healthcare System, and Brigham and Women’s Hospital in Massachusetts used thousands of genetic markers to develop and validate polygenic risk scores (PRS) for six common illnesses. These findings may eventually provide clinical laboratories and anatomic pathology groups with useful biomarkers and diagnostic tests.

The focus of the ongoing GenoVA study is to “determine the clinical effectiveness of polygenic risk score testing among patients at high genetic risk for at least one of six diseases measured by time-to-diagnosis of prevalent or incident disease over 24 months,” according to the National Institutes of Health.   

The scientists used data obtained from 36,423 patients enrolled in the Mass General Brigham Biobank. The six diseases they researched were:

The polygenic scores were then tested among 227 healthy adult patients to determine their risk for the six diseases. The researchers found that:

  • 11% of the patients had a high-risk score for atrial fibrillation,
  • 7% for coronary artery disease,
  • 8% for diabetes, and
  • 6% for colorectal cancer.

Among the subjects used for the study:

  • 15% of the men in the study had a high-risk score for prostate cancer, and
  • 13% of the women in the study had a high score for breast cancer. 

The researchers concluded that the implementation of PRS may help improve disease prevention and management and give doctor’s a way to assess a patient’s risk for these conditions. They published their findings in the journal Nature Medicine, titled, “Development of a Clinical Polygenic Risk Score Assay and Reporting Workflow.”

“We have shown that [medical] laboratory assay development and PRS reporting to patients and physicians are feasible … As the performance of PRS continues to improve—particularly for individuals of underrepresented ancestry groups—the implementation processes we describe can serve as generalizable models for laboratories and health systems looking to realize the potential of PRS for improved patient health,” the researchers wrote.

Using PRS in Clinical Decision Support

Polygenetic risk scores examine multiple genetic markers for risk of certain diseases. A calculation based on hundreds or thousands of these genetic markers could help doctors and patients make personalized treatment decisions, a core tenet of precision medicine.

“As a primary care physician myself, I knew that busy physicians were not going to have time to take an entire course on polygenic risk scores. Instead, we wanted to design a lab report and informational resources that succinctly told the doctor and patient what they need to know to make a decision about using a polygenic risk score result in their healthcare,” epidemiologist Jason Vassy, MD, told The Harvard Gazette. Vassy is Associate Professor, Harvard Medical School at VA Boston Healthcare System and one of the authors of the research.

Jason Vassy, MD
“This is another great example of precision medicine,” Jason Vassy, MD (above), Adjunct Assistant Professor, General Internal Medicine at Boston University School of Medicine, told WebMD. “There’s always been a tantalizing idea that someone’s genetic makeup might help tailor preventative medicine and treatment.” Personalized clinical laboratory testing is increasingly becoming based on an individual’s genetics. (Photo copyright: Harvard Medical School.)

Increasing Diversity of Patients in Genomic Research

The team did encounter some challenges during their analysis. Because most existing genomic research was performed on persons of European descent, the risk scores are less accurate among non-European populations. The researchers for this study addressed this limitation by applying additional statistical methods to qualify accurate PRS calculations across multiple racial groups.

“Researchers must continue working to increase the diversity of patients participating in genomics research,” said Matthew Lebo, PhD, Chief Laboratory Director, Laboratory Molecular Medicine, at Mass General Brigham and one of the authors of the study. “In the meantime, we were heartened to see that we could generate and implement valid genetic scores for patients of diverse backgrounds,” he told The Harvard Gazette.

The team hopes the scores may be utilized in the future to help doctors and patients make better decisions regarding preventative care and screenings.

“It’s easy to say that everyone needs a colonoscopy at age 45,” Vassy told WebMD. “But what if you’re such a low risk that you could put it off for longer? We may get to the point where we understand risk so much that someone may not need one at all.”

Future of PRS in Clinical Decision Making

The scientists plan to enroll more than 1,000 patients in a new program and track them for two years to assess how medical professionals use PRS in clinical care. It is feasible that patients who are at high risk for certain diseases may opt for more frequent screenings or take preventative medicines to mitigate their risk.

“Getting to that point will take time,” Vassy added. “But I can see this type of information playing a role in shared decision making between doctor and patient in the near future.”

The team also established resources and educational materials to assist both doctors and patients in using the scores.

“It’s still very early days for precision prevention,” Vassy noted, “but we have shown it is feasible to overcome some of the first barriers to bringing polygenic risk scores into the clinic.”

More research and studies are needed to prove the effectiveness of using PRS tests in clinical care and determine its role in customized treatment plans based on personal genetics. Nevertheless, pathologists and medical scientists will want to follow the GenoVA study.  

“It is probably most helpful to think of polygenic risk scores as a risk factor for disease, not a diagnostic test or an indication that an individual will certainly develop the disease,” Vassy said. “Most diseases have complex, multifactorial etiologies, and a high polygenic risk score is just one piece of the puzzle.”

Pathologists and clinical laboratory managers may want to stay informed as researchers in the GenoVA study tease new useful diagnostic insights from their ongoing study of the whole human genome. Meanwhile, the GenoVA team is moving forward with the 1,000-patient study with the expectation that this new knowledge may enable earlier and more accurate diagnoses of the health conditions that were the focus of the GenoVA study.

JP Schlingman

Related Information:

Genetic Risk Scores Developed for Six Diseases

Development of a Clinical Polygenic Risk Score Assay and Reporting Workflow

What If You Knew Your Unique Risk for Every Disease?

Polygenic Risk Scores May Assist Decision-making in Primary Care

Maryland’s Statewide Value-Based Payment Models Benefit both Healthcare Providers and Patients

By shifting away from fee-for-service, the state encouraged collaboration between hospitals and physicians to improve care and lower costs

Maryland “leads the way” in value-based payment reform, according to a series of articles published in Health Affairs. “The evidence is clear,” the article declares, “Maryland’s application of uniform prices within global budgets lowers total care costs, reduces unnecessary utilization, and incentivizes proactive preventive and chronic disease management care. Can other states implement Maryland-like payment models and achieve similar financial success?” It’s a fair question.

It is widely-known that clinical laboratory testing is integral to early and accurate diagnosis, and, under Maryland’s current reimbursement model, hospital/health system C-suite administrators have recognized that a robust clinical laboratory service is invaluable to showing progress toward cost containment and patient outcomes goals. But how did that come about? And what can other states learn from Maryland’s success?

Focusing on Better Patient Outcomes at Reduced Costs

Maryland’s current value-based payment arrangement set its first roots back in 2014. That is the year when the state of Maryland and the federal Centers for Medicare and Medicaid Services (CMS) announced a “new initiative to modernize Maryland’s unique all-payer rate-setting system for hospital services aimed at improving patient health and reducing costs,” declared a press release at that time.

Dubbed Maryland’s “All-Payer Model,” the press release went on to say, “This initiative will replace Maryland’s 36-year-old Medicare waiver to allow the state to adopt new policies that reduce per capita hospital expenditures and improve health outcomes as encouraged by the Affordable Care Act. Under this model, Medicare is estimated to save at least $330 million over the next five years.” Did that happen? Apparently so.

The state designed its “All-Payer Model” hospital payment system to render reimbursements based on populations served and the quality of care provided. The program focused on better patient outcomes and higher quality care at a reduced cost, instead of concentrating on the volume of care. The system incentivized hospitals to prevent readmissions, infections, and other potentially avoidable events. 

“By shifting away from traditional fee-for-service payment, Maryland’s new model encourages collaboration between hospitals and physicians to improve patient care, promotes innovative approaches to prevention, and accelerates efforts to avoid unnecessary admissions and readmissions,” said pediatrician Joshua Sharfstein, MD, Vice Dean for Public Health Practice and Community Engagement at the Johns Hopkins Bloomberg School of Public Health in a 2014 CMS press release.

Sharfstein was the Secretary of Maryland’s Department of Health from 2011 to 2014.  

Then, in 2019, Maryland implemented the successor to the state’s “All-Payer Model” dubbed the “Total-Cost-of-Care (TCOC) Model.”

According to the CMS, whereas the All-Payer Model “established global budgets for certain Maryland hospitals to reduce Medicare hospital expenditures and improve quality of care for beneficiaries,” the TCOC “builds on the success of the Maryland All-Payer Model by creating greater incentives for healthcare providers to coordinate with each other and provide patient-centered care, and by committing the State to a sustainable growth rate in per capita total cost of care spending for Medicare beneficiaries.”

The TCOC began on January 1, 2019, and runs through December 31, 2026.

Nicole Stallings of the Maryland Hospital Association
“Our focus is really on the health of our communities,” Nicole Stallings of the Maryland Hospital Association told State of Reform. “We don’t have a public hospital system, we don’t have tiered hospitals, we don’t have hospitals that are having to close because we are able to spread cost really equitably across our system. Equity being a core pillar is something that we know is critically important to maintain. We want to see more alignment there as we now try to tackle these population health goals. But we believe there’s more collaboration happening here than anywhere else,” she added. Clinical laboratories have an important role to play in population health. (Photo copyright: Center Maryland/Vimeo.)

Results of Maryland’s All-Payer-Model Program

In general, an all-payer system allows a state to manage healthcare prices via rate setting where all healthcare payers, including the government, private insurers, and employer healthcare plans, pay similar prices for services provided at individual hospitals.

When it announced the results of the five-year All-Payer-Model program, Maryland’s Health Services Cost Review Commission—the state agency responsible for regulating cost and quality of hospital care in Maryland—declared the program’s targets had been achieved. They included:

  • 1.92% average annual growth per capita in hospital revenue (goal was to be less than or equal to 3.58%).
  • $1.4 billion cumulative Medicare savings in hospital expenditures.
  • 53% reduction in hospital-acquired conditions (goal was 30% reduction over five years).
  • Below national average for hospital readmissions of Medicare patients within five years.
  • All of Maryland’s 47 acute-care hospitals paid based on health populations served—not number of services rendered—with 98% of total hospital revenue under Global Budget Revenue (GBR) payment method.

In addition, the Maryland HSCRC report indicated that innovative care was a key tenet of the model and that hospitals benefitted from being given the ability to:

  • Invest in new healthcare programs that improve collaboration with other providers in the community.
  • Implement new clinical protocols, patient safety techniques, and follow-up procedures for high-risk patients at hospital discharge.
  • Create hubs of care to triage needs, coordinate important services, and ensure patients in need are connected to services outside the hospital.

After the success of the Maryland All-Payer Model, the state’s Total-Cost-of-Care Model program continued to focus on healthcare cost savings to Medicare. But it introduced population health improvement activities across the entire healthcare delivery system.

Future of Maryland’s Total-Cost-of-Care Model Program

Maryland’s TCOC Model program seeks more than $1 billion in Medicare savings by the end of 2023, or the fifth performance year of the program. According to the CMS Innovation Models webpage, Maryland’s TCOC Model includes the following three programs:

  • The Hospital Payment Program, where each hospital receives a population-based payment amount which covers all hospital services provided during a year.
  • The Care Redesign Program, which allows hospitals to make incentive payments to nonhospital healthcare providers who partner with hospitals to provide care.
  • The Maryland Primary Care Program, which incentivizes primary care providers to offer advanced care services to their patients.

An analysis of the first two years of the TCOC program found some significant improvements particularly in the areas of care management, access, and continuity.

In the first performance year of Maryland’s TCOC model, the state reduced spending by $365 million, relative to national trends, according to a Mathematica implementation report.

Part of the success of the model is due to its use of global, fixed budgets that are set for every hospital. Rates are established by an independent commission which prevents cost shifting and provides a more equitable system for patients where they pay the same price for the same service at all hospitals throughout the state, Mathematica noted. 

“We believe [global budgets are] a real distinguishing factor, because unlike the rest of the country, our hospitals aren’t paid more to do more,” said Nicole Stallings, told State of Reform. Stallings is Chief External Affairs Officer and Senior Vice President, Government Affairs and Policy at the Maryland Hospital Association (MHA).

Expanding Maryland’s All-Payer-Model Program to Other States

In 2016, CMS established the Center for Medicare and Medicaid Innovation (CMMI) to identify ways to improve healthcare quality and reduce overall costs in the Medicare, Medicaid, and Children’s Health Insurance Program (CHIP) programs. Maryland’s All-Payer model has produced the most savings out of any of the projects and experimental payment programs researched by CMMI. The success of Maryland’s programs prompted CMMI to look at expanding similar programs in other states.  

Reductions in hospital costs combined with improved outcomes can only benefit patients and the healthcare industry in the long run. Since clinical laboratory testing is integral to early diagnoses and treatment of diseases, under Maryland’s current reimbursement model a robust clinical laboratory service is invaluable for succeeding at cost containment and patient outcome goals.   

JP Schlingman

Related Information:

Meaningful Value-Based Payment Reform, Part 1: Maryland Leads the Way

Meaningful Value-Based Payment Reform, Part 2: Expanding The Maryland Model to Other States

The National Implications of Maryland’s All-Payer System

The Total Cost of Care Model: Uniquely Maryland, Uniquely Successful

CMS and Maryland Announce Joint Initiative to Modernize Maryland’s Health Care System to Improve Care and Lower Costs

Maryland All-Payer Model to Deliver Better Care and Lower Costs

CMS: Maryland All-Payer Model

CMS: Maryland Total-Cost-of-Care Model

Maryland’s All-Payer Model Results

Evaluation of the Maryland Total Cost of Care Model: Implementation Report

Maryland Total Cost of Care Model Reduced Spending by $365 Million in First Year

Los Angeles Reaches $26 Million Settlement with Sameday Health and its Contract Doctor Over Alleged Phony COVID-19 Lab Test Results That Put Patients at Risk and Cost Insurers Millions

Company was accused of manipulating clinical laboratory reports from previous COVID-19 tests to forge new results, and sending “negative” test results to patients even though their tests had never been completed

National COVID-19 testing chain Sameday Health (a.k.a., Sameday Technologies) will pay $22.5 million—and its contracted doctor an additional $3.9 million—to settle a case with the City of Los Angeles and the Los Angeles County Attorney’s Office over alleged falsifying, faking, and failing to deliver more than 500 COVID-19 test results to consumers.

According to an announcement from the Los Angeles City Attorney’s Office, the settlements require Sameday Health and physician Jeffrey Toll, MD, to pay restitution and civil penalties, and to comply with permanent injunctions prohibiting them from participating in the alleged activities that led to the City Attorney’s investigation.

“If you get a negative test, you assume it’s safe to go to work, visit family and friends, or take a vacation. But the victims of this alleged scheme might unknowingly have spread COVID to others or failed to receive timely and appropriate care themselves,” Los Angeles City Attorney Mike Feuer, JD, said in the announcement.

“We’ve intervened to protect consumers in numerous major COVID-related matters, but this may be the most significant consumer protection case to emerge from the pandemic,” he added.

Los Angeles City Attorney Mike Feuer, JD
Los Angeles City Attorney Mike Feuer, JD, (above) teamed with Los Angeles County District Attorney George Gascón to reach a $26 million settlement with Sameday Health of Venice, Calif., and its contracted physician over phony COVID-19 test results. “It’s beyond outrageous that anyone would falsify COVID tests, as we allege happened here,” Feuer said in a statement. Clinical laboratories will want to note the fervor at which state officials are pursuing million-dollar settlements in COVID-19 fraud cases. (Photo copyright: California Globe.)

The LA City Attorney’s Complaint Against Sameday Technologies

Sameday Technologies, which operates under the name Sameday Health, has 55 COVID-19 testing sites throughout the country, with 16 locations in Los Angeles County, including five in the city.

The complaint released by the LA City Attorney’s Office states that consumers “paid a premium to get a rapid COVID-19 PCR test from Sameday Technologies, Inc. (Sameday), a Venice, Calif.-based start-up turned national chain that promised reliable COVID-19 test results in 24- hours or less.”

Sameday did not own its own clinical laboratory and its primary third-party vendor labs “were only required to aim to deliver results to Sameday’s consumers within 24-hours or 48-hours of the laboratory receiving the consumers’ testing samples from Sameday, along with all of the paperwork and information necessary to track, process, and report the result.

“But Sameday, unable to meet its 24-hour guarantee, sent hundreds of customers fake test results and laboratory reports stating that they had tested negative for COVID-19, when in reality Sameday’s laboratories had not run (and in many cases had not even received) the consumers’ tests,” the attorneys’ complaint states.

In addition to forging and falsifying hundreds of test results, the LA City Attorney’s Office alleges Sameday committed insurance fraud by partnering with a doctor to steer insured customers into three-minute-long medically unnecessary consultations. Using a virtual call center of physicians, the attorney’s office states, Sameday “submitted claims to insurance companies with codes that falsely represented the length of the consultations, misrepresented the purpose of the tests and consults, and sometimes sought reimbursement for calls that never even happened.” The state maintains Sameday in one year made “millions of dollars” from California-based insurance claims alone.

Additional Settlement with LA-based Medical Internist

In a statement provided to the Los Angeles Times, Sameday Health stated it was founded in September 2020 “to make fast, reliable, COVID testing available to everyone.

“In the early days, amidst the chaos of massive surges in demand for services, and shortages in supplies, we failed to meet the standards for excellence our customers deserve,” the company said. “We have corrected the problems that arose back in 2020 and have made significant investments in compliance and systems to ensure that we meet our customers’ expectations. We agreed to settle with the City Attorney and the LA District Attorney in order to move forward and to allow the 1,200 men and women of Sameday to place their focus on providing top-level service to the communities we serve.”

Sameday’s founder and CEO Felix Huettenbach also is named in the settlement, having agreed to join with Sameday in paying $9.5 million in restitution and $13 million in penalties and to no longer access any test result or medical records belonging to any Sameday Health customers.

The Los Angeles Times reported that a separate $3.9 million settlement was reached with Jeffrey Toll, MD, a Los Angeles-based internist who serves as Medical Director for concierge medical practice Good Life Medical Services.

Feuer and Los Angeles County District Attorney George Gascón maintain Toll was a partner in Sameday Health’s alleged insurance fraud. In their complaint, they state patient phone calls would last two to three minutes and cost insurers about $450. In exchange, Toll allegedly gave Sameday Health a large portion of the profits, the complaint alleges.

Toll’s attorney D. Shawn Burkley, JD, of Werksman Jackson and Quinn LLP denied any wrongdoing, telling the Los Angeles Times, “We settled the matter, but we do not believe that Dr. Toll did anything that was unethical.”

Settlements with Toll and Sameday Health must still be approved by a judge.

Patients to Receive Refunds for PCR Clinical Laboratory Tests

In late April, Feuer announced that Californians who paid out of pocket for PCR tests from Sameday Health between October 1 and December 31, 2020, are expected to be issued refunds from the company as part of the settlement, Patch reported.

More than 800 million COVID-19 tests have been performed in the United States since the pandemic began in 2020, according to Our World in Data statistics. Though incidents of fraud have been rare, clinical laboratory managers and pathologists who read Dark Daily will be aware of the growing number of state and federal fraud investigations being opened since the COVID-19 pandemic began to wane.

In “Department of Justice Recovers $1.8B from Medical Laboratory Owners and Others Accused of Alleged Healthcare Fraud During COVID-19 Pandemic,” we covered how unscrupulous clinical laboratory operators quickly sought to take advantage of the critical demand for SARS-CoV-2 testing and defraud the federal government. And how, the resulting federal prosecutions involved dozens of medical laboratory owners and operators who paid back “hundreds of millions in alleged federal healthcare program losses,” according to Goodwin Life Sciences Perspectives.

The settlement with Sameday Health may serve to put other pandemic startups—and their clinical laboratories—on notice that deceitful and fraudulent practices will likely not go unnoticed by federal or state agencies.

Andrea Downing Peck

Related Information:

‘Beyond Outrageous’: L.A. Company Faked COVID Test Results, Authorities Allege

The People of the State of California versus Sameday Technologies, Inc.

Announcing $26 Million Settlement over Allegedly Fake COVID Test Results with Sameday Health, Others

Fraudulent COVID Testing Company to Refund Victims: LA City Attorney

Columbia University Researchers Say New High-Speed 3D Microscope Could Replace Traditional Biopsy, with Implications for Surgical Pathology

Columbia University’s MediSCAPE enables surgeons to examine tissue structures in vivo and a large-scale clinical trial is planned for later this year

Scientists at Columbia University in New York City have developed a high-speed 3D microscope for diagnosis of cancers and other diseases that they say could eventually replace traditional biopsy and histology “with real-time imaging within the living body.”

The technology is designed to enable in situ tissue analysis. Known as MediSCAPE, the microscope is “capable of capturing images of tissue structures that could guide surgeons to navigate tumors and their boundaries without needing to remove tissues and wait for pathology results,” according to a Columbia University news story.

The research team, led by Columbia University professor of biomedical engineering and radiology Elizabeth Hillman, PhD, described the technology in a paper published in Nature Biomedical Engineering, titled, “High-Speed Light-Sheet Microscopy for the In-Situ Acquisition of Volumetric Histological Images of Living Tissue.”

“The way that biopsy samples are processed hasn’t changed in 100 years, they are cut out, fixed, embedded, sliced, stained with dyes, positioned on a glass slide, and viewed by a pathologist using a simple microscope. This is why it can take days to hear news back about your diagnosis after a biopsy,” said Hillman in the Columbia news story.

“Our 3D microscope overcomes many of the limitations of prior approaches to enable visualization of cellular structures in tissues in the living body. It could give a doctor real-time feedback about what type of tissue they are looking at without the long wait,” she added in I News.

Hillman’s team previously used the technology—originally dubbed SCAPE for “Swept Confocally Aligned Planar Excitation” microscopy—to capture 3D images of neurological activity in living samples of worms, fish, and flies. In their recent study, the researchers tested the technology with human kidney tissue, a human volunteer’s tongue, and a mouse with pancreatic cancer.

Shana M. Coley, MD, PhD
“This was something I didn’t expect—that I could actually look at structures in 3D from different angles,” said nephropathologist and study co-author Shana M. Coley, MD, PhD (above), Director, Transplant Translational Research and Multiplex Imaging Center at Arkana Laboratories, in the Columbia news story. At the time of the Columbia study, Coley was an assistant professor at Columbia University and a renal pathologist at the Columbia University Medical Center. “We found many examples where we would not have been able to identify a structure from a 2D section on a histology slide, but in 3D we could clearly see its shape. In renal pathology in particular, where we routinely work with very limited amounts of tissue, the more information we can derive from the sample, the better for delivering more effective patient care,” she added. (Photo copyright: Arkana Laboratories.)

How MediSCAPE Works

Unlike traditional 3D microscopes that use a laser to scan tiny spots of a tissue sample and then assemble those points into a 3D image, the MediSCAPE 3D microscope “illuminates the tissue with a sheet of light—a plane formed by a laser beam that is focused in a special way,” I News reported.

The MediSCAPE microscope thus captures 2D slices which are rapidly stacked into 3D images at a rate of more than 10 volumes per second, according to I News.

“One of the first tissues we looked at was fresh mouse kidney, and we were stunned to see gorgeous structures that looked a lot like what you get with standard histology,” said optical systems engineer and the study’s lead author, Kripa Patel, PhD, in the Columbia news story. “Most importantly, we didn’t add any dyes to the mouse—everything we saw was natural fluorescence in the tissue that is usually too weak to see.

“Our microscope is so efficient that we could see these weak signals well,” she continued, “even though we were also imaging whole 3D volumes at speeds fast enough to rove around in real time, scanning different areas of the tissue as if we were holding a flashlight.”

A big advantage of the technology, Hillman noted, is the ability to scan living tissue in the body.

“Understanding whether tissues are staying healthy and getting good blood supply during surgical procedures is really important,” she said in the Columbia news story. “We also realized that if we don’t have to remove (and kill) tissues to look at them, we can find many more uses for MediSCAPE, even to answer simple questions such as ‘what tissue is this?’ or to navigate around precious nerves. Both of these applications are really important for robotic and laparoscopic surgeries, where surgeons are more limited in their ability to identify and interact with tissues directly.”

Clinical Trials and FDA Clearance

Early versions of the SCAPE microscopes were too large for practical use by surgeons, so Columbia post-doctoral research scientist Wenxuan Liang, PhD, co-author of the study, helped the team develop a smaller version that would fit into an operating room.

Later this year, the researchers plan to launch a large-scale clinical trial, I News reported. The Columbia scientists hope to get clearance from the US Food and Drug Administration (FDA) to develop a commercialized version of the microscope.

“They will initially seek permission to use it for tumor screening and guidance during operations—a lower and easier class of approval—but ultimately, they hope to be allowed to use it for diagnosis,” Liang wrote.

Charles Evans, PhD, research information manager at Cancer Research UK, told I News, “Using surgical biopsies to confirm a cancer diagnosis can be time-consuming and distressing for patients. And ensuring all the cancerous tissue is removed during surgery can be very challenging unaided.”

He added, “more work will be needed to apply this technique in a device that’s practical for clinicians and to demonstrate whether it can bring benefits for people with cancer, but we look forward to seeing the next steps.” 

Will the Light Microscope be Replaced?

In recent years, research teams at various institutions have been developing technologies designed to enhance or even replace the traditional light microscope used daily by anatomic pathologists across the globe.

And digital scanning algorithms for creating whole-slide images (WSIs) that can be analyzed by pathologists on computer screens are gaining in popularity as well.

Such developments may spark a revolution in surgical pathology and could signal the beginning of the end of the light microscope era.

Surgical pathologists should expect to see a steady flow of technologically advanced systems for tissue analysis to be submitted to the FDA for pre-market review and clearance for use in clinical settings. The light microscope may not disappear overnight, but there are a growing number of companies actively developing different technologies they believe can diagnose either or both tissue and digital images of pathology slides with accuracy comparable to a pathologist.

Stephen Beale

Related Information:

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