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.
“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.”
“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.)
“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.
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.
New technique could allow emergency responders to determine severity of LVO stroke while patient is still in the ambulance
Researchers at Brigham and Women’s Hospital in Massachusetts say they have developed a clinical laboratory test that can quickly determine whether a patient is experiencing one of the deadliest types of strokes, known as an ischemiclarge vessel occlusion (LVO) stroke. The development team believes this new assay could be deployed as a point-of-care test to enable faster diagnosis of stroke events.
The test combines measurement of two blood plasma biomarkers with an established clinical score used by clinicians and EMS personnel to assess stroke severity. Compared with current approaches, their technique more accurately differentiates LVO strokes from other types of strokes, making it more likely that patients receive appropriate treatment in a timely manner, the researchers said in a Brigham news release.
Dark Daily has long predicted that advances in technology and computing power would make it possible for pathologists and clinical laboratory scientists to combine multiple established biomarkers (individually not associated with the disease state targeted) with other clinical and patient data to create the ability to make an accurate and earlier diagnosis.
Ultimately, Brigham’s research could “aid in the development of a point‐of‐care diagnostic test capable of guiding prehospital LVO stroke triage,” wrote Joshua Bernstock, MD, PhD, Clinical Fellow in Neurosurgery at Brigham and Women’s Hospital, lead author of the study, and colleagues.
“We have developed a game-changing, accessible tool that could help ensure that more people suffering from stroke are in the right place at the right time to receive critical, life-restoring care,” said Joshua Bernstock, MD, PhD (above), Clinical Fellow in Neurosurgery at Brigham and Women’s Hospital and lead author of the Brigham study that developed the clinical laboratory test that the researchers say can enable emergency caregivers to determine quickly and accurately if a patient is having an ischemic large vessel occlusion (LVO) stroke. (Photo copyright: Brigham and Women’s Hospital.)
Early Identification of LVO Stroke
As explained in the news release, an LVO stroke is a type of ischemic stroke caused by obstruction in a major brain artery. The researchers noted that LVO strokes account for “62% of poststroke disabilities and 96% of poststroke death.”
These strokes are readily treatable using endovascular thrombectomy (EVT), in which the blockages are surgically removed, the news release note. However, the researchers observed that EVT “requires specialized teams and equipment, limiting its availability to comprehensive stroke centers and other EVT‐capable centers.”
This can lead to delays as patients are transferred to those facilities, worsening outcomes and increasing the risk of death, the researchers wrote in Stroke: Vascular and Interventional Neurology. So, early identification of LVO stroke is key to ensuring patients receive timely treatment.
Identifying False Negatives/Positives
One challenge, the news release notes, is that brain bleeds (hemorrhagic stroke) can present similar symptoms, yet require “vastly different” treatment.
“A growing body of work has, therefore, evaluated prehospital stroke assessment scales in an effort to identify LVO strokes in the field,” the researchers wrote. “However, such severity scales lack the sensitivity and specificity required for triaging LVO patients with confidence, resulting in false negatives in patients with LVO as well as false positives in patients with stroke mimics or hemorrhagic stroke.”
As explained by EMS Aware, these assessment scales, such as FAST-ED (field assessment stroke triage for emergency destination) and RACE (rapid arterial occlusion evaluation), attempt to determine the severity of a stroke by assigning scores based on symptoms such as facial palsy, arm weakness, and speech difficulties.
To develop their test, Bernstock and colleagues proposed combining the scales with measurement of two blood proteins:
In their study, they attempted to validate cutoff values for the biomarkers and scales.
To do so, the researchers analyzed data from 323 patients admitted to a Florida hospital with suspected stroke between May 2021 and August 2022. Each was assigned to one of four diagnostic categories based on clinical data from their medical records, which included results of computed tomography (CT scan) or magnetic resonance angiography (MRA). The diagnostic categories included:
The patients were assessed using five stroke severity scales. The researchers used frozen blood samples from the patients to measure the biomarkers. They then used this data to determine the likelihood of LVO stroke and compared the results with the diagnoses as determined by the clinical data.
“Combinations of the blood biomarkers with the scales FAST‐ED or RACE showed the best performance for LVO detection, with a specificity of 94% (for either scale combination) and a sensitivity of 71% for both scales,” the researchers wrote.
Sensitivity was higher in patients who presented within the first six hours from onset of symptoms.
“Critically, application of the biomarker and stroke scale algorithms ruled out all patients with hemorrhage,” the researchers wrote. However, they also suggested that their algorithm could be adjusted to enable early identification of hemorrhagic stroke.
The researchers noted that they chose biomarker cutoffs to maximize specificity, so “a certain number of LVOs are missed. However, as such patients default into ‘standard‐of‐care’ triaging pathways, such a decision is unlikely to represent much clinical risk.”
Testing in the Field
The Brigham researchers used established biological biomarkers combined with modern computing—in combination with the scores from a field assessment test—to develop their new clinical laboratory test that identifies the type of stroke.
Their next step is to carry out “another prospective trial to measure the test’s performance when used in an ambulance,” the news release states. “They have also designed an interventional trial that leverages the technology to expedite the triage of stroke patients by having them bypass standard imaging and move directly to intervention.”
“In stroke care, time is brain,” Bernstock said. “The sooner a patient is put on the right care pathway, the better they are going to do. Whether that means ruling out bleeds or ruling in something that needs an intervention, being able to do this in a prehospital setting with the technology that we built is going to be truly transformative.”
More research and clinical studies are needed. However, the fact that the Brigham team wants to deploy this approach in ambulances is an indication that there is high clinical value from this approach.
Clinical pathologists and medical laboratory managers will want to watch the ongoing development and deployment of this new assay, whether it is run in near-patient settings or core clinical laboratories in support of patients presenting in emergency departments.
Radiological method using AI algorithms to detect, locate, and identify cancer could negate the need for invasive, painful clinical laboratory testing of tissue biopsies
This will be of interest to histopathologists and radiologist technologists who are working to develop AI deep learning algorithms to read computed tomography scans (CT scans) to speed diagnosis and treatment of cancer patients.
“Researchers used the CT scans of 170 patients treated at The Royal Marsden with the two most common forms of retroperitoneal sarcoma (RPS)—leiomyosarcoma and liposarcoma—to create an AI algorithm, which was then tested on nearly 90 patients from centers across Europe and the US,” the news release notes.
The researchers then “used a technique called radiomics to analyze the CT scan data, which can extract information about the patient’s disease from medical images, including data which can’t be distinguished by the human eye,” the new release states.
The research team sought to make improvements with this type of cancer because these tumors have “a poor prognosis, upfront characterization of the tumor is difficult, and under-grading is common,” they wrote. The fact that AI reading of CT scans is a non-invasive procedure is major benefit, they added.
“This is the largest and most robust study to date that has successfully developed and tested an AI model aimed at improving the diagnosis and grading of retroperitoneal sarcoma using data from CT scans,” said the study’s lead oncology radiologist Christina Messiou, MD, (above), Consultant Radiologist at The Royal Marsden NHS Foundation Trust and Professor in Imaging for Personalized Oncology at The Institute of Cancer Research, London, in a news release. Invasive medical laboratory testing of cancer biopsies may eventually become a thing of the past if this research becomes clinically available for oncology diagnosis. (Photo copyright: The Royal Marsden.)
Study Details
RPS is a relatively difficult cancer to spot, let alone diagnose. It is a rare form of soft-tissue cancer “with approximately 8,600 new cases diagnosed annually in the United States—less than 1% of all newly diagnosed malignancies,” according to Brigham and Women’s Hospital.
In their published study, the UK researchers noted that, “Although more than 50 soft tissue sarcoma radiomics studies have been completed, few include retroperitoneal sarcomas, and the majority use single-center datasets without independent validation. The limited interpretation of the quantitative radiological phenotype in retroperitoneal sarcomas and its association with tumor biology is a missed opportunity.”
According to the ICR news release, “The [AI] model accurately graded the risk—or how aggressive a tumor is likely to be—[in] 82% of the tumors analyzed, while only 44% were correctly graded using a biopsy.”
Additionally, “The [AI] model also accurately predicted the disease type [in] 84% of the sarcomas tested—meaning it can effectively differentiate between leiomyosarcoma and liposarcoma—compared with radiologists who were not able to diagnose 35% of the cases,” the news release states.
“There is an urgent need to improve the diagnosis and treatment of patients with retroperitoneal sarcoma, who currently have poor outcomes,” said the study’s first author Amani Arthur, PhD, Clinical Research Fellow at The Institute of Cancer Research, London, and Registrar at The Royal Marsden NHS Foundation Trust, in the ICR news release.
“The disease is very rare—clinicians may only see one or two cases in their career—which means diagnosis can be slow. This type of sarcoma is also difficult to treat as it can grow to large sizes and, due to the tumor’s location in the abdomen, involve complex surgery,” she continued. “Through this early research, we’ve developed an innovative AI tool using imaging data that could help us more accurately and quickly identify the type and grade of retroperitoneal sarcomas than current methods. This could improve patient outcomes by helping to speed up diagnosis of the disease, and better tailor treatment by reliably identifying the risk of each patient’s disease.
“In the next phase of the study, we will test this model in clinic on patients with potential retroperitoneal sarcomas to see if it can accurately characterize their disease and measure the performance of the technology over time,” Arthur added.
Importance of Study Findings
Speed of detection is key to successful cancer diagnoses, noted Richard Davidson, Chief Executive of Sarcoma UK, a bone and soft tissue cancer charity.
“People are more likely to survive sarcoma if their cancer is diagnosed early—when treatments can be effective and before the sarcoma has spread to other parts of the body. One in six people with sarcoma cancer wait more than a year to receive an accurate diagnosis, so any research that helps patients receive better treatment, care, information and support is welcome,” he told The Guardian.
According to the World Health Organization, cancer kills about 10 million people worldwide every year. Acquisition and medical laboratory testing of tissue biopsies is both painful to patients and time consuming. Thus, a non-invasive method of diagnosing deadly cancers quickly, accurately, and early would be a boon to oncology practices worldwide and could save thousands of lives each year.
Insights learned from Canada’s experience may benefit clinical laboratories and anatomic pathology groups in the US as well
Canada continues to face a severe shortage of skilled healthcare professionals, especially among medical laboratory technologists (MLTs) and radiology technicians (RTs). According to the Canadian Society for Medical Laboratory Science (CSMLS), “In 2010, the Canadian Institute for Health Information (CIHI) identified that approximately half of all MLTs would be eligible to retire in 10 years, with the greatest impact felt in Canada’s rural and remote communities.” Today, “This staffing concern is currently affecting the professional community across all provinces and territories resulting in the decrease of workers, dramatically impacting organizations and their employees.”
One thing true of government-run healthcare programs is that they consistently underinvest in building new facilities, upgrading older facilities, and training/retaining enough physicians, nurses, and clinical laboratory/radiology workers. This is seen in the UK, Canada, New Zealand, and Australia, where varies combinations of facility, physician, and other healthcare professional shortages generate regular headlines about patient wait times—particularly for elective procedures—that may be six months to a year or more.
For example, officials at Pasqua Hospital in Regina, which serves patients in southern Saskatchewan, Canada, say diagnostics services may need to be shut down by the end of January as a result of “extended, chronic staffing shortages.”
“We’re barely struggling to keep up with urgent cases,” Christy Labreche, a nuclear medicine technologist told the Regina-Leader Post, which noted that people requesting non-urgent treatment may need to make appointments six to 12 weeks out.
Pasqua Hospital leaders have asked province officials to take “immediate action,” but they feel their concerns are “falling on deaf ears,” the Leader Post reported.
“For over a decade, we have been sounding the alarm on behalf of our members that provide a vital service in the continuum of care,” said nuclear medicine technologist Bashir Jalloh (above) in a CUPE statement. Jalloh is President of CUPE 5430, Saskatchewan’s largest healthcare union which represents medical technologists in a variety of specialties. “Now, as waitlists grow, we are at risk of more disruptions of services and communities on bypass for critical care at a time when wait lists are as long as ever.” Clinical laboratory leaders in the US can gain valuable insights from the struggle with shortages taking place in Canada. (Photo copyright: Regina-Leader Post.)
Chrobak noted the following reasons for the deficit of MLTs in Canada:
An aging workforce: Many current lab scientists are over age 50, signaling a “potential shortage of medical laboratory technologists when seasoned professionals retire.”
Lack of awareness and representation: Other healthcare fields may benefit by being in the public spotlight, while “opportunities and rewards” of a medical lab technology career may not be apparent to job seekers.
Insufficient funding for educational programs: The need for laboratory professionals may supersede “scarce healthcare dollars that fund education programs.”
Barriers to registration: International applicants may be challenged in “recognition of existing field-of-practice competencies.”
Solutions: Improve Recruitment, Retention
To address the MLT shortages across Canada, CAMLPR aims to step up the registration of people interested in the medical laboratory profession through a project in partnership with the Canadian government called the Flexible Pathways to Registration for Medical Laboratory Technologists. The goal is to develop competency standards for entering the profession, ease the registration process, and increase the supply of qualified health professionals in Canada, according to a news release.
This is not the first time Dark Daily has covered Canada’s lab worker shortages.
In “Clinical Laboratories Suffer During the ‘Great Resignation’,” we reported how the so-called “Great Resignation” caused by the COVID-19 pandemic has had a severe impact on clinical laboratory staffs, creating shortages of pathologists as well as of medical technologists, medical laboratory technicians, and other lab scientists who are vital to clinical laboratories in both Canada and the US.
And in “Lab Staffing Shortages Reaching Dire Levels,” Dark Daily’s sister publication, The Dark Report, noted that CAP Today characterized the current lab staffing shortage as going “from simmer to rolling boil” and that demand for medical technologists and other certified laboratory scientists far exceeds the available supply. Consequently, many labs use overtime and temp workers to handle daily testing, a strategy that has led to staff burnout and a high turnover rate.
Shortages in other areas of Canadian healthcare are on the rise as well, which we covered in “Number of Unfilled Medical Residencies Increases in Alberta and Other Areas of Canada.” We reported that, according to the Angus Reid Institute, approximately half of all Canadians cannot find a doctor or get a timely appointment with their current doctor. And that, just like in many parts of America, certain provinces are experiencing severe medical staffing shortages that includes clinical laboratories and pathology groups.
Global Insights May Offer Ideas
Dark Daily’s coverage of healthcare industry challenges in Canada, the US, and other countries is aimed at helping clinical laboratory managers and pathologists understand challenges faced by government-run healthcare systems, where there is constant pressure on the government to provide adequate funding. Capital is needed to modernize and expand hospitals and clinics. At the same time, there is need to expand training opportunities to solve the shortage of clinical laboratory scientists, medical laboratory and imaging technologists, doctors, nurses, and other medical professionals.
The insights gained by studying these healthcare systems may be of value to US-based hospitals and medical laboratories that face their own worker recruitment and retention issues.
Norwegian researchers reviewed large clinical trials of six common cancer screenings, including clinical laboratory tests, but some experts question the findings
Cancer screenings are a critical tool for diagnosis and treatment. But how much do they actually extend the lives of patients? According to researchers at the University of Oslo in Norway, not by much. They recently conducted a review and meta-analysis of 18 long-term clinical trials, five of the six most commonly used types of cancer screening—including two clinical laboratory tests—and found that with few exceptions, the screenings did not significantly extend lifespans.
The 18 long-term clinical trials included in the study were randomized trials that collectively included a total of 2.1 million participants. Median follow-up periods of 10 to 15 years were used to gauge estimated lifetime gain and mortality.
“The findings of this meta-analysis suggest that current evidence does not substantiate the claim that common cancer screening tests save lives by extending lifetime, except possibly for colorectal cancer screening with sigmoidoscopy,” the researchers wrote in their published paper.
The researchers noted, however, that their analysis does not suggest all screenings should be abandoned. They also acknowledged that some lives are saved by screenings.
“Without screening, these patients may have died of cancer because it would have been detected at a later, incurable stage,” the scientists wrote, MedPage Today reported. “Thus, these patients experience a gain in lifetime.”
Still, some independent experts questioned the validity of the findings.
Gastroenterologist Michael Bretthauer, MD, PhD (above), a professor at the University of Oslo in Norway led the research into cancer screenings. In their JAMA Internal Medicine paper, he and his team wrote, “The findings of this meta-analysis suggest that colorectal cancer screening with sigmoidoscopy may extend life by approximately three months; lifetime gain for other screening tests appears to be unlikely or uncertain.” How their findings might affect clinical laboratory and anatomic pathology screening for cancer remains to be seen. (Photo copyright: University of Oslo.)
Pros and Cons of Cancer Screening
The clinical trials, according to MedPage Today and Oncology Nursing News covered the following tests:
Mammography screening for breast cancer (two trials).
As reported in these trials, “colorectal cancer screening with sigmoidoscopy prolonged lifetime by 110 days, while fecal testing and mammography screening did not prolong life,” the researchers wrote. “An extension of 37 days was noted for prostate cancer screening with prostate-specific antigen testing and 107 days with lung cancer screening using computed tomography, but estimates are uncertain.”
The American Cancer Society (ACS) recommends certain types of screening tests to detect cancers and pre-cancers before they can spread, thus improving the chances for survival.
The ACS advises screenings for breast cancer, colorectal cancer, and cervical cancer regardless of whether the individual is considered high risk. Lung cancer screenings are advised for people with a history of smoking. Men who are 45 to 50 or older should discuss the pros and cons of prostate cancer screening with their healthcare providers, the ACS states.
A CNN report about the University of Oslo study noted that the benefits and drawbacks of cancer screening have long been well known to doctors.
“Some positive screening results are false positives, which can lead to unnecessary anxiety as well as additional screening that can be expensive,” CNN reported. “Tests can also give a false negative and thus a false sense of security. Sometimes too, treatment can be unnecessary, resulting in a net harm rather than a net benefit, studies show.”
In their JAMA paper, the University of Oslo researchers wrote, “The critical question is whether the benefits for the few are sufficiently large to warrant the associated harms for many. It is entirely possible that multicancer detection blood tests do save lives and warrant the attendant costs and harms. But we will never know unless we ask,” CNN reported.
Hidden Impact on Cancer Mortality
ACS Chief Scientific Officer William Dahut, MD, told CNN that screenings may have an impact on cancer mortality in ways that might not be apparent from randomized trials. He noted that there’s been a decline in deaths from cervical cancer and prostate cancer since doctors began advising routine testing.
“Cancer screening was never really designed to increase longevity,” Dahut said. “Screenings are really designed to decrease premature deaths from cancer.” For example, “if a person’s life expectancy at birth was 80, a cancer screening may prevent their premature death at 65, but it wouldn’t necessarily mean they’d live to be 90 instead of the predicted 80,” CNN reported.
Dahut told CNN that fully assessing the impact of cancer screenings on life expectancy would require a clinical trial larger than those in the new study, and one that followed patients “for a very long time.”
“From its title, one would have expected this paper to be based on analysis of individual lifetime data. However, it is not,” he wrote in a compilation of expert commentary from the UK’s Science Media Center. “The paper’s conclusions are based on arithmetic manipulation of relative rates of all-cause mortality in some of the screening trials. It is therefore difficult to give credence to the claim that screening largely does not extend expected lifetime.”
He also questioned the inclusion of one particular trial in the University of Oslo study—the Canadian National Breast Screening Study—“as there is now public domain evidence of subversion of the randomization in this trial,” he added.
Another expert, Leigh Jackson, PhD, of the University of Exeter in the UK, described the University of Oslo study as “methodologically sound with some limitations which the authors clearly state.”
But he observed that “the focus on 2.1 million individuals is slightly misleading. The study considered many different screening tests and 2.1 million was indeed the total number of included patients, however, no calculation included that many people.”
Jackson also characterized the length of follow-up as a limitation. “This may have limited the amount of data included and also not considering longer follow-up may tend to underestimate the effects of screening,” he said.
This published study—along with the range of credible criticisms offered by other scientists—demonstrates how analysis of huge volumes of data is making it possible to tease out useful new insights. Clinical laboratory managers and pathologists can expect to see other examples of researchers assembling large quantities of data across different areas of medicine. This huge pools of data will be analyzed to determine the effectiveness of many medical procedures that have been performed for years with a belief that they are helpful.
