Clinical laboratory scientists and microbiologists could play a role in helping doctors explain to patients the potential dangers of do-it-yourself medical treatments
Be careful what you wish for when you perform do-it-yourself (DIY) medical treatments. That’s the lesson learned by a woman who was seeking relief for irritable bowel syndrome (IBS). When college student Daniell Koepke did her own fecal transplant using poop from her brother and her boyfriend as donors her IBS symptoms improved, but she began to experience medical conditions that afflicted both fecal donors.
“It’s possible that the bacteria in the stool can influence inflammation in the recipient’s body, by affecting their metabolism and activating their immune response,” microbial ecologist Jack Gilbert, PhD, Professor and Associate Vice Chancellor at University of California San Diego (UC San Diego) told Business Insider. “This would cause shifts in their hormonal activity, which could promote the bacteria that can cause acne on the skin. We nearly all have this bacterium on skin, but it is often dormant,” he added.
A Fecal Microbiota Transplant (FMT) is a procedure where stool from a healthy donor is transplanted into the microbiome of a patient plagued by a certain medical condition.
Our guts are home to trillions of microorganisms (aka, microbes), known as the gut microbiota, that serve many important functions in the body. The microbiome is a delicate ecosystem which can be pushed out of balance when advantageous microbes are outnumbered by unfavorable ones. An FMT is an uncomplicated and powerful method of repopulating the microbiome with beneficial microbes.
“With fecal microbiome transplants there is really compelling evidence, but the science is still developing. We’re still working on if it actually has benefits for wider populations and if the benefit is long-lasting,” said Gilbert in a Netflix documentary titled, “Hack Your Health: The Secrets of Your Gut.”
“The microbial community inside our gut can have surprising influences on different parts of our body,” microbial ecologist Jack Gilbert, PhD (above), of the Gilbert Lab at University of California San Diego told Business Insider. “Stools are screened before clinical FMTs, and anything that could cause major problems, such as certain pathogens, would be detected. When you do this at home, you don’t get that kind of screening.” Doctors and clinical laboratories screening patients for IBS understand the dangers of DIY medical treatments. (Photo copyright: University of California San Diego.)
Changing Poop Donors
When Koepke began experiencing symptoms of IBS including indigestion, stabbing pains from trapped gas and severe constipation, she initially turned to physicians for help.
In the Netflix documentary, Koepke stated that she was being prescribed antibiotics “like candy.” Over the course of five years, she completed six rounds of antibiotics per year, but to no avail.
She also changed her diet, removing foods that were making her symptoms worse. This caused her to lose weight and she eventually reached a point where she could only eat 10 to 15 foods.
“It’s really hard for me to remember what it was like to eat food before it became associated with anxiety and pain and discomfort,” she said.
In an attempt to relieve her IBS symptoms, Koepke made her own homemade fecal transplant pills using donated stool from her brother. After taking them her IBS symptoms subsided and she slowly gained weight. But she developed hormonal acne just like her brother.
Koepke then changed donors, using her boyfriend’s poop to make new fecal transplant pills. After she took the new pills, her acne dissipated but she developed depression, just like her boyfriend.
“Over time, I realized my depression was worse than it’s ever been in my life,” Koepke stated in the documentary.
She believes the microbes that were contributing to her boyfriend’s depression were also transplanted into her via the fecal transplant pills. When she reverted to using her brother’s poop, her depression abated within a week.
Gilbert told Business Insider his research illustrates that people who suffer from depression are lacking certain bacteria in their gut microbiome.
“She may have had the ‘anti-depressant’ bacteria in her gut, but when she swapped her microbiome with his, her anti-depressant bacteria got wiped out,” he said.
FDA Approves FMT Therapy for Certain Conditions
Typically, the fecal material for an FMT procedure performed by a doctor comes from fecal donors who have been rigorously screened for infections and diseases. The donations are mixed with a sterile saline solution and filtered which produces a liquid solution. That solution is then administered to a recipient or frozen for later use.
On November 30, 2022, the US Food and Drug Administration (FDA) approved the first FMT therapy, called Rebyota, for the prevention of Clostridioides difficile (C. diff.) in adults whose symptoms do not respond to antibiotic therapies. Rebyota is a single-dose treatment that is administered rectally into the gut microbiome at a doctor’s office.
Then, in April of 2023, the FDA approved the use of a medicine called Vowst, which is the first oral FMT approved by the FDA.
According to the Cleveland Clinic, scientists are exploring the possibility that fecal transplants may be used as a possible treatment for many health conditions, including:
Doctors and clinical laboratories know that do-it-yourself medicine is typically not a good idea for obvious reasons. Patients seldom appreciate all the implications of the symptoms of an illness, nor do they fully understand the potentially dangerous consequences of self-treatment. Scientists are still researching the benefits of fecal microbiota transplants and hope to discover more uses for this treatment.
Clinical laboratories nationwide could follow Yale’s example and enact programs to bring much needed lab services to traditionally underserved communities
Ever since the COVID-19 pandemic drove up demand for telehealth medical services, mobile clinical laboratories have grown in popularity as well, especially among residents of remote and traditionally underserved communities. Now, several divisions of Yale University are getting in on the trend.
“Using a van retrofitted with laboratory-grade diagnostic equipment, the mobile clinic will employ SalivaDirect—a saliva-based COVID-19 PCR test developed at YSPH—to facilitate on-site testing with a turnaround time of two to three hours,” Yale Daily News reported.
Funded by a federal grant, the initial goal was to provide 400 free COVID-19 tests, but the program has exceeded that number. By April 10, the mobile lab had been deployed more than 60 times, appearing at events and pop-up sites throughout various communities in Connecticut, including regular stops at the WHEAT Food Pantry of West Haven.
“[The clinical laboratory-in-a-van] is a brilliant way to reduce the barriers to testing, instead taking the lab to communities who may be less likely—or unable—to access the necessary clinic or labs,” microbiologist Anne Wyllie, PhD, a research scientist who helped develop the PCR test deployed by the mobile lab told Yale Daily News. Wyllie works in the Department of Epidemiology of Microbial Diseases at Yale School of Public Health. “We are actively working with our community partners to identify how we can best serve their communities,” she added. (Photo copyright: Yale School of Medicine.)
Mobile Lab’s Capabilities
Collecting samples, processing, and delivering same-day COVID-19 results was the initial goal but that plan has expanded, Yale School of Medicine noted in a news release.
“Same-day onsite delivery of test results is an added benefit for communities and individuals without access to Wi-Fi or the ability to receive private health information electronically,” Yale added.
The mobile van is staffed with trained clinical laboratory technicians as well as community health navigators who provide both healthcare information and proper follow-up connections as needed for patients who receive positive COVID-19 results. The van runs off power from outdoor electrical outlets at each location and currently serves historically underserved populations in Hartford, Middlesex, Fairfield, New Haven, and New London counties, Yale noted.
“The van allows us to bring our services, as well as healthcare information, directly to communities where they are needed,” said Angelique Levi, MD, Associate Professor, Vice Chair and Director of Pathology Reference Services, and CLIA Laboratory Medical Director in the Department of Pathology at Yale University School of Medicine in a news release.
Launch of a High Complexity Molecular Lab on Wheels
YPL and YSPH collaborated to make the mobile lab a reality. YSPH created the saliva-based COVID-19 test and YPL “provided clinical validation necessary to get the testing method ready for emergency use authorization by the US Food and Drug Administration,” Yale noted.
“YPL recognized the need to be closer to the front lines of patient care and that retrofitting a fully licensed, high complexity molecular laboratory into a consumer-sized van was the right next step,” Chen Liu, MD, PhD, Chair of the Department of Pathology at Yale School of Medicine, noted in a Yale news release. This “gives us options to efficiently deliver accurate diagnostic information when and where it’s needed,” he added.
Throughout the COVID-19 pandemic, the Connecticut Department of Public Health, the City of New Haven, and various community organizations partnered with YPL, YSPH, and the SalivaDirect team to offer free SARS-CoV-2 testing to the public at two different sites in New Haven.
Principal investigators Levi and microbiologist Anne Wyllie, PhD, who helped develop the PCR test deployed by the mobile, lab led the Yale lab-in-a-van research project.
Flambeau Diagnostics, a biomedical company that specializing in mobile lab testing, worked with the Yale team to design and implement the mobile lab van.
“According to Wyllie, the new YSPH and YPL initiative utilizes one of the former Flambeau vans that had been retrofitted for clinical testing,” a Yale news release noted.
Kat Fajardo, Laboratory Manager at Yale University, added custom pieces of equipment to ensure seamless PCR testing. One was a Magnetic Induction Cycler (Mic) measuring only six by six inches. The Mic allowed for measurement of 46 biological specimens, while it’s diminutive size freed up space on the van’s countertop. This allowed lab techs to process specimens concurrently while also providing COVID-19 testing, according to a Yale news release.
Additionally, the van has a Myra portable robotic liquid handler which is “designed to automate the process of moving clinical specimens between vials,” the news release notes.
“What we wanted to do is run high complexity testing in the van, with a reduced timeframe, and then be able to get the results out to the patients as soon as we possibly could,” Fajardo stated.
Exploring the Mobile Laboratory’s Potential
According to a news release, YPL and YSPH consult with community partners to select locations for the mobile lab to visit. These partners include:
APT Foundation (New Haven County, in addition to others.
Although the van was initially used to provide SalivaDirect COVID-19 testing to vulnerable populations, YPL is working with its partners in those communities to identify other testing needs beyond COVID.
The Yale team is considering additional offerings and support such as the addition of a social worker as well as expanding lung health awareness beyond COVID-19 to other respiratory diseases. Also under consideration:
Vaccinations including for COVID-19 and Hepatitis B, and
Health education and materials for harm reduction and STI prevention, a Yale news release noted.
Yale’s Laboratory-in-a-Van program is a consumer-facing effort that is bringing much needed clinical lab services to traditionally underserved communities in Connecticut. Clinical laboratories throughout the nation could do the same with remote or homebound patients who cannot reach critical care.
Infection control teams and clinical laboratory managers may want to look at this new product designed to improve the diagnosis and treatment of sepsis
Accurate and fast diagnosis of sepsis for patients arriving in emergency departments is the goal of a new product that was just cleared by the federal Food and Drug Administration (FDA). It is also the newest example of how artificial intelligence (AI) continues to find its way into pathology and clinical laboratory medicine.
Sepsis is one of the deadliest killers in US hospitals. That is why there is interest in the recent action by the FDA to grant marketing authorization for an AI-powered sepsis detection software through the agency’s De Novo Classification Request. The DNCR “provides a marketing pathway to classify novel medical devices for which general controls alone, or general and special controls, provide reasonable assurance of safety and effectiveness for the intended use, but for which there is no legally marketed predicate device,” the FDA’s website states.
Unlike a single analyte assay that is run in a clinical laboratory, Prenosis’ AI/ML software uses 22 diagnostic and predictive parameters, along with ML algorithms, to analyze data and produce a clinically actionable answer on sepsis.
It is important for clinical laboratory managers and pathologists to recognize that this diagnostic approach to sepsis brings together a number of data points commonly found in a patient’s electronic health record (EHR), some of which the lab generated and others the lab did not generate.
“Sepsis is a serious and sometimes deadly complication. Technologies developed to help prevent this condition have the potential to provide a significant benefit to patients,” said Jeff Shuren, MD, JD, Director of the FDA’s Center for Devices and Radiological Health, in a statement. “The FDA’s authorization of the Prenosis Sepsis ImmunoScore software establishes specific premarket and post-market requirements for this device type.” Clinical laboratory EHRs contain some of the data points Prenosis’ diagnostic software uses. (Photo copyright: US Food and Drug Administration.)
How it Works
To assist doctors diagnose sepsis, the ImmunoScore software is first integrated into the patient’s hospital EHR. From there, it leverages 22 parameters including:
White blood cell count to produce a score that informs caregivers of the patient’s risk for sepsis within 24 hours, MedTech Dive reported.
Instead of requiring a doctor or nurse to look at each parameter separately, the SaMD tool uses AI “to evaluate all those markers at once”, CNBC noted. It then produces a risk score and four discrete risk stratification categories (low, medium, high, and very high) which correlate to “a patient’s risk of deterioration” represented by:
By sharing these details—a number from one to 100 for each of the 22 diagnostic and predictive parameters—Sepsis ImmunoScore helps doctors determine which will likely contribute most to the patient’s risk for developing sepsis, MedTech Dive reported.
“A lot of clinicians don’t trust AI products for multiple reasons. We are trying very hard to counter that skepticism by making a tool that was validated by the FDA first, and then the second piece is we’re not trying to replace the clinician,” Bobby Reddy Jr., PhD, Prenosis co-founder and CEO, told MedTech Dive.
Big Biobank and Blood Sample Data
Prenosis, which says its goal is the “enabling [of] precision medicine in acute care” developed Sepsis ImmunoScore using the company’s own biobank and a dataset of more than 100,000 blood samples from more than 25,000 patients.
AI algorithms drew on this biological/clinical dataset—the largest in the world for acute care patients suspected of having serious infections, according to Prenosis—to “elucidate patterns in rapid immune response.”
“It does not work without data, and the data started at Carle,” said critical care specialist Karen White, MD, PhD, Carle Foundation Hospital, St. Louis, MO, in the news release. “The project involved a large number of physicians, research staff, and internal medicine residents at Carle who helped recruit patients, collect data, and samples,” she said.
Opportunity for Clinical Laboratories
Sepsis is a life-threatening condition based on an “extreme response to an infection” that affects nearly 1.7 million adults in the US each year and is responsible for 350,000 deaths, according to US Centers for Disease Control and Prevention (CDC) data.
A non-invasive diagnostic tool like Sepsis ImmunoScore will be a boon to emergency physicians and the patients they treat. Now that the FDA has authorized the SaMD diagnostic tool to go to market, it may not be long before physicians can use the information it produces to save lives.
Clinical laboratory managers inspired by the development of Sepsis ImmunoScore may want to look for similar ways they can take certain lab test results and combine them with other data in an EHR to create intelligence that physicians can use to better treat their patients. The way forward in laboratory medicine will be combining lab test results with other relevant sets of data to create clinically actionable intelligence for physicians, patients, and payers.
Clinical studies show that new ‘cell-free’ test can predict cardiovascular disease risk better than standard HDL cholesterol test
Researchers from the National Institutes of Health (NIH) have developed a diagnostic assay that measures how well high-density lipoprotein (HDL)—the so-called “good” cholesterol—is working in the body. And their findings could lead to new clinical laboratory tests that supplement standard HDL level testing to better determine a person’s risk for heart disease.
Cholesterol tests are among the most commonly performed assays by clinical laboratories. A new test that reveals how well HDL is working in the body would certainly boost a medical laboratory’s test requisition volume.
“Measuring HDL function is limited to research labs and isn’t conducive to large-scale testing by routine clinical laboratories. To try to solve that problem, researchers from NHLBI’s Lipoprotein Metabolism Laboratory created a new diagnostic test,” noted an NHLBI news release.
“This is going to quicken the pace of basic research,” said Edward B. Neufeld, PhD, who along with guest researcher Masaki Sato, PhD, developed the test. “It increases the number of samples that you can study. It increases the number of experiments you can do.”
Such a new cholesterol test would quickly become one of the most commonly performed clinical lab tests because just about every American who has a physical gets cholesterol tests as part of that process.
“Other people may modify this or come up with better versions, which is fine with us,” Edward Neufeld, PhD (above), NHLBI Staff Scientist, said in a news release. “We just really wanted to tackle this problem of evaluating HDL function.” Clinical laboratories may soon have a new cholesterol test to supplement standard HDL level testing. (Photo copyright: ResearchGate.)
Faster Answers Needed about HDL
According to the NIH, the goal should go beyond measuring level of HDL as part of a person’s annual physical. What is also needed is finding out whether HDL cholesterol is effectively doing certain tasks, such as removing extra cholesterol from arteries and transporting it to the liver.
The NHLBI’s new cell-free test may make it possible to step up large-scale clinical testing of HDL function, according to the news release. As it stands now, HDL function study has been limited to research labs where testing involves “harvesting cells in the lab [which] can take days to process,” according to NIH Record.
“Most studies to date that have assessed CAD (coronary artery disease) risk by HDL functionality still use the CEC (cellular cholesterol efflux capacity) in vitro assay and are based on the use of radioisotopes (3H-cholesterol) and cultured cells, which is very labor intensive and impractical to do in a clinical laboratory,” the researchers wrote in The Journal of Clinical Investigation. They also pointed out that CEC batch-to-batch variability does not fit clinical laboratories’ need for standardization.
Advantages of NHLBI’s Test
To overcome these barriers, the NHLBI researchers created an HDL-specific phospholipid efflux (HDL-SPE) assay that has certain advantages over current HDL function assessments done in research labs.
According to the NIH, the HDP-SPE assay:
Is easy to replicate in clinical labs.
Is more suited to automation and large samples.
Offers up results in about an hour.
Is a better predictor of cardiovascular disease risk than HDL cholesterol testing for CAD risk.
“We developed a cell-free, HDL-specific phospholipid efflux assay for the assessment of CAD risk on the basis of HDL functionality in whole plasma or serum. One of the main advantages of the HDL-SPE assay is that it can be readily automated, unlike the various CEC assays currently in use,” the authors noted in their paper.
Here is how the test is performed, according to the NIH:
Plasma with HDL is separated from the patient’s blood.
“Plasma is added to donor particles coated with a lipid mixture resembling plaque and a fluorescent-tagged phospholipid” that only HDL can remove.
The fluorescent signal by HDL is then measured.
A bright signal suggests optimal HDL lipid removal function, while a dim light means reduced function.
The test builds on the scientists’ previous findings and data. In creating the new assay they drew on data from:
A study of 50 severe CAD and 50 non-CAD people.
A Japanese study of 70 CAD and 154 non-CAD participants.
Examined association of HDL-SPE with cardiovascular disease in a study of 340 patients and 340 controls.
“We have established the HDL-SPE assay for assessment of the functional ability of HDL to efflux phospholipids. Our combined data consistently show that our relatively simple HDL-SPE assay captures a pathophysiologically relevant parameter of HDL function that is at least equivalent to the CEC assay in its association with prevalent and incident CAD,” the researchers concluded in The Journal of Clinical Investigation.
Test May Be Subject to New FDA Rule
While HDL cardiovascular-related research is moving forward, studies aimed at the therapeutic side need to pick up, NIH noted.
“Someday we may have a drug that modulates HDL and turns out to be beneficial, but right now we don’t have that,” said Alan Remaley MD, PhD, NHLBI Senior Investigator and Head of the Lipoprotein Metabolism Laboratory, in the news release.
It may be years before the HDL-SPE test is used in medical settings, the researchers acknowledged, adding that more studies are needed with inclusion of different ethnicities.
Additionally, in light of the recently released US Food and Drug Administration (FDA) final rule on regulation of laboratory developed tests (LDT), the company licensed to bring the test to market may need to submit the HDL-SPE assay to the FDA for premarket review and clearance. That could lengthen the time required for the developers to comply with the FDA before the test is used by doctors and clinical laboratories in patient care.
“The timing of EWC with the release of this policy couldn’t be better,” CEO and founder of Momentum ConsultingValerie Palmieri told Dark Daily in an interview at Monday night’s opening reception. “It’s a great conference to not only catch up with colleagues but really hear and have those difficult discussions about where we are today, where we’re going, and where we need to be.”
Final LDT rule ‘radically’ different than draft
Tim Stenzel, MD, PhD, former director of the FDA’s Office of In Vitro Diagnostics called the finalized rule “radically different” from the proposed rule. In some ways it is less complex: “The bar is lower,” he said, noting that he was voicing his personal views and not those of the federal agency. “I was convinced that there would be lawsuits, but I’m now not sure if that’s advisable.”
Still, laboratory teams will have to parse the more than 500-page document to determine how the final rule relates to their specific circumstances. After that, it won’t be as challenging, Stenzel said.
His advice: First, read the rule. Second, reach out to FDA for help—he’s sure, he said, that the office is geared up to respond to a “ton of questions” about the implications for individual labs and are standing by to answer emails from labs. And, he added in a discussion session, emailing the agency is free.
The final rule will be in force 60 days after it’s published. Stenzel provided a timeline for some of the milestones:
1 Year: Comply with MD(AE) reporting and reporting of corrections and removals.
2 Years: Comply with labeling, registration and listing, and investigational use requirements.
3 Years: QS records and, in some cases, design controls and purchasing controls.
3.5 Years: Comply with high risk (class III) premarket review requirements.
4 Years: Comply with moderate and low-risk premarket review requirements.
Executive Chair and CEO of XiFin, Inc.Lâle White welcomed the audience with a morning keynote entitled “Big Changes in Healthcare” on new regulations and diagnostics players poised to reshape lab testing.
The diagnostics business is in constant flux, she noted, from payer requirements to greater regulatory and compliance burdens on labs. Other factors include the growing senior population and increasingly complex health conditions, rising costs throughout the healthcare ecosystem, falling funding and reimbursement, and staffing shortages.
As for the economic challenges, consumers are increasingly making decisions based on cost, convenience and quality. The population is shifting to Medicare advantage, which is more cost effective. But changes to the star ratings system will mean lower pay for payer organizations. Those companies will, in turn, mitigate their losses by making changes to pre-authorizations and tightening denials, even for clean claims.
Still, White said, more money isn’t the answer.
White urged the audience to use technology, including artificial intelligence and advances in genetic testing, to manage these and other industry changes.
“We need to optimize the tests we order,” she said. “And if we did that, lab diagnostics really has the potential to change the economics of health and improve outcomes.”
The FDA, Stenzel added, is “very interested” in stimulating innovation, building on the laboratory industry’s success in responding swiftly to the COVID pandemic and outbreaks of Monkey Pox, for example.
He shared lessons learned from recent public health emergencies, talked about CDC’s efforts to engage with clinical labs to improve future public health readiness and response and provided an overview of the CDC’s first laboratory-specific center.
“Laboratories are fundamental to public health,” he said. The industry is on the “front lines” when it comes to identifying threats, responding to them, and preparing for future responses.
Robert Michel, Editor-in-Chief of The Dark Report wrapped up the day’s regulatory discussions with a general session on the “regulatory trifecta” that includes the LDT final rule, CLIA regulations, and private payers’ policies for genetic claims.
