Technology like Apple’s VR/AR headsets may prove useful to clinical laboratories in accessioning and in pathology labs during biopsy grossing
In what has been billed as a first, medical teams in the US and UK used Apple’s Extended Reality (XR) Vision Pro headset system to assist in surgical procedures. The surgeons themselves did not wear the $3,500 headset. Instead, surgical nurses used the device for touch-free access to a software application that assisted them in setting up, organizing, and performing the operations. For pathologists and clinical laboratories, in the histology laboratory, such an arrangement involving XR headsets could be used when a biopsy is at the grossing station as well.
The headset software the team used during surgery was developed by eXpanded eXistence, Inc. (eXeX), a Florida-based company whose primary product is an iOS (Apple mobile operating system) application that provides similar functions for mobile devices. eXeX adapted the iOS app to work on Apple’s Extended Reality headset.
Extended Reality is an umbrella term for augmented reality (AR) and virtual reality (VR). Apple refers to the technology as “spatial” computing.
Within the clinical laboratory, XR headsets could be used in the accessioning process as the accessioner works through the steps to confirm all required information accompanies the test requisition and that the patient’s specimen is processed/aliquoted appropriately.
“The eXeX platform, enhanced by artificial intelligence, is designed not as a medical device but as an organizational and logistics tool. It aims to streamline the management of tens of thousands of items, including equipment, tools, technologies, consumables, implants, and surgical products,” said neurosurgeon Robert Masson, MD, eXeX’s founder and CEO, in a February news release.
Masson first deployed the software in his own surgical practice. Then in March, eXeX announced that a surgical team at Cromwell Hospital in London used the system in two microsurgical spine procedures, according to a March new release.
That news garnered media coverage in the UK as well as in US-based publications that follow Apple.
“We are in a new era of surgery, and for the first time, our surgical teams have the brilliance of visual holographic guidance and maps, improving visuospatial and temporal orientation for each surgical team and for each surgery in all specialties,” said neurosurgeon Robert Masson, MD (above), eXeX’s founder and CEO, in a press release. Clinical laboratories may one day use XR headsets in the histology lab at the grossing station. (Photo copyright: Masson Spine Institute.)
Surgical Process Not Glamorous, But Important
Despite being on a cutting-edge XR platform, the eXeX software addresses “the least glamorous part” of the surgical process, Masson told Gizmodo.
“People assume that surgical healthcare has got to be sophisticated and modern,” he said. “The reality is the way we organize it is probably the most archaic of all the major industries on the planet. It’s all memorization and guesswork with scribbles on pieces of paper.”
The advantage of an XR headset is that it allows use of the eXeX software in a sterile environment, he added. “The ability to interact with digital screens and holograms and lists and maps and products unlocks all kinds of possibilities. Suddenly, you’ve got an interactive digital tool that you can use without violating the sanctity of sterility.”
Does he foresee a future when the surgeons themselves use XR headsets in the operating room? Not necessarily, Masson told Gizmodo.
“There’s always a tendency to say, ‘look at this amazing tech, let’s put a screw in with it,’” he said. “Well, we’re already putting screws in without the headset, so it doesn’t really solve a problem. People tend to think of floating spines, floating heights, you know, an overlay that tells you where to put a catheter in the liver. Honestly, it’s all unnecessary because we already do that pretty well. What we don’t do really well is stay organized.”
Other XR Apps for Healthcare
In a news release, Apple showcased other healthcare apps for its Vision Pro platform.
Epic Systems, an electronic health record (EHR) system developer, has an app called Epic Spatial Computing Concept that allows clinicians “to easily complete charting, review labs, communicate using secure chat, and complete in-basket workflows through intuitive gestures, like simply tapping their fingers to select, flicking their wrist to scroll, or using a virtual keyboard or dictation to type,” Apple stated in the news release.
Stryker, manufacturer of Mako surgical robotic arms for joint-replacement procedures, has an Apple iOS app called myMako that “allows surgeons to visualize and review patients’ Mako surgical plans at any time in a brilliant, immersive visual experience,” Apple said.
Cinematic Reality, from Siemens Healthineers, is an Apple iOS app that “allows surgeons, medical students, and patients to view immersive, interactive holograms of the human body captured through medical scans in their real-world environment,” Apple said.
New Era in Technology
For the past 20 years, manufacturing companies have installed systems at workstations with audio and video that show each step in a work process and with written checklists on the computer screen. This allows workers to check off each required step as proof that each required work element was performed.
This is similar to professional pilots who use checklists at every step in a flight process. One pilot will read the checklist items, the other will perform the step and confirm it was complete.
These procedures are generally completed on computer displays, but with the advent of XR headset technology, these types of procedures are evolving toward mobility.
To prepare for the emergence of XR-based healthcare apps, the US Food and Drug Administration (FDA) has organized a research team to devise best practices for testing these headset devices, CNBC reported.
It will be some time before XR headset technology finds its way into histology laboratories, clinical laboratories, and pathology practices, but since the rate of technology adoption accelerates exponentially, it might not take very long.
Results of an earlier study in which locks of Beethoven’s hair underwent genetic analysis showed the composer ‘had a predisposition for liver disease and became infected with hepatitis B’
Here is an example of modern technologies being used with “historical biospecimens” to solve long-standing mysteries or questions about the illnesses of famous historical figures. Clinical laboratory scientists at the Mayo Clinic have used modern-day chemical analysis techniques to answer a 200-year-old question: What caused Ludwig van Beethoven’s deafness and other health problems?
“Such lead levels are commonly associated with gastrointestinal and renal ailments and decreased hearing but are not considered high enough to be the sole cause of death,” the authors wrote.
Beethoven’s death at age 56 has been attributed to kidney and liver disease, CNN reported. Even if the lead concentrations were not the sole cause, they would nevertheless be regarded as lead poisoning, lead study author Nader Rifai, PhD, told CNN.
“If you walk into any emergency room in the United States with these levels, you will be admitted immediately and you will undergo chelation therapy,” he said.
“It is believed that Beethoven died from liver and kidney disease at age 56. But the process of understanding what caused his many health problems has been a much more complicated puzzle, one that even Beethoven himself hoped doctors could eventually solve,” CNN reported, adding, “The composer expressed his wish that his ailments be studied and shared so ‘as far as possible at least the world will be reconciled to me after my death.’” Mayo clinical laboratory scientists are using chemical analysis on authenticated locks of Beethoven’s hair to do just that. (Photo copyright: Joseph Karl Stieler/Public Domain.)
Mass Spectrometry Analysis
Mayo Clinic’s metals laboratory, led by chemist Paul Jannetto, PhD, an associate professor in the Department of Laboratory Medicine and Pathology and Laboratory Director at the Mayo Clinic, performed the analysis on two authenticated locks of Beethoven’s hair, using inductively coupled plasma mass spectrometers.
The researchers found that one lock had 258 micrograms of lead/gram and the other had 380 micrograms. Normally they would expect to find less than four micrograms.
“These are the highest values in hair I’ve ever seen,” Jannetto told The New York Times. “We get samples from around the world and these values are an order of magnitude higher.”
The researchers also found that the composer’s hair had four times the normal level of mercury and 13 times the normal amount of arsenic.
Rifai and other researchers noted that Beethoven drank large amounts of plumbed wine, and at the time it was common to sweeten wine with lead acetate, CNN reported.
The composer also could have been exposed to lead in glassware. He likely absorbed high levels of arsenic and mercury by eating fish caught from the Danube River in Vienna.
David Eaton, PhD, a toxicologist, pharmacologist, and Professor Emeritus, Department of Environmental and Occupational Health Sciences at the University of Washington, told The New York Times that high levels of lead could have impaired Beethoven’s hearing through their effect on the nervous system. Additionally, he said the composer’s gastrointestinal ailments “are completely consistent with lead poisoning.”
Rifai told CNN that he’d like to study locks of hair from other 19th century Vienna residents to see how their lead levels compared with Beethoven’s.
Beethoven’s Genome and Genetic Predisposition for Liver Disease
Additional research published in May built on an earlier genomic analysis of Beethoven’s hair, which appeared in March 2023 in the journal Current Biology.
The international team included geneticists, archeologists, and immunologists who analyzed eight locks of hair attributed to the composer. They determined that five were authentic. One, known as the Stumpff Lock, appeared to be the best preserved. They used this lock to sequence Beethoven’s DNA.
“Although we could not identify a genetic explanation for Beethoven’s hearing disorder or gastrointestinal problems, we found that Beethoven had a genetic predisposition for liver disease,” the authors wrote. “Metagenomic analyses revealed furthermore that Beethoven had a hepatitis B infection during at least the months prior to his death. Together with the genetic predisposition and his broadly accepted alcohol consumption, these present plausible explanations for Beethoven’s severe liver disease, which culminated in his death.”
One surprising discovery was the likelihood of an extramarital affair on the composer’s father’s side, CNN reported. The researchers learned this in part by comparing his genetic profile with those of living relatives.
“Through the combination of DNA data and archival documents, we were able to observe a discrepancy between Ludwig van Beethoven’s legal and biological genealogy,” study coauthor Maarten Larmuseau, PhD, told CNN. Larmuseau is assistant professor, Faculty of Medicine, and head of the Laboratory of Human Genetic Genealogy at KU Leuven in Belgium.
The Mayo Clinic team used two locks authenticated in the 2023 study—the Bermann Lock and Halm-Thayer Lock—to perform their chemical analysis, CNN reported.
Beethoven’s Wishes
The earlier study noted that Beethoven wanted his health problems to be made public. In 1802, he wrote a document known as the Heiligenstadt Testament in which he asked that his physician, surgeon/ophthalmologist Johann Adam Schmidt, MD, discuss his disease after he died.
“For almost two years I have ceased to attend any social functions, just because I find it impossible to say to people: I am deaf,” Beethoven wrote at age 30, The New York Times reported. “If I had any other profession, I might be able to cope with my infirmity, but in my profession, it is a terrible handicap. And if my enemies, of whom I have a fair number, were to hear about it, what would they say?”
The authors of the Current Biology paper wrote, “Genomic sequence data from authenticated locks of Beethoven’s hair provide Beethoven studies with a novel primary source, already revealing several significant findings relating to Beethoven’s health and genealogy, including substantial heritable risk for liver disease, infection with HBV [Hepatitis B], and EPP [extra pair paternity]. This dataset additionally permits numerous future lines of scientific inquiry.
“The further development of bioinformatics methods for risk stratification and continued progress in medical genetic research will allow more precise assessments both for Beethoven’s disease risk and for the genetic inference of additional phenotypes of interest.
“This study illustrates the contribution and further potential of genomic data as a novel primary source in historical biography,” the scientists concluded.
The work of the clinical laboratory professionals at Mayo Clinic also demonstrates how advances in various diagnostic technologies can enable pathologists and lab scientists to participate in solving long-standing health questions about historical figures, especially if their hair or other types of specimens survived and can be used in the analysis.
This may be a new ‘sign of the times’ as hospitals, clinical laboratories, and other healthcare providers working with AI find they also need to hire their own prompt engineers
AI “prompting,” according to Florida State University, “refers to the process of interacting with an AI system by providing specific instructions or queries to achieve a desired outcome.”
According to workable.com, prompt engineers specialize “in developing, refining, and optimizing AI-generated text prompts to ensure they are accurate, engaging, and relevant for various applications. They also collaborate with different teams to improve the prompt generation process and overall AI system performance.”
Healthcare institutions are getting more serious about using AI to improve daily workflows and clinical care, including in the clinical laboratory and pathology departments. But adopting the new technology can be disruptive. To ensure the implementation goes smoothly, hospitals are now seeking prompt engineers to guide the organization’s strategy for using AI.
When Boston Children’s Hospital leaders set out to find such a person, they looked for an individual who had “a clinical background [and] who knows how to use these tools. Someone who had experience coding for large language models and natural language processing, but who could also understand clinical language,” according to MedPage Today.
“We got many, many applications, some really impressive people, but we were looking for a specific set of skills and background,” John Brownstein, PhD, Chief Innovation Officer at Boston Children’s Hospital and Professor of Biomedical Informatics at Harvard Medical School, told MedPage Today.
“It was not easy to find [someone]—a bit of a unicorn-type candidate,” noted Brownstein, who is also a medical contributor to ABC News.
After a four-month search, the hospital hired Dinesh Rai, MD, emergency room physician and AI engineer, for the position. According to Brownstein, Rai had “actually practiced medicine, lived in a clinical environment,” and had “successfully launched many [AI] applications on top of large language models,” MedPage Today reported.
“Some of the nuances I bring to the table in terms of being a physician and having worked clinically and understanding really deeply the clinical workflows and how we can implement the [AI] technology—where its limits are, where it can excel, and the quickest way to get things [done],” Dinesh Rai, MD (above), told MedPage Today. “I’m happy to be able to help with all of that.” Hospital clinical laboratory and pathology managers may soon by engaging with prompt engineers to ensure the smooth use of AI in their departments. (Photo copyright: LinkedIn.)
Prompt Engineers are like F1 Drivers
“It’s kind of like driving a car, where basically anyone can drive an automatic car, and anyone can go onto ChatGPT, write some text, and get a pretty solid response,” said Rai, describing the act of AI prompting to MedPage today.
Then, there are “people who know how to drive manual, and there are people who will know different prompting techniques, like chain-of-thought or zero-shot prompting,” he added. “Then you have those F1 drivers who are very intimate with the mechanics of their car, and how to use it most optimally.”
The American Hospital Association (AHA) believes that AI “holds great promise in helping healthcare providers gain insights and improve health outcomes.” In an article titled, “How AI Is Improving Diagnostics, Decision-Making and Care,” the AHA noted that, “Although many questions remain regarding its safety, regulation, and impact, the use of AI in clinical care is no longer in its infancy and is expected to experience exponential growth in the coming years.
“AI is improving data processing, identifying patterns, and generating insights that otherwise might elude discovery from a physician’s manual effort. The next five years will be critical for hospitals and health systems to build the infrastructure needed to support AI technology, according to the recently released Futurescan 2023,” the AHA wrote.
The graphic above is taken from the American Hospital Association’s article about Futurescan’s 2023 survey results on AI in healthcare. “Healthcare executives from across the nation were asked how likely it is that by 2028 a federal regulatory body will determine that Al for clinical care delivery augmentation (e.g., assisted diagnosis and prescription, personalized medication and care) is safe for use by our hospital or health systems,” AHA stated. This would include the use of AI in clinical laboratories and pathology group practices. (Graphic copyright: American Hospital Association.)
The AHA listed the top three opportunities for AI in clinical care as:
Clinical Decision Tools: “AI algorithms analyze a vast amount of patient data to assist medical professionals in making more informed decisions about care.”
Diagnostic and Imaging: The use of AI “allows healthcare professionals to structure, index, and leverage diagnostic and imaging data for more accurate diagnoses.”
Patient Safety: The use of AI improves decision making and optimizes health outcomes by evaluating patient data. “Systems that incorporate AI can improve error detection, stratify patients, and manage drug delivery.”
The hiring of a prompt engineer by Boston Children’s Hospital is another example of how AI is gaining traction in clinical healthcare. According to the Futurescan 2023 survey, nearly half of hospital CEOs and strategy leaders believe that health systems will have the infrastructure in place by 2028 to successfully utilize AI in clinical decision making.
“I’m lucky to [be] in an organization that has recognized the importance of AI as part of the future practice of medicine,” Rai told MedPage Today.
Pathologists and managers of clinical laboratories and genetic testing companies will want to track further advancements in artificial intelligence. At some point, the capabilities of future generations of AI solutions may encourage labs to hire their own prompt engineers.
Though only in early stages, findings could lead to a ‘therapeutic against current and newly-arising variants,’ say researchers
As SARS-CoV-2 changes and mutates, some therapeutic antibodies that were once highly effective in fighting the virus have lost potency. But now, in a proof-of-concept study, researchers from Boston Children’s Hospital have identified one antibody that neutralizes all known variants of the coronavirus, including the omicron variant. Microbiologists and clinical laboratory managers will find this intriguing, as most medical labs perform serology testing for SARS-CoV-2 antibodies.
The new antibody appears to be robust. It triggers several other types of antibodies as part of the immune response. If validated by further research, this discovery, the researchers state, may lead to new vaccines, better therapies, and improved treatments for COVID-19.
“We hope that this humanized antibody will prove to be as effective at neutralizing SARS-CoV-2 in patients as it has proven to be thus far in preclinical evaluations,” said geneticist Frederick Alt, PhD, Director of the Program in Cellular and Molecular Medicine at Boston Children’s Hospital and one of the leaders of the research. Clinical laboratories that perform serology testing for COVID-19 will be intrigued by this new line of research. (Photo copyright: PR Newswire.)
SP1-77 Antibody Outperforms All Others at Neutralizing SARS-CoV-2
To conduct their research, the team used genetically modified mice that basically have built-in human immune systems. These mice were originally utilized for seeking out antibodies to HIV, another virus that tends to mutate. Their immune systems can mimic what human immune systems encounter when a viral invader attacks.
The scientists inserted two human gene segments into the mice, which quickly produced antibodies resembling those made by humans. The mice were then exposed to the SARS-CoV-2 spike protein from the original coronavirus strain. The scientists found that the mice produced nine different families of antibodies that could bind to the spike protein.
The researchers then tested the effectiveness of those antibodies and found that three of the nine antibody families strongly neutralized the original SARS-CoV-2 coronavirus. In addition, one of the antibody families—dubbed SP1-77—was much more powerful and could neutralize the Alpha, Beta, Gamma, Delta, and all known Omicron strains of the SARS-CoV-2 virus.
New Monoclonal Antibody Products and Vaccines
If their findings are validated through further research, SP1-77 “would have potential to be a therapeutic against current and newly-arising variants of concern” according to the Science Immunology study. It also could be useful as part of a cocktail containing other antibody treatments for COVID-19 variants.
“SP1-77 binds the spike protein at a site that so far has not been mutated in any variant, and it neutralizes these variants by a novel mechanism,” said Tomas Kirchhausen, PhD, Senior Investigator, Program in Cellular and Molecular Medicine at Boston Children’s Hospital and one of the authors of the study in a statement announcing the study findings. “These properties may contribute to its broad and potent activity,” he added.
“This is very early-stage proof-of-concept work to illustrate that broadly neutralizing antibodies can be generated using a mouse model,” Amesh Adalja, MD, an infectious disease expert and senior scholar at the Johns Hopkins Center for Health Security, told Prevention. “Such work, if replicated and expanded, could form the basis of new monoclonal antibody products as well as a vaccine.”
The researchers have applied for a patent for the SP1-77 antibody as well as the mouse model they used to create it. Studies on the antibody are ongoing and have only been performed on mice and not humans. The scientists intend to execute further research on the innovative antibody and hope it will someday be used to help fight the COVID-19 virus and all its variants.
“We’d love to have a vaccine that is active against all circulating variants, including those yet to come,” Thomas Russo, MD, Professor and Chief of Infectious Disease, Department of Medicine, University at Buffalo told Prevention. “It’s the holy grail of vaccines.”
Microbiologists and clinical laboratories working with monoclonal antibodies to treat for COVID-19 infections will no doubt want to follow the Boston Children’s Hospital research closely as it may lead to new treatments and vaccines.
