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Clinical Laboratories and Pathology Groups

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Amazon One Medical Call Centers Found Wanting in Washington Post Report

Patients concerns about the quality of care provided since Amazon acquired One Medical in 2022 can affect clinical laboratory testing for those providers

Recently, The Washington Post reported on leaked documents that appear to indicate Amazon’s One Medical primary care call center was not using trained, certified medical professionals to field patient phone calls and provide telehealth guidance. Instead, The Post reported, “[One Medical’s] call center is staffed by contractors who receive about two weeks of medical training before responding to patient concerns,” and that, “They have missed urgent issues like blood pressure spikes and sudden stomach pain with blood in one patient’s stool,” MSN’s Business Insider reported.

The Washington Post, which is owned by Amazon founder Jeff Bezos, went on to report, “Amazon’s primary care clinic One Medical circulated talking points telling workers to claim that in cases when its call center failed to escalate potentially urgent calls to medical staff, patients ‘received the care they needed,’ according to screenshots of internal messages seen by The Washington Post.”

The Post’s report highlights the challenges some telemedicine providers using “non-physician” personnel are having in delivering quality primary care.

During the COVID-19 pandemic, social distancing and hospital lockdowns kept many people indoors and unable to access their doctors and clinical laboratories when they needed. As the pandemic progressed, enterprising mega corporations like Amazon saw an opportunity and invested heavily in bringing healthcare to patients where they live and shop.

Amazon, for example, announced in 2022 that it would be purchasing One Medical and all of its primary care clinics nationwide for $3.9 Billion.

“There is an immense opportunity to make the healthcare experience more accessible, affordable, and even enjoyable for patients, providers, and payers,” said Amir Dan Rubin, One Medical’s CEO, in an Amazon press release announcing the acquisition at that time. “We look forward to innovating and expanding access to quality healthcare services, together,” he added.

But it turns out, developing alternative pathways to primary care is not such an easy thing. According to Business Insider, some patients with One Medical are struggling to get adequate care, major patient concerns have been missed, and there are concerns over the efficacy of the services.

“The opportunity to transform healthcare and improve outcomes by combining One Medical’s human-centered and technology-powered model and exceptional team with Amazon’s customer obsession, history of invention, and willingness to invest in the long-term is so exciting,” said Amir Dan Rubin (above), One Medical’s CEO, in an Amazon press release. Clinical laboratories that service One Medical’s providers may want to follow this developing story. (Photo copyright: LinkedIn.)

Call Center Contractors Spark Concerns

One Medical was started by Harvard-trained internist Thomas Lee, MD, in an effort to streamline medical services to the benefit of stakeholders and patients, according to Forbes. This subscription based service offered patients 24/7 virtual care with access to in-person appointments.

“One Medical was founded in 2007 as a concierge medical network before going public in 2020 and purchasing Iora Health, a value-based provider for seniors, in 2021. By the end of 2022, a majority of One Medical’s revenue came from capitated contracts. The company currently operates more than 200 clinics and a telehealth service in a membership model,” Healthcare Dive reported.

But according to reports reviewed by journalists at The Washington Post, on more than one occasion elderly patients have been failed by the One Medical call center in Tempe, Arizona. Patients began to be rerouted to this call center about a year after the Amazon acquisition.

The Post reported that several patients reported symptoms such as pain and swelling, blood in stool, a spike in blood pressure and sudden rib pain, and that the call center failed to escalate these calls to clinical staff—instead simply scheduling an appointment sometimes for days later.

The workers at the Tempe call center included newly hired contractors with what The Post described as “limited training and little to no medical experience.” Internal sources at One Medical are raising the alarm bell about the dangers of Amazon’s frugal approach. “There were a lot of things slipping through the cracks,” one anonymous source told The Post.

Quantity over Quality

In an interview with PBS, Caroline O’Donovan, the reporter at The Washington Post who broke this story said, “In the documents that were leaked to us, there’s a doctor who wrote a note saying, ‘I don’t think these call center people even realize that they’re triaging patients, which is not something that they’re qualified to do.’”

Amazon contends that no one was harmed in the cases where protocol was not followed.

In an email statement concerning the Washington Post report, Amazon spokesperson Dawn Brun wrote, “While the patients ended up receiving the care they needed (during in-person visits with their providers), the initial call could have been managed more effectively,” The Post reported.

“We take patients’ feedback seriously and the [Washington Post] story mischaracterizes the dedication we have to our patients and care teams,” she added.

However, O’Donovan says that the patients—and some employees—she spoke with challenged that idea. “The patients I spoke to again and again—and some of the One Medical employees I spoke to—said there’s a difference between getting your phone call answered faster, literally someone picking up the phone, and actually getting your problem solved,” she told PBS.

When data-driven companies like Amazon get involved in healthcare certain care standards may be sacrificed in the name of optimization.

This story shows that there is not an easy solution/answer to developing alternative primary care pathways. Clinical laboratories have a stake in the evolution and developments in the field of primary care and telemedicine because often these patients need lab tests.

—Ashley Croce

Related Information:

Staff at Amazon’s One Medical Miss Urgent Issues Like Blood Pressure Spikes and Clots, According to New Report

Leaked Documents Reveal Patient Safety Issues at Amazon’s One Medical

One Medical: Playbook to Disrupt the Massive Healthcare Industry

Changes at Amazon-Owned Health Services Cause Alarm Among Patients, Employees

Patient Safety Concerns Arise over Amazon’s One Medical Call Centers after Document Leak

Amazon’s Health Clinic Pushed a Misleading Account of Call Center Errors

Amazon and One Medical Sign an Agreement for Amazon to Acquire One Medical

One Medical CEO Resigns from Amazon One Year after Acquisition

One Medical Founder Tom Lee on the Amazon Deal and Striking the Right Balance with Virtual Care

Amazon’s One Medical Faces Scrutiny over Call Center Practices

At-Home Paper Influenza Test Differentiates Strains, Gives Hope for Improved Screening and Surveillance of Viral Outbreaks

Researchers used CRISPR-based assays to develop new clinical laboratory point-of-care blood test which boasts accuracy, affordability, and accessibility

Here’s a novel use of paper as clinical laboratory test media. Researchers at Princeton University in New Jersey, the Massachusetts Institute of Technology’s Broad Institute, and Harvard University have developed an at-home paper-strip test that can not only identify the presence of influenza, but it can also differentiate between different strains of the flu bug.

According to UPI, the test can “distinguish between influenza A and influenza B—the two main types of seasonal flu—as well as identifying more virulent strains like H1N1 and H3N2.”

Many research teams are working to develop paper-based diagnostic screening tests because of their lower cost to produce and usefulness in remote locations. Should this near-patient point-of-care test become clinically viable, it could mean shorter times to answer, enabling speedier diagnoses and earlier start of treatment.

It also means patient specimens do not have to be transported to a clinical laboratory for testing. And reduced cost per test makes it possible to test more people. This serves the public health aspect of monitoring outbreaks of influenza and other diseases and gives hope for improved treatment outcomes.

“Being able to tease apart what strain or subtype of influenza is infecting a patient has repercussions both for treating them and public health interventions, said Jon Arizti Sanz, PhD, co-lead study author and postdoctoral researcher at the Broad Institute of Harvard and MIT, in a Broad Institute news release.

The researchers published their findings in The Journal of Molecular Diagnostics titled, “CRISPR-Based Assays for Point-of-Need Detection and Subtyping of Influenza.”

“Ultimately, we hope these tests will be as simple as rapid antigen tests, and they’ll still have the specificity and performance of a nucleic acid test that would normally be done in a laboratory setting,” Cameron A. Myhrvold, PhD (above), Assistant Professor of Molecular Biology at Princeton University in New Jersey, told CIDRAP. Influenza tests that can be performed at the point of care and in remote locations may reduce the number of screening tests performed by clinical laboratories. (Photo copyright: Michael James Butts/Hertz Foundation.)

Inspiration from Prior COVID-19 Test

According to an article published by the Center for Infectious Disease Research and Policy Research and Innovation Office (CIDRAP) at the University of Minnesota, the original test was developed in 2020 in a Harvard laboratory led by computational geneticist Pardis Christine Sabeti, MD, PhD, professor, Department of Organismic and Evolutionary Biology, and co-senior author of the study.

Her team developed their tests using Streamlined Highlighting of Infections to Navigate Epidemics (SHINE), “a clustered regularly interspaced short palindromic repeats (CRISPR)-based RNA detection platform,” the researchers wrote in their Journal of Molecular Diagnostics paper.

“SHINE has a runtime of 90 minutes, can be used at room temperature and only requires an inexpensive heat block to heat the reaction. The SHINE technology has previously been used to identify SARS-CoV-2 and later to distinguish between the Delta and Omicron variants,” Bioanalysis Zone reported.

“The test uses genetically engineered enzymes to identify specific sequences of viral RNA in samples,” the researchers told UPI. Originally designed to detect COVID-19, the team adapted the technology to detect influenza in 2022 “with the aim of creating a screening tool that could be used in the field or in clinics rather than hospitals or high-tech diagnostic labs,” they said.

Influenza A and B as well as H1N1 and H3N2 subtypes were the targets of the four SHINE assays. “When tested on clinical samples, these optimized assays achieved 100% concordance with quantitative RT-PCR. Duplex Cas12a/Cas13a SHINE assays were also developed to detect two targets simultaneously,” the researchers wrote in their paper.

The team used “20 nasal swabs from people with flu-like symptoms during the 2020-2021 flu season, nasal fluid from healthy people as the control, and 2016-2021 influenza sequences downloaded from the National Center for Biotechnology Information Influenza (NICB) database. They compared the results with those from quantitative reverse transcription-polymerase chain reaction (RT-PCR) tests,” CIDRAP reported.

The original 2020 test (shown above) takes 90 minutes to develop at room temperature. The test developers aim to drop this down to 15 minutes. In comparison, typical polymerase chain reaction (PCR) testing requires medical laboratories to have specialized equipment, trained staff, and prolonged processing times, the Broad Institute news release notes. (Photo copyright: Broad Institute.)

Implications of the New Tests

The ease of the new tests is an important development since approximately only 1% of individuals who come down with the flu see doctors for testing, according to the news release. And researchers had this in mind, looking at speed, accuracy, and affordability as a means to “improve outbreak response and infection care around the world,” UPI reported.

There are great benefits to strain differentiation that be achieved with the new test. Doctors are hopeful the test will help dial in the best treatment plans for patients since some strains are resistant to the antiviral medication oseltamivir (Tamiflu), UPI noted. This is significant since Tamiflu “is a common antiviral,” said Sanz in the Broad Institute news release.

“These assays have the potential to expand influenza detection outside of clinical laboratories for enhanced influenza diagnosis and surveillance,” the Journal of Molecular Diagnostics paper noted. This allows for more strategic treatment planning.

“Using a paper strip readout instead of expensive fluorescence machinery is a big advancement, not only in terms of clinical care but also for epidemiological surveillance purposes,” said Ben Zhang, an MD candidate in the Health Sciences and Technology at Harvard and co-first author of the study, in the Broad Institute news release.

Future Plans for Tests

“With further development, the test strip could be reprogrammed to distinguish between SARS-CoV-2 and flu and recognize swine flu and avian flu, including the H5N1 subtype currently causing an outbreak in US dairy cattle,” the study authors told CIDRAP.

The team is also looking at ways to help prevent H5N1 from crossing into human contamination, Sanz told UPI.

The new Princeton/MIT/Harvard tests echo the trend to bring in affordability and ease-of-use with accurate results as an end goal. Faster results mean the best treatments for each person can start sooner and may render the transport of specimens to a clinical laboratory as a second step unnecessary.

As research teams work to develop paper-based viral tests for their plethora of benefits, clinical laboratories will want to pay close attention to this development as it can have a big implication on assisting with future outbreaks.

Additional research is needed before these tests are going to be commonplace in homes worldwide, but this first step brings inspiration and hope of what’s to come. 

—Kristin Althea O’Connor

Related Information:

Simple Test for Flu Could Improve Diagnosis and Surveillance

Simple Paper-Strip Test Might Spot Flu, Identify Strain

CRISPR-Based Assays for Point-of-Need Detection and Subtyping of Influenza

Paper Strip Test Can Identify Flu Subtypes, May Have Other Applications, Scientists Say

Streamlined Inactivation, Amplification, and Cas13-based Detection of SARS-Cov-2

Paper Strip Test Using CRISPR and SHINE Technology Has Been Developed for Rapid Influenza Diagnosis

Researchers in China Develop AI-powered Tool That Can Diagnose Three Cancers Using a Drop of Dried Blood

Use of artificial intelligence in clinical laboratory testing could improve the diagnosis of cancer worldwide

In a proof of concept study, scientists at Shanghai Jiao Tong University in China have developed a clinical laboratory test that utilizes artificial intelligence (AI) to diagnose three types of cancer from a single drop of dried blood. The paper-based test was able to identify patients with colorectal, gastric, and pancreatic cancers and distinguish between patients with and without cancer.

The team’s goal was to develop a way to diagnose cancer while the disease is still in the earlier stages, especially in rural areas.

“Over a billion people across the world experience a high rate of missed disease diagnosis, an issue that highlights the need for diagnostic tools showing increased accuracy and affordability. In addition, such tools could be used in ecologically fragile and energy-limited regions, pointing to the need for developing solutions that can maximize health gains under limited resources for enhanced sustainability,” the researchers wrote in an article published in the journal Nature Sustainability titled, “A Sustainable Approach to Universal Metabolic Cancer Diagnosis.”

The researchers determined that by using less than 0.05 millimeters of dried blood, their test could accurately and quickly identify if a patient had cancer between 82% to 100% of the time.

According to Chaoyuan Kuang, MD, PhD (above), an oncologist at Montefiore Health System and assistant professor at the Albert Einstein College of Medicine, unlike liquid blood, dried serum can be “collected, stored, and transported at much lower cost and with much simpler equipment,” Live Science reported. “This could help democratize the availability of cancer early detection testing across the world,” he added. A paper-based clinical laboratory test that can detect and distinguish one cancer type from another would be a boon to cancer diagnosis worldwide. (Photo copyright: Albert Einstein College of Medicine.)

Improving Cancer Screening in Rural Areas

An earlier study conducted in China in 2022 examined results from 1,570 cancer survivors from both urban and rural areas of China. That study showed that 84.1% of the patients were diagnosed with cancer only after developing symptoms and that urban patients were more likely to be diagnosed in the early stages of cancer. In addition, rural patients also had less screening and treatment options available to them.

The researchers in this latest Chinese study tested their AI model on blood donors with and without cancer and compared the results to traditional liquid-blood biopsy tests.

“Based on modeling they performed, they reported the new tool could reduce the estimated proportion of undiagnosed cases of pancreatic, gastric, and colorectal cancers by about 20% to 50% if it was used for population-level cancer screening in rural China,” Live Science reported. 

The scientists used dried serum spots (DSS) and machine learning to perform the research. According to their Nature Sustainability paper, DSS can be challenging in cancer research because sensitive biomarkers in the samples are often degraded or have inadequate amount of blood for proper analysis. To circumvent these issues, the researchers used nanoparticle-enhanced laser desorption/ionization mass spectrometry (NPELDI MS) to increase reliability and sensitivity. Inorganic nanoparticles were applied to the samples to strengthen selectivity and refine metabolic compounds from the samples.

However, the study authors noted that “the adaptation of NPELDI MS to dried spot analysis has not been validated,” Interesting Engineering reported.

A ‘Great Start’

The machine learning algorithm the Chinese scientists created demonstrates that DSS samples can be used to preserve important biological markers and could be beneficial in the diagnosis of cancer. 

Their research indicated an overall reduction rate of undiagnosed cancers in the range of 20.35% to 55.10%. The researchers estimated the implementation of their AI tool could reduce the proportion of specific undiagnosed cancer cases in rural China by:

  • 84.30% to 29.20% for colorectal cancer,
  • 77.57% to 57.22% for gastric cancer, and
  • 34.56% to 9.30% for pancreatic cancer.

It’s a “great start,” Chaoyuan Kuang, MD, PhD, an oncologist at Montefiore Health System and assistant professor at the Albert Einstein College of Medicine told Live Science. “This cancer test won’t enter use for a long time,” he said. Nevertheless, the potential of the tool is “immense,” he added, but that “we are still years away from being able to offer this test to patients. 

“With further development, it could theoretically be used for the early detection of other types of cancer or for other diseases, or to monitor the progression of disease in patients who have already been diagnosed,” he noted.

Further research and clinical trials are needed before this AI tool can be used in a clinical diagnostic setting. This study is another example of researchers looking for cancer biomarkers in specimen types that are not tissue and further supports the hope that machine learning may one day detect cancer in earlier stages, increase survival rates, and save healthcare costs.

One factor motivating this type of research in China is the fact that the nation has more than 36,000 hospitals and approximately 20,000 anatomic pathologists. Of this total, only a minority of these pathologists have been trained to the standards of North America and Northern Europe.

Like other nations, China’s demand for subspecialist pathology services outstrips its supply of such pathologists. This is the reason why researchers in that country want to develop diagnostic assays for cancer and other diseases that are faster, cheaper, and comparable to a human pathologist in accuracy.

—JP Schlingman

Related Information:

Detecting Cancer in Minutes Possible with Just a Drop of Dried Blood and New Test, Study Hints

AI-powered Tool Detects Cancer in Minutes with One Drop of Blood

Dried Blood Spot Testing

A Sustainable Approach to Universal Metabolic Cancer Diagnosis

New Sustainable Diagnostic Approach Offers Precision Cancer Testing with Minimal Environmental Impact

The Urban-Rural Disparities and Associated Factors of Health Care Utilization Among Cancer Patients in China

University Hospitals Birmingham Claims Its New AI Model Detects Certain Skin Cancers with Nearly 100% Accuracy

UK Study Claims AI Reading of CT Scans Almost Twice as Accurate at Grading Some Cancers as Clinical Laboratory Testing of Sarcoma Biopsies

UK’s National Health Service Tests AI Tool That Can Spot Cancer in Mammograms Missed by Doctors

Mayo Clinic Scientists Use Chemical Analysis of Beethoven’s Hair to Determine Lead Poisoning May Have Contributed to Composer’s Hearing Loss and Other Health Ailments

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?

In a letter published in Clinical Chemistry, a journal of the Association for Diagnostics and Laboratory Medicine (ADLM) titled, “High Lead Levels in 2 Independent and Authenticated Locks of Beethoven’s Hair,” researchers with the metals laboratory within Mayo’s Division of Clinical Biochemistry and Immunology revealed analysis performed on authenticated locks of the composer’s hair. The results indicated extremely high concentrations of lead—64 to 95 times the expected level.

“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.

Rifai is a professor of pathology at Harvard Medical School and director of clinical chemistry at Boston Children’s Hospital.

“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.  

—Stephen Beale

Related Information:

High Lead Levels in 2 Independent and Authenticated Locks of Beethoven’s Hair

Locks of Beethoven’s Hair Offer New Clues to the Mystery of His Deafness

New Analysis of Beethoven’s Hair Reveals Possible Cause of Mysterious Ailments, Scientists Say

Beethoven May Have Had Lead Poisoning

Paul Jannetto, PhD, Contributes to Landmark Discovery of Beethoven’s Hair Lead Concentration

Beethoven Really Did Have Lead Poisoning, But That Didn’t Cause His Death

Genomic Analyses of Hair from Ludwig Van Beethoven

DNA from Beethoven’s Hair Unlocks Medical and Family Secrets

DNA Analysis of Beethoven’s Hair Reveals Health Issues—and a Family Secret

Brigham and Women’s Hospital Researchers Develop Implantable ‘Lab in a Patient’ to Test Effectiveness of Brain Cancer Drugs

Scientists reported positive Phase 1 trial results of their “intratumoral microdevice” in patients with glioma tumors

Here is an example of new microtechnology which has the potential to greatly shorten the time and improve the ability of physicians to determine which anti-cancer drug is most effective for an individual patient’s glioblastoma. As it is further developed, this technology could give anatomic pathologists and clinical laboratories an increased role in assessing the data produced by microdevices and helping physicians determine the most appropriate anti-cancer drug for specific patients.

In a news release, researchers at Brigham and Women’s Hospital (BWH) in Boston said they have developed an implantable “intratumoral microdevice” (IMD) that functions as a “lab in a patient,” capable of gauging the effectiveness of multiple drugs that target brain tumors. In a Phase 1 clinical trial, they tested the IMD on six patients with glioma tumors.

“In order to make the greatest impact on how we treat these tumors, we need to be able to understand, early on, which drug works best for any given patient,” study co-author Pier Paolo Peruzzi, MD, PhD, told the Harvard Gazette. “The problem is that the tools that are currently available to answer this question are just not good enough. So, we came up with the idea of making each patient their own lab, by using a device which can directly interrogate the living tumor and give us the information that we need.”

Peruzzi is Principal Investigator at the Harvey Cushing Neuro-Oncology Laboratories and Assistant Professor of Neurosurgery at Harvard Medical School.

The researchers published their findings in the journal Science Translational Medicine titled, “Intratumoral Drug-Releasing Microdevices Allow In Situ High-Throughput Pharmaco Phenotyping in Patients with Gliomas.” [PHOTO OF PERUZZI HERE

“Our goal is for the placement of these devices to become an integral part of tumor surgery,” said Pier Paolo Peruzzi, MD PhD (above) of Brigham and Women’s Hospital and Harvard Medical School in an article he co-wrote for Healio. “Then, with the data that we have from these microdevices, we can choose the best systemic chemotherapy to give to that patient.” Pathologists and clinical laboratories may soon play a role in helping doctors interpret data gathered by implantable microdevices and choose the best therapies for their patients. (Photo copyright: Dana-Farber Cancer Institute.)

New Perspective on Tumor Treatments

In a news story he co-wrote for Healio, Peruzzi explained that the microdevice—about the size and shape of a grain of rice—contains up to 30 tiny reservoirs that the researchers fill with the drugs they want to test. Surgeons implant the device during a procedure to remove the tumors.

The surgery takes two to three hours to perform, and during that time, the device releases “nanodoses” of the drugs into confined areas of the tumor. Near the end of the procedure, the device is removed along with tissue specimens. The researchers can then analyze the tissue to determine the effectiveness of each drug.

“This is not in the lab, and not in a petri dish,” Peruzzi told Harvard Gazette. “It’s actually in real patients in real time, which gives us a whole new perspective on how these tumors respond to treatment.”

The Healio story notes that gliomas are “among the deadliest brain cancers and are notoriously difficult to treat.” With current approaches, testing different therapies has posed a challenge, Peruzzi wrote.

“Right now, the only way these drugs are tested in patients is through what are called window-of-opportunity studies, where we give one drug to the patient before we resect the tumor and analyze the effect of the drug,” he said. “We can only do this with one drug at a time.”

Determining Safety of Procedure

The primary goal of the Phase 1 trial was to determine the safety of the procedure, Peruzzi noted. “To be in compliance with standard clinical practice and minimize risks to the patients, we needed to integrate the placement and retrieval of the device during an otherwise standard operation.”

The trial consisted of three men and three women ranging from 27 to 86 years old, with a median age of 76. Five were diagnosed with glioblastoma and one with grade 4 astrocytoma.

“None of the six enrolled patients experienced adverse events related to the IMD, and the exposed tissue was usable for downstream analysis for 11 out of 12 retrieved specimens,” the researchers wrote in Science Translational Medicine. They noted that application of the IMD added about 32 minutes to the time required for the surgery, equating to a cost increase of $7,800.

One drug they tested was temozolomide (TMZ), “the most widely used agent in this patient population,” they wrote. “Several patients in our trial received it systemically, either before or after IMD insertion, as part of the standard of care. Thus, although our trial was not designed to choose chemotherapy agents based on IMD data, we still could compare the observed clinical-radiological response to systemic TMZ with the patient-specific response to TMZ in the IMD-exposed tissue.”

One patient, the researchers noted, had not benefited from the drug “in concordance with the poor tissue response observed in the IMD analysis.” But in another patient, a 72-year-old woman, “IMD analysis showed a marked response to TMZ,” and she survived for 20 months after receiving the treatment “with radiological evidence of tumor response. This was despite having a subtotal tumor resection, in itself an unfavorable prognostic factor. The patient expired because of an unrelated cardiovascular event, although she had remained neurologically stable.”

Drug Duration Limitation

One limitation of the study was that testing the device during the tumor removal procedure limited the duration of the drug treatments, Peruzzi said. The Harvard Gazette noted that following their initial study, the researchers were testing a variation of the procedure in which the device is implanted three days before the main surgery in a minimally invasive technique. This gives the drugs more time to work.

Cancer researchers have theorized that common treatments for tumors can impair the immune system, Peruzzi wrote in Healio. “One thing we want to look at is which drugs can kill the tumor without killing the immune system as well,” he noted.

Future studies will determine the effectiveness of implanting microdevices into tumors to test therapies in vivo. Should they become viable, clinical laboratories and anatomic pathologists will likely be involved in receiving, interpreting, storing, and transmitting the data gathered by these devices to the patient’s doctors.

—Stephen Beale

Related Information:

Microdevices Implanted into Tumors Offer New Way to Treat Brain Cancer

Intratumoral Drug-Releasing Microdevices Allow In Situ High-Throughput Pharmaco Phenotyping in Patients with Gliomas

Microdevices Turn Brain Tumors into Tiny Labs

Devices Implanted into Brain Tumors During Surgery May Guide Treatment

Human Brain Tumor Implant Could Guide Personalized Therapies Tiny Implanted Devices Give Insights for Treating Brain Tumors

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