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Europe Implements New Anatomic Pathology Guidelines to Reduce Nurse Exposure to Formaldehyde and Other Toxic Histology Chemicals

University of Turin study in Italy shows under-vacuum sealing systems reduce exposure to formaldehyde by 75% among nurses handling tissue biopsy specimens during surgery

Histology technicians and anatomic pathology (AP) laboratories regularly handle dangerous chemicals such as formaldehyde. They understand the risks exposure brings and take precautions to minimize those risks. However, in operating suites worldwide, nurses assisting surgeons also are being exposed to this nasty chemical.

Nurses must place biopsies and other tissues into buckets of formaldehyde to preserve the tissue between the operating room (OR) and histology laboratory. Formaldehyde, along with toluene, and xylene, is used to process and preserve biopsy tissue, displace water, and to create glass slides. It is an important substance that has long been used to maintain the viability of tissue specimens. Thus, exposure to formaldehyde among nurses is well-documented.

According to a National Academy of Sciences report, formalin, a tissue preservative that is a form of formaldehyde, has been linked to:

·       Myeloid leukemia;

·       Nasopharyngeal cancer; and,

·       Sinonasal cancer.

However, as Dark Daily previously reported, “One alternative to storing specimens in buckets with formalin is to vacuum-seal specimens … [so] that both the quality management of the patient specimen and worker safety for handling the specimens are greatly improved.” (See Dark Daily, “Anatomic Pathology Labs Adopt New Ways to Package, Transport, and Store Specimens to Reduce Formalin and Improve Staff Safety in Operating Theaters and Histology Laboratories,” October 13, 2014.)

Now, motivated by increasing formaldehyde regulations in Europe, as well as the need to increase awareness of exposure risks, the University of Turin (Unito), and other hospitals in Italy’s Piedmont region, conducted a cross-sectional study of 94 female nurses who were being potentially exposed to formaldehyde.

Researchers Aim for “Formalin-Free” Hospitals

The Unito study showed that nurses using an under-vacuum sealing (UVS) system in ORs are exposed to levels of formaldehyde 75% lower than those who did not use the system. This study differs from other similar tests because the level of exposure is not just potential, due to environmental contamination, but confirmed with analytic data from specific urine analyses.

The researchers divided the nurses into two groups:

·       One group immersed samples in containers of formaldehyde following standard procedures;

·       The other group worked in operating rooms equipped with a UVS system.

The researchers described a UVS system that called for the tissue removed during surgery to be sealed in a medical grade vacuum bag and refrigerated at four degrees centigrade before being transferred to the lab for fixation.

One example of a UVS system is TissueSAFE plus, developed by Milestone Medical, located in Bergamo, Italy, and Kalamazoo, Mich. According to the company’s website, the system, “Eliminates formalin in the operating theatre and allows a controlled formalin-free transfer of biospecimens to the laboratory.”

The image above is from a research paper by Richard J. Zarbo, MD, Pathology and Laboratory Medicine, Henry Ford Health System. It describes “five validation trials of new vacuum sealing technologies that change the approach to the preanalytic ‘front end’ of specimen transport, handling, and processing, and illustrate their adaptation and integration into existing Lean laboratory operations with reduction in formalin use and personnel exposure to this toxic and potentially carcinogenic fixative.” (Image copyright: Henry Ford Health System/Springer International Publishing.)

 

Increased Scrutiny Leads to New Pathology Guidelines

In a paper published in Toxicology Research, a journal of The Royal Society of Chemistry, the researchers noted a marked difference related to the adoption of the under-vacuum sealing procedure, as an alternative to formaldehyde for preserving tissues. “Nurses, operating in surgical theatres, are traditionally exposed to formaldehyde because of the common and traditional practice of immersing surgical samples, of a size ranging between two and 30 centimeters, in this preservative liquid (three to five liters at a time) to be later transferred to a [histopathology] lab,” the authors wrote. “We evaluated the conditions favoring the risk of exposure to this toxic reagent and the effect of measures to prevent it.”

Throughout Europe, increased scrutiny has forced medical pathology associations to write new guidelines that accept alternative methods to formaldehyde-based tissue preservation methods.

“In Europe, and in Italy in particular, the level of attention to formaldehyde exposure in the public health hospital system has become very high, forcing pathology associations to rewrite guidelines,” Marco Bellini, General Manager of the Medical Division at Milestone Medical, told Dark Daily. “What makes this study unique from many other similar tests is that the level of exposure has been confirmed with data from specific urine analyses,” he added.

The Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPEC), a division of the International Academy of Pathology, wrote general guidelines for AP labs that have been accepted and officially published by the Italian Ministry of Health.

The main topic of these guidelines is the preanalytical aspects of specimen collection, transportation, and preservation, where the vacuum method has been indicated as a valid alternative to improve the standardization of these crucial steps in pathology. By moving the starting point for specimen fixation from the OR to the histology labs, parameters can be controlled and documented, with the main advantage of reducing formaldehyde exposure by operators at the collection point.

These guidelines will be presented at the European Society of Pathology (ESP) with the intent to extending them throughout Europe.

Toluene’s and Xylene’s Effects Studied 

Formaldehyde is not the only potentially harmful substance in the clinical laboratory. As previously noted, common solvents toluene and xylene also are potentially hazardous.

In fact, a study of pathologists, lab technicians, and scientists who work with toluene and xylene published in the Journal of Rheumatology found that the chance of acquiring Raynaud Syndrome (a vascular condition) doubled for those workers. (See Dark Daily, “Health of Pathology Laboratory Technicians at Risk from Common Solvents like Xylene and Toluene,” July 5, 2011.)

Medical laboratory leaders are reminded to initiate processes that ensure safe specimen handling, transport, and processing, as well as workflow changes that eliminate chemical odors in the lab. Studies, such as those cited above, may provide information necessary to affect change.

—Donna Marie Pocius

Related Information:

Formaldehyde Fact Sheet

Towards a Formalin-Free Hospital: Levels of 15-F2t-isoprostane and malondialdehyde to Monitor Exposure to Formaldehyde in Nurses from Operating Theatres

Histologic Validation of Vacuum Sealed, Formalin-Free Tissue Preservation, and Transport System

Notes Regarding the Use of Formalin, Reclassified as “Carcinogenic”

Formaldehyde Substitute Fixatives:  Analysis of Macroscopy, Morpholologic Analysis, and Immunohistochemical Analysis

Anatomic Pathology Labs Adopt New Ways to Package, Transport, and Store Specimens to Reduce Formalin and Improve Staff Safety in Operating Theaters and Histology Laboratories

Health of Pathology and Laboratory Technicians at Risk from Common Solvents Like Xylene and Toluene

National Academy of Sciences Confirms that Formaldehyde Can Cause Cancer in a Finding that has Implications for Anatomic Pathology and Histology Laboratories

Researchers in Two Separate Studies Discover Gut Microbiome Can Affect Efficacy of Certain Cancer Drugs; Will Findings Lead to a New Clinical Laboratory Test?

If the link between certain types of gut bacteria and improved effectiveness of certain cancer treatments can be leveraged, then medical laboratories could soon have another diagnostic tool to use in supporting physicians with cancer care

From improving treatments for chronic diseases to extending lives, gut microbiome (bacteria that is part of human microbiota) has been at the forefront of developing clinical laboratory testing and anatomic pathology diagnostic technologies in recent years. Now, two studies recently published in the online journal Science confirm research that the “composition” of gut bacteria may have a significant influence on the effectiveness of certain cancer drugs.

The goal of both studies was to determine whether there was a link between gut bacteria and the efficacy of cancer drugs known as PD-1 inhibitors. These drugs are used for several types of cancer, including:

  • Melanoma;
  • Lung;
  • Bladder; and,
  • Stomach cancers.

They function by freeing up the immune system to attack cancer cells.

Greater Bacterial Diversity in Gut Brings Improved Response to PD-1 Inhibitors

One of the studies, “Gut Microbiome Modulates Response to Anti–PD-1 Immunotherapy in Melanoma Patients,” found that a microbiome populated with “good” bacteria can elevate the potency of certain drug treatments. The researchers discovered that the gut bacteria in patients who responded well to PD-1 inhibitors differed from that found in patients who did not respond to the treatment.

For this study, researchers at the MD Anderson Cancer Center at the University of Texas collected oral, gut, and fecal microbiome samples and tumor biopsies from 112 patients with advanced melanoma. Clinical laboratorians took the samples before and after PD-1 treatments. They divided the patients into two groups—responders and non-responders—and profiled each microbiome using genetic sequencing.

“What we found was impressive: There were major differences both in the diversity and composition of the gut microbiome in responders versus non-responders,” Jennifer Wargo, MD, MMSc, leader of the study, told STAT. “Those who did well had greater bacterial diversity in their gut, whereas those whose tumors didn’t much shrink had fewer varieties of microbes present.”

Melanoma patients who experienced success with PD-1 therapy had a more diverse microbiome and higher concentrations of bacteria known as Ruminococcus and Faecalibacterium. Patients involved in the study who did not respond well to PD-1 therapy had the presence of another bacterium called Bacteroidales.

Jennifer Wargo, MD (above center) with her team at the MD Anderson laboratories. The researchers cautioned that clinical trials are needed before a definitive conclusion can be reached on whether altering gut bacteria can improve the effectiveness of PD-1 therapy. “If you’re changing the microbiome, depending on how you do it, it may not help you—and it might harm you,” Wargo emphasized in STAT. “Don’t try this at home.” (Photo copyright: MD Anderson.)

Antibiotics Can Reduce Effectiveness of PD-1Therapy

The other study, “Gut Microbiome Influences Efficacy of PD-1-based Immunotherapy Against Epithelial Tumors,” discovered that some drug therapies were less effective in patients who were also taking antibiotics to treat infections shortly before beginning treatment with PD-1 drugs.

Researchers for this study, led by Laurence Zitvogel, MD, PhD, of the Gustave Roussy Cancer Campus in Villejuif, France, examined 249 patients who were given a PD-1 inhibitor for lung, kidney, or urinary tract cancers. A little over one fourth of these patients had recently taken antibiotics, which can strip the gut of essential bacteria necessary to treat infections.

The team found that patients who had ingested an antibiotic relapsed faster and did not live as long as patients who had not taken an antibiotic before receiving PD-1 therapy. When they analyzed variances between patients who responded well to treatment versus patients who did not, they detected the presence of Akkermansia muciniphila, a mucin-degrading bacterium, in the responders.

Personalized Treatment Based on Each Patient’s Gut Microbiome

The culmination of this type of research raises questions about how cancer medications may interact with microbiomes.

“Should we be profiling the gut microbiome in cancer patients going into immunotherapy?” asked Wargo in the STAT article. “And, should we also be limiting, or closely monitoring, the antibiotic use in these patients?

“This is all very context-specific, and multiple different factors need to be considered on how best to change the microbiome,” she continued. “When it comes to optimizing cancer therapy, treatments will have to be heavily personalized, based on what a patient’s gut microbiome looks like already.”

Diagnostic tests that could determine whether a certain drug will be beneficial for a patient would perform a critical role in healthcare decision-making. Since cancer drug treatments can cost tens of thousands of dollars or more, it would be advantageous to know which therapies would be optimal for individual patients. The hope is that in the future, clinicians, working with anatomic pathologists and clinical laboratories, will have the tools needed to ascertain if patient’s microbiomes will best work with a particular drug and if they would likely encounter any side effects.

—JP Schlingman

Related Information:

Patients’ Gut Bugs May Play Role in Cancer Care

Gut Microbiome Modulates Response to Anti–PD-1 Immunotherapy in Melanoma Patients

Gut Microbiome Influences Efficacy Of PD-1–Based Immunotherapy Against Epithelial Tumors

Your Gut Bacteria Could Determine How You Respond to Cutting-edge Cancer Drugs

The Bacteria in Your Gut Could Help Determine if a Cancer Therapy Will Work

Attention Microbiologists and Medical Laboratory Scientists: New Research Suggests an Organism’s Microbiome Might Be a Factor in Longer, More Active Lives

Get the Poop on Organisms Living in Your Gut with a New Consumer Laboratory Test Offered by American Gut and uBiome

Mayo Clinic and Whole Biome Announce Collaboration to Research the Role of the Human Microbiome in Women’s Diseases Using Unique Medical Laboratory Tests

Netherlands University Researchers Question Validity of More Than 30,000 Published Scientific Studies; Findings Have Implications for Medical Laboratories

Radboud University researchers fear oncology, molecular biology, pharmacology, and other cell-centric medical research efforts are at risk due to verification that at least 30,000 studies published in 33,000 scientific journals included data derived from misidentified or contaminated cell lines

Many research findings that underpin the science behind various diagnostic technologies used regularly by clinical laboratories and anatomic pathology groups may not be valid. This is because a large number of published studies may have used misidentified or contaminated cell lines.

Biomedical scientists have known for a long time that many research papers exist containing reports on the wrong cells due to cell line misidentification. And yet, few studies have measured the true scope of the problem. Until now. Researchers at Radboud University in the Netherlands have determined that this problem may have influenced the findings of thousands of published research studies and upon which many other research studies were conducted.

Because clinical laboratories and anatomic pathology groups use assays and diagnostic tests that are developed as a result of these research studies, identifying how many published papers have inaccurate findings that cannot be duplicated would affect how and when it is appropriate for physicians to order certain medical laboratory tests and rely on the results.

Additionally, cancer research is based on cell line studies as well. Thus, it may prove necessary to restudy existing published findings and revise them as appropriate. In turn, these new findings might change how and when some cancer tests are ordered and the results interpreted.

Identifying Corrupted Published Data

Radboud researchers Serge P. J. M. Horbach, a doctoral student, and Willem Halffman, PhD, Associate Professor, Philosophy and Science Studies, used the Web of Science database to track down any scientific articles based on “known misidentified cell lines as listed by the International Cell Line Authentication Committee’s (ICLAC) Register of Misidentified Cell Lines,” according to an article in ScienceAlert.

“We considered a reference to this original article as a good proxy for the usage of a cell line,” the researchers noted in their study published in the journal PLOS ONE. “Since typically the original papers are focused on reporting the establishment of the cell line only.”

They focused on misidentified cell lines that were caused by HeLa cells, also known as “immortalized cells.” HeLa cells have been used in scientific research for decades. They were the first mass-producible cells that could be used in vitro, making them highly desirable for biomedical research.

However, the process of creating immortalized cells involves mutation, during which contamination can be introduced by other cells. Immortalized cells can be identified as one type of cell when in fact they are actually another type of cell.

Research scientists have been aware of this problem for about as long as immortalized cells have been in use. They attempt to take it into account when completing their analyses, though not always successfully.

The Radboud researchers found 32,655 records of primary literature based on contaminated cell lines. They then cross-referenced the ICLAC Register of Misidentified Cell Lines with a range of databases to determine if articles were available for each of the 451 cell lines listed on Table One of the ICLAC Register.

The databases they used included the:

With this information, they further researched published articles in the Web of Science database using cell line identifiers. They noted both primary literature and any citation report entries for each cell line.

The researchers noted in their published study, “As we only searched for cell lines known to be misidentified, this constitutes a conservative estimate of the scale of contamination in the primary literature. Moreover, to avoid false positives, we excluded several cell lines, such as the ones with non-unique identifiers or the cell lines for which verified stock is still in circulation.”

Their estimate for secondary contaminated literature based off primary articles is larger still. “In total, we can conservatively estimate the citations to the primary contaminated primary literature at over 500,000, excluding self-citations,” the authors noted in their PLOS ONE article. “Thereby leaving traces in a substantial share of the biomedical literature.” They concluded, “… the amount of research potentially building on false grounds remains worrisome.”

Impact of Contaminated Cell Lines on Research, Clinical Laboratory Communities

Many of the assays and diagnostic tests performed by clinical laboratories and pathology groups were developed using cell line research. Should further scrutiny into the ability to duplicate and verify study findings fail to produce positive outcomes, it might call into question the validity and appropriate use of these tests.

For the research community, these findings represent yet another call to promote accountability and define standards for verifying authenticity of cell lines to further strengthen research findings.

The Radboud researchers ranked the number of contaminated articles they discovered by research area. Top affected areas include:

  • Oncology
  • Molecular Biology
  • Pharmacology
  • Cell Biology
  • Immunology

 

The distribution of contaminated primary literature over the research areas as defined by Web of Science. Only the 25 most affected research areas are included. (Graphic copyright: PLOS ONE.)

Addressing the Problem of Cell Line Contamination and Misidentification

Adapting the ever-growing body of published medical literature to reflect the known misidentifications, as well as the possibility of invalid results, will be a major undertaking. Ultimately, resolving this problem could require changes to practices and procedures currently used by research facilities and medical laboratories.

While the cost to authenticate cell lines adds to the bottom line of research projects, the money spent on research that becomes invalidated by misidentified cell lines is far greater.

In a 2015 Retraction Watch article, Leonard P. Freeman, PhD, President, Global Biological Standards Institute, notes, “An NIH RePORT search identified 9,000 active projects using cell lines, totaling $3.7 billion. Required use of authentication techniques would affect over $900 million in research dollars annually.”

Additionally, failure to adapt authentication as a part of standard operations brings other consequences. “A 2004 survey reported that just one-third of laboratories authenticate their cell lines,” Freeman noted. “10 years later, a Sigma-Aldrich survey found that only 37% of respondents ‘validate the purity and identity before first use’ of cell lines. Understanding the existing barriers that prevent implementation of universal cell authentication is central to changing this sad state of affairs.”

Mixed Recommendations for Fixing Inaccurate Published Studies

Of course, none of this will change the vast body of archived literature that might contain errors due to misidentification. Recommendations for addressing this aspect of the problem vary. The Radboud study authors suggest posting notes on any previously published articles stating that misidentified cell lines were used.

However, in a STAT article, Ivan Oransky, MD, and Adam Marcus, Managing Editor, Gastroenterology and Endoscopy News, co-founders of Retraction Watch, recommend more severe measures. “When we polled readers of Retraction Watch last December about the issue, 55% said journals should correct papers known to describe contaminated or misidentified cell lines, and more than 40% said retraction was the right choice.”

Thanks to the Radboud study, as cell lines continue to power the innovations of modern biomedical research, concerns will surely increase surrounding cell-line authentication and research findings. For pathology groups and medical laboratories, staying abreast of these developments will work to ensure data validity and reduce reputation and liability concerns.

—Jon Stone

 

Related Information:

Over 30,000 Published Studies Could Be Wrong Due to Contaminated Cells

The Ghosts of HeLa: How Cell Line Misidentification Contaminates the Scientific Literature

The Economics of Reproducibility in Preclinical Research

Crosscontamination of Cells in Culture

Cell Authentication Survey Shows Little Progress in a Decade

Apparent HeLa Cell Contamination of Human Heteroploid Cell Lines

Some 30,000 Biomedical Publications Report on Misidentified Cells

Cell Line Misidentification: The Beginning of the End

Fixing Problems with Cell Lines

Thousands of Studies Used the Wrong Cells, and Journals Are Doing Nothing

We’re Wasting a Lot of Research Funding Using the Wrong Cell Lines. Here’s One Thing We Can Do

Misidentified and Contaminated Cell Lines Lead to Faulty Cancer Science, Experts Say

STR Analysis for Cell Line Authentication Gaining Traction in Research Community

 

EHR Systems Continue to Cause Burnout, Physician Dissatisfaction, and Decreased Face-to-Face Patient Care

New study published in the Annals of Family Medicine (AFM) indicates that despite efforts to improve EHR usability and efficiency, primary care physicians continue to spend more than 50% of their workdays on computerized physician order entry (CPOE) and other clerical tasks instead of engaging in direct patient care

Do electronic health record (EHR) systems improve or degrade the productivity of physicians? That question has been the subject of robust debate. Now comes a new study in a peer-reviewed journal with a surprising finding: physicians spend up to 50% or more of their workday on EHR-related tasks.

In theory, EHRs offer a wealth of benefits over traditional paper-based systems. In practice, however, between interoperability concerns and implementation costs, they have proven a daunting undertaking for even the largest healthcare systems.

While EHRs might offer easy access to patient data—including medical laboratory records and anatomic pathology reports—this information doesn’t enter itself into databases or make itself instantly accessible. That requires human interaction, which is time consuming and prone to errors.

Thus, research from the American Medical Association (AMA) and the University of Wisconsin revealing that the time it takes to enter data, address communications, and perform other clerical tasks adds up to more than 50% of a physician’s workday is of paramount importance. That’s because physician dissatisfaction and departures from medical practice have increased each year since the EHR revolution began, and reports are the situation is getting worse.

In their retrospective cohort study involving 142 family medicine physicians, published in the Annals of Family Medicine (AFM), Brian G. Arndt, MD, from the School of Medicine and Public Health, Department of Family Medicine and Community Health, University of Wisconsin, et al, reported that clinicians spend 52% of their 11.4-hour workday interacting with an EHR system. On average, nearly 1.5 hours of this EHR interaction occurred outside clinic hours during physicians’ personal time. The researchers assessed interactions using event logs from the Epic EHR system spanning from July 1, 2013, to June 30, 2016.

Researchers validated their data through direct observation of 14 nonresident family medicine physicians from May through June of 2016. This observation showed similar findings. During clinical hours, 60% of physician time related to non-EHR tasks, with 40% of time devoted to EHR tasks.

Documentation Burden Leads to Physician Burnout, Dissatisfaction

“Our family medicine physicians spent 44% of their workday (157 minutes) in the EHR doing clerical and other administrative tasks,” study authors reported. “Computerized physician order entry accounted for 12.1% of their clinic hours (43 minutes) in the EHR. The burden related to order entry has been associated with clinician burnout, dissatisfaction, and intent to leave practice.”

Researchers tracked various tasks and assigned them to categories. Of the tasks tracked, only 32.1% fell under the heading of “medical care.” Reviewing chart notes, chart medications, and problem lists topped medical care tasks.

Review of clinical laboratory results in charts ranked near the bottom, with only 2.5% of the total time spent performing medical care tasks. These tasks, however, could offer opportunities for medical laboratories to help physicians identify opportunities to optimize reporting and test-ordering processes and improve productivity for clinicians who are responsible for most of the data entry burden associated with EHRs.

One potential solution to EHR burnout involves the use of medical scribes who work with physicians during and after a patient’s visit inputting encounter data. Alan Bank, MD, cardiologist at Allina Health, and medical scribe Jaeda Roth, are shown above during a patient visit. Bank told the StarTribune  that he’s convinced scribes help doctors get more done and reduce billing errors. (Photo and caption copyright: Elizabeth Flores/StarTribune.)

Researchers also questioned the EHR’s role as a communication or telemedicine hub. “There is insufficient evidence that such asynchronous care improves health outcomes, cost, and overall healthcare use,” they noted.

However, even for intra-practice communications between healthcare professionals, EHRs may not be the most efficient approach. “Face-to-face communication is associated with increased efficiency,” the researchers noted. “Whereas more electronic communication among team members leads to greater clinician and staff dissatisfaction, as well as poorer clinical outcomes and increased healthcare use among patients with coronary artery disease.”

EHR Cost/Benefits Generate Debate

This latest study is not the first to suggest that EHRs are creating problems for clinicians. While there appear to be no trends between studies, multiple researchers have highlighted the workload created by EHR systems in recent years.

In a study published in the Annals of Internal Medicine (AIM), Christine A. Sinsky, MD, of the American Medical Association, et al, analyzed data from the observation of 57 US-based physicians in family medicine, internal medicine, cardiology, and orthopedics.

Comparing data across 430 hours of observation, researchers concluded, “For every hour physicians provide direct clinical face time to patients, nearly two additional hours are spent on EHR and desk work within the clinic day. Outside office hours, physicians spend another one to two hours of personal time each night doing additional computer and other clerical work.”

However, in a 2015 study published in the Annals of Family Medicine (AFM), Valerie Gilchrist, MD, Chair of the Department of Family Medicine and Family Health at the School of Medicine and Public Health, University of Wisconsin, et al, found lower numbers. Observing 27 community-based family physicians across a single practice day, the researchers found that 39% of the practice day on average was devoted to office-based time. Of that time, 61% was spent on medical care related tasks.

Building a Better EHR

While medical laboratories and diagnostic specialists—such as anatomic pathologists—can work with physicians to streamline ordering and reporting processes relating to EHRs, much of the burden comes from how EHR systems are designed and used.

In a 2016 New England Journal of Medicine Catalyst Panel on EHRsTait Shanafelt, MD, Director of the Mayo Clinic Department Program on Physician Wellness, noted that one of the most contested features of EHR systems in the US, according to the AMA and Mayo Clinic, is computerized physician order entry (CPOE).

Later in the discussion, Sinsky discussed a recent trip to the UK, where she observed general practitioners (GPs) at the National Health Service (NHS). She noted that most GPs loved their EHRs. However, those EHRs were designed with GP input to best work with an NHS GP’s typical workflows and procedures. She also noted that overall usage is different in the UK, as EHRs there are not tied into billing systems.

As Dark Daily has reported, up to 70% of data stored in a patient’s electronic health record is clinical pathology laboratory related. As newer EHRs replace outdated models, it will remain critical for healthcare professionals—including clinical laboratory professionals who generate most of the data stored in EHRs—to assess, track, and report on what is working with various platforms and what is not.

Communicating this end-user data to EHR developers is essential to designing EHRs that reduce unneeded burden and clerical load on physicians, rather than increasing it.

Clinical laboratories tat wish to take proactive steps might contact physicians and other professionals in their workgroups to tailor data generation, reporting, and ordering processes to the EHRs in use at those practices.

—Jon Stone

Related Information:

Primary Care Doctors Spend More Than 50% of Workday on EHR Tasks, American Medical Association Study Finds

Tethered to the EHR: Primary Care Physician Workload Assessment Using EHR Event Log Data and Time-motion Observations

Study: EHRs Bloat Clerical Workload for Docs

Harried Doctors Hail the Rise of the Medical Scribe

Type and Click Tasks Drain Half the Primary Care Workday

Allocation of Physician Time in Ambulatory Practice: A Time and Motion Study in 4 Specialties

Doctors Wasting Over Two-Thirds of Their Time Doing Paperwork

Physician Activities During Time Out of the Examination Room

Heavy Burden of EHRs Could Contribute to Physician Burnout

3D-Printed Robot May Change Breast Biopsies Surgery and Boost Accuracy of Anatomic Pathology Cancer Diagnoses

‘Stormram 4’ fits inside MRI bore and enables ‘nearly real-time imaging guidance’ to achieve sub-millimeter precision in reaching targets

Cancer surgeons perform an estimated 1.7 breast biopsies each year, according to the American Association of Preferred Provider Organizations. This makes the procedure a significant proportion of cases referred to anatomic pathologists. This surgery, however, is time-consuming and not always accurate due to shortcomings in existing surgical technology and to human error.

Now, a 3D-printed MRI-guided robotic biopsy system under development by researchers in the Netherlands may change how biopsies are performed and lead to more accurate biopsies and breast cancer diagnoses. Successful conclusion to this research could impact surgical pathology and medical laboratories worldwide.

“The Stormram 4 is a stimulus for the entire diagnostic phase of breast cancer,” the University of Twente (UT) stated in a press release. “Medical robotics is sure to become standard procedure in hospitals in the near future.”

The robotic system, dubbed Stormram 4, would be used to remove biological specimens during an MRI scan, not unlike today’s current biopsy procedures. However, the robotic system allows for sub-millimeter precision control of a single, thin biopsy needle.

The Stormram 4 (above) breast biopsy robot, developed by researchers at the University of Twente in The Netherlands, is constructed of 3D-printed plastic that is driven by rectilinear and curved air-pressure motors. This allows it to fit inside an MRI scanner’s narrow tunnel and operate while an MRI scan is taking place. Early research indicates that this device might make it possible to more precisely biopsy breast cancer tissue during surgery, thus improving the quality of the biopsies referred to anatomic pathologists. Click on the photo above to see a video of the robot in action. (Photo copyright: University of Twente.)

The robot was developed by:

Billed as the world’s smallest 3D-printed biopsy robot, Stormram 4 offers major advantages over conventional MRI-navigated biopsy techniques, according to Groenhuis. The robot offers sub-millimeter precision, which was achieved during tests conducted on models of breasts.

“The manual MRI-guided breast biopsy procedure is time-consuming and ineffective,” Groenhuis told Digital Trends. “It uses a thick needle, extracting large tissue samples, often in multiple attempts, to extract a representative biopsy sample.”

In contrast, he explained, “The robotic system can manipulate the needle more precisely toward target coordinates of the lesion inside the body, on the first attempt. This will improve the accuracy of the biopsy procedure compared to the current manual practice. Secondly, the needle insertion can be performed inside the MRI scanner itself, so that the needle can be followed under nearly real-time imaging guidance. The required time to perform the biopsy is also shorter, allowing more effective use of the MRI scanner facilities.”

Building a Robot Compatible with MRI Environment

Creating a robotic system that would be compatible with an MRI machine was the first hurdle researchers had to overcome. It meant metallic materials could not be used within the magnetic chamber of the MRI scanner. Researchers turned to 3D printing to create the Stormram 4 entirely from plastic. And they powered the system using “rectilinear and curved air pressure motors.”

“Current robotic systems cannot be used inside the MRI due to the high magnetic field,” Groenhuis explained in the Digital Trends article, “and therefore we initiated the development of an MRI-compatible robotic system for breast biopsy.”

It took several attempts to build a version of Stormram that would fit inside an MRI bore. The fourth iteration succeeded. Operators control the robot using five-meter-long air pipes operated from outside of the scanner to prevent the metal air valves used to drive the robot from interfering with the scan.

Though the device is in its final stage of development, Groenhuis told Digital Trends the Stormram 4 will need several years of additional development and trials to receive regulatory approval.

Robotics Expected to Improve Surgical Outcomes

Stormram 4 recently won a prestigious award in the 2017 Surgical Robotic Challenge at the international Hamlyn Symposium in London, the university noted in its press release. But the Stormram 4 is not the only surgical robot making headlines. MRI-compatible surgical robots offer the promise of becoming revolutionary tools as researchers develop machines to improve a range of surgical outcomes.

For example, at the Automation and Interventional Medicine (AIM) Robotics Research Laboratory at Worcester Polytechnic Institute (WPI) in Massachusetts, other MRI-guided medical robots are under development. These robots are designed to automate lead placement for deep brain stimulation during stereotactic neurosurgery for Parkinson’s Disease, and brachytherapy seed implantation for prostate cancer therapy, the WPI website notes.

These and other technology breakthroughs are changing the practice of surgical pathology. Consequently, clinical laboratories and In Vitro diagnostics (IVD) developers should expect be impacted as well.

—Andrea Downing Peck

 

Related Information:

About Breast Biopsy

UT Enters Battle Against Cancer with 3D-Printed Robot

3D-Printed Robot Designed to Take Biopsies in an MRI Scanner

Human Antibodies in Medical Laboratory May Be Key to Immunity and Preventing Diseases Such as Influenza A

Scientists with Francis Crick Institute and Ragon Institute have successfully created human antibodies in vitro that can be made to recognize specific antigens in the human body; Could lead to new treatments for cancer and other infectious diseases

It’s been long-recognized that the ability to design human antibodies customized to recognize specific antigens could be a game-changer in the diagnosis and treatment of many diseases. It would enable the creation of useful new clinical laboratory tests, vaccines, and similar therapeutic modalities.

Now an international research team has published the findings of its novel technique that was developed to generate human antibodies in vitro. The research was conducted at the Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), Harvard, and the Francis Crick Institute in London.

Antibodies and antigens are used in a large number of clinical laboratory and anatomic pathology tests and assays. In many cases, animal antibodies/antigens are used in test kits because they attract and bind to specific human antibodies/antigens that are biomarkers for diagnoses. Thus, as this technology is validated and further developed, it could be the source of useful biomarkers for lab tests as well as for vaccines.

Antibodies—also referred to as immunoglobulins—are made by the body’s B-lymphocytes (B cells) in response to antigens, such as bacteria, viruses, or other harmful substances. Each antibody has a special bearing on a particular antigen. For example, the human immunodeficiency virus (HIV) antibody and HIV antigen (p24) test screens and diagnoses people for HIV infection, explained LabTestsOnline.

Many medical laboratory tests use animal antibodies and antigens. But what if human antibodies could be generated and stimulated to recognize specific human antigens? That’s what the researchers believe they have done, according to a press release.

The Ragon Institute at MGH, MIT, and Harvard (above) was established in 2009 to find an HIV vaccine and to be a worldwide leader in the study of immunology. The Francis Crick Institute, formed in 2015, is a biomedical research institute using biology to understand health and disease. (Photo copyright: The Ragon Institute.)

The researchers know the novel technique they developed for generating human antibodies in vitro needs further development and validation. If this happens, the technique could one day be the source of useful biomarkers for medical lab tests, and may be a way to prevent infectious diseases.

“Specifically, it should allow the production of these antibodies within a shorter time frame in vitro and without the need for vaccination or blood/serum donation from recently infected or vaccinated individuals,” said Facundo D. Batista, PhD, in the press release. Batista is Principle Investigator with the Ragon Institute and led the research teams. “In addition, our method offers the potential to accelerate the development of new vaccines by allowing the efficient evaluation of candidate target antigens.”

Researchers Aim to Make Human Antibodies in Medical Laboratory

This international team of researchers sought to replicate in the lab—using patient blood samples—a natural human process for creation of antibodies from B cells. This is the process they wished to replicate:

·       Antibodies are made by the body’s B cells;

·       An antigen molecule is recognized by a B cell;

·       Plasma cells (able to secrete antibodies) develop;

·       An antibody binds to a particular antigen to fight an infection.

“B lymphocytes (B cells) play a critical role in adaptive immunity, providing protection from pathogens through the production of specific antibodies. B cells recognize and respond to pathogen-derived antigens through surface B cell receptors,” the researchers wrote in The Journal of Experimental Medicine (JEM).

Nanoparticles Key to the Approach

But finding an exact antigen is only one part of the B cell’s job. In the lab, B cells also need a trigger that enables them to grow and develop into plasma cells, which are key to fighting disease, the researchers noted.

“The in vitro activation of B cells in an antigen-dependent manner is difficult to achieve,” the authors stated in the JEM. “To overcome limitations, we developed a novel in vitro strategy to stimulate human B cells with streptavidin nanoparticles conjugated to both CpG and antigen. B cells producing antigen-specific antibodies were identified, quantified, and characterized to determine the antibody repertoire.”

According to the press release, “CpG oligonucleotides internalize into B cells that recognize the specific antigen.”

The statement, which garnered worldwide attention, noted the following steps taken by the researchers:

·       B cells from patient blood samples were isolated;

·       Then, they were treated with tiny nanoparticles coated with both CpG oligonucleotides and the right antigen;

·       These DNA molecules are unique, because they can activate toll-like receptor 9 (TLR9);

·       TLR9 develops into antibody-secreting plasma cells.

Results: Antibodies for Tetanus, Influenza, HIV

This method, according to the scientists, could be used in further research to develop antibodies to treat infectious diseases and cancer.

According to The Times of India,

·       “The team successfully demonstrated their approach using various bacterial and viral antigens, including the tetanus toxoid and proteins from several strains of influenza A;

·       “In each case, the researchers were able to produce specific, high-affinity antibodies in just a few days. Some of the anti-influenza antibodies generated by the technique recognized multiple strains of the virus and were able to neutralize its ability to infect cells;

·       “The procedure does not depend on the donors having been previously exposed to any of these antigens through vaccination or infection; and,

·       “Researchers were able to generate anti-HIV antibodies from B cells isolated from HIV-free patients.”

Research Suggests More Possibilities

While this highly scientific study may not be on the radar of most anatomic pathologists and medical laboratory leaders at the moment, it holds enormous promise to produce cures for infectious disease and more effective cancer treatments. This research project also demonstrates how new techniques using antibodies have the potential to create an entirely new generation of clinical laboratory assays that improve diagnostic accuracy and better inform physicians when they consider the most appropriate therapies for their patients.

—Donna Marie Pocius

Related Information:

Researchers Develop New Method to Generate Human Antibodies

Novel In Vitro Booster Vaccination to Rapidly Generate Antigen-Specific Human Monoclonal Antibodies

Human Antibodies Produced in Lab for First Time

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