LabMedica International April 2023

Identifying Prediabetics Before Symptoms

Ty pe 2 diabetes takes years to develop but is preventable if caught early. However, just 50% of people with prediabetes go on to develop full-blown diabetes over a period of 10 years. Unfortunately, current diabetes tests such as hemoglobin A1C

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New Method Detects RNA Viruses Faster and More Effectively than PCR

An innovative method to detect RNA viruses based on the triplex-forming probe technology paves the way for new options for detecting viruses such as SARS-CoV-2, the influenza A virus (H1N1) or the respiratory syncytial virus (RSV),

Test Detects Prostate Cancer at 94% Accuracy

a pathogen that affects newborn babies and needs careful differential diagnosis.

The new methodology, called the Triplex Enhanced Nucleic Acid Detection Assay (TENADA), is based on the ability of polypurine hairpins (PPRHs) designed

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Pr ostate cancer is the most common cancer in men.

For the first time in 20 years, cases of advanced prostate cancer are on the rise, according to new data from the “Cancer Statistics 2023” report released by The American Cancer Society (ACS). Currently, no single test is available for prostate cancer, although prostate-specific antigen (PSA) blood tests are the

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Liquid Biopsy Test for Brain Cancer

Glioblastoma (GBM) is a particularly aggressive type of brain cancer with a five-year survival rate of only 5%. Researchers have now identified a biomarker that could be used in blood tests to diagnose GBM, track its progression and guide treatment. This means non-invasive liquid biopsy for GBM could be a great help for patients, allowing them to receive the care they need

See article on page 10

First Lab-Based Blood Test for Evaluating Concussions

Abump, blow, or whiplash to the head is the main cause of traumatic brain injury (TBI), which can lead to shortand long-term detrimental effects. People affected by TBI may experience impaired memory, movement, sensation (such as hearing and vision), and emotional function (such as psychological symptoms

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Unique Biomarker Could Improve Early Alzheimer’s Diagnostics

Patients with Alzheimer’s disease experience endothelial injury, or damage to the cells lining the tiny blood vessels in the brain. Previous research has focused on changes visible in brain tissue under a microscope including the beta-amyloid pro-

tein and another protein, called tau. Beta-amyloid is a naturally occurring protein that clumps together in abnormal levels among patients with Alzheimer’s to form plaques which get collected between neurons and disrupt cell function. Tau is a protein that

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Image: 3D illustration showing atherosclerosis with atheromatous plaque inside an artery, leading to narrowing of the blood vessel (Shutterstock).

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First Lab-Based Blood

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Test for Evaluating Concussions

and personality changes). The effects of TBI can last for a few days post-injury or become permanent. For a long time, the process for standard concussion evaluation has remained the same, where the physician relies on subjective Glasgow Coma Scale assessments and CT scans to detect brain tissue damage or lesions. Now, the first commercially available laboratory TBI blood test in the U.S. helps doctors evaluate patients with concussion by ruling out the need for a CT scan.

Abbott Diagnostics (Lake Bluff, IL, USA; www.abbott.com) has received U.S. Food and Drug Administration clearance for the first commercially available laboratory TBI blood test, making it widely available to hospitals in the U.S. The Alinity i TBI test measures complementary biomarkers in blood plasma and serum - Ubiquitin C-terminal Hydrolase L1 (UCH-L1) and Glial Fibrillary Acidic Protein (GFAP), that, in elevated concentrations, are tightly correlated to brain injury. It provides test results with 96.7% sensitivity and 99.4% negative predictive value. By testing for these two biomarkers immediately after an injury, health care providers can decide on the appropriate next steps and devise a treatment plan for the patients. The test is for use to aid in the evaluation of patients, 18 years of age or older, presenting with suspected mild traumatic brain injury (Glasgow Coma Scale score 13-15) within 12 hours of injury, to assist in determining the need for a CT (computed tomography) scan of the head. The test had earlier received European Union clearance and has been available in markets outside the U.S. since 2021.

The test, which runs on Abbott’s Alinity i laboratory instrument, will help clinicians quickly and objectively evaluate people with mild TBIs (concussions). A patient visiting the hospital within 12 hours of suspected mTBI

can be administered the Alinity i test. The process involves obtaining a blood sample from the arm, sending it to the lab for preparation and running the test on the Alinity i instrument. The test results are usually available in 18 minutes, and can be shared with the relevant healthcare providers for immediate evaluation. Negative results on the test prevent additional CT scans and eliminate waiting time at the hospital, thus reducing the cost burden on the healthcare system and patients, as well as reducing time spent in the emergency department.

“People sometimes minimize a hit to the head, thinking it’s no big deal. Others wonder if a visit to the doctor or emergency room for a possible concussion will provide them with meaningful answers or care,” said Beth McQuiston, M.D., medical director in Abbott’s diagnostics business. “Now that this test will be widely available in labs across the country, medical centers will be able to offer an objective blood test than can aid in concussion assessment. That’s great news for both doctors and people who are trying to find out if they have suffered a traumatic brain injury.”

Laser-Light Method Uses AI-Assisted Imaging to Identify Bacteria in Fluids

The commonly used traditional culturing techniques often require several hours or even days for completion. Now, a revolutionary approach promises to deliver faster, more precise, and cost-effective microbial assays of almost any fluid one wishes to test for microbes.

Scientists at Stanford University (Stanford, CA, USA; www.stanford.edu) have created an innovative adaptation of the technology in an old inkjet printer and combined it with AI-assisted imaging to develop a faster, cheaper way to spot bacteria in blood, wastewater, and more. The method involves shining a laser on a drop of blood, mucus, or wastewater, and then using the light reflecting back to positively identify bacteria in the sample. The new test can be carried out within minutes and offers hope for improved and rapid detection of infections, more effective

utilization of antibiotics, safer food products, enhanced environmental surveillance, and speedier drug development processes.

The novelty of this discovery lies not in the fact that bacteria possess unique spectral fingerprints, which has been established for years, but rather in how the research team has managed to extract these spectra amidst the blinding array of light emanating from every sample. A single milliliter of blood can contain billions of cells, merely a tiny fraction of which may be microbes. Therefore, the challenge was to identify a way to exclusively distinguish and amplify the light emanating just from the bacteria. The team pursued different scientific approaches, blending a decades-old computing technology – the inkjet printer – with two of the most advanced technologies of our times, artificial intelligence and nanoparticles.

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Image: The Alinity i TBI lab test will run on the Alinity i laboratory instrument (Photo courtesy of Abbott)

Laser-Light Method Uses AI-Assisted Imaging to Identify Bacteria in Fluids

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The researchers found a solution to the difficulties of handling biological samples by modifying the printer to use acoustic pulses in order to put samples to paper. This method results in each printed blood dot being just two trillionths of a liter in volume, making them incredibly small - over a billion times smaller than a raindrop. Due to their tiny size, these droplets may contain just a few dozen cells. To enhance the bacteria detection process, the researchers infused the samples with gold nanorods, which act like antennas that draw laser light towards any present bacteria and amplify the signal to 1500 times its original strength. With appropriate isolation and amplification, the bacterial spectra clearly stand out for identification. The researchers also utilized machine learning to analyze the spectra of each printed dot and identify any telltale signatures of bacteria in the sample.

Ground-Breaking Test Assesses Expansion and Persistence of CAR-T Therapy in Cancer Patients

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Eurofins Viracor LLC (Lenexa, KS, USA; www.eurofins-viracor.com) has launched the ExPeCT CAR-T multiplexed quantitative real-time PCR (qPCR) assay that acts as a powerful diagnostic tool to monitor and optimize CAR-T therapy involving patients with pre-B cell acute lymphoblastic leukemia and B cell lymphomas. The test, based on a method developed by Eurofins Viracor, is designed to help clinicians better understand how CAR-T therapy is performing for their patients. The test marks an important step forward in the evaluation and management of CAR-T therapy in cancer patients by helping clinicians to make more informed decisions about the best course of treatment for their patients.

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himeric Antigen Receptor T-Cell (CAR-T) therapy is a revolutionary form of immunotherapy that utilizes genetically engineered T-cells to attack cancer cells and has demonstrated promise in treating various types of cancers. Research has shown that the persistence and expansion of CAR-T therapy are important indicators of how long the therapy can remain effective in the patient. Now, a ground-breaking test provides clinicians with an accurate and comprehensive assessment of the CAR-T cell population in the patient's body and offers insights to therapy effectiveness.

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Recombinant ELISAs Increase Efficiency of CMV Serodiagnosis in Pregnant Women

ytomegalovirus (CMV) is a virus that is prevalent across the world and poses a significant risk during pregnancy due to vertical transmission to the fetus. Long-term sequelae in newborns can be particularly severe when primary maternal infection occurs in the first trimester. Hence, screening for CMV throughout pregnancy is important to identify primary infections and establish the timepoint of infection. Many pregnant women have previously been infected with CMV, as shown by the presence of IgG antibodies, although about 0.5% seroconvert during pregnancy.

Classical CMV serology for risk assessment involves the use of lysate-based tests to determine IgM antibodies, IgG seroconversion and IgG avidity. However, this approach usually requires two sequential samples to provide meaningful results, particularly if pre-pregnancy samples are unavailable for comparison. Antibodies against the recombinant antigens p52 (IgM) and glycoprotein B (IgG) have previously proved to be accurate second-line markers for confirmation of results and for dating infections. p52 IgM is a specific marker of the early phase of infection, while anti-gB IgG represents a late-phase marker that could serve as an alternative to high-avidity IgG.

The Randox Lipoprotein(a) assay is intended for the quantitative in vitro determination of Lp(a) in serum or plasma, suitable for automated, semi-automated and manual use.

Image: Screening for CMV throughout pregnancy is important to identify primary infections and to establish the timepoint of infection (Photo courtesy of EUROIMMUN)

In a collaborative study, scientists at Limbach Labor MVZ Westmecklenburg (Schwerin, Germany; www.labor-schwerin.de) investigated the efficiency of using anti-p52 IgM and anti-gB IgG as first-line tests for CMV serological screening. They examined routine serum samples from 553 pregnant women using two different strategies: determination of IgM, IgG and avidity using lysate-based ELISAs or determination of anti-p52 IgM and anti-gB IgG using recombinant ELISAs from EUROIMMUN (Luebeck, Germany; www.euroimmun.com). The study aimed to categorize patients into the following groups: susceptible to infection, acute primary infection, recurrent infection/reactivation or past infection.

Using the lysate-based assays, 84.6% of samples yielded conclusive results in first-line testing, while the remaining 15.4% required follow-up testing of a consecutive sample. In contrast, measurement of anti-p52 IgM and anti-gB IgG produced conclusive results in firstline testing for 92.8% of samples, with only 7.2% requiring follow-up. Thus, the number of samples requiring follow-up could be significantly reduced using the recombinant test strategy.

The authors concluded that the first-line use of ELISAs measuring anti-p52 IgM and anti-gB IgG increases the number of conclusive results derived from an initial serum sample while requiring a considerably lower number of tests as compared to the lysate-based approach. This could have significant practical relevance by reducing the laboratory workload and the costs involved in maternal CMV serodiagnostics. The study was published on January 26 in the Journal of Virological Methods.

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Blood Test Detects Prostate Cancer at 94% Accuracy

most commonly used, along with physical examinations, MRI scans and biopsies. However, PSA blood tests can give unreliable results, making them unsuitable for routine screening for prostate cancer. Among people who have a prostate biopsy due to elevated PSA level, only about a quarter are found to have prostate cancer. Hence, there is a need for a blood test that can detect prostate cancer with greater accuracy. New research now shows that the (Prostate Screening EpiSwitch) ‘PSE’ blood test is 94% accurate and much superior than the currently used PSA blood test.

The new PSE test, developed by researchers at the University of East Anglia (UEA, Norfolk, UK; www.uea.ac.uk) in collaboration with Oxford Biodynamics (Oxford, UK; www.oxfordbiodynamics.com) and colleagues, combines the traditional PSA test with an epigenetic EpiSwitch test and demonstrates significant potential as an accurate and rapid cancer screening diagnostic. The UEA researchers conducted a pilot study involving 147 patients in which they compared the results of the new test with those of the standard PSA test. They found that PSE significantly enhances the overall detection accuracy for at men at risk of prostate cancer.

“When tested in the context of screening a population at risk, the PSE test yields a rapid and minimally invasive prostate cancer diagnosis with impressive performance. This suggests a real benefit for both diagnostic and screening purposes,” said Prof Dmitry Pshezhetskiy, from UEA’s Norwich Medical School.

“There is a clear need in everyday clinical practice for a highly accurate blood test that can screen men for prostate cancer and accurately identify those at risk, while sparing those who up to now would be subject to unnecessary, expensive and invasive procedures,” added Dr. Jon Burrows, Chief Executive Officer at Oxford Biodynamics.

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Blood Test to Separate Bacterial and Viral Infections Could Reduce Antibiotic Overuse

n developing countries, most antibiotic prescriptions are not only unnecessary - an estimated 70% to 80% of them are given for viral infections – they are also harmful, as overuse of antibiotics accelerates antibiotic resistance. A similar problem exists in the U.S., where an estimated 30% to 50% of antibiotic prescriptions are given for viral infections. Now, a new gene expression-based test could allow doctors around the world to quickly and accurately distinguish between bacterial and viral infections, thereby cutting down on antibiotic overuse. The test developed by scientists at Stanford Medicine (Stanford, CA, USA; www.med. stanford.edu) is one of a new crop of diagnostic tests that look at the host response - that is, how the patient’s immune system is reacting - to identify the type of infection.

Current host-response tests can distinguish extracellular bacterial infections from viral infections with more than 80% accuracy, but they identify only 40% to 70% of intracellular infections. As these tests have been designed with data from Western Europe and North America, they often fail to account for the types of infections prevalent in low- and middle-income countries. They have trouble distinguishing the more subtle differences between intracellular bacterial infections and viral infections. In developing countries, common bacterial infections like typhus and tuberculosis are caused by intracellular bacteria, which replicate inside human cells.

To develop a diagnostic test that can separate both types of bacterial infections from viral infections, scientists used publicly available gene expression data from 35 countries. These included 4,754 samples from people of various ages, sexes and races with known infections. The diversity of patients, infections and types of data is more representative of the real world, according to the researchers. Using machine learning and half of these samples, they identified eight genes that are expressed differently in bacterial versus viral infections. They validated their eightgene test on the remaining samples and new samples.

They found that these eight genes could distinguish intracellular and extracellular bacterial infections from viral infections with high accuracy, achieving 90% sensitivity and 90% specificity. It is the first diagnostic test to meet (and ex-

ceed) the standards proposed by the World Health Organization and the Foundation for Innovative New Diagnostics. The researchers hope that the new diagnostic test can eventually be translated into a POC test and adopted by doctors in both developed and developing countries, as it requires only a blood sample and can be performed in 30 to 45 minutes.

“Accurately diagnosing whether a patient has a bacterial or viral infection is one of the biggest global health challenges,” said Purvesh Khatri, PhD, associate professor of medicine and biomedical data science, and the senior author. “We’ve shown that this eight-gene signature has higher accuracy and more generalizability for distinguishing bacterial and

Image: New blood test to identify infections could reduce global antibiotic overuse (Photo courtesy of Pexels)

viral infections, irrespective of whether they are intracellular or extracellular, whether a patient is in a developed or developing country, a man or a woman, an infant or an 80-year-old.”

Digital Microscopy and AI Clinical and Research Applications

Innovative Blood Test Poised to Replace Stress Tests, Angiograms

Cardiovascular disease (CVD) remains one of the leading causes of death globally, with coronary heart disease (CHD) being the most common type of CVD and the primary cause of heart attacks. Now, a new test aids in the early detection of coronary heart disease to better enable the management of this condition for preventing a symptomatic event such as a heart attack.

Cardio Diagnostics Holdings Inc. (Chicago, IL, USA; www.cardiodiagnosticsinc.com) has launched PrecisionCHD, the first integrated epigenetic-genetic blood test for the early detection of coronary heart disease. Using epigenetic (DNA methylation) and genetic (single nucleotide polymorphism) biomarkers along with a proprietary machine-learning model developed by analyzing billions of genomic and epigenomic data points, PrecisionCHD detects coronary heart disease with better than 75% sensitivity in both men

and women.

Importantly, PrecisionCHD is accompanied by a provider-only Actionable Clinical Intelligence platform, which maps a patient’s unique biomarker profile onto modifiable risk factors like diabetes, hypertension, hypercholesterolemia, and smoking, which are considered to be critical drivers of coronary heart disease. The non-invasive, simple test offers healthcare providers a complement to traditional CHD diagnostic solutions and provides an informative, personalized patient report of CHD status.

“The launch of PrecisionCHD represents a leap forward in cardiovascular medicine. I’m beyond thrilled that we’re able to make the promise of precision cardiovascular medicine a reality,” said Robert Philibert, MD Ph.D., the company’s Chief Medical Officer and Co-Founder. “Clinicians seeking to assess coronary heart disease status in their patients no

Image: PrecisionCHD is the first integrated epigenetic-genetic-based blood test for the early detection of coronary heart disease (Photo courtesy of Cardio Diagnostics)

longer have to worry about their ability to obtain an exercise stress test or angiogram. Now, clinicians can have a blood sample drawn in their office or a kit sent to their patient’s home for this highly sensitive test.”

New Device Detects Cancer Cells, Prevents Invasive Biopsies

Cancer is a major contributor to illness and death, and those with suspected cancer may need surgery for a diagnosis, especially for liver, colon or kidney tumors. Unfortunately, biopsies can be uncomfortable, costly, and increase the risk of complications due to surgery. To resolve this problem, researchers have created a new device that can detect and analyze cancer cells from blood samples. This could eliminate the need for a biopsy surgery, as well as allow doctors to monitor treatment progress more accurately.

Researchers from the University of Technology Sydney (UTS, Sydney, Australia; www.uts.edu.au) have developed the Static Droplet Microfluidic device,

which can quickly detect tumor cells that have migrated away from a primary tumor and into the bloodstream. The device utilizes a distinctive metabolic signature of cancer to separate tumor cells from regular blood cells. After tumor cells are located with the device, they can then be studied genetically and molecularly to support diagnosis and classification of the cancer, allowing for more personalized treatment options.

Circulating tumor cells are a precursor of metastasis, which is responsible for approximately 90% of all cancer-related deaths. Studying these cells may offer greater understanding of the biology behind cancer metastasis, which can help in the develop-

ment of new treatments. The current liquid biopsy solutions are slow, expensive, and require specialist operators, restricting their use in clinical settings. This new technology is designed to be integrated into research and clinical labs without needing expensive and complex equipment or a trained operator, making it practical and cost-effective for doctors to diagnose and monitor cancer patients.

“Managing cancer through the assessment of tumor cells in blood samples is far less invasive than taking tissue biopsies. It allows doctors to do repeat tests and monitor a patient’s response to treatment,” said Prof. Majid Warkiani from the UTS School of Biomedical Engineering.

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Novel Microscopy Technique

Comes Closer to Diagnostic Use

Diagnostic imaging plays a crucial role in aiding physicians and researchers in understanding internal body structures, thus improving clinical analysis and medical intervention. Scientists continually explore new avenues to utilize imaging technologies to gain insight into human health. A pioneering imaging method called Brillouin microscopy enables the mapping of cell and tissue stiffness, often linked to early symptoms of ailments such as cancer and Alzheimer's. This method is distinct from conventional imaging modalities such as confocal fluorescence microscopy, as it allows label-free and non-contact acquisition of key mechanical information like viscosity and stiffness of biological specimens. Now, researchers are striving to re fine Brillouin microscopy, which can answer many important questions in biophysics and mechanobiology.

Brillouin microscopy, an optical im aging method rooted in Brillouin light scattering (BLS), was first introduced by French physicist Léon Brillouin in 1922. When light interacts with a substance, thermal fluctuations or molecular vibrations within the ma terial cause the light to scatter result ing in BLS. These vibrations can be influenced by various factors such as compression, water content, heat, or material stiffness. Among these fac tors, stiffness is incredibly valuable for the diagnostic application of Brillouin microscopy. Changes in cell stiffness, often linked to the progression of ailments like cancer metastasis, are challenging to measure since cells are microscopic and situated in very delicate tissues.

In conventional approaches, prepared cells are measured on a petri dish or other rigid substrates. However, Brillouin microscopy relies solely on a laser beam to investigate the mechanical properties, enabling measurement when cells are in their physiological conditions. As no physical interaction is required, Brillouin technology is less invasive and more convenient. The technology is important for understanding embryonic tissue development, particularly to gain a better understanding of birth-related diseases and disorders.

Researchers at Wayne State University (Detroit, MI, USA; www. wayne.edu) examined the use of dual line-scanning Brillouin microscopy (dLSBM) to overcome two significant limitations - acquisition speed and irradiation doses - that hinder its widespread usage in biomedicine. The application of dLSBM yielded 50 to 100 times faster speeds than its

counterpart, with a reduction of 80 times light irradiation levels for 2D and 3D mechanical mapping.

“With this innovation, we can acquire one mechanical image of cell clusters in a few minutes,” said Jitao Zhang, assistant professor of biomedical engineering (BME) at Wayne State University. “This improved acquisition speed is important because it allows us to investigate details of cell behaviors in almost real time.”

“Due to the 3D structure of an embryo, traditional contact-based techniques encounter big challenges for in vivo measurement,” added Zhang. “Since Brillouin microscopy works in a non-contact manner, it sometimes becomes the only available choice.”

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Novel Microscopy Technique Comes Closer to Diagnostic Use

CLINICAL CENTRIFUGE

Genetic Test Predicts Whether Bowel Cancer Patients Can Benefit From Chemotherapy

Late-stage bowel cancer patients usually undergo a series of chemotherapies and targeted medicines for cancer treatment. However, the responses to the last-line chemotherapy treatment trifluridine/tipiracil differ significantly amongst them, with some experiencing good, long-term responses but others receiving no benefits as their cancers become resistant to each treatment. Now, researchers have discovered that a genetic test, an established part of standard care in the UK and globally to predict patients' responses to other targeted cancer drugs, can also predict whether chemotherapy will work for bowel cancer patients. This discovery could aid in sparing patients from unnecessary toxicity and debilitating side effects by avoiding treatments that will not benefit them.

A team of researchers, including investigators from Imperial College London (London, UK; www.imperial.ac.uk), has discovered that a particular mutation - referred to as KRASG12 - in the KRAS gene is linked to a lower survival rate in treated patients. On the other hand, another mutation was found to be associated with a three-fold increase in survival. The study's results suggest that patients with KRASG12 mutations - constituting nearly 28% of all bowel cancer patients - gain no benefit from trifluridine/tipiracil and should consider partaking in clinical trials rather than enduring unnecessary toxicity. Conversely, patients without KRAS mutations may benefit from trifluridine/tipiracil, while those with a KRASG13 mutation are likely to respond well to treatment.

As part of standard NHS care, patients with advanced bowel cancer are already given gene tests to search for mutations in KRAS and identify those who can benefit from a targeted medicine called cetuximab. Doctors can now use the same test right away to commence treatment with trifluridine/tipiracil based on this evidence. The researchers have asked regulators to quickly incorporate the findings into guidelines which would make it standard to use the test for directing treatment with trifluridine/tipiracil.

“This is the first time we have a genomic marker already used in the clinic that can tell us whether a patient’s cancer will be sensitive or resistant to chemotherapy. We hope doctors will use this data to improve care for patients with advanced bowel cancer without delay,” said Professor Nicola Valeri, Honorary Professor of Gastrointestinal Oncology at Imperial College London and the ICR. “It will be difficult for some patients to find out that this last-line drug will not benefit them, but this test will mean they are able to avoid unnecessary side effects and have a better quality of life with advanced cancer. Fortunately, our findings also reveal a group of patients who see substantial benefits from taking this type of chemotherapy.”

Image: A genetic test could guide the use of cancer chemotherapy (Photo courtesy of Pexels)

AI Application in Pathology Reveals Novel Insights into Endometrial Cancer Diagnostics

Endometrial carcinoma is the most common cancer of the gynecologic tract. Now, researchers have shown the power of artificial intelligence (AI) can be applied to endometrial carcinoma microscopy images, offering novel insights that could improve diagnosis and treatment of uterine cancer.

In the past years, researchers at Leiden University (Leiden, the Netherlands; www.universiteitleiden.nl) had played a leading role in the development of a novel tumor classification system based on molecular alterations, resulting in four endometrial cancer subtypes. This time, the team set out to investigate if it was possible to predict these molecular classes, based on microscopy-images alone. The researchers applied artificial intelligence on microscopy images of thousands of endometrial carcinoma images from patients that participated in the study.

The team developed a model that robustly predicts the four molecular classes of endometrial carcinomas based on one (hematoxylin and eosin)-stained microscopy slide image, which is the standard histological stain used in diagnostics for assessment of tumor grading and histological subtyping. This model was not “a black-box”, but through reverse-engineering the researchers were able to show which image-features were relevant for its predictions. The model provided the

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ICU Patient Studies Show Critical

Importance of iMG

Patients Undergoing Continuous Renal Replacement Therapy (CRRT)

Hutten et. al.1 found that patients receiving CRRT with citrate anticoagulation had normal tMg levels, but low iMg levels. This is due to magnesium ions being bound by citrate, and the citrate-magnesium complex being measured as tMg. These patients are actually hypomagnesemic but would not be recognized as such if only tMg were measured.

Adult tMg (mg/dL)

Surgical ICU Patients

Yeh et. al.2 found that 21% of tMg tests which were reported as normal were hypermagnesemic based on iMg. This exposes patients to potential risks associated with undetected hypermagnesemia, including prolonged days on the ventilator, muscle weakness, QT prolongation, and cardiac arrhythmia. In addition, there were many patients with low tMg and normal iMg, which led to unnecessary Mg supplementation and repeat blood draws.

2.Yeh, et al. Total and ionized magnesium testing in the surgical intensive care unit - Opportunities for improved laboratory and pharmacy utilization. J Crit Care, 2017, 42, 147-151.

1.Hutten et al., Ionized and not total magnesium as a discriminating biomarker for hypomagnesaemia in continuous venovenous haemofiltration patients. Nephrol Dial Transplant, 2021.

AI Application in Pathology Reveals Novel Insights into Endometrial Cancer Diagnostics

Cont’d from page 12

team with important novel insights that can be utilized in future studies to further improve diagnostics, prognostication, and management of endometrial cancer patients.

“The application of AI in pathology is emerging,” said Dr. Tjalling Bosse at Leiden University. “In this project we studied the morphology of tumors that shared the same molecular alteration to better understand the effect these changes have on the appearance of the tumor. With this work, the computer model has directed us to areas in- and outside the tumor that are important.”

“In cancer diagnostics, the number of variables (molecular, tumor morphology, patient data) has increased exponentially and has complexified patient prognosis prediction,” added Sarah Fremond. “Through training unbiased AI models, AI predictions can also teach pathologists in return by, for instance, identifying novel morphological details on microscopy slide images with prognostic value.”

Low-Cost Portable Sensor Detects Heavy Metals in Sweat

Heavy metals like lead and cadmium can be found in batteries, cosmetics, food and many other things that have become a part of daily life. However, they become toxic if they accumulate in the human body and can cause several health problems. Expensive equipment and a controlled laboratory environment are usually required to detect heavy metals in body fluids. Researchers have now developed a portable sensor made of simple materials that can detect heavy metals in sweat, which is easily sampled.

Humans discharge heavy metals mostly through sweat and urine. The analysis of these biofluids forms a key part of toxicological tests as well as treatment. As compared to other gold-standard tests for detecting heavy metals in biofluids, the new sensor developed by researchers at the University of São Paulo (São Paulo, Brazil; www5.usp.br) is simple in terms of the materials used to manufacture it and the production stages it goes through. The device is connected to a potentiostat, a portable instrument that determines the concentration of each metal by measuring differences in potential and current between electrodes. The result is displayed on a computer or smartphone using appropriate application software. The system is so simple that it can be used by non-specialists without training, as well as by technicians in hospitals, clinics and doctor’s offices.

“We get important information on a person’s health by measuring their exposure to heavy metals. High levels of cadmium can lead to fatal problems in the airways, liver and kidneys. Lead poisoning damages the central nervous system and causes irritability, cognitive impairment, fatigue, infertility, high blood pressure in adults and delayed growth and development in children,” said Paulo Augusto Raymundo Pereira, last author of the article. “The world needs flexible sensors that are easily, cheaply and rapidly mass-produced, as our device is, for on-site detection, continuous monitoring and decentralized analysis of hazardous compounds.”

“The base of the device is polyethylene terephthalate (PET), on top of which is a conductive flexible copper adhesive tape, a label of the kind you can buy from a stationer’s, with the sensor printed on it, and a protective layer of nail varnish or spray,” said Robson R. da Silva, co-author of the article. “The exposed copper is removed by immersion in ferric chloride solution for 20 minutes, followed by washing in distilled water to promote the necessary corrosion. All this ensures speed, scalability, low power and low cost.”

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New Method Detects RNA Viruses Faster and More Effectively than PCR

by the cancer therapy group at the University of Barcelona (Barcelona, Spain; www.fbg. ub.edu) to capture viral RNA and form a high-affinity triplex. When this hybrid structure is connected to a molecular probe and placed in contact with the sample from the affected patient, a detection signal of the viral agent is obtained. One advantage in the detection of viral RNA is that the PPRH methodology can be applied without the intervention of reverse transcriptase - the enzyme that converts RNA to DNA - or the thermocycler (the device that amplifies samples of genetic material with the polymerase chain reaction or PCR). In addition, it has a sensitivity and specificity equivalent to that of the PCR test and can provide results in less than an hour.

As part of the study, the team used the sandwich hybridization strategy in several biodetection devices. This strategy uses two oligonucleotides: a triplex-forming PPRH hairpin acting as a capture probe and a labeled duplex-forming DNA oligonucleotide acting as a detection probe. This methodology was implemented in a compact electrochemical device that integrates a two-electrode electrochemical cell on a chip and a fluidic component on paper, and in a thermal lateral flow system implemented in nitrocellulose and using plasmonic nanoparticles and thermal paper.

Scientific literature describes PPRHs as tools for gene silencing of several genes primarily involved in cancer. Additionally, they have also been incorporated as probes in biosensors for the detection of small RNA molecules (miRNA), to determine DNA methylation status and for the diagnosis of pneumonia caused by the fungus Pneumocystis jirovecii. Now, the new TENADA methodology proves to be effective not only in the detection of viral particles. The high affinity of PPRHs for viral RNA is a property that can be applied to inhibit the virus replication process. As a result, the antiviral properties of the polypurine hairpin clips CC1PPRH and CC2PPRH in cells of the VeroE6 lineage infected with SARS-CoV-2 virions are now also being studied.

“PPRHs are unmodified single-stranded DNA hairpins consisting of two specular domains of antiparallel polypurines,” explained Professor Carlos J. Ciudad, from the UB’s Department of Biochemistry and Physiology. “These domains, connected to each other by a thymidine loop, are linked by intramolecular reverse-Hoogsteen bonds. The molecular hairpins can bind specifically to polypyrimidine sequences in single-stranded DNA (ssDNA), double-stranded DNA (dsDNA) or RNA viruses via Watson-Crick bonds, thus forming an antiparallel triplex.”

Image: New method detects RNA viruses based on triplex-forming probe technology (Photo courtesy of University of Barcelona)

Status Mono is intended for the qualitative detection of infectious mononucleosis heterophile antibodies in whole blood, serum or plasma. It offers a single reagent procedure that provides results in 3-8 minutes.

Infrared Signature for Mobile Phone Detects Malaria

ptical microscopy, rapid diagnostic tests (RDTs) and molecular tests are the three main diagnostic techniques currently available for malaria diagnosis. Microscopy is the traditional way of detecting malaria parasites in stained thick or thin peripheral blood films using Giemsa, Wrights or Fields stains.

RDTs detect malaria antigens in blood by targeting falciparum-specific protein such as histidine-rich protein II (HRP-II) or lactate dehydrogenase (LDH). RDTs are simple, relatively cheap and can be used in remote areas without specialized equipment or need for electricity. However, RDTs can only reliably detect 50-100 parasites/µL. Molecular tests such as polymerase chain reaction (PCR) are currently the most accurate and the most sensitive techniques for detecting malaria in low or sub-microscopic samples, for mixed infections and for differentiating Plasmodium species

An international team of Tropical Medicine Specialists aided by those at The University of Queensland (Brisbane, Australia; www. uq.edu.au) hypothesized that the presence of malaria parasites in red blood cells produce unique infrared signatures that could potentially be used for malaria detection. They used a handheld near infrared spectrometer reflective (NIRS) model to non-invasively collect spectral signatures from the right and left ears, arms and fingers of malaria positive and negative individuals living in a malaria endemic area in Brazil where both P. falciparum and P. vivax are prevalent at a 30%/70% ratio. A total of 60 patients were scanned and a total of 360 spectra were collected. The infection status and Plasmodium species type were confirmed by microscopy and standard PCR.

The scientists used the NIRvascan NIRS model G1 (Allied Scientific Pro, Gatineau, Canada; www.alliedscientificpro.com). The

model used is a diffuse reflectance spectrometer with wavelength ranging from 900-1700nm, a 5000:1 signal to noise ratio and an optical resolution of 10nm pixel resolution. It has an inGaAs detector (Hamamatsu Photonics, Shizuoka, Japan; www.hamamatsu.com), and it weighs 136g and measures 82.2 × 63× 40 mm. It is rechargeable and can be operated by either a computer or a smartphone via Bluetooth.

The investigators reported that results from PCR confirmed 27/60 (45%) people scanned were positive with malaria while the rest were malaria negative. Of the malaria positive individuals, 75% (N=20) and 25% (N=7), were infected with P. vivax and P. falciparum, respectively. Results from microscopy indicated that out of the 27 infected patients, 7.4% (two subjects) had extremely high parasitaemia, 18.5% (five subjects) had moderate parasitaemia, 44.4% (12 subjects) had low parasitaemia and 29.6% (eight subjects) had very low parasitaemia.

Spectra collected from the ear produced the most accurate prediction of infection in the independent subjects with an accuracy of 92% (N=24), sensitivity of 100% (N=11) and specificity of 85% (N=13). Comparatively, the accuracy, sensitivity and specificity of the spectra collected from the finger was 70% (N=24), 72% (N=11) and 69% (N=13), respectively whereas spectra of the arm resulted into a predictive accuracy of 72% (N=24), sensitivity of 59% (N=11) and specificity of 85% (N=13).

The authors concluded that their proofof-concept study provides insights on the potential application of NIRS and machine learning techniques for rapid, non-invasive and large-scale surveillance of malaria and potentially other human pathogens. The study was published on December 7, 2022 in the journal PNAS Nexus.

D-Dimer Blood Test Detects Prosthetic Joint Infections as Accurately as Standard Tests

Periprosthetic joint infection (PJI) is a serious complication of failed total hip or knee replacement and among the primary causes of implant failure. Diagnosing PJI can be highly challenging because there is no single test that can claim to have 100% accuracy in determining or ruling out its presence. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), which are two common markers of inflammation, are recommended as screening tests for patients suspected of having PJI. However, both these markers have limitations, such as a high rate of false-negative results when PJI is present. Plasma D-dimer, a test commonly used for certain blood clot-related disorders, is also a potentially useful marker of infection and has been validated for use in the diagnosis of PJI. However, some studies have raised concerns over the diagnostic performance of D-dimer testing for PJI, and its true accuracy is still unknown. Now, a new study suggests that the measurement of plasma D-dimer levels

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Image: The malaria detection tool collects an infrared signature for a mobile phone to process (Photo courtesy of The University of Queensland)

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D-Dimer Blood Test Detects Prosthetic Joint Infections as Accurately as Standard Tests

In the new study, researchers at Thomas Jefferson University (Philadelphia, PA, USA; www.jefferson.edu) compared plasma D-dimer and other tests for the diagnosis of PJI. Over a four-year period, the study prospectively enrolled 502 patients undergoing revision knee or hip arthroplasty, irrespective of their surgical indication. All the patients underwent a blood draw just before their surgery to measure their levels of D-dimer, CRP, and ESR, and fibrinogen. After applying the 2018 International Consensus Meeting definition of PJI, the researchers found 23% of the patients had PJI. The four tests had "comparable accuracy" for the diagnosis of PJI. Sensitivity (ability to detect PJI when present) was 81.3% for D-dimer, 90.4% for CRP, 73.9% for ESR, and 74.7% for fibrinogen. On the other hand, specificity (correctly showing that PJI was not present) was 81.7% for D-dimer, 70.0% for CRP, 85.2% for ESR, and 75.4% for fibrinogen. For all four measures, the values were higher for patients who were shown to have PJI.

However, in some patient subgroups, D-dimer offered a diagnostic advantage. In a sub-analysis that excluded patients with certain health conditions associated with inflammation, the D-dimer test outperformed ESR, fibrinogen, and CRP in recognizing the presence of PJI. D-dimer also performed best in detecting PJI caused by slow-growing "indolent" organisms, with higher values for both sensitivity and specificity. Additionally, all the four tests showed a better diagnostic performance in patients with suspected PJI in the knee, as compared with PJI in the hip. The report is the largest prospective study evaluating the performance of different laboratory tests for suspected PJI and support D-dimer testing as a valuable tool for the often-difficult diagnosis of PJI. There is a need for further studies, and no universal diagnostic cutoff point can be determined due to known variations in D-dimer measurement, according to the researchers.

"We found that plasma D-dimer was noninferior to serum CRP and ESR in the diagnosis of PJI and may be a useful adjunct when screening patients undergoing revision total joint arthroplasty," said Javad Parvizi, MD, FRCS, and colleagues of Rothman Orthopedic Institute at Thomas Jefferson University.

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can provide useful information when making the difficult diagnosis of PJI.

Liquid Biopsy Test Detects and Monitors Brain Cancer

more quickly. Such a liquid biopsy test could potentially have enormous value in treating GBM.

Researchers at Penn State College of Medicine (Hershey, PA, USA; www.med.psu.edu) studied an antigen receptor, called interleukin-13 receptor α2 (IL13Rα2), which increases in the tumor tissue of over 75% of GBM patients. The team examined the utility of IL13Rα2 as a biomarker for GBM by analyzing the tumor tissue and blood plasma of 79 patients with primary GBM, along with the blood plasma of 23 control patients, from two separate health systems. The control patients had been primarily diagnosed with either spinal stenosis or arteriovenous malformation but did not suffer from any malignancy or chronic inflammation.

In the patients’ plasma, the team specifically examined extracellular vesicles, which are small particles released by cells and carry material from those cells. The researchers found that GBM patients had significantly high IL13Rα2 levels in their blood plasma as compared to control patients and that the IL13Rα2 was mostly concentrated on extracellular vesicles derived from tumor cells. It was also found that these IL13Rα2 levels in blood plasma were correlated with the IL13Rα2 levels in the patients’ tumors.

The finding is significant as IL13Rα2 has been demonstrated to have a patchy distribution in GBM tumors, raising doubts over whether a needle biopsy or small sample of tumor tissue is representative of the tumor as a whole. In addition, the researchers found that elevated levels of IL13Rα2 in both plasma and tumors were a predictor of longer overall survival. In fact, patients with high levels of plasma IL13Rα2 had a 6.5 month longer median overall survival as compared to patients with low levels.

“Patients normally receive imaging, such as MRI or CT scans, to diagnose and track the progression of brain tumors, but it can be difficult for physicians to tell from those scans if the patient is getting better or worse because they don’t provide detail at the cellular or molecular level,” said Vladimir Khristov, graduate and medical student, Penn State. “That is why we need a supplemental diagnostic test to help physicians determine if the tumors are responding to therapy and regressing, or if they are getting worse and need additional treatment.”

“A liquid biopsy may facilitate diagnosis and more importantly provide a better understanding of the tumor’s response to treatment in a way that is lacking with our current technologies,” added Brad Zacharia, associate professor of neurosurgery and of otolaryngology, Penn State.

Image: Blood test for brain cancer may be on horizon (Photo courtesy of Pexels)

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Autoimmunity-Associated T Cell Receptors Recognize HLA-Variant-Bound Peptides

The immune response in autoimmune disease recapitulates that of responses directed against infection, except that self-antigens are, or become, the target of the adaptive immune system. These self-antigens may drive a process that is localized within a specific organ, such as the thyroid gland (Grave’s disease, Hashimoto’s thyroiditis) or brain (multiple sclerosis).

Autoimmune disease occurs when an immune response attacks one’s own tissues. Like all adaptive immune responses, it is focused on specific antigens by T-cell receptors and B-cell receptors. In contrast to infection, the antigens that these cells recognize are processed from proteins within the target organ and this drives a chronic inflammatory process that disrupts the normal function of the tissue.

A large international team of immunologists partially led by those at Washington University School of Medicine in St. Louis (St Louis, MO, USA; www.medicine.wustl.edu) investigated the theory that some T cells that react to microbes also may react to normal human proteins, causing autoimmune disease. The autoimmune diseases ankylosing spondylitis, which involves arthritis in the spine and pelvis, and acute anterior uveitis, which is characterized by inflammation in the eye, are both strongly associated with an HLA variant called HLA-B*27.

The team devised a method to identify protein fragments that drive a T cell response when combined with HLA-B*27, and mapped the fragments against the human genome and five bacterial genomes to identify proteins from which the fragments may have originated. They isolated orphan T cell receptors (TCRs) expressing a disease-associated public β-chain variable region–complementary-deter-

mining region 3β (BV9–CDR3β) motif2,3,4 from blood and synovial fluid T cells from individuals with ankylosing spondylitis (AS) and from the eye in individuals with acute anterior uveitis (AAU).

These TCRs showed consistent β-chain variable region (AV21) chain pairing and were clonally expanded in the joint and eye. The investigators used HLA-B*27:05 yeast display peptide libraries to identify shared self-peptides and microbial peptides that activated the AS- and AAU-derived TCRs. Structural analysis revealed that TCR cross-reactivity for peptide–MHC was rooted in a shared binding motif present in both self-antigens and microbial antigens that engages the BV9–CDR3β TCRs.

Michael Paley, MD, PhD, an Assistant Professor of Medicine and a co-author of the study, said, “For ankylosing spondylitis, the average time between initial symptoms and actual diagnosis is seven to eight years. Shortening that time with improved diagnostics could make a dramatic impact on patients' lives, because treatment could be initiated earlier. As for therapeutics, if we could target these disease-causing T cells for elimination, we could potentially cure a patient or maybe even prevent the disease in people with the high-risk genetic variant. There's a lot of potential for clinical benefit here.” The study was published on December 7, 2022 in the journal Nature.

Image: A T cell receptor that recognizes a human protein fragment (left) is remarkably similar to one that recognizes a bacterial protein fragment (right), and to two receptors capable of recognizing both human and bacterial protein fragments (middle) (Photo courtesy of Washington University School of Medicine)

Sepsis Host-Response PCR Test Enables Early Targeted Therapies

Sepsis is a leading cause of hospital deaths, resulting in significant human and economic costs. The lack of effective antimicrobials to treat sepsis leads to the death of 11 million people annually. Delayed diagnosis of sepsis can increase the risk of developing septic shock by 4-9% per hour. Early identification of sepsis in patients with ambiguous symptoms can help healthcare professionals provide timely targeted treatment, even before the results of confirmatory tests such as microbiology cultures are available. Now, a host (patient) immune response test can identify 19 mRNA biomarkers of infection, sepsis and septic shock, and can also be used to monitor patient response to treatment.

AcuSept from Acumen Diagnostics Pte. Ltd. (Singapore; www.acumen-diagnostics.com) is a sepsis host-response blood test based on specific biomarkers that evaluates the host's immune response dysregulation during systemic infection and sepsis by analyzing the gene expression signature of 19 leukocyte mRNA biomarkers, using RT-PCR. The sepsis PCRbased diagnostic test generates results within five hours of patient sample collection.

AcuSept results provide valuable information about infection and sepsis risk and progression. The test can diagnose culture-negative sepsis, which can be difficult to detect

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Unique Biomarker Could Improve Early Alzheimer’s Diagnostics

collects inside neurons. In patients with Alzheimer’s, tau detaches from the microtubules that act as structural supports for neurons and sticks to other tau molecules to form dense tangles. Researchers are yet to determine which of these changes causes Alzheimer’s and could be due to the disease. For some time now, endothelial damage has been considered secondary to amyloid and tau toxicity, although recent research has begun to shed light on the significant role played by the endothelium and other vascular constituents in setting off the cascade of events that lead to Alzheimer’s disease.

Researchers at University of New Mexico (Albuquerque, NM, USA; www.hsc.unm.edu) have now identified a new protein in the cerebrospinal fluid that can reliably detect endothelial injury in patients with Alzheimer’s disease. Using this biomarker, they found that endothelial injury is a key contributor to cognitive impairment during the earliest pre-symptomatic stages of the disease as well. The findings raise hope for millions of people with Alzheimer’s, as they could pave the way for further research into drug interventions for preventing damage to the brain endothelium.

The researchers conducted a study involving 700 cognitively normal participants who had biomarker evidence of Alzheimer’s disease and had undergone detailed clinical, cognitive, MRI and PET scans and biomarker assessments including measurement of vascular-endothelial cadherin (VEC), a novel marker of endothelial injury. The research team discovered elevated cerebrospinal fluid levels of VEC as compared to controls in even the earlier stages of Alzheimer’s, prior to the onset of memory loss. Upon combining with established Alzheimer’s biomarkers, such as amyloid and tau, the cerebrospinal fluid levels of VEC enhanced the ability of these markers to detect early Alzheimer’s pathology. The researchers also found that the VEC levels correlated with cognitive outcomes to the same extent as amyloid and tau in these early preclinical stages, even after adjusting for imaging measures of small vessel disease.

The research suggests that toxic levels of amyloid and abnormal accumulations of tau cause endothelial injury, while increased amyloid and tau levels may be owing to endothelial injury. The researchers hypothesize that some form of microcirculatory failure occurs that begins in the capillaries, where the endothelial cells are damaged. Going forward, the team plans to conduct further research to understand how the endothelium is involved in Alzheimer’s disease. Their work could pave the way for further research into drug intervention for preventing and/or healing endothelial injury.

“Our study suggests that endothelial damage plays an important role very early in the course of Alzheimer’s disease, and is directly linked to memory, cognitive functions and synaptic plasticity,” said University of New Mexico neurologist Rawan Tarawneh, MD. “We found that we could measure endothelial injury reliably in the brain of Alzheimer’s disease patients and that endothelial injury actually correlates with cognitive outcomes, to a similar degree as amyloid and tau. We have also identified several pathways by which the endothelium influences memory and learning independently of amyloid and tau. So, this is proving that, yes, endothelium – the lining of the blood vessels – has a direct correlation with cognitive impairment.”

Sepsis Host-Response PCR Test Enables Early Targeted Therapies

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using traditional microbiology culture tests that are slower and less sensitive. By overcoming these limitations, AcuSept enables patient triage and monitoring and can be used as a complementary tool to clinical assessments and other diagnostic parameters. AcuSept can inform the selection of appropriate treatment bundles based on the severity risk of sepsis, from early sepsis to severe sepsis and septic shock, and allows for the monitoring of patient response to treatment.

Acumen's clinical studies have demonstrated that AcuSept outperforms other single-biomarker tests in detecting sepsis, and is highly effective in diagnosing culture-negative sepsis. The test's superior positive and negative predictive values enable it to detect infection in patients, providing supplementary information to pathogen identification tests. With AcuSept test results, doctors can gain crucial insights into a patient's condition, allowing for more comprehensive assessments and targeted treatment decisions with greater speed.

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Image: Researchers have identified a new biomarker of early-stage Alzheimer’s disease (Photo courtesy of Pexels)

Novel Non-Sputum Based Technology Quickly Detects Active TB

TB, caused by Mycobacterium tuberculosis, is a serious global health concern that results in 10 million new cases and 1.7 million deaths annually. According to the latest report by the World Health Organization, TB is the 13th leading cause of death worldwide, and the second leading infectious disease killer after COVID19. The presence of Latent Tuberculosis Infection (LTBI) is a critical issue, as it serves as a reservoir for TB bacteria and increases the risk of developing active TB. Alarmingly, one-third of the world's population is infected with TB, and 5 to 10% of those with LTBI will progress to active TB within the first five years after initial infection.

The current gold standard diagnostic tests for detecting active TB infection are the sputum smear and culture tests. Unfortunately, these methods have several limitations, including the need for collecting sputum, trained personnel, cost, lengthy processing time, and inadequate sensitivity. Similarly, conventional tests for differentiating latent TB from uninfected individuals, such as tuberculin skin tests (TST) and interferon gamma release assays (IGRA), are not effective in distinguishing active TB from latent infection. Despite advancements in rapid molecular diagnostic techniques for TB, there remains a significant need for a time-efficient, cost-effective, and non-sputum-based point-of-care (POC) test. Now, researchers at Wayne State University (Detroit, MI, USA; https://wayne.edu) have discovered a new technology that can rapidly and easily detect active TB infection antibodies.

For over 15 years, a dedicated research group at Wayne State has been focusing on developing technology for detecting antibodies related to various respiratory diseases. The team has successfully created an innovative non-sputum-based approach and identified multiple novel immune-epitopes that differen-

tially bind to specific immunoglobulin (IgG) found in individuals who are infected with TB. By measuring the levels of epitope-specific IgG in the serum, this breakthrough technology can distinguish active TB from LTBI subjects, healthy individuals, and other respiratory diseases. This simple and non-sputum-based serological POC-TB test is highly sensitive and specific, making it an ideal option to differentiate active TB from LTBI.

The researchers had earlier developed a T7 phage antigen display platform and after immunoscreening of large sets of serum samples, they identified 10 clones that differentially bind to serum antibody (IgG) of active TB patients differentiating TB from other respiratory diseases. One of these high-performance clones had homology to the Transketolase (TKT) enzyme of TB bacteria that is an essential enzyme required for the intracellular growth of the bacteria in a host. The researchers hypothesized that abundance of IgG in sera against the identified novel neoantigen that they named as TKTµ could differentiate between active TB, LTBI and other non-TB granulomatous lung diseases like sarcoidosis. The team developed a novel direct Peptide ELISA test to quantify the levels of IgG in serum samples against TKTµ. The research team designed two additional overlapping M.tb TKT-peptide homologs with potential antigenicity corresponding to M.tbspecific transketolase (M.tb-TKT1 and M.tbTKT3) and hence standardized three Peptide ELISA (TKTµ, M.tb TKT1 and M.tb TKT3) for the TB serodiagnosis.

After development and standardization of a direct peptide ELISA for three peptides, the research team tested 292 subjects, and their TKT-peptide ELISA results revealed that TB patients had significantly higher levels of TKT-specific antibodies than healthy controls or those with LTBI. The higher levels of TKT-specific antibodies can be attributed to

Image: Researchers have discovered a new technology that will quickly and easily detect active TB infection antibodies (Photo courtesy of Wayne State University)

growing M.tb bacteria in active TB patients. TKT plays a crucial role in the transition from the dormant to the proliferative phase, and TKT specific IgG can reveal differences between active TB and LTBI. Consequently, IgG-based serodiagnosis of TB utilizing TKTpeptide ELISA holds promise. The current commercially available serological TB tests exhibit inadequate sensitivity and specificity. However, the ELISA results from the newly discovered TKT peptides demonstrated high sensitivity and specificity. The research team's findings indicate that IgG antibodies against transketolase have the potential to distinguish active tuberculosis.

“Our TKT peptide ELISA test requires chemically synthesized TKT peptides to coat the wells in the ELISA plate, less than 100µl blood serum sample from patient, detection reagents and an ELISA plate reader,” said Lobelia Samavati, M.D., professor in the Center for Molecular Medicine and Genetics in the School of Medicine, who led the research team. “We are extremely enthusiastic about our technology and the fact that with a simple test we can differentiate active TB from LTBI and other respiratory diseases. We believe that our method and TKT peptide ELISA can fit the requirements of the World Health Organization and the Centers for Disease Control and Prevention as a POC screening method.”

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TSH (THYROID STIMULATING HORMONE) TEST GOLDSITE DIAGNOSTICS

The Kemilo TSH Kit is used on the Kemilo CLIA platform for the quantitative determination of TSH (Thyroid Stimulating Hormone). It uses an all-in-one cartridge for a single test and is based on the classic CLIA technology.

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PCR Panels for Acute GI Infections Can Lower Hospitalization and Antibiotic Use

Acute gastroenteritis impacts adults across all age groups and incurs enormous healthcare expenses. Now, a new study comprising 40,000 hospital visits across various geographic locations has revealed that a single stool sample analysis using multiple polymerase chain reaction (PCR) panels is capable of identifying more pathogens, especially diarrhea-causing E. coli and enteric viruses, faster than a traditional diagnostic workup.

Research conducted by the University of Washington School of Medicine (Seattle, WA, USA; www.uwmedicine.org) found that the application of multiplex PCR resulted in a higher number of patients being discharged, reducing hospitalization rates during the following month. The cost of care for these patients was similar to those undergoing traditional stool work-up along with follow-up visits. Typically, conventional workups involve testing a stool culture for a single suspect species of pathogen, using a single pathogen PCR test or identifying a pathogen with the help of microscopy, immunology or an ova and parasites test. Additionally, the researchers found that using multiplex PCR (consisting of 12 or more panels) led to a decrease in the administration of antibiotics to hospitalized patients.

“Earlier studies showed that large multiplex PCR panels improve the speed and accuracy of diagnostic testing in patients with acute gastroenteritis, but their impact on costs and clinical outcomes had been uncertain,” said Ferric C. Fang, M.D., Professor of Laboratory Medicine, Pathology and Microbiology at the University of Washington School of Medicine, Seattle. “Our study shows that the benefits of multiplex panels can be achieved without increasing overall healthcare costs, and also facilitates more appropriate use of antibiotics.”

“This study illustrates the power of big data to analyze the healthcare impacts of diagnostic testing and help laboratories select testing approaches that improve meaningful clinical outcomes,” Fang said

Hand-Held POC Biosensor Quickly and Accurately Detects Oral Cancer

Oral cancer is the 13th most common type of cancer globally, and oral squamous cell carcinomas (OSCCs) account for more than 90% of oral cancers. An estimated 300,000 new cases and 145,000 deaths worldwide were attributed to oral cancer in 2012. Since oral cancer occurs in one of the most accessible sites in the body, it can be easily treated if detected promptly. If caught early in the disease state, oral cancers that remain localized and are two centimeters or smaller can be cured and five-year survival rates exceed 90%. Now, researchers have developed a breakthrough hand-held biosensor that enables quick and accurate detection of oral cancer.

The biosensor developed by a group of researchers from the University of Florida (Gainesville, FL, USA; www.ufl.edu) and National Yang Ming Chiao Tung University (Hsinchu, Taiwan; www.nycu.edu. tw) consists of a sensor strip, similar to a glucose strip, and a circuit board (a hand-held terminal like a glucometer) for detection.

"Typically, test fluid is introduced into a small liquid channel on the tip of the sensor strips," said Minghan Xian, co-author and a researcher at the University of Florida. "A few electrodes sit within the liquid channel, and the surface of these electrodes contain antibodies to specific proteins present within human oral cancer lesions. Short electrode pulses get sent through these electrodes during detection, and then the circuit board module analyzes this signal and outputs a four-digit number that correlates to its concentration."

As far as applications, there's tremendous interest within the sensor and medical communities to develop semiconductor- and electrochemical-based biomarker detection. The team is now looking forward to demonstrating their integrated solution for cancer and other disease detection via a handheld point-of-care device with a short detection time and low detection limit. They also hope their work will inspire further research into this topic.

"The next step in this continuum is to conduct the analysis using in vivo samples of CIP2A – a biomarker of OSCC – in oral cancer and non-oral cancer patients with biopsy as a gold standard," added Xian.

Thermo-Resistant (- 60 °C to 300 °C) Fully Washable & Flexible Suitable for central sterilization services Sterilizable

Image: Sampling a single stool using multiple PCR panels can identify more pathogens rapidly (Photo courtesy of Pexels)

Blood Test 24 Hours After Start of Chemotherapy Predicts Survival

Acute myeloid leukemia is an aggressive blood cancer with poor survival. Despite high rates of initial chemotherapy response, patients often relapse due to the selection and development of chemotherapy-resistant leukemic cells. The response to therapy is currently measured after weeks to months of treatment, thereby losing important time. Now, researchers have found a new method that within hours can predict if certain cancer patients will survive or not after chemotherapy.

Researchers at the University of Bergen (Bergen, Norway; www.uib.no) have discovered that an immediate response to chemotherapy can be measured by investigating the functional properties of the leukemic cells. In their study, the researchers employed mass cytometry to investigate intracellular signaling networks in peripheral blood samples from 32

newly-diagnosed acute myeloid leukemia patients during the first 24 hours of standardized induction chemotherapy. By correlating initial intracellular signaling response to five-year overall survival, the researchers demonstrated that early response evaluation by mass cytometry at 24 hours can identify patients with suboptimal treatment response to standard induction therapy.

"When treating patients with leukemia, it is challenging to quickly follow if the patient is responding to therapy or not," said Benedicte Sjo Tislevoll, researcher at the University of Bergen and leader of the new study. "Our results show that the protein ERK1/2 increases within the first 24 hours of chemotherapy in patients who have a poor response to therapy. We believe that this protein is responsible for the cancer cells' resistance to chemotherapy

Image: A new method can quickly predict if certain cancer patients will survive or not after chemotherapy (Photo courtesy of Pexels)

and can be used to distinguish responders from non-responders."

"We think that this is an important key in our understanding of cancer, and our aim is to use this information to change treatment early for patients who are not responding to therapy," Tislevoll concluded.

Test Identifies Prediabetics Before Symptoms Appear

and fasting glucose are incapable of accurately identifying prediabetic individuals who are at the highest risk of progression. Now, a blood test can identify high-risk, asymptomatic patients with prediabetes who cannot be detected by standard diabetes tests, hemoglobin A1C and glucose. The blood test meets a critical clinical need as it can be used by physicians to identify patients closest to developing type 2 diabetes and provide treatment to prevent the onset of the disease.

GlycoMark from Precision Diabetes, Inc. (Raleigh, NC, USA; www.precisiondiabetesinc. com) is an FDA-cleared, non-fasting serum or plasma test for monitoring blood glucose variability in people with diabetes. The GlycoMark test provides quantitative measurement of 1,5-anhydroglucitol (1,5-AG) in serum or

plasma. As the GlycoMark test reflects a progressive decline of functional beta-cell mass, it can identify prediabetic patients with the highest risk of developing diabetes before the first symptoms develop. Most high-risk patients can prevent the development of type 2 diabetes by making lifestyle changes such as eating a well-balanced diet, exercising and maintaining a healthy body weight.

In a new study, the GlycoMark blood test has shown that it can identify high-risk, asymptomatic patients with prediabetes, not detected by standard diabetes tests, hemoglobin A1C

and glucose. The finding is extremely important as there is a significant clinical need for a sensitive and robust biomarker of functional beta-cell mass (beta cells are cells in the pancreas that produce insulin). A functional beta-cell mass biomarker is essential to identify which prediabetic individuals have the highest risk of progression to diabetes.

“This study not only has significant clinical implications as there has been a long search for an accurate biomarker of beta-cell function, but given the sheer numbers of people with prediabetes, it is important to target the highest-risk patients from a public health and economic standpoint,” said Eric Button, CEO of Precision Diabetes, Inc. “GlycoMark will be an important tool in stratifying these patients for follow-up treatment.”

229 LMI-04-23 COM

The Hb-Total quantitative test is an immunochromatographic rapid test for the quantitative determination of hemoglobin total in whole blood samples with a measuring range of

230 LMI-04-23

LINKXPRESS COM

CKD TEST RANDOX LABORATORIES

The Randox Chronic Kidney Disease (CKD) arrays utilize patented Biochip Technology, enabling early multiplex detection of CKD from a single sample for earlier intervention through treatment and preventing further kidney damage.

Cont’d from cover

IFCC Elects Leadership for 2024-2026 Term

PIFCC President who will stay as IFCC Past President.

The IFCC also announced results of elections concluded on Feb. 28, 2023, determining the Regional Federation Representatives to the IFCC Executive Board. The elected representatives are as follows:

African Federation of Clinical Chemistry (AFCC): Prof. Rajiv Erasmus (South Africa); Arab Federation of Clinical Biology (AFCB): Dr. Osama Najjar (Palestine); Asia-Pacific Federation for Clinical Biochemistry and Laboratory Medicine

tion of Clinical Chemistry and Laboratory Medicine (EFLM): Prof. Mario Plebani (Italy); Latin-American Confederation of Clinical Biochemistry (COLABIOCLI): Dr. Eduardo Freggiaro

try and Laboratory Medicine (NAFCC): Dr. David Grenache (USA).

At the same elections concluded on Feb. 28, 2023, Tricia Ravalico (Abbott Diagnostics) was elected Corporate Representative to the IFCC Executive Board.

The three-year term starts on Jan. 1, 2024 and ends on Dec. 31, 2026. The IFCC wishes to thank all candidates that participated and campaigned in the IFCC electoral process and extends its appreciation for their steadfast commitment to serving IFCC.

IFCC Launches New and Modernized Website

Greatnews! IFCC is happy to announce the launch of a new and modernized website, a positive step towards improving its online presence and making it more user-friendly for its members and visitors. This modernized website provides various benefits, such as improved navigation, faster load times, enhanced mobile responsiveness, better accessibility, and improved content organization. This new website assists IFCC in achieving its organizational goals by providing a platform for disseminating information, promoting its activities, connecting with members and stakeholders, and enhancing its brand reputation.

Overall, the launch of a new and modernized website by IFCC is a positive step towards enhancing its digital presence and providing a better user experience for its members and visitors.

We thank Insoft for their partnership and their support for many years and we welcome Digiwedo as our new partner for the new website. Take a look at the new IFCC website (www.ifcc.org) and email us for any suggestions!

Prof. Sergio Bernardini IFCC Secretary

Dr. Alexander Haliassos IFCC Treasurer

Tricia Ravalico IFCC Corporate Representative

Prof. Khosrow Adeli IFCC President

Prof. Tomris Ozben IFCC President-Elect

Prof. Rajiv Erasmus AFCC

Dr. Osama Najjar AFCB Dr. Tony Badrick APFCB

Prof. Mario Plebani ELFM

Dr. Eduardo Freggiaro COLABIOCLI

Dr. David Grenache NAFCC

EDITORIAL

By Katherina Psarra, MSc, PhD

Dear Colleagues,

We are already in the middle of April, leaving behind Easter holidays. We will all meet in Rome very soon.

Go through President Prof. Khosrow Adeli’s message and you will learn everything about the upcoming EuroMedLab 2023. Lots of people (more than ever) from all over the world will attend the meeting and will stroll in the Eternal City’ s streets. The exhibition will be immense, and

CELME 2023

5th Symposium

CUTTING EDGE OF LABORATORY MEDICINE IN EUROPE ANALYTICAL PERFORMANCE SPECIFICATIONS: MOVING FROM MODELS TO PRACTICAL RECOMMENDATIONS Prague, October 12–13, 2023

JOIN US

Join us to share the latest innovative thinking in the delivery of the best laboratory medicine activities. Learn from expert innovators presenting new ways of solving the financial, quality and organizational problems we all have to face.

If you want to lead your laboratory service to ‚first class‘ performance then join us and experience the shared opinion of like-minded professionals.

the Scientific program will meet everyone’s expectations.

In the last issue we listened to the music of voices from so many places around the world but in this issue, we will listen to the music of planet earth as we will read about the need to transform our labs into green labs, trying not to contribute to the climate crisis. There is no time for postponement.

In the meantime, don’t forget to visit the brand new IFCC website.

See you in Rome, but until then go through this really interesting issue and find out what we can do to save our planet. It is singing into our ears asking for help.

Cheers to 5 Years of Healthcare Excellence: UNIVANTS Turns 5!

Frommitigating disease outcomes, to screening, to reducing uncertainty, to mit igation of healthcare costs, these are just some of the remarkable outcomes asso ciated with recognized best practices of the UNIVANTS of Healthcare Excellence Program. The UNIVANTS of Healthcare Excellence Program seeks to amplify, recognize and celebrate impressive outcomes enabled by laboratory medicine and in partnership with interdisciplinary teams. This year, however, UNIVANTS is also celebrating a HUGE milestone – 5 year anniversary.

Across these 5 years of recognizing teams, galvanizing change and inspiring measurably better health outcomes, the UNIVANTS award program has recognized 53 best practices to date spanning different disease states, geographies, interdisciplinary teams and laboratory testing. In its 5th year, UNIVANTS will recognize additional teams from the 2022 award applications with impressive collaborations and awe-inspiring outcomes – be the first to know by visiting www.univantsHCE.com on June 26th for the global unveiling.

To further mark the occasion of such a monumental anniversary, the UNIVANTS of Healthcare Excellence Program, in partnership with AACC, will be hosting the inaugural UNI5K fun walk/run in honor of the power of laboratory medicine on Monday, July 24, 2023. Join friends, colleagues and teammates in this health-centered celebration. To register and/or learn more, please visit UNI5K | AACC.org.

Organized by :

Symposium Secretariat: CZECH SOCIETY OF CLINICAL BIOCHEMISTRY

www.celme2023.cz

As the UNIVANTS of Healthcare Excellence program has moved from its infancy to the global, prestigious program that it is today, we thank all program partners, advocates, champions, and YOU. The improvements to patient care and outcomes, enhanced decision-making and reduced healthcare costs (to name a few impressive KPIs) would not be possible without the insights and motivation of laboratory medicine professionals. As we think about all that has been accomplished thus far, exciting opportunities exist in healthcare today and we look forward to the outcomes yet to be realized.

To learn more and apply to the UNIVANTS of Healthcare Excellence program, please visit www.univantsHCE.com

Sverre Sandberg, Mauro Panteghini, Tomáš Zima symposium chairs

„The aim of this conference is to go through and discuss the three different models agreed by the Milan 2014 EFLM Strategic Conference to set APS for the medical laboratory and to give practical examples on how this can be done“.

Under Auspices:

MESSAGE FROM THE PRESIDENT

By Khosrow Adeli • President, IFCC

TheXXV IFCC-EFLM WORLDLAB-EUROMEDLAB CONGRESS is set to be the largest and most well-attended event in IFCC’s 70-plus year history, and it’s just here! I encourage everyone to join in the academic sessions, industry exhibits, and other activities at this esteemed scientific event, taking place from May 21-25, 2023, in the beautiful and historic city of Rome, Italy. Rome provides the perfect backdrop for this event, as a vibrant global city with a rich history, stunning architecture, and cosmopolitan vibe. The organizing and scientific conference committees have been hard at work planning exceptional scientific and social programs that will be enjoyed by all attendees. The program features an impressive international faculty, along with industry workshops and exhibits. Don’t miss out on this fantastic opportunity to participate in a top-notch scientific event!

A record number of scientific abstracts (over 2100), a record number of industry exhibits (over 100), and a record number of registrations (>3500 delegates, >1700 visitors, >3300 corporate representatives) all clearly indicate that the IFCC-EFLM WorldLab-EuroMedLab Congress will set the all-time record in attendance and will bring together the largest number of laboratory specialists and industry leaders from around the world. The WorldLab/ EuroMedLab Congresses have become a leading platform for laboratory medicine and clinical chemistry, facilitating scientific exchange and advancement among scientists, laboratory specialists, clinicians, and industry colleagues. The 2023 EuroMedLab Congress promises to offer a diverse range of innovative education opportunities, including lectures, symposia, recent advancements in clinical practice and science, poster presentations, and industry exhibits, as well as a fantastic social program. Attendees will have the opportunity to interact with distinguished experts from around the world, while also earning Continuing Education (CE) credits through the EFLM CPECS accreditation program. As the IFCC continues to grow and expand its international reach, we remain committed to advancing better healthcare worldwide and keeping our field at the forefront of scientific advancement.

In addition to the main congress, four special satellite events have been organized that will provide additional educational opportunities including the 16th International Congress of Pediatric Laboratory

Medicine; the IFCC Forum for Young Scientists; Clinical Mass Spectrometry: Validation and Accredition of IVD and Laboratory Developed Test (LTD) in the New “Regulation EU 2017/746”; as well as Point-of-Care Testing: Home, Hospital and Beyond. For further information on “Satellite Meetings” visit the conference website: www.2023roma.org

I am eagerly anticipating the opportunity to meet many of you in Rome at the end of May, and I sincerely hope that you will relish both the exceptional scientific program and the stunning beauty of Rome during the upcoming congress.

Cheers, Khosrow 

IFCC Working Group on Method Evaluation Protocols

(WG-MEP) Gets Down to Work

“To do a good job, an artisan needs the best tools” (Chinese proverb)

By

Methodevaluation is the systematic investigation of the performance of a laboratory method under scientifically sound procedures to determine whether it meets predefined criteria; which has been determined according to clinical needs (Definition of the WG). It is a foundation of the total quality system for laboratory medicine and a critical activity that helps the laboratory decide whether a method is fit for clinical deployment. It also provides crucial objective data to the laboratory for subsequent planning of internal quality control and participation in external quality assurance programs. Despite its importance, method evaluation remains one of the tasks laboratories find challenging to perform. This may be partly related to a lack of evidence-based documents that are freely available to guide laboratories through this process (Figure 1).

A new IFCC Working Group on Method Evaluation Protocols (WG-MEP) has been formed in 2022 under the umbrella of the Emerging Technologies Division to address this gap. The purposes of the WG-MEP include the following:

1. Review and summarise the literature and guidelines on method evaluation procedures used in clinical laboratories.

2. Provide high-level guidance and incorporate evidence-based procedures for method evaluation, taking into account the intended clinical application of the measurement procedure.

3. Engage key stakeholders on method evaluation procedures, including and not limited to IFCC members and clinical stakeholders.

4. Develop and disseminate educational resources for clinical stakeholders, to inform best practices for method evaluation protocols.

The Working Group recently produced an Opinion piece that documented an overview of the status, challenges, and needs of method evaluation from the perspective of clinical laboratory medicine (doi: 10.1515/cclm-2022-0878). The key high-level aspects of clinical laboratory method evaluation were recognized as well as aspects that may be inappropriate or inappropriately applied. The need for harmonization for each of these areas is apparent and requires considerable work through the availability of guidance documents that are relevant to clinical laboratories. Consistent with this, educational activities and professional collaborations are essential to promote and improve the practice of method evaluation procedures.

During the remainder of the first term of the WG-MEP, it is planned and proposed several educational activities to disseminate good laboratory practices in method evaluation. The WG-MEP will work with related scientific, academic, and clinical bodies to collaborate on common objectives. This includes organizing symposiums and workshops at international scientific events, together with a proposal for a traveling lecturer program to promote the guidelines and recommendations globally.

Working group members: R. Greaves, Co-Chair, 2022-24 (AU); TP Loh, Co-Chair, 2022-24 (SG); B. Cooke, Member (AU); C. Markus, Member (AU); M. Tran, Member (VN); R. Zakaria, Member (AU); CS Ho, Consultant (CN); M. Pieri, Corr Member (IT); S. Ignjatović, Corr Member (RS); B. Varela, Corr Member (UY); H. Hakan, Corr Member (TR); N. Alawneh, Corr Member (PS); H. Bayat, Corr Member (IR);

IFCC OFFICE

Via Carlo Farini 81, 20159 Milan, ITALY Tel: (39) 02-6680-9912

E-mail: ifcc@ifcc.org • Web: www.ifcc.org

Staff Members: Paola Bramati, Silvia Cardinale, Silvia Colli-Lanzi, Smeralda Skenderaj

T Nakagawa, Corr Member (JP).

WG-MEP Co-Chairs: Prof. Ronda Greaves Murdoch Children’s Research Institute, Victoria, Australia; Dr. Tze Ping Loh, Clinical Chemistry Division, National University Hospital, Singapore

Photo: The WG-MEP members at their inaugural meeting (L-R and top to bottom): C. Markus (AU, member), S. Colli Lanzi (IFCC office), M. Tran (VN, member), S. Bernardini (IT, ETD chair), R. Greaves (AU, WG co-chair), R. Zakaria (AU, member), B. Cooke (AU, member), TP Loh (SG, WG co-chair)

Figure 1: Main components of method evaluation protocols. Note: reference intervals/decision limits are considered separately.

The views and positions expressed in the IFCC News section are those of the IFCC or the individual authors, and do not necessarily represent the views or positions of LabMedica magazine or its publishers.

Werfen Acquisition Expands Footprint in Specialized Diagnostics

Werfen (Barcelona, Spain; www.werfen. com) has successfully completed the acquisition of Immucor, Inc. (Norcross, GA, USA; www.immucor.com) after receiving the required regulatory and antitrust approvals. In November 2022, Werfen reached an agreement to acquire Immucor, a privately held in vitro diagnostics (IVD) company with a strong presence in the global Transfusion and Transplant markets, for approximately USD 2 billion. The Transfusion and Transplant product lines complement Werfen's existing

Hemostasis, Acute Care, and Autoimmunity business lines, expanding its portfolio of Specialized Diagnostic solutions for hospitals and clinical laboratories.

With the integration of Immucor, Werfen has expanded its presence as a company of reference in the Specialized Diagnostics market and grown its portfolio of diagnostic

Siemens and Hamamatsu Forge Digital Pathology Alliance

Today, digital pathology is at a tipping point, with the evolution from glass to digital already transforming standards of care. This transformation is being driven by the technological combination of high-speed, high-resolution imaging; trusted medical data storage; fast, secure data transmission; and intuitive, inter-operable workflows with continual improvements in AI.

Siemens Healthineers (Erlangen, Germany; www.siemenshealthineers.com) has entered into a multi-year distribution agreement with Hamamatsu (Shizuoka, Japan; www.hamamatsu.com), under which Hamamatsu will provide NanoZoomer whole slide scanners to support Siemens’ expansion into digital pathology in the Americas and Europe.

Hamamatsu, a leading manufacturer of photonics devices, including whole slide scanners for digital pathology, has more than 60 years of experience in photonics engineering. The company has developed NanoZoomer scanners which are renowned for their image quality, reliability, and ease of use. Siemens has decades of experience in diagnostics, enterprise imaging, and healthcare IT. The partnership with Hamamatsu NanoZoomer whole slide scanners will help Siemens close the gap between radiology and pathology to achieve full potential of digital operations in patient care.

"We now complement our portfolio for digital pathology with the products and expertise of Hamamatsu," added Christian Zapf, Head of Digital & Automation at Siemens Healthineers. "Together with our strong Syngo Carbon portfolio in enterprise imaging IT, we can now help our customers to comprehensively gain the benefits of a digital transformation in digital pathology."

solutions for hospitals and clinical laboratories. Additionally, Werfen will have seven technology centers and employ more than 7,000 people worldwide; with a direct presence in over 30 countries and across more than 100 territories through distributors.

"During our more than 50-year history, we have demonstrated our strong commitment to expand our IVD business through organic growth, complemented with highly strategic acquisitions," said Carlos Pascual, CEO of Werfen.

Roche and Eli Lilly to Collaborate on Blood Test for Early Alzheimer's Diagnosis

Roche Diagnostics (Basel, Switzerland; www.roche.com) has entered into a collaboration with Eli Lilly and Company (Indianapolis, IN, USA; www.lilly.com) to support the development of Roche’s Elecsys Amyloid Plasma Panel (EAPP) – an innovative blood test that aims to facilitate the earlier diagnosis of Alzheimer’s disease.

The EAPP measures phosphorylated Tau (pTau) 181 protein assay and apolipoprotein (APOE) E4 assay in human blood plasma. Elevations in pTau181 happen during the initial stages of Alzheimer’s, while the presence of APOE4 is the most common genetic risk factor for Alzheimer’s disease. The test result is meant to be considered by clinicians alongside other clinical information to decide on further confirmatory testing using amyloid positron emission tomography (PET) or cerebrospinal fluid (CSF) testing. Patients who test negative using the EAPP are not likely to be amyloid positive and need to be examined for other factors that may be causing their cognitive decline. Roche was granted the EAPP Breakthrough Device Designation by the U.S. Food and Drug Administration in July 2022.

“We are excited to be collaborating with Lilly on such an important area of unmet medical need,” said Matt Sause, CEO of Roche Diagnostics. “Today, over 55 million people are living with dementia and this is projected to increase to nearly 140 million by 2050. Collaboration is essential to ensure these people receive a timely and accurate diagnosis. The Elecsys Amyloid Plasma Panel has the potential to streamline a person's journey to diagnosis and, therefore, access to future treatment options.”

Integra Biosciences Acquisition Expands Reach in Growing NGS Market

ext-generation sequencing (NGS) is a rapid and inexpensive approach for examining the genome - the entire set of an organism's DNA. It has gained immense popularity since its inception almost two decades ago due to its throughput, speed, cost-effectiveness, and capacity to scale it up for larger projects. Consequently, NGS has transformed the spheres of genomic diagnostics, environmental science, reproductive health, forensics, and agriculture in recent times.

INTEGRA Biosciences (Hudson, NH, USA; www.integra-biosciences.com) has acquired Miroculus (San Francisco, CA, USA; www. miroculus.com), a biotech company focused on developing automation solutions that streamline NGS protocols. The acquisition will allow INTEGRA to extend its reach in the growing NGS market, providing novel process auto-

mation solutions to assist academic, research and diagnostics laboratories in saving time and speeding up discovery in this dynamic field.

Miroculus was set up with the objective of conceiving inventive and exclusive tools to enable high-quality scientific research worldwide. The company has extensive expertise in the fields of biochemistry, bioanalytics, molecular biology, and materials science. Miroculus began by developing a prototype system for miRNA detection, but soon recognized the technology’s potential for other applications, particularly for automating complex genomics protocols and making them easier and more accessible. Currently, Miroculus focuses on creating intuitive and flexible platforms based on its patented technology, simplifying complex NGS protocols and enabling researchers to translate their discoveries into practical solutions that are accessible to everyone.

The acquisition will boost company growth and unlock new opportunities for INTEGRA and Miroculus. INTEGRA expects the initiation of various genomics-based initiatives soon and is confident that the acquisition will contribute significantly to advancing scientific discovery in the vital field of genomics.

“The global NGS market has been growing exponentially in recent years, and seems set to continue doing so,” said Urs Hartmann, CEO of INTEGRA. “We have acquired this promising start-up because we recognize the huge potential of its revolutionary digital microfluidics technology for automating and miniaturizing genomic protocols. Miroculus' proprietary platform delivers assay flexibility and automation capacity, which enables seamless workflow integration. This will help to remove process bottlenecks and advance science – one of INTEGRA’s primary goals.”

For a free listing of your event or a paid advertisement contact: LabMedica International Calendar

E-mail: info@globetech.net

2023

MAY

ECV 2023 – 8th European Congress of Virology. May 4-7; Gdansk, Poland; eusv-congress.eu

ISLH 2023 – International Society for Laboratory Hematology. May 11-13; New Orleans, LA, USA; islh.org

Immunology 2023 – Annual Meeting of the American Association of Immunologists (AAI). May 11-15; Washington, DC, USA; immunology2023.org

14th Uruguayan Congress of Clinical Biochemistry. May 11-13; Montevideo, Uruguay; congresoabu2023.org

ECE 2023 – 25th European Congress of Endocrinology. May 13-16; Istanbul, Turkey; ese-hormones.org

QICL 2023 – 14th International & 20th National Congress on Quality Improvement in Clinical Laboratories. May 16-19; Tehran, Iran; iqctehran.ir

IFCC-EFLM WorldLab & EuroMedLab 2023 –25th International Congress of Clinical Chemistry and Laboratory Medicine. May 21-25; Rome, Italy; 2023roma.org

SLAS Europe 2023 Conference and Exhibition. May 22-26; Brussels, Belgium; slas.org/ europe2023

Hospitalar 2023. May 23-26; Sao Paulo, Brazil; hospitalar.com

JUNE

106th Annual Meeting of the German Society for Pathology. Jun 1-3; Leipzig, Germany; pathologie-dgp.de

EHA 2023 – Annual Congress of the European

Hematology Association. Jun 8-11; Frankfurt, Germany; ehaweb.org

EAACI 2023 – Annual Congress of the European Academy of Allergy & Clinical Immunology. Jun 9-11; Hamburg, Germany; eaaci.org

ESHG 2023 – European Human Genetics Conference. Jun 10-13; Glasgow, UK; 2023.eshg.org

UKMedLab23 – National Meeting of the Association for Clinical Biochemistry and Laboratory Medicine. Jun 12-14; Leeds, UK; acb.org.uk

ASM Microbe 2023 – American Society for Microbiology. Jun 15-19; Houston, TX, USA; asm.org

33rd Regional Congress of the International Society of Blood Transfusion (ISBT). Jun 1721; Gothenburg, Sweden; isbtweb.org

AMP Europe 2023 – Association of Molecular Pathology. Jun 18-20; Milan, Italy; amp-europe-congress.com

48th CBAC – Congress of the Brazilian Society of Clinical Analysis. Jun 18-21; Florianopolis, Brazil; sbac.org.br/cbac

FOCIS 2023 – Annual Meeting of the Federation of Clinical Immunology Societies. Jun 2023; Boston, MA, USA; focisnet.org

FIME 2023 – Florida International Medical Expo. Jun 21-23; Miami, FL, USA; fimeshow.com

ASV 2023 – 42nd Annual Meeting of the American Society of Virology. Jun 24-28; Athens, GA, USA; asv.org

ISTH 2023 Congress – International Society on Thrombosis and Haemostasis. Jun 24-28, Montreal, Canada; isth2023.org

ESHRE 2023 – 39th Meeting of the European Society of Human Reproduction and Embryology. Jun 25-28; Copenhagen, Denmark; eshre.eu

JULY

Analytica Lab Africa 2023. Jul 5-7; Johannes-

Advertising Index

burg, South Africa; analytica-africa.com

APCCMI 2023 – 19th Asia Pacific Congress of Clinical Microbiology and Infection. Jul 6-8; Seoul, Korea; apccmi2023.com

47th FEBS Congress 2023 – Federation of European Biochemical Societies. Jul 8-12; Tours, France; febs.org

FEMS 2023 – 10th Congress of European Microbiologists. Jul 9-13; Hamburg, Germany; fems2023.org

Analytica China. Jul 11-13; Shanghai, China; analyticachina.com

2023 AACC Annual Scientific Meeting & Clinical Lab Expo. Jul 23-27; Anaheim, CA, USA; meeting.aacc.org

AUGUST

MedLab Asia 2023. Aug 16-18; Bangkok, Thailand; medlabasia.com

SEPTEMBER

Thailand LAB International 2023. Sep 6-8; Bangkok, Thailand; thailandlab.com

ECP 2023 – 35th Congress of the European Society of Pathology. Sep 9-13; Dublin, Ireland; esp-congress.org

EUROTOX 2023 – 57th Congress of the European Societies of Toxicology. Sep 10-13; Ljubljana, Slovenia; eurotox2023.com

ACBICON 2023 – 48th Annual Conference of Association of Clinical Biochemists of India. Sep 13-16; Thiruvananthapuram, India; acbindia.org.in

India Lab Expo & Analytica Anacon India. Sep 14-16; Hyderabad, India; analyticaindia.com

Arab Lab 2023. Sep 19-21; Dubai, UAE; arablab.com

Analitica Latin America 2023. Sep 26-28; Sao Paulo, Brazil; analiticanet.com.br

BCLF 2023 – 30th Meeting of the Balkan Clinical Laboratory Federation. Sep 27-30; Herceg

Novi, Montenegro; bclf2023.org

OCTOBER

ECC 2023 – 44th European Congress of Cytology. Oct 1-4; Budapest, Hungary; cytology2023.eu

CAP23 – Annual Meeting of the College of American Pathologists. Oct 7-10; Chicago, IL, USA; cap.org

DKLM 2023 – Annual Congress of the German Society for Clinical Medicine and Laboratory Medicine (DGKL). Oct 10-12; Mannheim, Ger many; dgkl.de

JFBM 2023 – Journées Francophones de Biolo gie Médicale. Oct 11-13; France; jfbm.fr

CELME 2023 5th Symposium: Cutting Edge of Laboratory Medicine in Europe. Oct 12-13; Prague, Czech Republic; celme2023.cz

60th Annual Scientific Conference of the Aus tralasian Association of Clinical Biochem istry and Laboratory Medicine (AACB). 16-19; Brisbane, Australia; aacb.asn.au

ASHI 2023 – 49th Annual Meeting of the American Society for Histocompatibility and Immunogenetics. Oct 16-20; San An tonio, TX, USA; ashi-hla.org

MedLab Africa 2023. Oct 17-19; Johannes burg, South Africa; africahealthexhibition.com

ASCP 2023 – Annual Meeting of the Amer ican Society for Clinical Pathology. Oct 1820; Long Beach, CA, USA; ascp.org

LABCLIN 2023 – 17th National Congress of the Spanish Societies for Clinical Labo ratory (AEBM-ML, AEFA & SEQCML).

18-20; Zaragoza, Spain; seqc.es

EndoBridge 2023. Oct 19-22; Antalya, Tur key; endobridge.org

63rd Annual Academic Assembly of the Japan Society of Clinical Chemistry (JSCC). Oct 27-29; Toyama, Japan; jscc-jp.gr.jp

34th National Congress of the Turkish Bio chemical Society. Oct 29 - Nov 1; Fethiye, Turkey; turkbiyokimyadernegi.org.tr

NOVEMBER

ASHG 2023 – Annual Meeting of the American Society of Human Genetics. 1-5; Washington, DC, USA; ashg.org

44th Annual Meeting of the American College of Toxicology (ACT). Nov 12-15; Orlando, FL, USA; actox.org

MEDICA 2023. Nov 13-16; Dusseldorf, Ger many; medica-tradefair.com

AMP 2023 – Annual Meeting & Expo of the Association for Molecular Pathology. Nov 16-18; Salt Lake City, UT, USA; amp.org

71st Annual Scientific Meeting of the American Society of Cytopathology (ASC). Nov 16-19; Austin, TX, USA; cytopathology.org

JIB 2023 – Journées de l’innovation en biologie. Nov 17-18; Paris, France; jib-innovation.com

34th Regional Congress of the International Society of Blood Transfusion (ISBT). Nov 1821; Cape Town, South Africa; isbtweb.org

IUIS 2023 – International Union of Immunological Societies. Nov 27 - Dec 2; Cape Town, South Africa; iuis2023.org

DECEMBER

ASI 2023 – 51st Annual Scientific Meeting of the Australian and New Zealand Society for Immunology. Dec 4-8; Auckland, New Zealand; asi2023.org

UAE; medlabme.com

Labquality Days 2024 – International Congress on Quality in Laboratory Medicine. Feb 8-9; Helsinki, Finland; labqualitydays.fi

MARCH

ICE 2024 – 21st International Congress of Endocrinology. Mar 1-3; Dubai, UAE; isendo.org

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