LabMedica International May 2021 by Globetech

V I S I T

WORLD’S CLINICAL LABORATORY NEWS LEADER ISSN 1068-1760

Vol. 38 No.3 • 5/2021

RNA-Sequencing Predicts Immunotherapy Success

rothelial carcinoma, also known as transitional cell carcinoma (TCC), is by far the most common type of bladder cancer. Urothelial cells also line other parts of the urinary tract, such as the part of the kidney that connects to the ureter (called the

DAILY CLINICAL LAB NEWS

New Methods Advance Cervical Cancer Screening

ervical cancer, which is almost always caused by human papillomavirus (HPV), is the world’s fourth-most common cancer, with more than 500,000 cases diagnosed annually. The Papanicolaou (Pap) test, introduced in the 1940s by George

Cont’d on page 11

Papanicolaou, helps pathologists examine the morphology of exfoliated cervical cells. About 80% of cervical cancer can be prevented by well-organized, high-quality screening programs using Pap smears with three- to four-year screening intervals. Cont’d on page 12

port-related concussion is defined as a traumatic brain injury induced by biomechanical forces that typically results in the rapid onset of short-lived impairment of neurological function that resolves spontaneously. A high percentage of cases may go misdiagnosed or unidentified. The development and validation of objective diagnostic tools for concussion, both within traditional

R E A D E R

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Genome Sequencing Identifies Myeloma Precursor and Progression Risk

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pecific targeting of the BcrAbl1 enzyme by tyrosine kinase inhibitors (TKI) revolutionized the management of chronic myeloid leukemia (CML) to the point that TKIs can offer near normal life expectancy for CML patients. However, some CML patients do not achieve optimal response at defined treatment time points, and others even develop TKI

See article on page 4 I

Salivary Markers Detect Sports Concussions

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onitoring the extent of anti-SARSCoV-2 T cell activity in recovered or vaccinated populations will determine if and when booster vaccinations will be required.

Digital PCR Detects Chronic Myloid Lukemia

T-Cell Lymphocytes Can Seek and Destroy SARS-Cov-2 Variants

ultiple myeloma (MM) is the second most common hematological malignancy and is consistently preceded by the asymptomatic expansion of clonal plasma cells, termed either monoclonal gammopathy of undetermined significance (MGUS) Cont’d on page 14

Swamped by Surge in Testing Demand, Mid-Sized Labs Turn to Automation Solutions

he clinical laboratory has gone through trial by fire in 2020, where total testing was 245% of baseline volumes, with around 55% being SARS-CoV-2 molecular tests. Despite vaccines, many industry players suggest SARS-CoV-2 testing volumes would not be impacted in the near term, and the

demand for COVID-19-related testing will continue through 2021 and potentially into 2022. This means that testing-volume pressure on labs is going to continue. Labs of all sizes are facing the same challenges: Shortage of laboratory technologists and technicians, historic financial pressures Cont’d on page 33

INSIDE

COVID-19 Update. . . . . 5 Clinical News. . . . . . 4-26 IFCC News. . . . . . . . . . 25 Product News . . . . . 6-28 Industry News . . . . . . . 29 Events Calendar . . 30-31

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LabMedica International

T-Cell Lymphocytes Can Seek and Destroy SARS-Cov-2 Variants

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EDITORIAL BOARD

Graham Beastall United Kingdom Claus Christiansen Denmark Hernán Fares Taie Argentina Bernard Gouget France Maurizio Ferrari Italy Jocelyn M. Hicks United States Anders Kallner Sweden Tahir S. Pillay South Africa Andreas Rothstein Colombia Dmitry B. Saprygin Russia Praveen Sharma India Rosa I. Sierra-Amor Mexico Peter Wilding United States Andrew Wootton United Kingdom A GLOBETECH PUBLICATION

Published in cooperation with the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). LabMedica International • LabMedica en Español • LabMedica.com HospiMedica International • HospiMedica.com • MedImaging.net TradeMed.com • LabMedicaExpo.com • LinkXpress.com

Image: Immune T cells lymphocytes can seek and destroy a cell (green) infected with and making copies of SARS-CoV-2 (yellow) (Photo courtesy of US National Institute of Allergy and Infectious Diseases)

ue to the proofreading ability of the coronavirus (CoV) RNA-dependent RNA polymerase, the evolution of the global SARS-CoV-2 viral population during the current pandemic has been relatively constrained as compared to other endemic RNA viruses that do not possess this ability. During late 2020, three distinct variants that each possessed a significantly increased amount of amino acid polymorphisms were identified in association with spikes in cases of COVID-19 in the United Kingdom (variant B.1.1.7), South Africa (variant B.1.351), and Brazil (variant B.1.1.248). These variants all possess the N501Y mutation in the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, a primary target for neutralizing antibody (NAb) binding. A collaborating team of scientists led by the Johns Hopkins University School of Medicine (Baltimore, MD, USA) analyzed blood cell samples from 30 people who had contracted and recovered from coronavirus disease 2019 (COVID-19) prior to the emergence of virus variants. Most (60%) individuals included in the analysis were male and samples were collected a median of 42.5 days (interquartile range, 37.5-48 days) from initial diagnosis. The team aimed to determine whether CD8+ T cells in the blood could still recognize the three main SARS-CoV-2 variants. Peripheral blood mononuclear cell (PBMC) samples from the patients were collected and examined across six different human leukocyte antigen (HLA) haplotypes (HLAA*01:01, HLA-A*02:01, HLA-A03:01, HLA-A*11:01, HLA-A*24:02 and HLA-B*07:02). A multiplexed peptide-MHC tetramer staining approach permitted the screening of 408 potential SARS-CoV-2 candidate epitopes for CD8+ T cell recognition. T cells were

also evaluated using a 28-marker phenotypic panel (Immunoscape Pte. Ltd, Singapore). A total of 52 unique epitope responses were found and were directed against several structural and non-structural viral proteins. For controls, CD8+ T cells were probed for reactivity for up to 20 different SARSCoV-2-unrelated control peptides per HLA (Adenovirus-, CMV-, EBV-, Influenza-, and MART-1-derived epitopes). The team reported that only one mutation found in the B.1.351-Spike overlapped with a previously identified epitope (1/52), suggesting that virtually all anti-SARS-CoV-2 CD8+ T-cell responses should recognize these newly described variants. This mutation is the D80A mutation in the Spike protein, and occurs in the third residue of the RFDN VLPF epitope. This is a HLA*A24:02restricted epitope for which a CD8+ T cell response was detected in 1/5 HLA*A24:02+ individuals, and at a low frequency (0.005 of total CD8+ T-cells), indicating this is not a high-prevalence epitope. The authors concluded that their data highlighted the potential significant role of a multi-epitope T cell response in limiting viral escape, and partly mediate protection from disease caused by the SARS-CoV-2 variants. It is important that vaccines used for widespread campaigns generate strong multivalent T-cell responses in addition to neutralizing antibody (Nab) and other humoral responses in order to optimize efficacy against the current SARS-CoV-2 and emerging strains. It will be important to continue to monitor the breadth, magnitude, and durability of the anti-SARS-CoV-2 T cell responses in recovered and vaccinated individuals as part of any assessment to determine if booster vaccinations are needed. The study was published on March 30, 2021 in the journal Open Forum Infectious Diseases.

Dan Gueron Raymond L Jacobson, PhD Gerald M Slutzky, PhD Andreas Rothstein Sanjit Dutt Carolyn Moody Andrea Kropp Dr. Jutta Ciolek Parker Xu David Gueron Stan Caines

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ISSN 1068-1760

Vol.38 No.3. Published, under license, by Globetech Media LLC; Copyright © 2020. All rights reserved. Reproduction in any form is forbidden without express permission. Opinions expressed are solely those of the authors, and do not represent an endorsement, or lack thereof, by the Publisher of any products or services. Teknopress Yayıncılık ve Ticaret Ltd. Şti. adına İmtiyaz Sahibi: M. Geren • Yazı işleri Müdürü: Ersin Köklü Müşir Derviş İbrahim Sok. 5/4, Esentepe, 34394 Şişli, İstanbul P. K. 1, AVPIM, 34001 İstanbul • E-mail: Teknopress@yahoo.com Baskı: Postkom A.Ş. • İpkas Sanayi Sitesi 3. Etap C Blok • 34490 Başakşehir • İstanbul Yerel süreli yayındır. Yılda sekiz kere yayınlanır, ücretsiz dağıtılır.

LabMedica International May/2021

COVID -19 Diagnostics Update

he report that follows provides a selection of news and advances announced from March 15 to April 30, 2021. For a recap of earlier developments, the reader is invited to refer to previous issues of LabMedica or visit our website at www. LabMedica.com. Non-Invasive Skin Swab Samples Enough to Quickly Detect COVID-19, Finds New Study Non-invasive skin swab samples are enough to quickly detect COVID-19, according to findings of a new study by researchers at the University of Surrey (Guildford, Surrey, UK; www.surrey.ac.uk). The team collected sebum samples from 67 hospitalized patients - 30 who had tested positive for COVID-19 and 37 who had tested negative and found that patients with a positive COVID-19 test had lower lipid levels - or dyslipidemia - than their counterparts with a negative test.

tation chemistry to detect SARS-CoV-2 antibodies in a drop of blood in less than an hour. The pinprick test that accurately measures the concentration of coronavirus antibodies in blood in under one hour costs about a tenth of the current tests based on ELISA (enzyme-linked immunosorbent assay)-based methods which are considered the gold standard when it comes to measuring antibody concentration as a strength of individual immune response. Highly Accurate Prognostic Test Predicts Personalized Risk of Severe Illness Due To SARS-CoV-2 Virus Oxford BioDynamics Plc (Oxford, England; www.oxfordbiodynamics.com) has launched its EpiSwitch COVID-19 Severity Test (CST), based on the company’s EpiSwitch 3D genomics platform. Requiring only a routine blood draw, this important prognostic test is

able to identify high-risk individuals who, if exposed to the SARS-CoV-2 virus, are likely to experience the most severe COVID-19 complications and will potentially require hospitalization and intensive care unit (ICU) support. First Hybridization Capture-Based Next-Generation Sequencing SARSCoV-2 Assay Receives FDA EUA Twist Bioscience Corporation (San Francisco, CA, USA; www.twistbioscience.com) and Biotia, Inc. (New York, NY, USA; www. biotia.io) have received Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA) for the SARSCoV-2 Next-Generation Sequencing (NGS) Assay. The SARS-CoV-2 NGS Assay, an in vitro diagnostic test, has become the first hybridization capture-based NGS SARS Cont’d on page 6

Roche Launches New SARSCoV-2 Variant Test to Monitor Emerging Coronavirus Mutations Roche (Basel, Switzerland; www. roche.com) has launched the cobas SARS-CoV-2 Variant Set 1 Test to detect and differentiate mutations found in variants that originated in the UK (B.1.1.7), South Africa (B.1.351), and Brazil (P.1). The cobas SARS-CoV-2 Variant Set 1 Nucleic Acid test for use with the cobas 6800/8800 Systems is an automated, multiplex, real-time reverse transcription polymerase chain reaction (RT-PCR) assay for the rapid in vitro qualitative detection and discrimination of select SARS-CoV-2 mutations E484K, N501Y and del 6970. The test contains the respective primers and probes provided in the ready-made 384-test cassette. Direct, Cost-Effective COVID-19 Tests Identify UK/South African SARS-CoV-2 Variant and Reduces Test Time from Days to Hours Scientists at the Ben-Gurion University of the Negev (Be’er Sheva, Israel; www.bgu.ac.il) have developed direct rapid cost-effective COVID-19 tests that successfully identify the UK or South African variant of the SARSCoV-2 virus. The tests reduce the time needed to determine whether an infection is caused by a variant from days to hours. Low Cost Pinprick COVID-19 Test Detects SARS-CoV-2 Antibodies in Drop of Blood in Under an Hour A new COVID-19 serology test developed by researchers at the University of Toronto (Toronto, ON, Canada; www.utoronto.ca) uses highly sensitive protein complemen-

LabMedica International May/2021

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HANDHELD PREGNANCY TEST

HEMOSTASIS SYSTEM

COAGULATION ANALYZER

The i-STAT Total β-hCG is a handheld point of care pregnancy test using whole blood to provide lab-quality, quantitative and qualitative results, which can be documented automatically with the i-STAT 1 Wireless System.

The ACL Elite Pro hemostasis system offers random-access processing for minimized turnaround time with STAT PT and aPTT available in eight minutes. It is ideal for lower-volume hemostasis labs.

The ARES coagulation analyzer offers four test channels with a normal test time of 20-60 seconds and a maximum test time of 600 seconds. It offers 24 sample positions and can store up to 10,000 test results.

ABBOTT DIAGNOSTICS

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INSTRUMENTATION LAB

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COVID -19 Diagnostics Update Cont’d from page 5

CoV-2 assay to be granted FDA EUA. New Mass Spectrometry-Based Technique Enables Ultrafast Identification of COVID-19 Biomarkers Researchers from Charité – Universitätsmedizin Berlin (Berlin, Germany; www.charite.de) and the Francis Crick Institute (London, UK; www.crick.ac.uk) have developed a mass spectrometry-based technique that is capable of measuring samples containing thousands of proteins within just a few minutes and enables ultrafast identification of COVID-19 biomarkers. The researchers also demonstrated the technique’s potential by using blood plasma collected from COVID-19 patients. Using the new technology, they identified 11 previously unknown proteins which are markers of disease severity. Novel 15-Minute Microfluidic DLD Assay Could Assess Severity of Immune Response to COVID-19 Infection Researchers at Singapore-MIT Alliance for Research and Technology (SMART; Singapore; www.smart.mit.edu) have developed a novel deterministic lateral displacement (DLD) assay that is capable of rapidly assessing host inflammatory response, allowing patients, such as those with COVID-19 infection, exhibiting life-threatening hyper-aggressive immune response to be identified and treated expeditiously, potentially making the difference between life or death. The new label-free immune profiling assay that profiles the rapidly changing host immune response in case of infection, is a departure from existing methods that focus on detecting the pathogens themselves, which can often be at low levels within a host. This novel technology presents a host of advantages over current methods, being both much faster, more sensitive and accurate. New COVID-19 Diagnostic Test Detects SARS-COV-2 Virus Even When It Mutates A team of scientists led by Nanyang Technological University (Singapore; www.ntu.edu.sg) has developed a COVID-19 diagnostic test that can detect the SARS-COV-2 virus even after it has gone through mutations. The test called the VaNGuard (Variant Nucleotide Guard) test makes use of a gene-editing tool known as CRISPR, which is used widely in scientific research to alter DNA sequences and modify gene function in human cells under lab conditions, and more recently, in diagnostic applications.

LINEAR CHEMICALS

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New Portable Test Detects SARS-CoV-2 Antibodies in People Who Have Tested Positive for COVID-19 A new easy-to-produce test developed by an international research team led by scientists at the University of Oxford (Oxford, UK; www. ox.ac.uk) quickly detects coronavirus spike-protein binding antibodies in people who have tested positive for COVID-19. The portable test spots the presence of virus-fighting antibodies rather than a coronavirus infection, can be adapted to work on blood from a finger prick - making it quick and easy to use. The research team trialed the test on patients with COVID-19, but now hope to adapt it to identify those who have successfully generated antibodies after a vaccine, versus those who may need a booster. AI Software-Powered Device That Enables Ground-Breaking 20-Second COVID-19 Diagnosis Secures CE Mark Approval Newsight Imaging Ltd. (Ness Ziona, Israel; www.nstimg.com) has received CE marking for its SpectraLIT device that enables a ground-breaking 20-second COVID-19 diagnosis and is powered by Virusight Diagnostic Ltd.’s (Ramat Gan, Israel; www.virusight.co.il) AI software. The SpectraLIT device is a miniature spectrometer with advanced capabilities, operated by AI classification algorithms and developed by Virusight, Newsight’s joint venture with Sheba Medical Center’s ARC Innovation Center (Tel HaShomer, Israel; www.sheb aonline.org). The testing procedure is easy to operate, with immediate results for symptomatic and asymptomatic patients. The AI software was successfully clinically tested by a US medical institute. New Technology Halves Time Currently Taken To Identify If Positive COVID-19 Sample Contains Variant of Concern A groundbreaking new technology to rapidly detect new COVID mutations indicating whether positive test samples contain known variants is being trialed by the UK government in NHS Test and Trace (England; www.nhs.uk) laboratories. The technology – known as ‘genotype assay testing’ – is set to halve the time it currently takes to identify if a positive COVID-19 sample contains a variant of concern, and could be used in addition to standard testing for COVID-19 to identify cases quickly. Fast, Portable Test Can Diagnose COVID-19 and Track Variants Clinicians using a new viral screening test developed by researchers at The Salk Institute for Biological Studies (La Jolla, CA, USA: www.salk. edu) can not only diagnose COVID-19 in a matter of minutes with a portable, pocket-sized machine, but can also simultaneously test for other viruses – like influenza – that might be mistaken for the coronavirus. The Cont’d on page 8 LabMedica International May/2021

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CTFR GENOTYPING ASSAY

REAL-TIME PCR INSTRUMENT

ADAMTS13 ACTIVITY ASSAY

The CE marked INNO-LiPA® CFTR Extra is a line probe assay, intended for the simultaneous in vitro detection and identification of 18 human Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene mutations.

The m2000 RealTime System is a polymerase chain reaction (PCR) platform that allows laboratories to simplify the complex process of molecular diagnostics while minimizing contamination.

The HemosIL ACUSTAR ADAMTS13 Activity Assay is the only automated, on-demand test to aid in the diagnosis and monitoring of Thrombotic Thrombocytopenic Purpura (TTP), with first results produced in approximately 30 minutes.

FUJIREBIO

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COVID -19 Diagnostics Update Cont’d from page 6

new test, dubbed NIRVANA, can also sequence the SARS-CoV-2 virus, providing valuable information on the spread of COVID-19 mutations and variants. SARS-CoV-2 Test Uses Innovative Digital Microfluidics Technology for Accurate RT-PCR Testing with Rapid Turn-Around Time A new RT-PCR test from Baebies (Durham, NC, USA; www.baebies. com) uses innovative digital microfluidics (DMF) technology for the qualitative detection of RNA from the SARS-CoV-2 virus in nasopharyngeal and nasal swab specimens within 17 minutes. Baebies has received acknowledgement from the US Food & Drug Administration (FDA) for the company’s Emergency Use Notification (EUN) for an RT-PCR test to detect SARS-CoV-2 on its FINDER 1.5 Instrument. Handheld Device Combines Nanomaterial-Based Sensors with Neuromorphic Processor Chip to Detect SARS-CoV-2 Antibody in Seconds Brainchip Research Institute (Perth, Australia; www.brainchipinc. com) has entered into a research collaboration with Biotome Pty Ltd. (Perth, Australia; www.biotome.com.au) to develop a handheld device that uses nanomaterial-based sensors in combination with a neuromorphic processor chip will give accurate results for SARS-CoV-2 antibody detection in seconds. First COVID-19 Antibody Test Receives FDA EUA for Use with Home Collected Dried Blood Spot Samples The US Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) to Symbiotica, Inc. (Vacaville, CA, USA; www.symbioticainc.com) for its COVID-19 Self-Collected Antibody Test System, making it the first antibody test for use with home collected dried blood spot samples. Symbiotica’s COVID-19 Self-Collected Antibody Test System has been authorized for prescription use with a fingerstick dried blood sample that is self-collected by an individual age 18 years or older or collected by an adult from an individual five years of age and older. Samples collected at home are then sent to a Symbiotica laboratory for analysis. New All-In-One COVID-19 Test Kit Identifies 99.9% of All Known SARS-CoV-2 Strains A COVID-19 molecular test kit from Lucira Health, Inc. can successfully identify the “double mutant” variant of the SARS-CoV-2 virus.

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The Lucira single-use COVID-19 All-In-One Test Kit has been found to be reactive to at least 99.9% of all known SARS-CoV-2 strains. The LUCIRA COVID-19 All-In-One Test Kit Test Kit fits in the palm of a hand, extracts genetic material from the virus and amplifies it similar to PCR lab tests. Diagnostic Microchip Inserted Under Skin Can Detect COVID-19 An implantable microchip developed by medical researchers at the US Pentagon’s Defense Advanced Research Projects Agency (DARPA; Arlington, VA, USA; www.darpa.mil) can detect COVID-19 when inserted under the skin. The microchip, embedded in a tissue-like gel, would continuously test the chip recipient’s blood for presence of the coronavirus. Upon detecting COVID-19, the chip would alert the patient to conduct a self-administered rapid blood test to confirm the positive result. Nanoparticle Technology Based Digital Reader Supports High-Sensitivity, High-Specificity Rapid COVID-19 Testing A new 15-minute COVID-19 antigen rapid test (ART) for a nanoparticle technology-based rapid test platform from AnteoTech Ltd. (Queensland, Australia; www.anteotech.com) has received the Conformitè Europëenne (CE) Mark registration. The company has received the (CE) Mark registration for its EuGeni Reader and in vitro rapid diagnostic test for the detection of SARS-CoV-2 nucleocapsid antigen, the COVID-19 ART. AnteoTech’s SARS-CoV-2 Ag rapid test is the first test to be used with EuGeni, a fast, accurate and compact solution for rapid point-of-care testing. First-Ever Single-Use, PCR Quality OTC COVID-19 At-Home Test Granted FDA EUA The US Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) to Lucira Health, Inc. (Emeryville, CA, USA; www.lucirahealth.com) for the first-ever single use, over the counter (OTC) sale of a COVID-19 test kit that delivers PCR quality molecular accuracy in 30 minutes or less at home. Lucira has received EUA from the FDA for its LUCIRA CHECK IT test kit that is now authorized and available for individuals with or without COVID-19 symptoms. This primarily US designed and manufactured product is the first FDA authorized, prescription, molecular diagnostic test for COVID-19 that can be self-administered by patients at home or used in a physician’s office. Portable COVID-19 Test Instrument Uses Bulk Acoustic Wave Technology to Achieve SARS-CoV-2 Antigen Testing in 20 Minutes A new COVID-19 test platform from Qorvo Biotechnologies, LLC (Greensboro, NC, USA; www.qorvobiotech.com) represents a paradigm Cont’d on page 9 LabMedica International May/2021

COVID -19 Diagnostics Update Cont’d from page 8

shift in diagnostic testing capability by using high frequency Bulk Acoustic Wave (BAW) sensors to achieve SARS-CoV-2 antigen testing in approximately 20 minutes. Qorvo has been granted emergency use authorization (EUA) by the U.S. Food and Drug Administration (FDA) for its Qorvo Omnia SARS-CoV-2 Antigen Test. The Qorvo Omnia platform features a portable test instrument, microfluidic cartridge and secure connectivity. The microfluidic cartridge design enables specific binding with additional wash steps similar to central lab instrument operation and demonstrated results including 100% specificity during clinical trials. COVID-19 Antibody Test Results May Vary Based on Gender, New Study Suggests A study by researchers at Cardiff Metropolitan University (Cardiff, UK; www. cardiffmet.ac.uk) suggests that clinical laboratories should anticipate gender-dependent differences in COVID-19 antibody levels as the findings showed these levels are significantly higher in males and that antibodies may last for four times longer in males. The study found that males are four times more likely to retain antibodies for longer than females, making it important for clinical laboratories to recognize that COVID-19 test results may vary based on gender.

merase chain reactions (qPCR). COVID-19 Testing May Be Here to Stay, Suggests Study of ‘Breakthrough’ Cases A study by scientists at The Rockefeller University (New York, NY, USA: www.rocke feller.edu) of rare cases in which people who have been fully vaccinated against COVID and are immune to the virus can nevertheless develop the disease suggests that COVID testing may be here to stay. The new findings suggest that these so-called breakthrough cases may be driven by rapid evolution of the virus, and that ongoing testing of immunized individuals will be important to help mitigate future outbreaks. New Analytical Technique that Detects Presence of Viruses in 20 Seconds Promises to Speed up COVID-19 Testing A new concept developed by scientists at Lancaster University (Lancaster, UK; www.

lancaster.ac.uk) for rapidly analyzing for the presence of a virus from colds to coronaviruses has the potential to speed up COVID-19 testing as well as enhance the ability to test a large number of samples quickly. The methodology that is based on analyzing chemical elements has been adapted from an analytical technique used to identify metallic nanoparticles and is able to detect the presence of viruses within just 20 seconds. New CRISPR Discovery Paves Way for Novel COVID-19 Testing Method A novel diagnostic technology developed by scientists from the Julius Maximilian University of Würzburg (Würzburg, Germany; www.uni-wuerzburg.de) that has the potential to detect a variety of disease-related biomarkers in just one test can make tests for corona and other pathogens much more efficient. Cont’d on page 10

COVID-19 Tests Accuracy May Vary by Time of Day, Finds New Study The accuracy of gold-standard COVID-19 PCR tests of nasopharyngeal swab samples may vary by time of day, according to a new study by researchers at Vanderbilt University (Nashville, TN, USA; www.vanderbilt. edu). The researchers analyzed 31,094 tests performed in symptomatic and asymptomatic individuals at 127 testing sites, including 2,438 tests that showed COVID-19. They found that the report tests were most likely to be positive around 2 p.m. - and the proportion of positive tests in the early afternoon was two-fold higher than the lowest proportion seen at other times of the day. New Molecular Clamping Technology Rapidly Detects Raging New SARS-CoV-2 Variants A new study has demonstrated enhanced sensitivity and specificity using DiaCarta Inc.’s (Richmond, CA, USA; www.diacarta.com) proprietary XNA-based molecular clamping technology that uses innovative synthetic Xenonucleic acid molecular oligomers (XNA) which hybridize with target wild-type DNA sequences, acting as molecular clamps, to enable the accurate amplification of mutant sequences only, using quantitative real-time poly-

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POC ANALYZER

NUCLEIC ACID EXTRACTOR

MOLECULAR ANALYZER

The Epithod 616 is a semi-automatic analyzer for point-of-care testing to measure HbA1c, Glycated Albumin, CRP, Hemoglobin and μAlbumin.

The Singu20 Nucleic Acid Extractor uses the magnetic bead method to extract nucleic acid, taking 9-18 minutes from loading sample to completing the extraction. The device is disinfected by ultraviolet lamp to avoid pollution.

Revogene is a flexible molecular platform capable of single analyte and multiplex testing that is packaged in a small footprint and can help standardize testing throughout the health system.

DXGEN

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SINGUWAY BIOTECH

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COVID -19 Diagnostics Update Cont’d from page 9

The discoveries have paved the way for a completely new diagnostic platform with LEOPARD - a CRISPR-based method that is highly multiplexable, with the potential to detect a variety of disease-related biomarkers in just one test. 20-Minute COVID-19 Test Pairs Mass Spectrometer with Machine Learning to Detect SARS-CoV-2 in Nasal Swabs A novel COVID-19 test developed by researchers at UC Davis Health (Sacramento, CA, USA: www.health.ucdavis.edu) uses an analytical instrument known as a mass spectrometer, which is paired with a powerful machine-learning platform to detect SARS-CoV-2 in nasal swabs. The novel method has shown to be 98.3% accurate for positive COVID-19

tests and 96% for negative tests. The accuracy matches or outperforms many of the current COVID-19 screening tests. The new testing method may allow for the rapid screening of large numbers of individuals for businesses, schools, venues and other large facilities. Two-Step Prognostic Test Can Predict Severe COVID-19 Cases Even Before Serious Symptoms Appear Researchers at University of California (UCI; Irvine, CA, USA: www.uci.edu) have developed a two-step prognostic test that can help predict a COVID-19 patient’s response to SARS-CoV-2 infection. The test combines a disease risk factor score with a test for antibodies produced early in the infection. It could be administered at the time of diagnosis to help

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guide therapeutic choices before the most severe symptoms appear. Novel Capsule-Based Smell Test Could Help Diagnose COVID-19 in Broader Population A new smell test developed by researchers at Queen Mary University of London (London, UK; www.qmul.ac.uk) has been found to be easy to use in patients with Parkinson’s disease, and could also be helpful in diagnosing COVID-19 in the broader population. The novel smell testing kit uses capsules of aromatic oils placed between two strips of single-sided tape. To take the smell test, the capsules are simply crushed between the fingers and the tape strip peeled to release the aroma contained within the capsules. Based on a person’s ability to recognize these smells, a score would be generated that can be sent to their GP if they are experiencing a loss of smell.

Leukocyte Epigenomics and Artificial Intelligence Predict Late-Onset Alzheimer’s

lzheimer’s Disease (AD) is the most common form of age-related dementia, accounting for 60%–80% of such cases. The disorder causes a wide range of significant mental and physical disabilities, with profound behavioral changes and progressive impairment of social skills. AD is a complex disorder influenced by environmental and genetic factors. Genome-wide association studies (GWAS) have identified several late-onset AD (LOAD)-associated risk loci proliferation in peripheral blood leukocytes including in T-lymphocytes, B-lymphocytes, polymorphonuclear leucocytes, monocytes, and macrophages have been reported. A team of Medical Scientists mainly from the Oakland University-William Beaumont School of Medicine (Royal Oak, MI, USA; https://oakland.edu) evaluated the utility of leucocyte epigenomic-biomarkers for

Alzheimer’s Disease (AD) detection and elucidated its molecular pathogeneses. The team studied blood samples from two dozen Alzheimer’s disease patients and the same number of cognitively health controls. Approximately 500 ng of genomic DNA was extracted from each of the 48 samples, which subsequently were bisulfite converted using the EZ DNA Methylation-Direct Kit (Zymo Research, Orange, CA, USA; www.zymoresearch.com). They performed genome-wide DNA methylation analysis of the blood samples using Infinium MethylationEPIC BeadChip array (Illumina, San Diego, CA, USA; www. illumina.com). Artificial Intelligence (AI) analysis was performed using a combination of CpG sites from different genes. They also used six artificial intelligences approaches to analyze their dataset, including support vector machine, random forest, and deep learning.

Image: The EZ DNA Methylation-Direct Kit (Photo courtesy of Zymo Research)

Deep learning is a branch of machine learning that aims to mimic the neural networks of animal brains. The team reported that each of the AI approaches could predict Alzheimer’s disease with high accuracy, yielding areas under the Cont’d on page 11 LabMedica International May/2021

COVID -19 Diagnostics Update

RNA-Sequencing Predicts Immunotherapy Success

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renal pelvis), the ureters, and the urethra. The standard treatment for metastatic urothelial cancer of the bladder has been platinum-based chemotherapy, though the landscape has changed dramatically in recent years with the advent of PD-1 and PD-L1 immune checkpoint inhibitors, but only 20% to 25% of patients with bladder cancer respond to treatment. A multidisciplinary team of medical scientists led by Icahn School of Medicine at Mount Sinai, New York, NY, USA; www.mountsinai. org) uncovered gene signatures representing adaptive immunity and pro-tumorigenic inflammation that were responsible for sensitivity or resistance to immune checkpoint inhibitors, drugs that help the body’s immune system recognize and attack cancerous cells. The team used both bulk and single-cell RNA sequencing of human bladder tumors to study resistance to immunotherapy. Bulk sequencing examines the mix of genes expressed by every individual cell within a tumor, while single-cell sequencing zeroes in on gene expression by each individual cell, which yields unprecedented knowledge of the complexity and heterogeneity of cells that comprise tumors. The scientists reported that the adaptive immune response:protumorigenic inflammation signature expression ratio, coined the 2IR score, best correlated with clinical outcomes, and was externally validated. Mapping these bulk gene signatures onto scRNA-seq data uncovered their underlying cellular diversity, with prominent expression of the protumorigenic inflammation signature by myeloid phagocytic cells. However, heterogeneity in expression of adaptive immune and protumorigenic inflammation genes was observed among single myeloid phagocytic cells, quantified as the myeloid single cell immune:protumorigenic inflammation ratio (Msc2IR) score. Single myeloid phagocytic cells with low Msc2IR scores demonstrated upregulation of proinflammatory cytokines/chemokines and downregulation of antigen presentation genes, were unrelated to M1 versus M2 polarization, and were enriched in pretreatment blood samples from patients with PD-L1 blockade–resistant metastatic urothelial cancer. Matthew D. Galsky, MD, a Professor of Medicine and senior author of the study, said, “If the tumor microenvironment is weighted more toward adaptive immunity, there’s a better chance of positive outcomes from immunotherapy. On the other hand, if the tumor microenvironment is leaning toward pro-tumorigenic inflammation, then PD-1/ PD-L1 checkpoint inhibitors alone are unlikely to be successful, and new combination approaches may be needed.”

The authors concluded that the balance of adaptive immunity and protumorigenic inflammation in individual tumor microenvironments is associated with PD-1/PD-L1 resistance in urothelial cancer with the latter linked to a proinflammatory cellular state of myeloid phagocytic cells detectable in tumor and blood. The study was published on April 9, 2021 in the journal Clinical Cancer Research. Image: Histopathology from a transurethral biopsy of urothelial carcinoma of the urinary bladder (Photo courtesy of KGH)

Leukocyte Epigenomics and Artificial Intelligence Predict Late-Onset Alzheimer’s

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curve (AUC) of at least 0.93. Deep learning further improved upon that with an AUC of 0.99 and a sensitivity and specificity of 97% using intragenic markers. Similar results could be reached with intergenic markers, as well. The group noted that the addition of conventional clinical predictors or mental state analyses did not further improve performance. The analysis highlighted a number of genes and pathways known to be disrupted in Alzheimer’s disease. Epigenetically altered genes included, for instance, CR1L and CTSV, which are involved in the morphology of the cerebral cortex, as well as S1PR1 and LTB4R, which are involved in inflammatory response. Ray O. Bahado-Singh, MD, a Professor of Obstetrics and Gynecology and lead author of the study, said, “We found that the genetic analysis accurately predicted the absence or presence of Alzheimer’s, allowing us to read what is going on in the brain through the blood. The results also gave us a readout of the abnormalities that are causing Alzheimer’s disease. This has future promise for developing targeted treatment to interrupt the disease process.” The study was published on March 31, 2021 in the journal PLOS ONE.

LabMedica International May/2021

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The Allplex SARS-CoV-2 Variants I Assay is intended for the detection and differentiation of three mutation sites in S gene for the identification of SARS-CoV-2 variants.

HUMASIS

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New Methods Advance Cervical Cancer Screening

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However, this approach has yet to similarly impact developing countries. Of the approximately 311,000 annual deaths from cervical cancer, more than 85% of these occur in low- and middle-income countries (LMICs). An effective cytology-based screening program necessitates high-quality cytology laboratories, properly trained personnel, and repeated screening at regular intervals due to the low sensitivity of a single Pap test; such ingredients are still not achievable across many LMICs. In this regard, new point-of-care (POC) technologies have been developed to provide test results in real time, improve the efficiency of techniques, and increase screening for cervical cancer. A recent review article prepared by investigators at Massachusetts General Hospital (Boston, USA; www.massgeneral.org) examined and discussed some of the latest innovations. The review highlighted how emerging advances in nanotechnologies and machine learning could (1) complement or supplant existing methods of cervical cancer screening and (2) directly circumvent existing screening obstacles in LMICs. Among the newest developments described in the review were: 1. Multiplexed fluorescence platform for detecting antibodies to HPV 16 E7. The development of HPV-related cancers is associated with IgG antibodies, primarily to the oncoproteins E6 and E7. The antibodies to HPV E7 were more frequently detected in women with invasive cervical cancer (30.3%) than women with CIN 2/3 (19.5%) and CIN 0/1 (6.6%). A POC multiplexed fluorescence screening platform has been explored for detecting antibodies to HPV 16 E7 oncoprotein in patient plasma. Inexpensive interference filters and readout electronics were used to help leverage time integration of output signals for improved accuracy. 2. Enzyme-assisted nanocomplexes for visual identification of nucleic acids. A molecular platform named enVision (enzyme-assisted nanocomplexes for visual identification of nucleic acids) purportedly enables visual and modular detection of HPV nucleic acids (both DNA and RNA) without target nucleic acid amplification. Detection occurs through three functional steps: target recognition, target-independent signal enhancement, and visual detection. 3. AmpFire Multiplex HPV Assay. The AmpFire Multiplex HPV Assay developed by Atila Biosystems (Mountain View, CA, USA; www.atilabiosystems.com) detects 15 highrisk HPV genotypes while simultaneously genotyping HPV 16 and HPV 18 in a single tube. The multiplex assay uses sequence-specific primers to

target HPV genotypes of interest and amplify their respective sequences in an isothermal amplification system. Once amplified, specific molecular beacon probes are bound to the products to create a detectable fluorescence signal. The key component that separates this assay from other commercial ones is that the tests detect HPV in formalin-fixed, paraffin-embedded (FFPE) samples. 4. Artificial Intelligence Monitoring for HPV (AIM-HPV) In addition to advancing hardware technologies, an Artificial Intelligence Monitoring for HPV (AIM-HPV) platform leverages deep learning tactics to facilitate POC analyses. Here, digital microholography readily produces high-quality image data, even at sub-micron levels, through a simple, lens-free optical system. The platform detects target nucleic acids within cervical brushings introduced into a disposable DNA extraction kit. Senior author of the review Dr. Caesar Castro, associate professor of oncology at Massachusetts General Hospital, said, “The Pap smear has done wonders in terms of reducing mortality from a cancer that is very treatable when caught early and almost invariably fatal when it is caught late. And it is not even a great test. Part of its imperfection is that there is subjectivity to it. The trained eye is the limiting step in the process. The untrained eye, or relatively untrained eye, can miss cancers.” The review of advances in cervical cancer detection was published in the March 30, 2021, online edition of the journal Biophysics Reviews. Image: Artificial intelligence monitoring for HPV (AIM-HPV) device for point-of-care HPV testing (Photo courtesy of Ismail Degani, Center for Systems Biology, Massachusetts General Hospital) LabMedica International May/2021

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The Seegene STARlet IVD is an easy-to-use liquid handling workstation from primary sample tube to nucleic acid (NA) extraction and PCR setup. It provides convenient process of the lab works by minimizing hands-on time and maximizing assay reliability.

The GLINE-2019-nCoV Antigen Saliva is a rapid antigen salivary test that detects nucleocapsid protein of the SARS-CoV-2 virus based on colloidal gold immunochromatography assay (CGIA).

The VisioNize Pipette Manager is a standalone touch server that reacts in real-time with Eppendorf Xplorer and Eppendorf Xplorer plus electronic pipettes via Wi-Fi technology.

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Digital PCR Detects Chronic Myloid Lukemia

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resistance. Therefore, molecular monitoring is crucial for clinical management of CML. Digital PCR (dPCR) offers high reproducibility, precision and increased sensitivity for rare target detection. Medical Scientists from various disciplines at the Masaryk University (Brno, Czech Republic; www.muni.cz) performed a retrospective analysis of 70 clinical samples from chronic phase CML patients and 15 samples from healthy volunteers used as BCR-ABL1 negative controls. Reverse-transcription (RTqPCR) quantification of BCR-ABL1 in K562 cells was performed on an Applied Biosystems 7300 Real-Time PCR System (Waltham, MA, USA; www.thermofisher.com). The Xpert BCR-ABL Monitor test (Cepheid, Sunnyvale, CA, USA; www.cepheid.com) was used for quantification of BCR-ABL1 in clinical CML samples. All dPCR measurements were performed on the on QX200 Droplet Digital PCR System (Bio-Rad, Hercules, CA, USA; www.

bio-rad.com). The investigators reported that despite overall correlation of ratios, they observed significant differences in copy numbers quantification between RT-qPCR and dPCR. In the samples containing high transcript levels (10%–0.1% BCR-ABL1IS), RT-qPCR detected significantly more BCR-ABL1 copies than dPCR (P < 0.0001). Conversely, in the sample with low transcript levels (0.0032% BCRABL1IS), RT-qPCR quantified significantly less BCR-ABL1 copies compared to dPCR. Moreover, in all sample categories dPCR detected significantly less ABL1 copies. A total of 44 CML patients, routinely monitored by GeneXpert, were tested by dPCR. The team observed significant differences in the ratios measured by dPCR and GeneXpert in the 36 patients with low transcript levels (≤0.1% BCR-ABL1IS), which also resulted in low correlation between the methods. The authors concluded that their study demonstrated that droplet dPCR, tested with

standard EAC assays, provided a detection limit of above three BCR-ABL1 copies/sample, which corresponded to sensitivity of conventional quantitative methods. Nevertheless, dPCR categorized more than 50% of the CML patients into different MR categories compared to quantitative GeneXpert. The study was published in the May, 2021 issue of the journal Practical Laboratory Medicine. Image: The QX200 Droplet Digital Polymerase Chain Reaction (PCR) Systems provide ultrasensitive and absolute nucleic acid quantification. (Photo courtesy of Bio-Rad)

Genome Sequencing Identifies Myeloma Precursor and Progression Risk

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or smoldering myeloma (SMM). These two precursor conditions are found in 2%–3% of the general population aged older than 40 years. Only a small fraction of MGUS will ultimately progress to MM, whereas ~60% of persons with SMM will progress within 10 years of initial diagnosis. Currently, the differentiation between MGUS and SMM is based on indirect measures and surrogate markers of disease burden. Hematologists and Oncologists at the Memorial Sloan Kettering Cancer Center (New York, NY, USA; www.mskcc.org) and their colleagues interrogated genome sequence data for 80 multiple myeloma, 18 MGUS, and 14 SMM cases, including a single SMM case classified as high risk based on an

available prognostic model. The team compared genome features in 17 precursor cases that progressed to multiple myeloma within two years and 15 stable precursor cases, uncovering a set of “myeloma-defining genomic events” that included chromothripsis, aneuploidy, driver gene mutations, apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) mutational profiles, and templated insertions. For all samples, bone marrow plasma cells (BMPCs) were isolated from bone marrow aspirates and sorted on a BD FACSAria III instrument (BD Biosciences, San Jose, CA, USA; www.bdbiosciences.com). For matched control DNA from each patient, bone marrow T cells or peripheral blood mononuclear cells were used. The T cells were isolated from the

BM aspirates and sorted also using the BD FACSAria III. Standard input whole-genome sequencing were run on a NovaSeq 6000 in a 150 bp/150 bp paired-end run (Illumina, San Diego, CA, USA; www.illumina.com). The scientists reported that clinically stable cases of MGUS and SMM are characterized by a different genomic landscape and by differences in the temporal acquisition of myeloma-defining genomic events in comparison to progressive entities. In contrast, the investigators reported, the more clinically stable set of precursor gammopathies were missing such alterations. They also tended to surface in individuals diagnosed with MGUS or SMM somewhat later in life (between around 28 and 65 years old), compared to precursor Cont’d on page 16 LabMedica International May/2021

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The CFX Opus 384 Real-Time PCR System can analyze 384 wells and deliver a more uniform thermal performance. It offers expanded connectivity and network storage drive access for excellent data management.

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Synovial Fluid Neutrophils Phenotyped In Oligoarticular Juvenile Idiopathic Arthritis

uvenile idiopathic arthritis (JIA) is an inflammatory rheumatic joint disease affecting children. Despite disease onset being at a young age, symptoms may be lifelong and include irreversible joint damage or growth disturbances. The most common subtype in the Western world is oligoarticular, commonly characterized by asymmetric disease onset with inflammation in one to four large joints. Neutrophils are the most prevalent immune cells in the synovial fluid in inflamed joints of children with oligoarticular juvenile idiopathic arthritis. A multidisciplinary team of medical scientists at Lund University (Lund, Sweden; www.lu.se) obtained neutrophils from paired blood and synovial fluid from 17 patients with active oligoarticular JIA were investigated phenotypically and 13 functionally (phagocytosis and oxidative burst, by flow cytometry). In a subset of six patients, blood samples were also obtained during inactive disease at a follow-up visit. The presence of CD206-expressing neutrophils was investigated in synovial biopsies from four patients by immunofluorescence. Total white blood cell counts and relative frequency of neutrophils were investigated in the blood and synovial fluid samples on an XN-350 instrument (Sysmex Corporation, Kobe, Japan; www.sysmex.co.jp). Synovial, oral, and purified cell samples were washed with PBS after staining. Samples were analyzed on a FACS Canto II flow cytometer (BD Biosciences, San Jose, CA, USA; www.bdbiosciences.com) or a CytoFLEX (Beckman Coulter, Brea, CA, USA; www.beckmancoulter. com). Neutrophil maturity was determined using surface markers. Others methods used by the scientists included immunofluorescence staining of synovial tissue biopsies; stimulation of healthy blood neutrophils with JIA synovial fluid; investigating neutrophils from the healthy oral cavity; and neutrophil effector function. The team reported that neutrophils in synovial fluid had an activated phenotype, characterized by increased CD66b and CD11b levels, and most neutrophils had a CD16hi CD62Llow aged phenotype. A large proportion of the synovial fluid neutrophils expressed CD206, a mannose

receptor not commonly expressed by neutrophils, but by monocytes, macrophages, and dendritic cells. CD206-expressing neutrophils were also found in synovial tissue biopsies. The synovial fluid neutrophil phenotype was not dependent on transmigration alone. Functionally, synovial fluid neutrophils had reduced phagocytic capacity and a trend towards impaired oxidative burst compared to blood neutrophils. In addition, the effector functions of the synovial fluid neutrophils correlated negatively with the proportion of CD206+ neutrophils. The authors concluded that neutrophils in the inflamed joint in oligoarticular JIA were altered, both regarding phenotype and function. Neutrophils in the synovial fluid were activated, had an aged phenotype, had gained monocyte-like features, and had impaired phagocytic capacity. The impairment in phagocytosis and oxidative burst was associated with the phenotype shift. They speculated that these neutrophil alterations might play a role in the sustained joint inflammation seen in JIA. The study was published on April 9, 2021 in the journal Arthritis Research & Therapy. Image: The CytoFLEX Flow Cytometer has a large dynamic range to resolve dim and bright populations in the same sample (Photo courtesy of Beckman Coulter)

Genome Sequencing Identifies Myeloma Precursor and Progression Risk

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conditions in those with progressive disease, who were diagnosed between the ages of five and 46 years. The authors concluded that despite its lim-

ited sample size, their study provides proof of principle that whole genome sequencing (WGS) has the potential to accurately differentiate stable and progressive precursor conditions in low disease burden clinical states. The application of

this technology in the clinic has the potential to significantly alter the management of individual patients, but will require confirmation in larger studies. The study was published on March 25, 2021 in the journal Nature Communications. LabMedica International May/2021

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Coagulation Dysfunction and Infection Evaluated in Patients with AECOPD

hronic obstructive pulmonary disease (COPD) is one of the common chronic airway obstructive diseases, characterized by persistent respiratory symptoms and airflow limitation. In acute exacerbation stage (AECOPD), patients developed respiratory failure often have circulatory and coagulation dysfunction, which was considered the cause of thrombosis events in the patients. Although the inflammation in the early stage of COPD only involves the trachea and lung, hypoxia and further acute inflammation are systemic. In acute exacerbation stage, patients developed respiratory failure often have circulatory and coagulation dysfunction, which was considered the cause of thrombosis events in the patients. The coagulation abnormality could cause pulmonary embolism, myocardial infarction, cerebral infarction, and other thrombosis events in COPD patients. Respiratory and Critical Care Medicine Scientists from the Anhui Medical University (Hefei, China; www.ahmu.edu.cn) performed

a retrospective clinical study to investigate the factors correlated to abnormal coagulation status in COPD from November 2016 to November 2019. A total of 135 AECOPD, 44 stable stage COPD patients, and 135 healthy controls were enrolled in this study. The coagulation parameters, blood gas indexes and blood routine examination results were collected and analyzed. The scientists reported that white blood count (WBC), neutrophil count, neutrophil percentage (N%), platelet (PLT), prothrombin time (PT), international normalized ratio (INR), fibrinogen (FIB), and activated partial thromboplastin time (APTT) increased, plasma thrombin time (TT) decreased in AECOPD group compared with the control group. In AECOPD group, PT, APTT, and FIB were positively correlated with neutrophils and C-reaction protein levels. PT was positively correlated with partial pressure of carbon dioxide (PCO2) and negatively with pH. Thrombosis was observed in five acute exacerbation and three stable stage COPD patients.

In 38 patients with abnormal blood gas analysis indexes, PT level was negatively correlated with pH, positively correlated with arterial partial pressure of carbon dioxide (PaCO2) levels indicating abnormal coagulation status was correlated to hypercapnia and acidosis. The authors concluded that their study revealed that coagulation dysfunction existed in AECOPD patients. The abnormal coagulation was correlated to infection and hypercapnia and might be the main cause of thrombosis in the patients. The study was published on March 25, 2021 in the Journal of Clinical Laboratory Analysis. Image: Histology comparison of airway features in (A) a healthy individual and (B) in a patient with chronic obstructive pulmonary disease where airways are narrowed by infiltration of inflammatory cells, mucosal hyperplasia, and deposition of connective tissue in the peribronchiolar space (Photo courtesy of University of Leuven)

Circulating Calprotectin as Biomarker in Neutrophil-Related Inflammation

alprotectin (CLP) acts as an endogenous ligand of different cell-surface proteins like Toll-like receptor 4 and receptor of advanced glycation end-products facilitating a local proinflammatory effect. CLP is mostly secreted through an active, calcium-dependent Protein Kinase C (PKC) pathway, next to the passive leakage from necrotic cells and release in neutrophil extracellular traps (NET). Since CLP is released at the local site of inflammation, CLP plasma levels have been suggested to be a biomarker that reflects local disease activity in inflammatory diseases, in contrast to conventional acute-phase proteins such as C-reactive protein (CRP), which are

mainly produced by hepatocytes after non-specific, systemic inflammatory activity. In addition to mirroring local inflammation processes, CLP is relatively stable and easily measurable in blood. Biomedical Scientists at the Onze-LieveVrouw Hospital (OLV, Aalst, Belgium; www. olvz.be) and their colleagues established reference values for 100 healthy volunteers (median age [range] = 42 years [21–64]; 58% female). At time of sampling, all healthy volunteers had no physical complaints and had CRP levels of less than 5.0 mg/L. To evaluate pre-analytical conditions, four rheumatoid arthritis (RA) patients (age = 60 years [56–73];

50% female) with active disease, median CRP 14.2 mg/L (range = 2.7–73.3 mg/L)] were included. Circulating CLP was measured in serum and plasma with the EliA Calprotectin 2 assay, a sandwich-principle-based fluoro-enzyme-immunoassay (FEIA) on the Phadia 200 instrument (serum/plasma protocol, Thermo Fisher Scientific, Freiburg, Germany; www. thermofisher.com), which uses monoclonal mouse anti-calprotectin antibodies highly specific for calprotectin’s heterodimeric complexes. Different sample types were investigated: serum with/without gel separator, Cont’d on page 19 LabMedica International May/2021

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Protein Biomarker Controls Dosage of Highly Toxic Cisplatin in Cancer Patients

A team of Japanese investigators has identified a protein biomarker that may help clinicians control the dosage of the highly toxic chemotherapeutic drug cisplatin. While cisplatin (CDDP) is effective in many types of cancers - including testicular cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer, esophageal cancer, lung cancer, mesothelioma, brain tumors, and neuroblastoma - in high doses it causes cytotoxic effects that may worsen patients’ condition. Thus, a marker of sensitivity to CDDP is necessary to enhance the safety and efficiency of CDDP administration. In this regard, investigators at Niigata University (Japan; www. niigata-u.ac.jp) and their collaborators focused on the protein adipose most abundant 2 (APM2) to examine its potential as a marker of CDDP sensitivity. The relationship of APM2 expression with the mechanisms of CDDP resistance was examined in vitro and in vivo using hepatocellular carcinoma (HCC) cells, tissues, and serum from 71 HCC patients treated initially with intrahepatic arterial infusion of CDDP followed by surgical resection. The

Circulating Calprotectin as Biomarker in NeutrophilRelated Inflammation

predictability of serum APM2 for CDDP sensitivity was assessed in an additional 54 HCC patients and 14 gastric cancer (GC) patients. Results revealed that APM2 expression in CDDP-resistant HCC was significantly higher both in serum and the tissue. Bioinformatic analyses and histological analyses demonstrated upregulation of the ERCC6L (DNA excision repair protein ERCC6-like) gene by APM2, which was thought to account for the degree of APM2 expression. Serum APM2 levels and chemosensitivity for CDDP were assessed, and the cut-off value of serum APM2 for predicting the sensitivity to CDDP was determined to be 18.7 micrograms/milliliter. This protein concentration was evaluated in 54 HCC and 14 GC patients for its predictability of CDDP sensitivity, resulting in predictive value of 77.3% and 100%, respectively. “Our results demonstrate a significant re-

LabMedica International May/2021

lationship between the high level of APM2 expression in serum, cancerous cells in the liver, the surrounding liver tissue, and cisplatin resistance. The study reveals that APM2 expression is related to cisplatin sensitivity,” said first author Dr. Kenya Kamimura, lecturer in the division of gastroenterology and hepatology at Niigata University. “The serum APM2 can be an effective biomarker of the liver and gastric cancer cells for determining the sensitivity to cisplatin. The results of the study would provide an advantage for the technicians, allowing easy adaption in small local clinics.” Dr. Kamimura said, “To the best of our knowledge, this is the first report to demonstrate that the serum level of APM2 can be the predictor of the CDDP chemosensitivity. This study thus represents a milestone for detecting CDDP sensitivity, and further studies will help modify APM2 expression, which could contribute to the chemosensitization of the tumor.” The cisplatin resistance study was published in the March 18, 2021, online edition of the journal Scientific Reports.

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heparin, EDTA and citrate plasma, pre-centrifugation time (<2 hours, 6 hours, 24 hours), storage condition (2–8 °C, 18–25 °C, 30 °C) and storage time (24 hours, 72 hours, 7 days). The investigators reported that in healthy controls, baseline CLP concentrations in serum were more than double the concentration in EDTA and citrate plasma (0.909 µg/mL versus 0.259 µg/mL and 0.261 µg/mL respectively). Heparin, EDTA and citrate stabilized CLP concentrations for up to 6 hours before centrifugation, whereas significant increases in CLP levels were observed when serum was left untreated during that time period. The authors concluded that their data revealed that in both healthy controls and RA patients serum CLP levels are considerably higher in serum than in plasma. The establishment of reference values in healthy controls showed that 95% upper limits were both sample type- and CRP-dependent. Serum tubes need to be centrifuged within two hours and plasma tubes within six hours after blood collection. All investigated sample types can be stored refrigerated (2–8 °C) for up to seven days, at room temperature (18–25 °C) for up to 24 hours, frozen (−20 °C) for up to three months and can have five freeze-thaw cycles without a relevant change in CLP concentration. The study was published on March 6, 2021 in the journal Clinica Chimica Acta.

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Arecent paper identified a lipid biomarker indicative of cellular senescence and described a method to evaluate its effect on the molecular events that lead to senescence. Cellular senescence is a stress or damage response that causes a cell to stop dividing, and, since senescent cells are not dead, to secrete numerous factors with potent biological activities. This senescence-associated secretory phenotype (SASP) has been characterized largely for secreted proteins that participate in embryogenesis, wound healing, inflammation, and many age-related conditions. By contrast, the lipid components of the SASP have not been well documented. In the current study, investigators at the Buck Institute for Research on Aging (Novato, CA, USA; www.buckinstitute.org) focused on the large array of oxylipins, bioactive lipid metabolites derived from the oxygenation of polyunsaturated fatty acids, which are synthesized by senescent cells. The study was performed on human cells growing in culture and with mice. Results revealed that senescent cells activated the biosynthesis of several oxylipins, which promoted segments of the SASP and reinforced the cell division blockade. Notably, senescent cells synthesized and accumulated an unstudied intracellular prostaglandin, 1a,1b-dihomo-15-deoxy-delta-12,14-prostaglandin J2. The released form, 5-deoxy-delta-12,14-prostaglandin J2, could serve as a biomarker of senolysis in culture and in vivo.

In addition, the PGJ2 prostaglandin was shown to have a functional role in senescence. Inhibiting its synthesis allowed a subset of cells to escape senescence, continue dividing, and present a less inflammatory SASP profile. In contrast, addition of the prostaglandin to non-senescent cells drove them into senescence by activating the RAS cancer-promoting gene, which is also known to trigger senescence. “The list of age-related diseases definitively linked to cellular senescence keeps growing, as does the number of biotech companies racing to develop drugs to eliminate senescent cells,” said senior author Dr. Judith Campisi, professor of biogerontology at the Buck Institute for Research on Aging. “While the field has never been more promising, the lack of a simple biomarker to measure and track efficacy of these treatments has been a hindrance to progress. We are excited to bring this new biomarker to the field and look forward to it being used in the clinic. We hope that identifying and including these bioactive lipids as part of the SASP will encourage researchers working in a broad range of fields to take a new look at cellular senescence. The fact that one of these lipids ends up being a simple non-invasive biomarker for tracking the efficacy of treatments is a huge plus for those of us working to stem the ravages of age-related disease.” The study was published in the April 2, 2021, online edition of the journal Cell Metabolism. LabMedica International May/2021

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Type 1 Diabetes Onset Preceded by Gene Expression Changes

ype 1 diabetes (T1D) results from insufficient insulin production and is thought to result from an immune reaction against the body’s own pancreatic β cells. The exact cause of T1D remains unknown, although asymptomatic islet autoimmunity lasting from weeks to years before diagnosis raises the possibility of intervention before the onset of clinical disease. The number, type, and titer of islet autoantibodies are associated with long-term disease risk, but do not cause disease, and robust early predictors of individual progression to T1D onset remain elusive. Gene expression changes in the blood appear to precede the onset of symptoms in children with T1D, pointing to the possibility of predicting T1D development with blood tests in the future. An international consortium of Medical Scientists led by those at the Jeffrey Cheah Biomedical Centre Cambridge, UK; www.jcbc.cam. ac.uk) analyzed transcriptome patterns of more than 2,000 peripheral blood samples collected over time from 401 children from birth to age 15 who went on to develop either islet autoimmunity or T1D. The team

Image: Inflammation of the pancreatic islets with mononuclear cells including T-cells is the hallmark of Type 1 diabetes (Photo courtesy A. van Halteren)

used transcriptional network analyses, gene expression-based immune cell type frequency predictions, and other approaches, they went on to compare the samples with one another and with those from unaffected, Cont’d on page 23

Vitamin D Deficiency Linked to Metabolic Changes in Lupus Patients

ystemic lupus erythematosus (SLE), is the most common type of lupus. SLE is an autoimmune disease in which the immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs. It can affect the joints, skin, brain, lungs, kidneys, and blood vessels. Metabolic syndrome is a cluster of conditions that occur together, increasing the risk of heart disease, stroke and type 2 diabetes. These conditions include increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels. Metabolic syndrome is increasingly common, and up to one-third of adults in the USA have it. A large team of immunologists and their international colleagues working with the University of Birmingham (Birmingham, UK; www. bham.ac.uk) examined vitamin D levels in 1,163 patients with SLE across 33 centers in 11 countries. Clinical, laboratory and therapeutic data were collected. Vitamin D level was defined according to tertiles based on distribution across this cohort, which were set at T1 (10–36 nmol/L), T2 (37–60 nmol/L) and T3 (61–174 nmol/L). Metabolic syndrome was defined according to the 2009 consensus statement from the International Diabetes Federation. Insulin resistance was determined using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) model. Linear and logistic regressions

were used to assess the association of variables with vitamin D levels. The team reported that of the 1,847 patients, 1,163 (63%) had vitamin D measured and 398 (34.2%) subjects were in the lowest 25(OH)D tertile. Metabolic syndrome was present in 286 of 860 (33%) patients whose status could be determined. Patients with lower 25(OH)D were more likely to have metabolic syndrome and higher HOMA-IR. The metabolic syndrome components, hypertension, hypertriglyceridemia and decreased high-density lipoprotein (HDL) were all significantly associated with lower 25(OH)D. Increased average glucocorticoid exposure was associated with higher insulin resistance. John A. Reynolds, MD, a Consultant Rheumatologist and a senior author of the study. said, “Our results suggest that co-existing physiological abnormalities may contribute to long-term cardiovascular risk early on in systemic lupus erythematosus. We found a link between lower levels of vitamin D and metabolic syndrome and insulin resistance.” The authors concluded that metabolic syndrome and insulin resistance are associated with lower vitamin D in patients with SLE. Further studies could determine whether vitamin D repletion confers better control of these cardiovascular risk factors and improve long-term outcomes in SLE. The study was published originally published on February 8, 2021 in the journal Rheumatology. LabMedica International May/2021

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LabMedica International

Single-Cell Transcriptomic Analysis Traces Neuroblastomas to Developing Adrenal Neuroblasts

euroblastoma is the most common cancer in infants and the third-most common cancer in children after leukemia and brain cancer. Approximately one in every 7,000 children is affected at some time and about 90% of cases occur in children less than five years old, and it is rare in adults. Neuroblastoma is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands, but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the abdomen, neck, or chest, or a painless bluish lump under the skin. Pediatric Oncologists at the Hopp Children’s Cancer Center Heidelberg (Heidelberg, Germany; www.kitz-hei delberg.de) analyzed samples from 17 fresh-frozen developing human adrenal glands using droplet-based single-nucleus RNA-seq. These samples represented seven developmental time points ranging from seven weeks post-conception to 17 weeks post-conception. They clustered the cells and assigned them to major cell types based on the markers they expressed, but focused much of their analysis on adrenal medullary cells such as Schwann cell precursors, chromaffin cells, and neuroblasts. By comparing these normal developing human adrenal gland cells to cells from 14 neuroblastomas also analyzed by single-nucleus RNA-seq, the team found that the tumors resembled differentiating adrenal neuroblasts and they also noticed some differences by tumor type. For instance, MYCN-amplified neuroblastoma cells were most similar to normal neuroblasts from seven or eight weeks post-con-

ception, while lower-risk neuroblastomas included more cells resembling late neuroblasts. This suggested that low-risk tumors might develop from cells further along in the development and differentiation process. They confirmed this finding by projecting single neuroblastoma cells onto diffusion maps of normal adrenal medullary cells to again find neuroblastoma cells mapped to normal neuroblasts and that low-risk tumors were more similar to differentiated neuroblasts and high-risk ones to earlier-state neuroblasts. They additionally found that differentiation markers varied between high-risk and low-risk tumors. The scientists then examine whether MYCN, often amplified among high-risk tumors, can suppress differentiation. In an inducible MYCN knock-down model of MYCN-amplified neuroblastoma cells, they found that elevated MYCN can induce de-differentiation and activate proliferation. At the same time, though, activating TFAP2B, a transcription factor that is highly expressed in normal neuroblasts but not in high-risk neuroblastomas, restores differentiation signatures. The authors concluded that the identification of tumor-related transcriptional changes and molecular mechanisms underlying impaired differentiation may guide future studies on the functional evaluation of candidate genes, refined risk classification and generation of clinically relevant neuroblastoma models. Moreover, they have provided the framework to evaluate therapeutic concepts that are based on induction of differentiation. The study was published on March 25, 2021 in the journal Nature Genetics.

Image: Bone marrow aspirate from a child with a mediastinal tumor shows an invasion with neuroblastoma cells and characteristic images of neuropile threads (Photo courtesy of Mohammed Bensalah, MD, Amina Lyagoubi, and Rachid Seddik)

Type 1 Diabetes Onset Preceded by Gene Expression Changes

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age-matched controls, leading to a pre-symptomatic autoimmune signature in affected children that appeared to reflect enhanced natural killer (NK) cell activity. The team identified and interpreted age-associated gene expression changes in healthy infancy and age-independent changes tracking with progression to both T1D and islet autoimmunity, beginning before other evidence of islet autoimmunity was present. They combined multivariate longitudinal data in a Bayesian joint model to predict individual risk of T1D onset and validated the association of a NK cell signature with progression and the model’s predictive performance on an additional 356 samples from 56 individuals in the independent Type 1 Diabetes Prediction and Prevention study. They also characterized the gene expression shifts corresponding to specific

LabMedica International May/2021

endotypes of T1D, including a fast-progressing form of the disease involving autoantibodies that target insulin and a form with autoantibodies that target the glutamic acid decarboxylase enzyme in the pancreas. The team’s findings suggested that detecting gene expression changes in the first 18 months of a child’s life could eventually help in finding and perhaps treating children who are on track to develop T1D or pancreatic islet beta-cell autoimmunity, marked by gradual islet cell autoantibody (IAbs) seroconversion, before symptoms develop. Eoin McKinney, MBChB, PhD, an Immunologist and senior author of the study, said, “Together, our results indicate that T1D is characterized by early and longitudinal changes in gene expression, informing the immunopathology of disease progression and facilitating prediction of its course.” The study was published on March 31, 2021 in the journal Science Translational Medicine. LINKXPRESS COM

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Serum Amyloid A Levels Linked to Likelihood of Severe COVID-19

esults of research papers published during the current pandemic suggest that increased levels of the blood biomarker serum amyloid A predict development of severe or fatal forms of COVID-19. Serum amyloid A (SAA) proteins are a family of apolipoproteins associated with high-density lipoprotein (HDL) in plasma. Acute-phase serum amyloid A proteins (A-SAAs) are secreted during the acute phase of inflammation. A-SAA genes and proteins are significantly activated during the acute phase response, which comprises a number of phenomena that occur in the presence of inflammation and infection, e.g., increased temperature and hormonal and metabolic alterations. Circulating SAA concentrations, typically low under physiological circumstances, can increase up to 1000-fold within the first 24 to 48 hours of an acute phase response. This is the consequence of increased synthesis in the liver that is triggered by several stimuli, including tumor necrosis factor (TNF), interleukin (IL)-1beta, IL-6, and interferon gamma

NOVATEC IMMUNDIAGNOSTICA

(IFN-gamma). SAA, in turn, can activate the complement system and further increase the synthesis of TNF, IL-1beta, and IL-6, and activate other proinflammatory cytokines such as IL-1alpha and IL-23. Two systematic reviews and meta-analyses on a relatively limited number of studies, had reported a significant and positive association between SAA concentrations and COVID-19 severity. Thus, it was plausible that the acute increase in SAA concentrations in patients with COVID-19 might not only reflect the presence of an acute phase response, but also herald the development of a cytokine storm and, consequently, multi-organ failure and an increased risk of adverse outcomes. In this light, investigators at Flinders University (Adelaide, Australia; www. flinders.edu.au) and the University of Sassari (Italy; www.uniss.it) analyzed results from nineteen published studies involving 5617 COVID-19 patients to determine if a link could be demonstrated between SAA levels and COVID-19. The investigators reported that pooled re-

sults indicated that SAA concentrations were significantly higher in patients with severe disease and non-survivors than in patients with mild disease or controls. SAA concentrations were significantly and positively associated with higher COVID-19 severity and mortality. “Our analyses showed that COVID-19 patients with severe disease or who eventually died had significantly higher levels of SAA when compared to patients with mild COVID-19,” said senior author Dr. Arduino Mangon, professor of clinical pharmacology at Flinders University. Patients with severe forms of coronavirus disease 2019 have excessive inflammation, alterations in clot formation, and significant damage in several organs, particularly the lung, the kidney, the heart, and the liver. This chemical [SAA] may help, together with other patient characteristics, in predicting which COVID-19 patients are likely to deteriorate and require aggressive management.” The serum amyloid A study was published in the March 15, 2021, online edition of the International Journal of Infectious Diseases.

Blood-Based Markers Tied to Brain Cell and Memory Loss

revious studies have linked elevated levels of plasma total tau and neurofilament light chain (NfL) with worse cognition and neuroimaging measures of cortical thickness, cortical atrophy, white matter hyperintensity, or white matter integrity. Neurodegeneration, or brain cell loss, is characteristic of many disorders including Alzheimer’s disease, vascular dementia, and Lewy body dementia. Causes and location of neurodegeneration in the brain vary with disease. In Alzheimer’s disease, amyloid plaques and neurofibrillary tangles contribute to neurodegeneration and there tends to initially be more brain cell loss in the temporal lobe. In

vascular-related cognitive impairment, infarct, white matter hyperintensities, and microbleeds can contribute to cognitive changes. Neurologists at the Mayo Clinic (Rochester, MN, www.mayoclinic.org) and their colleagues included 995 participants without dementia who were enrolled in the Mayo Clinic Study on Aging. All had concurrent plasma NfL and Totaltau, cognitive status, and neuroimaging data. Follow-up was repeated approximately every 15 months for a median of 6.2 years. Plasma NfL and T-tau were measured on the Simoa HD-1 Platform (Quanterix, Billerica, MA, USA; www. quanterix.com). The scientists reported that baseline plasma

NfL, compared to T-tau, was more strongly associated with cognitive and neuroimaging outcomes in all analyses. The combination of having both elevated NfL and T-tau at baseline, however, was more strongly associated at cross-section with worse global cognition and memory and with neuroimaging measures including temporal cortex thickness and increased number of infarcts. Longitudinally, T-tau did not add to the prognostic value of NfL. Analyses using Alzheimer’s Disease Neuroimaging Initiative (ADNI) had similar result. Michelle M. Mielke, PhD, a Professor and a senior author of the study, said, “For prognosis Cont’d on page 28 LabMedica International May/2021

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LabMedica International

A Mass Spectrometry Approach To Monitoring Progress of Multiple Myeloma

n easy to perform mass spectrometry (MS) approach enables monitoring the progress of multiple myeloma by tracing unique clonal immunoglobulin gene fingerprints in blood samples. Due to improved treatment, more patients with multiple myeloma (MM) reach a state of minimal residual disease (MRD). Different strategies for MM MRD monitoring that are currently available include flow cytometry, allele-specific oligonucleotide–quantitative PCR, next-generation sequencing, and mass spectrometry (MS). The last three methods rely on the presence and the stability of a unique immunoglobulin fingerprint derived from the clonal plasma cell population. A novel approach for generating immunoglobulin fingerprints in MRD patients was developed by investigators at Radboud University Medical Center (Nijmegen, the Netherlands; www.umcn.nl) and colleagues at Erasmus Medical Center (Rotterdam, the Netherlands; www.erasmusmc.nl). They created an analysis pipeline based on MiXCR (a universal tool for fast and accurate analysis of T- and B- cell receptor repertoire sequencing data) and HIGH-VQUEST (V-QUERy and STandardization – part of the international ImMunoGeneTics (IMGT) information system. IMGT/HighV-QUEST is the high-throughput version of IMGT/V-QUEST for the analysis of thousands of immunoglobulin (IG)

possible to very accurately show whether the number of cancerous cells in the bone marrow is increasing in a patient. In time, this blood test could potentially replace the current bone marrow puncture.” Image: Artist’s depiction of myeloma cells producing monoclonal proteins of varying types (Photo courtesy of Wikimedia Commons)

Novel Urine-based Liquid Biopsy for Early Detection of Aggressive Prostate Cancer

recent paper described the development of a new urine-based test for the detection of aggressive prostate cancer, which promises improvement upon current biomarker assays. Investigators at the University of Michigan (Ann Arbor, USA; www.umich.edu) explained that despite advances in the field, early detection of aggressive prostate cancer (PCa) remains challenging. Among these advances was a clinical-grade urine test (Michigan Prostate Score [MiPS]) for individualized aggressive PCa risk prediction that had been developed by the same group of investigators. The MiPS combined serum prostate-specific antigen (PSA), the TMPRSS2:ERG (T2:ERG) gene fusion, and PCA3 lncRNA (long noncoding RNA) in whole urine after digital rectal examination (DRE). In the current study, the investigators sought to improve on MiPS with a novel next-generation sequencing (NGS) multi-biomarker urine assay for early detection of aggressive Pca. To do this, the investigators created a urinebased liquid biopsy technique that employed next-generation genomic sequencing to analyze RNA in samples collected from men following a

and T cell receptor (TR) rearranged nucleotide sequences per run. IMGT/HighV-QUEST was developed to cope with the problematic analysis of antigen receptor data from NextGeneration Sequencing (NGS). The investigators used these analysis techniques to identify clonal molecular fingerprints and their clonotypic peptides based on transcriptomic datasets. The investigators reported in the March 12, 2021, online edition of the journal Clinical Chemistry that the analysis pipeline was successfully validated in MM cell lines. In a cohort of 609 patients with MM, they demonstrated that the most abundant clone harbored a unique clonal molecular fingerprint and that multiple unique clonotypic peptides compatible with MS measurements could be identified for all patients. Furthermore, the clonal immunoglobulin gene fingerprints of both the light and heavy chain remained stable during MM disease progression. Senior author, Dr. Joannes F. M. Jacobs, a medical immunologist at Radboud University Medical Center, said, “The disease is found almost everywhere in the bone marrow, but in some areas you there are more cancerous cells than in other areas. So if you take a biopsy where there are fewer cancer cells, the test result does not accurately reflect the real situation. The new method makes it much easier to follow the progression of multiple myeloma. With a single drop of blood, it is

LabMedica International May/2021

Image: Micrograph showing a prostate cancer (conventional adenocarcinoma) with perineural invasion (Photo courtesy of Wikimedia Commons)

digital rectal exam. Machine learning was used to identify 15 RNA transcripts that together comprised the new Urine Prostate Seq [UPSeq] test. The UPSeq model was trained on 73 patients and validated on a set of an additional 36 patients representing the entire prostate cancer spectrum, from benign to grade group (GG) five Cont’d on page 26 LINKXPRESS COM

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The FilmArray EZ is a CLIA-waived system for near patient molecular testing that enables decentralized molecular testing throughout a provider network it offers an intuitive and simplified user interface and results report. LINKXPRESS COM

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High Liver Enzymes Increase Diabetes Risk in Hispanic Adults

on-alcoholic fatty liver disease (NAFLD) has been associated with increased risk of incident diabetes, but such evidence is lacking in the Hispanic/Latino population, which has high prevalence of obesity and NAFLD. NAFLD, also known as metabolic (dysfunction) associated fatty liver disease (MAFLD), is excessive fat build-up in the liver without another clear cause such as alcohol use. There are two types; non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), with the latter also including liver inflammation. Medical Scientists at the Albert Einstein College of Medicine (Bronx, NY, USA; https:// einsteinmed.org) analyzed data from 6,928 adults participating in the Hispanic Community Health Study/Study of Latinos (mean age, 38 years). Participants did not have diabetes at a baseline visit from 2008 to 2011 and returned for a follow-up examination a mean six years after baseline from 2014 to 2017. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) levels were measured at baseline. The team placed participants into quartiles for ALT, AST and GGT based on their baseline levels. Incident diabetes was identified at follow-up through laboratory measurements or the use of diabetes medication.

The scientists reported that of the 738 participants who had diabetes during follow-up, 533 were identified through blood tests. Adults were more likely to develop diabetes if they were men, older or of Puerto Rican background or had a lower education level, higher BMI, higher waist circumference or a lower score on an alternative healthy eating index. adults in the highest ALT quartile had a greater risk for developing diabetes compared with those in the lowest quartile (Relative Risk [RR] = 1.51). Participants in the highest quartile for GGT also had an increased risk for diabetes at follow-up compared with the lowest quartile (RR = 2.39). Both associations remained after adjusting for baseline fasting glucose. After adjusting for homeostatic model assessment of insulin resistance, only a high GGT level was significantly associated with incident diabetes. The risks for incident diabetes with ALT and GGT were similar for all Hispanic backgrounds except for Dominican ethnicity. ALT and GGT were both associated with incident diabetes regardless of obesity status. Those who had a high ALT and were light or moderate alcohol drinkers had an increased risk for incident diabetes (RR = 1.5), but there was no increased risk for those who did not drink. In addition to using liver

enzyme testing to screen Hispanic adults for their diabetes risk, the findings revealed that lifestyle modifications can reduce a person’s risk for both NAFLD and diabetes. Carmen R. Isasi, MD, PhD, FAHA, an associate professor and the senior author of the study, said, “Hispanics are at high risk of diabetes and its complications and are also at high risk for nonalcoholic fatty liver disease (NAFLD). Liver enzymes could be a simple clinical tool to screen individuals for diabetes risk, in addition to traditional factors.” The authors concluded that higher ALT and GGT levels are associated with increased risk of developing diabetes among Latinos. Liver enzyme tests might aid in diabetes prevention by identifying high-risk individuals. The study was originally published online on January 21, 2021 in the journal Diabetic Medicine. Image: Elevated liver enzymes are associated with incident diabetes in US Hispanic/ Latino adults (Photo courtesy of Judy George, BA, MBA)

Novel Urine-Based Liquid Biopsy for Early Detection of Aggressive Prostate Cancer

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Pca. The area under the receiver operating characteristic curve (AUC) of UPSeq was compared with PSA, MiPS, and other existing models/biomarkers for predicting GG three or higher PCa. Results revealed that UPSeq demonstrated high analytical accuracy and concordance with MiPS, and was able to detect expressed germline HOXB13 and somatic SPOP mutations. These results underlined the potential utility

of this novel urine-based RNA NGS assay to supplement PSA for improved early detection of aggressive Pca. “The problem is that a patient can have multiple areas of cancer in the prostate and these areas may be different than each other,” said senior author Dr. Simpa Salami, assistant professor of urology at the University of Michigan. “Because of this, both prostate biopsies and MRI scans can miss evidence of aggressive

disease. So, this urine test is designed to tell us what is really happening throughout the whole prostate. A novel aspect of this test is that it can detect inheritable mutations in the HOXB13 gene that could warn us that the patient’s family members may also be at higher risk for prostate cancer.” The UPSeq test was described in the March 31, 2021, online edition of the journal European Urology Oncology. LabMedica International May/2021

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LabMedica International

Salivary Markers Detect Sports Concussions

cont’d from cover

clinical settings and pitch side at sporting events are being studied. Several blood biomarkers have been intensively studied, including S100β, glial fibrillar acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neuron-specific enolase (NSE), Tau, neurofilament light protein (NFL) and beta-amyloid protein. A team of medical scientists associated with the University of Birmingham (Birmingham, UK; www.bham.ac.uk) obtained saliva from male professional players in the top two tiers of England’s elite rugby union competition across two seasons (2017–2019). Samples were collected preseason from 1,028 players, and during standardized head injury assessments (HIAs) at three time points (in-game, postgame, and 36–48 hours post-game) from 156 of these. Samples were also collected from controls (102 uninjured players and 66 players sustaining a musculoskeletal injury). Saliva was collected in by passive drool in Oragene-RNA RE100 or CP-190 saliva self-collection kits (DNA Genotek, Ottawa, ON, Canada; https://dnagenotek. com) containing an RNA stabilizing solution preserving the samples for up to eight weeks. Diagnostic small non-coding RNAs (sncRNAs) were identified with next generation sequencing and validated using quantitative PCR in 702 samples. A predictive logistic regression model was built on 2017–2018 data (training dataset) and prospectively validated the following season (test dataset). The amplification was performed in a LightCycler 480 RealTime PCR System (Roche Diagnostics, Rotkreuz, Switzerland; www.diagnostics.roche.com) in 384 well plates. The investigators reported that the head injury assessment (HIA) process confirmed concussion in 106 players (HIA+) and excluded this in 50 (HIA−). They found 32 small non-coding RNAs (sncRNAs) were significantly differentially expressed across these two groups, with let-7f-5p showing the highest area under the curve (AUC) at 36–48 hours. Additionally, a combined panel of 14 sncRNAs could differentiate concussed subjects from all other groups, including players who were HIA− and controls, immediately after the game (AUC 0.91) and 36–48 hours later (AUC 0.94). When prospectively tested, the panel confirmed high predictive accuracy (AUC 0.96) post-game and (AUC 0.93) at 36–48 hours. The authors concluded that the detection of signatures of concussion at early time points in saliva (a non-invasively sampled biofluid) presents both at the pitch side, and in primary care and emergency medicine departments, an opportunity to develop a new and objective diagnostic tool for this common

LabMedica International May/2021

clinical presentation. In addition, sncRNAs may be an important tool in developing understanding of the pathophysiology of concussion. The study was published on March 23, 2021 in the journal British Journal of Sports Medicine. Image: The DNA Genotek CP-190 saliva self-collection kits (Photo courtesy of Kyodo International Inc)

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Serious Infections Prevalent in ANCA-Associated Vasculitis

nti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are among the rheumatic diseases with the highest mortality and morbidity, due to their major multi-organ involvement (lungs, kidneys) and their relapsing nature requiring aggressive immunosuppressive treatment. Serious infections (SI) are common in patients with ANCA-AAV) like granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Real-life data regarding their incidence and predisposing factors, after the introduction of B cell depleting agents, are limited while data quantifying the risk per treatment modality and year of the disease are missing. Clinical Immunologists at the Hippokration General Hospital (Athens, Greece; www.hippocrateon.com) and their colleagues conducted a multicenter, observational, retrospective study of patients with AAV followed in three referral centers in the Athens. The study included 162 patients with GPA (63%) and MPA (37%), males 51.9%, mean age 60.9 years, ΑΝCA+ 86%, and generalized disease 80%. During follow-up (891.2 patient-years, mean 5.4 years), 67 serious infections (SI) were recorded in 50 patients at an incidence rate of 7.5 /100 patient-years. The team collected from each participant age, sex, date of diagnosis, diseases severity, disease activity at baseline (Birmingham Vasculitis Activity Score), ANCA serology, organ involvement, relapses, renal function [estimated glomerular filtration rate (eGFR) by CKD-EPI formula] during first induction of remission course) and treatment patterns (treatment types and duration for each treatment, both for induction and maintenance of remission as well as initial glucocorticoids (GC) dose at diagnosis). SI was defined those needing hospitalization or intravenous antibiotics as well as opportunistic infections. Given the high frequency of herpes zoster (HZ) in AAV population and the accompanying morbidity of this infection, all cases of HZ were considered as SI irrespective of hospitalization need. The scientists found that the incidence of SI among patients undergoing induction treatment with cyclophosphamide was 19.34/100

Cont’d from page 24

patient-years compared with 11.34/100 for those whose induction regimen was with rituximab, for an incidence rate ratio for cyclophosphamide of 4.24. Patients with ANCA-associated vasculitides granulomatosis with polyangiitis and microscopic polyangiitis continued to have significant morbidity and mortality despite improvements in treatment, such as the wider use of rituximab, and the incidence of serious infections remained high. Mean baseline estimated glomerular filtration rate (GFR) was 59.1 mL/min, and in almost a quarter of patients, the baseline GFR was below 30 mL/min. Renal replacement therapy and/or plasma exchange was needed at baseline for 6.2%. Site of infection was the respiratory tract in 45% of patients, and the gastrointestinal tract and urinary tract in 9% each. The infection was herpes zoster in 24% and bacteremia in 9%. The authors concluded that in this real-life study of patients with AAV, the SI incidence was higher during cyclophosphamide compared to rituximab (RTX) induction while there was no difference between RTX and other agents used for maintenance therapy. Higher disease activity at baseline and need for plasmapheresis and/or dialysis were independent factors associated with an SI. The study was published on March 20, 2021 in the journal Arthritis Research & Therapy. Image: Besides the typical periglomerular localization, a diffuse interstitial leukocyte infiltration is very common in ANCA-associated vasculitis (Photo courtesy of Dr. Franco Ferrario and Dr. Maria Pia Rastaldi)

Blood-Based Markers Tied to Brain Cell and Memory Loss

purposes, neurofilament light better predicted the rate of neurodegeneration and cognitive decline, regardless of what the cause of neurodegeneration might be. NfL also may help

determine how fast someone declines and how effective future therapies might be in slowing this decline.” The authors concluded that overall, plasma NfL had better utility as a prognostic marker of

cognitive decline and neuroimaging changes. Plasma T-tau adds cross-sectional value to NfL in specific contexts. The study was presented on April 18, 2021 at the American Academy of Neurology Annual Meeting. LabMedica International May/2021

Edited by Katherina Psarra MSc, PhD

IFCC members may send news to: Katherina Psarra, MSc, PhD, Dept of Immunology – Histocompatibility, Evangelismos Hospital, Ipsilantou 45-47, Athens 10676, Greece4; Email: enews@ifcc.org

NEWS

IFCC Launches Task Force to Promote Global Lab Quality

Task Force GLQ members during their inaugural meeting: Prof. K. Adeli, IFCC President and Prof. D.Kinniburgh, IFCC Secretary, participated in the meeting.

ith the beginning of 2021, the IFCC Executive Board has established a new Task Force on Global Lab Quality (TF-GLQ). The international TF that comprises 15 members and eight corresponding members has started its operative work. What is the rationale for this new global initiative? High standards of laboratory quality are not met in all countries. The ultimate goal of the TF’s work is to implement an international IQC and EQA program to improve the overall quality of laboratory practices on a global scale.

Two major initiatiatives pursued • A survey was conducted in which member states answered questions on their countries’ actual situation concerning IQC and EQA programs and on their willingness to participate in a pilot project; • An initial request for proposals was circulated to vendors of IQC materials and EQA programs and interest to provide such materials was expressed by a number of commercial and not-for-profit vendors.

The survey The response rate to the survey was remarkable: 54 responses were received from IFCC national societies (response rate: > 50%), of which several expressed interest to participate in the pilot program. Based on individual countries’ most urgent needs to improve lab quality, ten countries from Europe, Africa, Latin America and Asia have been selected to participate in the pilot

LabMedica International May/2021

program. Each of those ten countries can appoint up to five participating laboratories for the pilot program.

The test menu The TF-GLQ discussed most suitable tests and proposed a test menu for the pilot program: From 25 finally selected tests, eight are immunoassays and 17 tests represent a comprehensive metabolic panel. Next TF-GLQ working steps include the fine-tuning of individual country programs (not all participating laboratories may want to apply all 25 tests).

Suitable vendors In order to obtain a more accurate proposal from possible vendor partners, TF-GLQ will provide specifics on the pilot program to vendors and need to decide whether regional or global solutions are more meaningful. For example, EQA solutions may be procured more regional (several vendors), whereas IQC materials could be supplied globally (one or few vendors). Once decided, vendors must be chosen through an open-bidding process to provide EQA materials and software for the EQA program. IFCC sponsored pilot project In contrast to the previous DQCML program (Developing Quality Competence in Medical Laboratories), IFCC will financially sponsor the pilot program: Participating labs will receive the

IQC materials (i.e., standards and controls) and EQA logistics free of charge.

Other TF-GLQ tasks There are many remaining tasks to be addressed, including: • Understand requirements of country-specific issues and training needs; • Assign scientific support teams to train and support staff on site at participating laboratories; • Plan for maintenance and monitoring of the IQC program by IFCC; • Through on-site visits, evaluate the preparedness of the participating laboratories for subscription to the EQA program and identify gaps that must be addressed; • Develop detailed written guidelines for the participating laboratories; • Dispatch scientific support teams to help initiate the EQA program at the participating labs. Expert teams will be formed by the taskforce from IFCC membership and will include both senior and young scientists. For more information, please visit the following link: www.ifcc.org/executive-board-and-council/ebtask-forces/task-force-on-global-lab-quality/ CONTRIBUTED BY: Prof. Egon Amann, IFCC Task Force on Global Lab

Quality (TF-GLQ) Chair, University of Applied Sciences, Hochschule Hamm-Lippstadt, Marker Allee 76-78, 59063 Hamm DE Dr. Qing Meng, IFCC Task Force on Global Lab Quality (TF-GLQ) Chair, Clinical Chemistry and Special Chemistry Laboratories, Dept. of Laboratory Medicine, University of Texas, MD Anderson Cancer Center, Houston, TX, USA

News from the World of the International Federation of Clinical Chemistry and Laboratory Medicine Visit www.ifcc.org for more information

NEWS

Editorial

By Katherina Psarra MSc, PhD

Dear colleagues, hope you all enjoy spring at its best, hope at its best. I am sure you will find a lot of very interesting material in this IFCC corner and you will be excited about the activities already taking place or planned for the near future in IFCC among them the IFCC Webinars series. The message of our president, Prof. Khosrow Adeli, announces very important matters, like changes in the planning of conferences and like the new

THE WORLD OF IFCC

initiative of the IFCC Task Force on Global Lab Quality (TF-GLQ) planning a pilot program for external quality assurance (EQA) in developing countries. All the committees seem to be very active. Dr Bernard Gouget’s article is about the vaccine passport. Is it ethical, is it democratic? Teamwork awarded by Univants is inspiring too. The articles in this issue underline teamwork. Go through the issue, dear colleagues. I am sure that you will find a lot of interesting information. Spring and good weather are here to stay, and vaccines cover more and more of the population. Our next issue will be even more hopeful!

Japan Society of Clinical Chemistry

2020 JSCC Awards Honor Two Japanese Scientists

he Japan Society of Clinical Chemistry (JSCC) Technology Award is presented each year to a scientist who has made outstanding academic research in clinical chemistry. At the award presentation, held at the 60th Annual Meeting of JSCC held in Tokyo, on Oct. 30-Nov. 1, the 2020 award winners Mr. Masaki Kobayashi and Ms. Yuri Matsuki were congratulated by Dr. Masato Maekawa, president of JSCC, for their outstanding work in clinical chemistry.

Masaki Kobayashi

Yuri Matsuki

Masaki Kobayashi Wins 2020 JSCC Academic Award Masaki Kobayashi, MS (LS Business, Sysmex Corporation) is the winner of the 2020 JSCC Academic Award, in recognition for his work entitled “Development of OncoGuideTM NCC OncoPanel System”. The OncoGuide™ NCC OncoPanel System was jointly developed by Sysmex and the National Cancer Center in Japan, and became Japan’s first national insurance system for cancer genome profiling in June 2019. This system analyzes solid tumors without specifying the type of cancer, obtains a profile for 114 cancer-related genes, and detects genetic aberration (Mutations, Amplification, Rearrangement). Since non-tumor cells (whole blood) from the same patient are used as controls for tumor tissue (matched pair test), this system is able to exclude patient-specific genetic polymorphisms, detect somatic gene mutations, and calculate tumor mutation burden (TMB) with high accuracy. Matched pair testing is also able to distinguish between germline gene mutations and somatic mutations, thus expanding the drug options. This system showed the following clinical performance in the second phase of the TOP-GEAR project at the National Cancer Center. At least 1 genetic aberration was detected in 156 of the

JUNE 26-30, 2022

187 cases (83%) for which gene profiling data were obtained. In addition, 109 cases (58%) were found to have actionable gene aberrations that have diagnostic and therapeutic significance and 25 cases (13%) have since received molecular‐targeted therapy according to their gene aberrations. In addition, germline mutations causing hereditary cancers were identified in 3% patients. They will continue to promote research and development in order to contribute to medical care in the field of genetic testing and in various other fields. Yuri Matsuki Wins 2020 JSCC Technology Award Yuri Matsuki (Nittobo Medical Co., Ltd.) is the winner of the 2020 JSCC Technology Award, in recognition for her work entitled, “Development of Reagent ‘N-Assay LA IgG4 Nittobo’ for an open system automatic analyzer. Autoimmune pancreatitis (AIP) is known as one of IgG4-related diseases (IgG4-RD). In 2001, Hamano et al. (Shinshu University, Nagano, Japan) reported for the first time in the world that the AIP shows high level of IgG4 in patient’s serum. When the usefulness of IgG4 began to be recognized, IgG4 could only be measured with a reagent from a dedicated automatic analyzer (nephelometry method), which was owned by some major commercial laboratories. Since an open system automatic analyzer was widely used in Japan, general medical institutions did not have a nephelometry analyzer. Therefore, it took several days to a week from the request of the medical institution to obtain the result of IgG4. It was quite difficult for clinicians to use IgG4 value in real time due to the situation. Contributed by Dr. Hideo Sakamoto, International Exchange Committee of JSCC LabMedica International May/2021

News from the World of the International Federation of Clinical Chemistry and Laboratory Medicine Visit www.ifcc.org for more information

MESSAGE FROM THE PRESIDENT By Khosrow Adeli

•

NEWS

President, IFCC

y sincere greetings to you all during these challenging times around the world. Despite entering the third wave of the pandemic, we remain positive about the eventual return to normalcy, thanks to the rapid global vaccination efforts. In waiting for a return to normalcy, the IFCC Executive Board has taken the opportunity to review and revise its conference schedule. Going forward, the IFCC will have one main international conference each year, alternating between the IFCC EuroMedLab in Europe and the IFCC WorldLab in another region. This new schedule offers consistency, prevents overlap, and ultimately will make it easier for all of our IFCC members and regions to regularly attend and participate in these important scientific events. In line with this new conference schedule, the Executive Board has also decided to include all regional federations as conference partners. Now, we are working towards creating new guideline documents for all future conferences to aid in the planning, organization, and execution of these events, thus enhancing the conference experience for all attendees. The new IFCC Task Forces also continue to make progress on a number of fronts. The IFCC Task Force on Global Lab Quality (TF-GLQ) has been planning a pilot program for external quality assurance (EQA) in developing countries. Recently, a survey and a call for applications to participate was sent out and a large number of national societies responded. After extensive discussion, the TF-GLQ has selected ten member countries for participation in the initial pilot program for both iQC and EQA (selected countries include: Malawi, Zambia, Bosnia, Georgia, Serbia, Sri Lanka, Indonesia, Bolivia, Columbia, Peru). Each country will select five laboratories within the region, resulting in a total of 50 participating laboratories. To start, the IFCC will support these laboratories in assessing their preparedness for the iQC and EQA program and addressing existing gaps by securing material and software and developing detailed guidelines for the program. When international travel is permitted, scientific support teams will be dispatched to initiate the program, and once initiated, a plan for maintenance and monitoring will be developed. Eventually, the global quality program will be expanded to include other geographical regions and additional laboratory tests. If interested, members can learn more about the TF-GLQ at www. ifcc.org/executive-board-and-council/ eb-task-forces/task-force-on-global-labquality/. Additionally, the Task Force on COVID-19 has recently developed a

new IFCC interim guidelines on rapid point-of-care antigen testing for SARS-CoV-2 detection in asymptomatic and symptomatic individuals (the guideline document is in press in CCLM, 2021). This document summarizes available data on the performance of currently available SARS-CoV-2 antigen rapid detection tests and provides interim guidance on clinical indications and target populations, assay selection, evaluation, test interpretation and limitations, and pre-analytical considerations. We hope this information aids in the successful implementation of rapid antigen testing protocols to assist global efforts in identifying and isolating SARS-CoV-2 cases earlier. While the pandemic lingers on, there is optimism that life may return to some normalcy in some parts of the world later this summer or fall. I hope we can all focus on the positive and get excited for the future yearly IFCC conferences, startup of the new IFCC programs, and much more. Should you have any feedback, questions, or concerns, please feel free to email me at president@ifcc.org.

Till next time ☺ Khosrow

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LabMedica International May/2021

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NEWS

News from the World of the International Federation of Clinical Chemistry and Laboratory Medicine Visit www.ifcc.org for more information

VIEWPOINT

Coronavirus Vaccine Passports: A Giant Puzzle! by Dr. Bernard Gouget

Chair-IFCC Committee on Mobile Health and Bioengineering in Laboratory Medicine (C-MHBLM), co-Chair IFCC-TF on History, SFBC-International Committee, President-Human Health Care Committee-Cofrac, President-National Committee for selection of the French Reference Laboratories, MoH

hat figure will give the true measure of the calamity that has worn down our societies for more than a year? Global coronavirus cases have reached their highest levels yet, and the consequences of this surge are especially dire in India, which accounts for a third of new infections worldwide. The magnitude of the toll will not show the indirect losses either, all those invisible victims due to postponed operations and medical examinations and delays in diagnosis and treatment. This figure will also not do justice to the colossal efforts, countries, and especially health professionals, have extended to contain it. Infections from SARS-CoV-2 coronavirus are still spreading in several countries. An R just above 1 is enough to reignite this spread. With an R<0.7, infections decrease and with the reduction of cases, we can hope to get the epidemic back under control. Of course, the presence of variants and a less strict lockdown can change the game. But the important thing is to go beyond living with it and move toward a strategy of suppressing the virus. Betting only on vaccines seems haphazard and risky if new variants are emerging to jeopardize the effectiveness of vaccines, if vaccines are not dispensed at the desired rate and if persistent side effects are encountered with some vaccines, imperiling population compliance. Successful countries rely on two pillars: an effective vaccination campaign and adequate measures to minimize virus circulation. It is better from a health, social and economic standpoint to resolve the crisis as quickly as possible rather than let the circulation of the virus drag on and plague society. In the public sphere, if not everyone is protected, it is necessary to maintain preventative measures. Now that the COVID-19 vaccines are here, patients want fast access to them. They carry the promise of family and workplace reunions and new adventures. Countries are thinking about new ways to open their economies safely, or as safely as possible, and to allow their citizens to rediscover a safe social and work life. As COVID-19 vaccination rolls out in parts of the world, many countries have started to implement or are considering the use of COVID-19 “vaccine passports”, paper or digital forms certifying that a person has been vaccinated against COVID-19, for purposes of international travel. Some countries are using them for domestic travel and/or access to certain establishments, activities, and events. The US, UK, and EU are interested, Israel has implemented it. The hope is that vaccine passports will pave the way for economic recovery and restore people’s freedoms, but is it evidence-based and does it violate people’s right to choose? The concept of documenting vaccinations is being taken to new levels of sophistication, and experts predict that electronic verification will soon become commonplace. There are evidence vaccine passports could motivate skeptical citizens to get shots particularly if travel companies and others moved to require proof of vaccination. Vaccine passports could unlock world travel. Countries very dependent on tourism will be able to use the passport to protect their population from the risk of contamination from the outside. Proof of vaccination for travel is not new. Having to show COVID credentials internationally does not pose new ethical problems since the system already exists for diseases such as yellow fever. However, the coronavirus has introduced a potential need to modernize obsolete paper standards. Implementing functional vaccine passports and storing and sharing them and protecting the personal data that they contain are some of the challenges facing designers around the world. While the precise form of these vaccine certificates remains to be determined, dozens of digital applications are in the pipeline. The source of data, the storage thereof, and the information disclosed depend on the group or company that provides the tool. A paper option, with barcodes or QR codes has been proposed by a good number of these applications for people who do not have mobile phones. The challenge is immense. For months, the entrance of travellers into many countries has been conditioned on providing negative COVID-19 test results. Currently, it is easier to obtain the results of this test than it is to prove immunization status. So, to prove that they may enter a country, travellers provide scraps of paper or emails from laboratories, sometimes in a language unknown to the people checking them, and the absence of a standardized format has

led to substantial confusion. Multiple international organizations have already launched efforts to set standards and coordinate the design and implementation of vaccine passports for international travel, to coordinate among member states to provide a public health response to the international spread of diseases. The European Commission plans to set up a digital green certificate this summer to facilitate free and safe travel in the EU during the COVID-19 pandemic. This certificate will prove that an individual has been vaccinated for COVID-19, has received a negative screening test result, or has recovered from COVID-19. It will be available free of charge, in electronic or paper form, and will include a QR code to ensure its security and authenticity. The Commission will set up a portal to ensure that all the certificates can be verified throughout the EU and it will support Member States in the technical implementation of the certificates. The digital certificate will not discriminate against those who have not been vaccinated; the Commission proposes creating not only an interoperable vaccine certificate, but also certificates for COVID-19 screening tests and certificates for people who have recovered from COVID-19. The U.S. government is exploring COVID-19 vaccine certifications for use internationally and domestically. The administration has said that a vaccine passport may be required in the future for international travelers entering the U.S., but it will not impose a federal requirement for domestic purposes. However, it is working with the private sector to develop standards around such certifications. A COVID-19 vaccine certification for international travel could be used by governments in several ways, such as allowing an individual to move across borders more freely by potentially bypassing travel restrictions like testing or quarantine requirements upon arrival. The challenge is to standardize how data in vaccination records are tracked. Creating an environment where vulnerable populations can move around safely and know that people are safe and vaccinated would be an excellent scenario. One thing is sure: it is necessary to homogenize the data included in the various vaccine passports in view of their international use in several languages. It is still an ongoing question as to how populations that are either ineligible or unable to receive the COVID-19 vaccine will be included in a COVID-19 vaccine passport system. A set of standards needs to be defined on which the whole world can rely. One of the most significant hurdles is the sheer number of passport initiatives underway. The Biden administration identified at least 17 of them Last March. Japan Airlines and Quantas are currently testing the CommonPass application. This technology should enable individuals to prove their COVID-19 status and present vital information concerning vaccination, regardless of the language and standards adopted from one region to another. For international travel, vaccine passports may be useful for several years and could be required in one form or another. This is no worse than the requirement to be tested within the past three days. Nationally, since it is hoped that most of the population will be vaccinated in the next few months, setting up a general passport forces us to think about the constraints that this would entail. If it is well designed, it should not pose a risk regarding personal data nor become a means for the administration to have intrusive access to the health status of fellow citizens. But it could become oppressive if one is required to show it on a bus, or to go into a store to buy a magazine, etc. The free choice to be vaccinated is lost and some people might be offended by the discrimination this could create between supposedly free and equal citizens. Admittedly this could offer a breath of fresh air to occupations that have suffered (culture, tourism, hospitality), but if vaccine doses are hard to come by and as long as all those who wish to be vaccinated have not been able to do so, it becomes difficult to practice at the national level. This could be seen as a surreptitious way of making the vaccine more or less compulsory. It is better to encourage people to be vaccinated, especially people exposed to patients in the workplace. Should we go further and move from injunction to obligation? There is no doubt that the effects could be counterproductive. If it is required, this means that we cannot reassure people of its safety. Proper education is better than authoritarianism. Many countries have sought magical solutions to stop the pandemic. The urgency of the moment is not so much the passport but the vaccination. The most obvious issue is that it is still unclear whether vaccination prevents transmission, and what are the strength and duration of immunity provided. Vaccinated people may still be able to unknowingly spread the virus. That is why, on Feb 7, the WHO released a statement dissuading nations from Cont’d on page 33 LabMedica International May/2021

To view this issue in interactive digital magazine format visit www.LinkXpress.com

Industry News

Swamped by Surge in Testing Demand, Mid-Sized Labs Turn to Automation Solutions

cont’d from cover

on hospitals and health systems, and physically and mentally exhausted laboratory professionals -- a pre-pandemic problem that has since been exacerbated. However, the Total Laboratory Automation (TLA) solutions that cater to labs processing high sample volumes remain out of reach for smaller volume labs due to space requirements and infrastructure constraints. Now with a workflow automation solution designed to serve medium-sized laboratories, clinical labs that run fewer than 5,000 tests a day can enjoy the same benefits as a larger-volume lab. The DxA 5000 Fit, just introduced globally by Beckman Coulter (www.beckman.com; Brea, CA, USA), is based on a comprehensive workflow automation platform that, through pre-analytical, analytical, and post-analytical au-

tomation, reduces manual steps by up to 80%, thereby conserving precious human resources for higher-value clinical work. The new system offers intelligent routing with dynamically calculated route planning for rapid and consistent TAT, with STATs always prioritized to deliver results faster. Additionally, its flexible design can be adapted to meet a mid-volume lab’s space and infrastructure constraints. “At Beckman Coulter, we believe that medium-size labs should be able to leverage the benefits of automation to address their challenges. Just because your lab is not processing a higher number of samples, doesn’t mean you have to sacrifice the benefits of intelligent laboratory automation and settle for a marginally automated workcell-plus solution,” said Dr. Peter Soltani, senior vice president & general manager, hematology, urinalysis & workflow information

technology solutions at Beckman Coulter. “This is why we have launched DxA 5000 Fit, the first compact workflow automation solution that’s the right fit for mid-volume labs because automation should be for all labs.” The DxA 5000 Fit, just launched globally by Beckman Coulter, is a workflow automation system dedicated to the needs of medium-sized labs that run fewer than 5,000 tests a day.

Global Digital PCR and Real-Time PCR Market Growth Driven by Increasing Cases of Infectious Diseases

Increasing cases of infectious diseases, rising geriatric population and growing number of genetic disorders will propel the growth of the global digital PCR and real-time PCR market over the next decade. Additionally, PCR advances, fulfillment of the human genome project, and expanding R&D will increase the utilization of biomarker profiling for sickness diagnostics, thus further driving market growth. These are the latest findings of TMR Research (San Francisco, CA, USA), a provider of customized market research and consulting services. The interest in genomic examination strategies has increased consistently during the most recent decade due to their expanding use in the analysis of major illnesses (like HIV, tuberculosis, intestinal sickness, and hepatitis) and hereditary problems (like malignancy). The development in the commonness of target illnesses worldwide, combined with the demonstrated adequacy of qPCR and dPCR examination in the determination and assessment of sickness-causing microorganisms, will drive the utilization of clinical indicative tests (including

Coronavirus Vaccine Passports: A Giant Puzzle! Cont’d from page 32 using vaccine passports as a requirement for entry or exit, stating that there are still critical unknowns and there is a need for further scientific investigation into COVID-19 vaccine products and recently reiterated its opposition. It should be ensured that vaccine passports are standardized internationally in design and use, also that they do not violate ethical standards or antidiscrimination laws. We must not forget that most people in low and middle-income countries do not have access to COVID 19 vaccines and may not until 2023 or later…Reliable and accessible proof of the protection conferred by COVID-19 vaccination could accelerate travel and reopening of the economy, but the obstacles to large-scale adoption of a vaccine passport system, as well as problems of data privacy or interoperability and equity, are so substantial that such a system seems premature today.

LabMedica International May/2021

qPCR and dPCR investigation) and support market development. Geographically, North America is expected to dominate the global digital PCR and real-time PCR market, followed by Europe. The development of the North American qPCR and dPCR market will be driven by an expanded selection

of innovative and novel genomic examination items (including progressed qPCR and dPCR items), accessibility to R&D financing for genomic research, growing utilization of PCR methods in clinical diagnostics and criminology, and early commercialization of qPCR/dPCR items.

ATTENTION: Due to the CORONAVIRUS PANDEMIC, many events are being rescheduled for a later date, converted into virtual venues, or altogether cancelled. Please check with the event organizer or website prior to planning for any forthcoming event

Events Calendar For a free listing of your event or a paid advertisement in this section contact:

International Calendar LabMedica International E-mail: info@globetech.net

MAY ISLH 2021 – International Society of Laboratory Hematology. May 4-7; Virtual Venue; Web: www.islh.org Immunology 2021 – Annual Meeting of the American Association of Immunologists (AAI). May 10-15; Virtual Venue; Web: www.immunology2021.org ASRI 2021 – 40th Annual Meeting of the American Society for Reproductive Immunology. May 14-21; Virtual Venue, USA; Web: www. theasri.org ECE 2021 – 23rd European Congress of Endocrinology. May 22-26; Virtual Venue; Web: www.ese-hormones.org KoreaLab 2021. May 25-28; Seoul, Korea; Web: www.korealab.org AFCB Congress 2021 – Arab Federation for Clinical Biochemistry and Laboratory Medicine. May 27-29; Beirut, Lebanon; Web: www. ifcc.org JUNE ExpoMED Eurasia 2021. Jun 2-4; Istanbul, Turkey; Web: expomedistanbul.com

ASCO 2021 – Annual Meeting of the American Society of Clinical Oncology. Jun 4-8; Virtual Venue; Web: am.asco.org

professional.diabetes.org/scientific-sessions

FOCIS 2021 – Annual Meeting of the Federation of Clinical Immunology Societies. Jun 8-11; Virtual Venue; Web: www.focisnet.org Virtual Pathology Days 2021 – German Society for Pathology. Jun 8-12; Virtual Venue; Web: www.pathologie-dgp.de

ESHRE 2021 – 37th Annual Meeting of the European Society of Human Reproduction and Embryology. Jul 26-30; Virtual Venue; Web: www.eshre.eu/ESHRE2021 JULY ECCMID 2021 – 31st European Congress of Clinical Microbiology & Infectious Diseases. Jul 9-12; Virtual Venue; Web: www.eccmid.org

26th Annual Congress of the European Hematology Association (EHA). Jun 9-17; Virtual Venue; Web: ehaweb.org

EAACI Hybrid Annual Congress 2021 – European Academy of Allergy and Clinical Immunology. Jul 10-12; Krakow, Poland; Web: www. eaaci.org

ESHG 2021 – European Human Genetics Conference. Jun 12-15; Virtual Venue; Web: www. eshg.org

IAS 2021 – 11th International AIDS Society (IAS) Conference on HIV Science. Jul 18-21; Virtual Venue; Web: ias2021.org

BIO International Convention 2021 Jun 10-18; Virtual Venue; Web: convention.bio.org UKMedLab21 – Annual Conference of the Association for Clinical Biochemistry & Laboratory Medicine (ACB). Jun 14-18; Virtual Venue; Web: www.acb.org.uk

ASV 2021 – 40th Annual Meeting of the American Society of Virology. Jul 19-23; Virtual Venue; Web: asv.org/asv2021 AUGUST

FIME 2021 – Florida International Medical Expo. Sep 1-3; Miami, FL, USA; Web: www. fimeshow.com Thailand LAB International 2021. Sep 1-3; Bangkok, Thailand; Web: www.thailandlab.com ECI 2021 – 6th European Congress of Immunology. Sep 1-4; Virtual Venue; Web: eci2021.org 43rd Annual Meeting of the European Thyroid Association (ETA). Sep 4-7; Virtual Venue; Web: www.eta2021.com ESCV – 23rd Annual Meeting of the European Society for Clinical Virology. Sep 15-17; Virtual Venue; Web: www.escv2021.org ExpoMedical 2021. Sep 22-24; Buenos Aires, Argentina; Web: www.expomedical.com.ar AFCC Congress 2021 – African Federation of Clinical Chemistry. Sep 23-25; Lusaka, Zambia; Web: www.ifcc.org India Lab Expo & Analytica Anacon India. Sep 23-25; Hyderabad, India; Web: www.analyticaindia.com

World Microbe Forum – American Society for Microbiology (ASM) & Federation of European Microbiological Societies. Jun 20-24; Virtual Venue; Web: www.worldmicrobeforum.org

11th African Congress of Immunology – Federation of African Immunological Societies. Aug 1-5; Lilongwe, Malawi; Web: www.faisafrica. com

Medlab Middle East 2021. Jun 21-24; Dubai, UAE; Web: www.medlabme.com

Medical Fair India 2021. Aug 19-21; New Delhi, India; Web: www.medicalfair-india.com

SLAS Europe 2021 Conference & Exhibition – Society of Laboratory Automation and Screening. Jun 22-25; Vienna, Austria; Web: slaseurope2020.org

IFBLS 2021 – International Federation of Biomedical Laboratory Science. Aug 24-28; Copenhagen Denmark; Web: ifbls2021.org

73rd AACC Annual Scientific Meeting & Clinical Lab Expo – American Association for Clinical Chemistry. Sep 26-30; Atlanta, GA, USA; Web: www.aacc.org

33rd Congress of the European Society of Pathology (ESP). Aug 29-31; Virtual Venue; Web: www.esp-congress.org

EUROTOX 2021 – 56th Congress of the European Societies of Toxicology. Sep 26 - Oct 1; Virtual Venue; Web: eurotox-congress.com

81st Scientific Sessions of the American Diabetes Association. Jun 25-29; Virtual Venue; Web:

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LabMedica International May/2021

ASHI 2021 – 47th Annual Meeting of the American Society for Histocompatibility & Immunogenetics. Sep 27 – Oct 1; Orlando, FL, USA; Web: www.ashi-hla.org

MEDICA 2021. Nov 15-18; Dusseldorf, Germany; Web: www.medica-tradefair.com

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AMP 2021 –Annual Meeting & Expo of the Association for Molecular Pathology. Nov 18-20; Philadelphia, PA, USA; Web: www.amp.org

EASD 2021 – 57th Annual Meeting of the European Association for the Study of Diabetes. Sep 27 - Oct 1; Virtual Venue; Web: www. easd.org

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Analitica Latin America 2021. Sep 28-30; Sao Paulo, Brazil; Web: www.analiticanet.com.br

ASCP 2021 – Annual Meeting of the American Society for Clinical Pathology. Oct 27-29; Boston, MA, USA; Web: www.ascp.org

58th Annual Scientific Conference of the Australasian Association of Clinical Biochemistry and Laboratory Medicine (AACB). Sep 28-30; Brisbane, Australia; Web: www.aacb.asn.au 90th Annual Meeting of the American Thyroid Association (ATA). Sep 29 - Oct 3; Virtual Venue; Web: www.thyroid.org OCTOBER

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ECC 2021 – 43rd European Congress of Cytology. Oct 3-6; Wroclaw, Poland; Web: cytology2021.eu

61st Annual Academic Assembly of the Japan Society of Clinical Chemistry. Nov 5-7; Fukuoka, Japan; Web: jscc-jp.gr.jp

Journées Francophone de Biologie Médicale (JFBM). Oct 6-8; Rennes, France; Web: www. jfbm.fr

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MEDLAB Asia Pacific 2021. Oct 20-22; Bangkok, Thailand; Web: www.medlabasia.com

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Pittcon 2022. Mar 5-9; Atlanta, GA, USA; Web: pittcon.org IMPE 2022 – 11th International Meeting of Pediatric Endocrinology. Mar 19-22; Buenos Aires, Argentina; Web: www.impe2022.org COLABIOCLI 2022 – 25th Latin American Congress of Clinical Biochemistry. Mar 28 - Apr 2; Leon, Mexico; Web: colabiocli2022.com

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Labquality Days 2022 – International Congress on Quality in Laboratory Medicine. Feb 10-11;

WSPID 2022 – 12th World Congress of the World Society for Pediatric Infectious Diseases. Feb 22-24; Virtual Venue; Web: wspid2021. com

India Lab Expo & Analytica Anacon India. Apr 20-21; Mumbai, India; Web: www.analyticaindia.com

Arab Lab 2021. Nov 15-17; Dubai, UAE; Web: www.arablab.com

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Helsinki, Finland; Web: www.labqualitydays.fi

Zdravookhraneniye 2021 – Russian Health Care Week. Dec 6-10; Moscow, Russia; Web: www.zdravo-expo.ru/en

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IFCC WorldLab Seoul 2022 – 24th International Congress of Clinical Chemistry and Laboratory Medicine. Jun 26-30; Seoul, Korea; Web: www. ifcc.org ICE 2022 – 20th International Congress of Endocrinology. Aug 25-28; Singapore; Web: www.isendo.org APFCB 2022 – 16th Congress of the Asia-Pacific Federation of Clinical Biochemistry and Laboratory Medicine. Oct 15-18; Sydney, Australia; Web: apfcbcongress2022.org

Advertising Index Page

Vol. 38 No. 3 5/2021

Inq.No. Advertiser

Page

– AACC. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 123 Alcor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 125 Bioperfectus. . . . . . . . . . . . . . . . . . . . . . . . . . 25 109 DiaSys. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 – Euromedlab 2021. . . . . . . . . . . . . . . . . . . . . . 33 113 Euroimmun . . . . . . . . . . . . . . . . . . . . . . . . . . 13 121 Instrumentation Laboratory . . . . . . . . . . . . . . 21 – LabMedica. . . . . . . . . . . . . . . . . . . . . . . . . . . 19 105 NG-Biotech. . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 102 Nova Biomedical . . . . . . . . . . . . . . . . . . . . . . . 2 115 Nova Biomedical . . . . . . . . . . . . . . . . . . . . . . 15 117 Randox. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 111 Awareness. . . . . . . . . . . . . . . . . . . . . . . . . . . 11 103 Snibe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 136 Snibe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 – TradeMed. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 120 Vicotex. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 107 Vircell. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Provided as a service to advertisers. Publisher cannot accept responsibility for any errors or omissions.

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