LabMedica International September 2016 by Globetech

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W O R L D ’ S C L I N I C A L L A B O R AT O R Y N E W S L E A D E R ISSN 1068-1760

Vol. 33 No. 5 • 8-9/ 2016

DAILY CLINICAL LAB NEWS

Urine Dipstick Test For Malaria Diagnosis

Molecular Diagnostics Identifies Resistance Biomarkers of Bloodstream Infection

alaria is the world’s most important tropical parasitic disease and a leading cause of death worldwide and the disease is caused by the parasite, Plasmodium species and transmitted to humans by infected mosquitoes. Symptoms include fever and usually appear 10 to 15 days after someone is bitten by an infected mosquito.

olecular diagnostics allow for rapid identification and detection of resistance markers of bloodstream infection, with a potential for accelerated antimicrobial optimization and improved patient outcomes. Bloodstream infections (BSIs) are associated with significant health care cost and prolonged hospital stays.

Rapid initiation of effective antimicrobial treatment is a mainstay of therapy because delay is associated with increased morbidity and mortality. Novel methods that allow for rapid identification of pathogens, with the ability to detect resistance markers, are, therefore, promising tools to significantly affect overall patient care.

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IVD Industry Mobilizes to Provide Zika Diagnostics

Blood Clots Detected By Simple POC Test atients with cardiovascular disease, hypertension, atrial fibrillation, congestive heart failure, kidney disease and others who are at risk for blood clotting are especially vulnerable when blood-thinning medication levels get too weak or too strong. A test has been designed to give each patient the ability to keep a careful check on their levels by monitoring the changes that occur relative to previous tests. The technology can also be

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Novel Blood Biomarker Identified for Autism

Special Section: Zika Update (Pages 8-11)

arly intervention is the key to the best treatment for autism spectrum disorder (ASD), which affects about 1 in 70 children. Unfortunately, most children are not diagnosed until about age four, when communication and social disabilities become apparent. Blood biomarkers have been identified that could distinguish the majority of ASD study participants versus a control group of similar age range. In

New Optimized Tests for Reliable Zika Diagnosis High-Resolution Zika Detection With CRISPR Technology Image: Courtesy of EUROIMMUN

Urine Trumps Blood For Zika Testing Zika Test Cleared for Emergency Use Multiplex Molecular Test For Three Arboviruses

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System Improves Accuracy of Low Cell Counts in Cerebrospinal Fluid Samples new technology offers quantitative determinations of red blood cells (RBCs) and total nucleated cells (TNCs) in Cerebrospinal Fluid (CSF), thereby greatly improving on the challenges of diagnosing low cell counts.

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Blood Marker Determines Response To Colorectal Cancer Drug

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marker has been identified that shows up in a blood test that determines which patients with colorectal cancer that has metastasized would benefit from receiving the drug cetuximab. Only a proportion of patients with colorectal cancer receiving cetuximab derive benefit from the drug; however,

other than the Rat sarcoma gene(RAS) and B-RAF oncogene (BRAF) mutations, no biomarkers have been identified as clinically useful predictors of response to cetuximab. Scientists at the Princess Margaret Cancer Centre (Toronto, ON, Canada; www.uhn.ca) and their international Cont’d on page 7

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LabMedica International

Blood Clots Detected By Simple POC Test

Scientists at the Keck School of Medicine (Los Angeles, CA, USA; www.keck.usc.edu) determined the impact of a molecular blood-culture assay that identifies a broad-spectrum of pathogens and resistance markers in pediatric patients with gram-positive bloodstream infections. The team collected data on the time to antimicrobial optimization, the length of hospitalization, and the hospital cost following implementation of a rapid assay were prospectively collected and compared with corresponding preimplementation data. Blood culture samples from pediatric patients, aged one day to 21 years, who presented with a blood culture positive for a gram-positive bacteria targeted by the GramPositive Blood Culture Nucleic Acid Test (BC-GP, Nanosphere Inc., Northbrook, IL, USA; www.nanosphere.us) were included. The microbiology laboratory operates and offers all tests 24 hours/day, seven days/week. Input from the infectious disease team was dependent on consultation request. Institutional policy mandates a consultation for all BSIs caused by Staphylococcus aureus. All blood culture V

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EDITORIAL BOARD Graham Beastall United Kingdom Claus Christiansen Denmark Hernán Fares Taie Argentina Bernard Gouget France Jocelyn M. Hicks United States Anders Kallner Sweden Tahir S. Pillay South Africa Christopher Price United Kingdom Andreas Rothstein Colombia Dmitry B. Saprygin Russia Rosa I. Sierra-Amor Mexico Gérard Siest France 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) and European Federation of Clinical Chemistry and Laboratory Medicine (EFLM). HospiMedica International • HospiMedica en Español • HospiMedica China LabMedica International • LabMedica en Español • LabMedica China Medical Imaging International • Bio Research International • Medimaging.net HospiMedica.com • LabMedica.com • BiotechDaily.com • TradeMed.com

tential blood-clotting problems early enough, we hope to prevent potential injury or death and the exorbitant associated costs.” The study was presented at the 8th International Conference on Porous Media and Annual Meeting of the International Society for Porous Media, held May 9-12, 2016, in Cincinnati, OH, USA. Image: Nanofiber membranes inside a paper-porous test strip form the basis of blood clot test (Photo courtesy of the University of Cincinnati).

Molecular Diagnostics Identifies Resistance Biomarkers of Bloodstream Infection cont’d from cover

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calibrated to a specific patient’s condition. For example, a patient whose normal blood coagulation rate is significantly different from the general population because of a genetic disorder can use a tailor-made test kit that includes a different porous membrane. Scientists at the University of Cincinnati (OH, USA; www.uc.edu) used nanofiber membranes inside paperbased porous materials housed within a plastic cassette, which can quickly reveal the level of the blood’s ability to clot, and all from the convenience of the patient’s home with a simple finger stick to draw a drop of blood. While slight changes in the level of coagulation properties will occur normally depending on certain food intake and overall health conditions. A major change in levels immediately shows up on the paper-based test stick resulting in clotting patterns registering on one end of the spectrum or the other and will put up a red flag before any physiological trouble starts. Andrew Steckl, PhD, a professor of electrical engineering, said, “We have developed a blood screening device for patients on medications like Coumadin, warfarin or other blood thinners who need to monitor their blood-clotting levels on a regular basis. Patients can soon monitor their blood coagulation characteristics from home quickly and painlessly before making needless trips to the laboratory or hospital. By identifying po-

specimens were obtained and processed using the BacT/ALERT (bioMérieux; Durham, NC, USA; www. biomerieux-usa.com) automated blood culture system. There were 440 episodes from 383 patients included: 221 preimplementation episodes and 219 postimplementation episodes. The BC-GP assay implementation significantly reduced the average time of Gram stain report to organism identification from 24.8 hours to 3.8 hours. In addition, time from Gram stain notification to detection of methicillin-resistant S. aureus, methicillin-resistant S. epidermidis, and vancomycin-resistant enterococci was significantly shortened by 45.9 hours following BC-GP assay implementation (49.7 hours versus 3.8 hours). Median length of stay for patients admitted to general pediatric units was 1.5 days shorter, and median hospital cost was USD 3,757 less after implementation. For S. aureus bloodstream infections, median length of stay and hospital cost were decreased by 5.6 days and USD13, 341 respectively. The authors concluded that implementation of molecular assay for the detection of gram-positive pathogens and resistance markers significantly reduced time to identification and resistance detection, resulting in accelerated optimization of therapy, shorter length of stay, and decreased health care cost. Implementation of the BC-GP assay contributed to a reduction in time to appropriate antimicrobial therapy, regardless of patient population, and a decrease in length of stay (LOS) and overall hospital costs among patients without other significant comorbidities. Further integration with the antimicrobial stewardship team may further improve time to optimal therapy and patient outcome. The study was published in the March 2016 issue of the journal Archives of Pathology & Laboratory Medicine.

Dan Gueron Joseph Ciprut Raymond L Jacobson, PhD Jacqueline Miller, PhD Andreas Rothstein Gerald M Slutzky, PhD Marcela Jensen Brenda Silva Paul Mills Doris Mendieta Dr. Jutta Ciolek Carolyn Moody Arda Turac Elif Erkan

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ISSN 1068-1760 Vol.33 No.3. Published, under license, by Globetech Media LLC; Copyright © 2016. 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. S¸ti. adına ˙Imtiyaz Sahibi: M. Geren • Yazı is¸leri Müdürü: Ersin Köklü Müs¸ ir Dervis¸ ˙Ibrahim Sok. 5/4, Esentepe, 34394 S¸is¸ li, ˙Istanbul P. K. 1, AVPIM, 34001 ˙Istanbul • E-mail: Teknopress@yahoo.com Baskı: Promat Web Ofset Tesisi • Orhangazi Mahallesi 1673. Sokak, No: 34 • 34510 Esenyurt, B. Çekmece • ˙Istanbul Yerel süreli yayındır. Yılda sekiz kere yayınlanır, ücretsiz dag˘ıtılır.

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LabMedica International

Urine Dipstick Test for Malaria Diagnosis cont’d from cover

While easily treated, proper early diagnosis is critical to successful management, since many diseases in tropical areas of the world are characterized by fever, but left untreated the parasites multiply in the liver and can become life-threatening. A Nigerian scientist and a team at Johns Hopkins University (Baltimore, MD, USA; www. jhu.edu) have developed a Urine Malaria Test (UMT), currently in clinical validation, is indicated for use in individuals who present with fever suspected of being malaria. The UMT, which licensed with exclusive global rights from Johns Hopkins University, incorporates a novel dipstick technology that is ideal for rapid point-of-need diagnosis of clinical malaria from urine instead of blood, and offers significant advantages over microscopy and other malaria diagnostics, which require the use of blood. The UMT dipstick detects novel Plasmodium proteins shed in the urine of febrile malaria patients and can be performed and read by persons with little or no training. These novel proteins or fragments are not cleaved by any known proteases, are highly immunogenic and elicit early immune response, and thus present as early markers of clinical malaria. The UMT is a sensitive and specific im-

munochromatographic lateral flow assay, which can be easily performed by an untrained individual using a urine sample. To perform, the test strip is dropped into a clean container with as little as 100 μL of urine, allowed to flow up the strip for 1 to 2 minutes, and incubated at room temperature for 20 minutes. If two visible lines appear on the strip, the test is positive; if one line appears, the test is negative. The UMT demonstrates equivalent performance compared to commercially available blood-based rapid tests for the diagnosis of clinical malaria, with a limit of detection of 125 parasites/μl, well within the 100 to 200 parasites/μl analytical performance range recommended for malaria rapid diagnostic tests by the World Health Organization (Geneva, Switzerland; www.who.int). The UMT is being manufactured by Fyodor Biotechnologies, Inc (Baltimore, MD, USA; www.fyodorbio.com).

Image: The Urine Malaria Test (UMT), an immunochromatographic lateral flow assay (Photo courtesy of Fyodor Biotechnologies).

System Improves Accuracy Of Low Cell Counts in Cerebrospinal Fluid Samples dvanced Instruments, Inc. (Norwood, MA, USA; www.aicompanies.com) has received 510(k) clearance from the US Food & Drug Administration (FDA) to market its GloCyte Automated Cell Counter System and GloCyte Low and High Level Controls. The patented GloCyte System is intended to provide a quantitative determination of red blood cells (RBCs) and total nucleated cells (TNCs) in CSF collected from adult and pediatric patients. Currently, low cell counts often present a challenge to standard methods. The system provides superior accuracy of low cell counts in cerebrospinal fluid samples. It was introduced at the 67th AACC Annual Scientific Meeting & Clinical Lab Expo in Philadelphia (July 31 - August 4). “To date, there has not been a way to provide dependable, low cell counts,” said John Coughlin, president and CEO, Advanced Instruments, “We use a novel combination of fluorescence, microscopy with digital image analysis principles, highly specific reagents, and an intelligent counting algorithm to provide accurate and precise cell counts. We are very excited as this marks a major achievement in giving laboratories a new way to obtain reliable and timely CSF results.” Additional benefits of the GloCyte System are that the test requires only 30 microliters of sample per test, it uses disposable test cartridges ensuring no sample carryover and easy disposal, and it includes built-in quality control of Levey-Jennings charts and an audit table. The company expects to begin GloCyte shipments in September 2016.

LabMedica International August-September/2016

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Biomarker Identifies Uveal Melanoma Patients At Risk for Metastasis veal melanoma is a cancer (melanoma) of the eye involving the iris, ciliary body, or choroid, collectively referred to as the uvea. Tumors arise from the pigment cells (melanocytes) that reside within the uvea giving color to the eye. Uveal melanoma (UM) can be classified by gene expression profiling (GEP) into Class 1 (low metastatic risk) and Class 2 (high metastatic risk), the latter being strongly associated with mutational inactivation of the tumor suppressor gene BRCA1 Associated Protein-1 (Ubiquitin CarboxyTerminal Hydrolase (BAP1). Scientists at the University of Miami Miller School of Medicine (Miami, FL, USA; www.miami.edu) performed genome-wide analysis of messenger ribonucleic acid (mRNA) isolated from five class 1 uveal melanomas that metastasized and eight class 1 tumors that did not metastasize. A total of 389 consecutive patients with UM were assigned to Class 1 or Class 2 using a prospectively validated 12-gene prognostic classifier. Selected tumors were further analyzed using global GEP and single nucleotide polymorphism microarrays. PRAME (preferentially expressed antigen in melanoma) mRNA expression was analyzed in 64 Class 1 tumors by quantitative polymerase chain reaction (PCR). Among 64 class 1 uveal melanoma samples analyzed by quantitative PCR, 39 (61%) had low levels of PRAME mRNA (PRAME negative) and 25 (39%) had high levels of PRAME mRNA (PRAME positive). None of the patients with PRAME-negative tumors developed metastasis while seven of the patients with PRAME-positive tumors did. The 5-year actuarial rate of metastasis was 0% for

Class1PRAME–, 38% for Class1PRAME+, and 71% for Class 2 tumors. Median metastasis-free survival for Class1PRAME+ patients was 88 months, compared to 32 months for Class 2 patients. J. William Harbour, MD, the senior author of the study said, “We were surprised to find that one biomarker alone PRAME was sufficient to identify the subgroup of class 1 tumors with increased metastatic risk. These findings could have immediate clinical impact. The data imply that patients with class 1 uveal melanomas with increased PRAME expression should be managed differently than patients with class 1 uveal melanomas without PRAME expression. They should be monitored more closely for metastatic disease and they should be considered for clinical trials of adjuvant therapy.” The study was published on March 1, 2016, in the journal Clinical Cancer Research. Image: A cancer of the iris known as uveal melanoma (Photo courtesy of Dr. Jonathan Trobe, MD). LabMedica International August-September/2016

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LabMedica International

Novel Blood Biomarker Identified for Autism cont’d from cover

addition, the biomarker was significantly correlated with the level of communication impairment, suggesting that the blood test may give insight into ASD severity. Scientists at the University of Texas Southwestern Medical Center (Dallas, TX, USA; www. utsouthwestern.edu) recruited for an ASD group 74 male subjects with a median age of 5.6 years; 60 males with a median age of 6.3years for a typically developing group (TD), 10 ASD females and 20 TD females. For a control group 53 adult male serum samples were obtained whose median age was 69 years. A fasting blood draw was performed on all ASD and TD subjects. Since other studies have found abnormalities in the immune systems of autistic

children, the scientists set out to search for antibodies in the blood related to ASD. The teams used various techniques to isolate biomarkers. These included peptoid library synthesis, on-bead magnetic screening, peptoid enzyme-linked immunosorbent assay (ELISA), affinity purification of peptoid-binding proteins, gel electrophoresis and Coomassie Blue staining. The investigators found that found that boys with ASD had significantly reduced levels of a serum immunoglobulin G1 (IgG1) antibody. Investigating further, they analyzed 25 peptoid compounds that bound to IgG1 and zeroed in on one, ASD1, that was 66% accurate in diagnosing ASD.

When combined with thyroid stimulating hormone level measurements, the ASD1-binding biomarker was 73% accurate at diagnosis. Girls made up a small ratio of the study group, and the biomarker did not correlate as strongly with ASD diagnosis as with boys. Dwight German, PhD, a Professor of Psychiatry and senior author of the study said, “Numerous investigators have long sought a biomarker for ASD. The blood biomarker reported here along with others we are testing can represent a useful test with over 80% accuracy in identifying ASD.” The study was published in the June 2016 issue of the journal Scientific Reports.

Blood Marker Determines Response to Colorectal Cancer Drug cont’d from cover

colleagues used formalin-fixed and paraffin-embedded (FFPE) normal and tumor tissue samples from local sites were archived at a central tumor bank, where a single 1.2-mm diameter core was taken from each block. Extracting DNA from glass slides (some over a decade old) yielded highly variable success; thus, only DNAs obtained from cores were analyzed. DNA was extracted using the QIAamp FFPE DNA Kit (Qiagen, Hilden, Germany; www.qiagen.com). DNA quantity (spectrophotometry) and quality (polymerase chain reactions) were checked. DNA was genotyped blindly by Transgenomic, Inc (New Haven, CT, USA; www.transgenomic.com) using Sanger sequencing. Geoffrey Liu, MD, a senior scientists and lead author said, “Our study discovered that the blood marker Fc- receptor FCGR2A identifies a new group of patients that will benefit from taking cetuximab. With this finding, we believe we are now on the way to move it into the clinical setting to provide patients targeted, effective treatment. Our finding, which resulted from analyzing archived tumor and normal tissue samples from some of the 572 patients enrolled in that trial, further refines this quest and defines another subset of patients who will respond to the drug. So instead of looking at aspects in the tumors, which is where RAS mutations show up, we looked at certain things in the blood and normal tissues that we could measure for heritable genetic variations.” The study was published on May 15, 2016, in the journal Clinical Cancer Research.

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Special Section: Zika Update Optimized Tests for Highly Reliable Diagnosis of Zika pon finding that several conventional Zika virus tests are not sufficiently reliable, scientists have developed and made available optimized assays as well as a control for quantifying Zika virus RNA in patient samples (blood and urine). Diagnosing viruses reliably is of major importance for individual patients and for monitoring and research on virus spread in populations. Currently, acute Zika infections are predominantly confirmed by genetic analysis. Six tests developed prior to the outbreak are currently being used. However there has been concern that numerous Zika infections are going undetected: can they detect viral RNA at very low concentrations? Are they sensitive enough to identify Zika virus strains? Are their results comparable to each other? A scientific team from the German Center for In-

fection Research (DZIF; Braunschweig, Germany; www.dzif.de/en) and the University of Bonn (Bonn, Germany; www.uni-bonn.de), led by Prof Felix Drexler and Prof Christian Drosten, has now carefully examined the existing tests and developed optimized assays. The team previously developed the globally used, standardized test for the MERS pathogen. All currently used PCR assays test for Zika virus RNA; they differ especially in examining different regions. PCR tests are suitable for early virus detection in the first weeks after onset of symptoms, whereas serological tests for patient antibodies to Zika virus are recommended for use after the 8th day. Toward minimizing diagnostic uncertainties, the team initially compared the commonly used PCR tests for sensitivity. The comparison confirmed the concerns: that some of the tests were not sensitive enough to detect low concentrations of viruses. Additionally, not all virus strains are detected uniform-

Image: A transmission electron micrograph (TEM) of Zika Virus particles (red) (Photo courtesy of the CDC / Cynthia Goldsmith).

ly across the testing systems. Comparability between the assays is limited. The researchers assume that, depending on the system, 20-80% of patients may be incorrectly diagnosed, if serological testing methods are not used for further analysis. The team consequently developed two optimized PCR tests, as well as a “calibrator” control that not only validates each test but also quantifies the viral RNA in the sample. The calibrator is synthetically constructed RNA that contains all the different viral RNA target zones used in the different conventional PCR tests. “With our study, we especially wanted to call attention to the fact that a negative PCR test is not necessarily reliable,” explained Prof. Drexler. The researchers have already made their results freely available prior to publication on the World Health Organization (WHO) server. The test protocols and calibrator can be ordered free of charge. The project was supported by DZIF and the European Union. In such outbreak situations, all parties involved should exchange data as early as possible and have access to the best diagnostic tools available. The study, by Corman VM et al, was published online April 19, 2016, in the Bulletin of the World Health Organization.

CRISPR-Based Technology Enables High-Resolution Zika Detection on Low-Cost Paper Discs uilding off their earlier innovative development in “programmable diagnostics”, researchers on an international, multi-institutional team recently joined efforts to quickly prototype their low-cost rapid test with the goal that it could soon be used to screen samples (blood, urine, or saliva) for Zika virus and strain identification. The team, led by synthetic biologist Prof. James Collins, Wyss Institute for Biologically Inspired Engineering at Harvard University (Boston, MA, USA; http://wyss.harvard.edu) and Massachusetts Institute of Technology (USA), has developed the paper-based system for strain-specific detection as an inexpensive method to help slow the spread of Zika outbreak, and potentially of other future pandemic diseases. “The growing global health crisis caused by the Zika virus propelled us to leverage novel technologies we have developed in the lab and use them to create a workflow that could diagnose a patient with Zika, in the field, within 2-3 hours,” said Prof.

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Collins. “We hope a tool like this can help reduce the impact of the outbreak until a vaccine can be developed,” said co-first author Dr. Keith Pardee, University of Toronto (Canada). In 2014, the team developed a breakthrough method for embedding synthetic gene networks – which could be used as programmable diagnostics and sensors – on small paper discs. Stirred by the then-ongoing Ebola outbreak in Africa, they demonstrated a proof-of-concept color-changing diagnostic that could screen for Ebola by embedding in paper a novel kind of synthetic biomolecular sensor designed to screen for specific RNA sequences, which could mark not only genetic signatures of Ebola but also other RNA viruses (e.g. Zika, SARS, measles, influenza, hepatitis C, West Nile fever). A major challenge was the extremely low concentration of virus normally found in blood, urine, and saliva. Now, using blood samples from monkeys infected with Zika virus as well as virus recovered from cells infected in the laboratory, the team has validated a next-generation technique that overcomes this problem. With field-use in mind, the team designed a simple modular workflow comprising 3 steps: amplification, Zika detection, and CRISPR-aided strain identification. Once a sample’s RNA has been amplified, it is added onto freeze-dried paper discs containing biomolecular components. The droplet of amplified RNA activates the freeze-dried components so that the discs will change color to indicate a positive result for Zika virus. While the result can be read with the naked eye similar to a home pregnancy test, a specially designed electronic reader can also be used to get faster results and could, one day, quantify the amount of viral load in a sample. If Zika is detected, the third step involves mixing a sample with a freeze-dried CRISPR (i.e. CRISPR-Cas9) cocktail and then using that mixture to wet another set of color-changing paper discs. Depending on the type of Zika strain in the sample, these discs undergo another set of visible color changes. Leveraging CRISPR’s talent for sequence recognition, this third step enables discriminate between strains whose genetic profiles differ by as little as one nucleotide – providing single-base resolution. Although synthetic biologists and genetic engineers usually put CRISPR to work inside living cells, the team discovered that it functions just as well – and even better in some cases – when freeze -dried. “We have tested our diagnostic systems against closely-related strains of the Dengue virus and found that within the first two steps, our system can readily distinguish Zika from Dengue,” said co-first author Prof. Alexander Green, PhD, Arizona State University (USA), “Addition of the third CRISPR-based step – deploying Cas9 on a paper-based platform for the first time – only enhances the accuracy of detection. As we prepare this technology for

LabMedica International August-September/2016

translation, we plan to validate our system against dozens or even hundreds of clinical samples.” The ability to pinpoint a strain-specific diagnosis in the field could prove valuable to national and global health organizations for tracking the spread of a viral outbreak in real-time and for preparing containment strategies and treatment plans. The cost-effective diagnostic platform could be tailored to identify a range of pathogens. What’s more – the method is robust and could be used to quickly respond and develop new diagnostics: “In response to an emerging outbreak, we envision a custom-tailored diagnostic system could be ready for use within one week’s time,” said Prof. Collins, “We are currently pursuing multiple opportunities cont’d on page 10

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Special Section: Zika Update

Image: Illustration of Zika virus in blood

Special Section: Zika Update

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cont’d from page 9

to secure private and public funding in order to commercialize this diagnostic system and make it available to the world’s health responders.” “The ability to recapitulate the genetic machinery of living cells in ordinary freeze-dried paper provides a way to develop revolutionary sensors and diagnostics in a fraction of the time and with higher sensitivity and specificity than more conventional assays,” said Wyss Institute founding director Prof. Donald Ingber, MD, PhD. The study, by Pardee, Green, Takahashi, Braff, Lambert et al, was published May 6, 2016, in the journal Cell.

Urine Trumps Blood for Zika Testing imited data suggest Zika virus is excreted in multiple body fluids, including urine and saliva and that urine and saliva might be more appropriate specimens than blood samples for evaluating Zika virus disease. The interim diagnostic testing guidance for the Zika virus recommends real-time reverse transcription-polymerase chain reaction

(rRT-PCR) testing for urine specimens obtained two weeks after the illness starts. The Zika virus ribonucleic acid (RNA) is almost undetectable in blood samples after the first week of illness. Scientists from the Centers for Disease Control and Prevention (CDC, Atlanta GA, USA; www.cdc. gov) and their colleagues collected multiple specimen types from persons with suspected Zika virus disease. Urine specimens were collected from 70 patients with suspected Zika virus disease from zero to 20 days after symptom onset. In 66 cases, persons had urine and serum specimens collected on the same day. The majority of these persons were female (64%), white (77%), and Hispanic (71%), with a median age of 46 years, age range 23 to76 years. Zika virus rRT-PCR was performed at the Bureau of Public Health Laboratories (BPHL, Tampa, FL, USA; www.floridahealth.gov) using a laboratory-developed test based on a previously published protocol using two RT-PCR targets. The teams found urine samples were the best at flagging Zika, with 93% of specimens collected within 20 days of symptoms first appearing showing positive results.

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Image: A black cartridge containing the innovative paper-based diagnostic for detecting Zika virus: areas that have turned purple indicate samples infected with Zika virus, while yellow areas indicate Zika-free samples (Photo courtesy of Wyss Institute at Harvard University).

Urine specimens also displayed positive results 82% of the time when samples were collected more than five days after symptoms cropped up. Urine samples were positive 95% of the time when the specimens were obtained the same day or within five days of illness onset as compared to 56% for blood samples. The authors concluded that the results of testing conducted suggest that urine might be the preferred specimen type to identify acute Zika virus disease. Rates of detection from urine were higher than from serum, even during the first few days after symptom onset and continuing after day five, when no serum specimens tested in this evaluation had detectable RNA. Among pregnant women, this ability to confirm Zika virus is important because close monitoring during pregnancy is recommended for women with confirmed Zika virus disease. The ease of collection of urine specimens is an additional advantage. This report also demonstrated that saliva specimens (another specimen that is easily obtained) can also yield a higher rate of RNA detection than serum even during the first five days; the detection rate in saliva also approaches the detection rate in urine. However, no cases were identified through saliva testing alone. The study was published on May 13, 2016, in the journal Morbidity and Mortality Report.

Zika Test Authorized by FDA for Emergency Use NEW: RUSSIAN EDITION

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he first test submitted by a commercial lab provider in the US for Zika infection was granted US Food & Drug Administration (FDA)’s Emergency Use Authorization (EUA). The molecular test is intended for the qualitative detection of RNA from the Zika virus in human serum specimens from certain individuals. Quest Diagnostics (Madison, NJ, USA; www. questdiagnostics.com), was granted the EUA for the Zika Virus RNA Qualitative Real-Time RT-PCR test (Zika RT-PCR test). The proprietary test was developed by the reference laboratory business of Quest’s subsidiary Focus Diagnostics, Inc. This test has not been FDA cleared or approved beyond the EUA designation. Until now, the only FDA EUA authorized Zika tests were available from the US Centers for Dis-

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ease Control and Prevention (CDC) and were only used in qualified laboratories designated by the CDC. “The availability of our new molecular Zika test provides physicians broad access to a diagnostic tool for managing the Zika outbreak,” said Rick L. Pesano, MD, PhD, vice president, research & development, Quest Diagnostics, “Quest’s expertise in molecular, infectious disease, and women’s health diagnostics, and relationships with half of the country’s physicians and hospitals, allow us to quickly make useful tests widely available for clinical use. This capability uniquely positions Quest to complement the response of public health laboratories for Zika outbreaks where access to FDA-authorized diagnostic tests can potentially influence the quality of patient management.” The EUA authorizes use of the Zika RTPCR test by qualified laboratories designated by Focus Diagnostics, including potentially at any CLIA high-complexity laboratory in the Quest Diagnostics network. For now, only the Focus Diagnostics reference laboratory in San Juan Capistrano (CA, USA) will perform this test. Quest Diagnostics also plans to offer serological test services assuming FDA-authorization of serological test kits for emergency use. The Zika RT-PCR test is intended only for qualitative detection of RNA from Zika virus in human serum specimens from patients meeting CDC Zika virus clinical criteria (e.g. clinical signs and symptoms associated with Zika virus infection) and/or CDC Zika virus epidemiological criteria (e.g. history of residence in or travel to a geographic region with active Zika transmission at the time of travel, or other epidemiologic criteria for which Zika virus testing may be indicated). Within the US, positive results of this test must be reported to CDC. The diagnosis of Zika virus infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidence in addition to identification of Zika virus. Negative results do not preclude Zika virus infection and should not be used as the sole basis for patient management decisions.

Scientists at the Stanford University School of Medicine, Stanford, CA, USA; www.med.stanford. edu) evaluated the single-reaction multiplex rRTPCR for Zika virus, CHIKV, and DENV (referred to as the ZCD assay) by testing clinical samples from persons with suspected cases in Nicaragua. They tested 216 samples by using the ZCD assay and the pan–DENV-CHIKV rRT-PCR, which is a validated duplex assay containing the DENV and CHIKV primers and probes used in the ZCD assay. All rRT-PCR reactions were performed on an ABI 7500 instrument (Applied Biosystems, Foster City, CA, USA; www.appliedbiosystems.com). A total of 173 samples were positive, 25 for DENV alone, 110 for CHIKV alone, or 38 for both. The ZCD assay and pan–DENV-CHIKV rRT-PCR showed very

good agreement for DENV detection. The two assays demonstrated good agreement for CHIKV detection and the cycle threshold (Ct) for the 35 CHIKV discrepant samples were reached significantly later than the 113 concordant samples. Of the 56 Zika virus–positive samples in the ZCD assay, 39 were positive only for Zika virus, and 17 showed evidence of mixed infection. The authors concluded that the single-reaction multiplex ZCD assay detected and differentiated Zika virus, CHIKV, and DENV. This assay should streamline molecular workflow and decrease test costs while improving detection of these three human arboviruses. The study was published in the July 2016 issue of the journal Emerging Infectious Diseases.

Multiplex Molecular Test Developed for Three Arboviruses linical manifestations of Zika virus, chikungunya virus and dengue virus infections can be similar. To improve virus detection, streamline molecular workflow, and decrease test costs, a multiplex realtime reverse transcription polymerase chain reaction (rt-PCR) for these viruses has been developed and evaluated. The diagnosis of human Zika virus infections is confounded by a nonspecific clinical presentation, which overlaps substantially with that of dengue virus (DENV) and chikungunya virus (CHIKV) and by cross-reaction with DENV immunoglobulin M (IgM) and DENV nonstructural protein 1 in assays for Zika virus.

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POC DIAGNOSTIC SERVICE

ZIKA DIAGNOSTIC TEST

Mast Group

TTP

Vircell

The DiscMaster 4 is designed for dispensing Antibiotic Susceptibility Test (AST), Combination and Identification discs within the Mastdiscs range. It is available in a convenient 6-place format, and offers an in-use shelf life of 4 weeks for all antimicrobials including the carbapenem group.

The Desktop Biology is designed to enable POC diagnostic providers to rapidly convert their biological assay into a market-ready system. The service offers a seamless approach for companies looking to accelerate the development of their assay to a product for use in diagnostics or research.

The AmpliRun ZIKA virus RNA Control is designed for use as quantified positive controls in conventional or RT-PCR, enabling the amplification of the desired target. The control comes lyophilized and a resuspension vial is provided within the kit with molecular biology grade water.

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Parsortix System Detects Prostate Cancer in Clinical Application he current gold standard for detection is the prostate-specific antigen (PSA) blood test, which is known to have low sensitivity and low specificity with high levels of false positives, and the digital rectal exam (DRE), which is less effective than the PSA test. Where the PSA level is high or the DRE indicates an enlarged prostate, a solid prostate biopsy will be undertaken to detect cancer and assess the aggressiveness of the disease. This process results in many men having invasive biopsies unnecessarily. Scientists at Barts Cancer Institute (London, UK; www.bci.qmul.ac.uk) used a prostate cancer detection system to detect prostate cancer and to assess its aggressiveness, all through a simple blood test. This is crucial because it means that men with low level disease could avoid unnecessary and potentially harmful solid biopsy and surgical intervention instead having “active surveillance”, whereas men

with an aggressive form of disease could be fasttracked for further investigation and treatment. The key findings of the study were that the Parsortix system (ANGLE plc; Guildford, UK; www. angleplc.com) detected circulating tumor cells (CTCs) in 100% of the metastatic prostate cancer patients. The patients with localized disease included patients with early stage disease, determined by clinical investigation including the Gleason score of solid tissues taken through invasive procedures, where the decision had been taken that “active surveillance” was appropriate rather than medical intervention. Even for these earliest stage, indolent cancer patients, the Parsortix system harvested CTCs that could be detected in 75% of these patients. The number of mesenchymal CTCs harvested by the Parsortix system was compared to the Gleason score for each of the patients and there was found to be a good correlation suggesting that Par-

sortix liquid biopsy may be able to provide the same or similar information as the invasive solid biopsy in assessing the aggressiveness of the cancer. The status of the patient, metastatic or localized, was analyzed against the number of mesenchymal CTCs harvested by the Parsortix system. Separately the status of the patient, metastatic or localized, was analyzed against the patient’s Gleason score. Comparison of the results suggests that the Parsortix system may be able to indicate the metastatic or localized status of the patient with a higher level of accuracy than the Gleason score. Yong-Jie Lu, MD, PhD, Reader in Medical Oncology, said, “The Parsortix system enables investigation of the mesenchymal CTCs in the patient blood and the results of our work to date suggests this has the potential to become a noninvasive liquid biopsy for prostate cancer. The exciting part of this study is the potential for the Parsortix system to be used to assess the severity of the disease as well as to detect it. This meets a key medical need to avoid over-treatment as well as to ensure treatment is available for patients who need it.” The study was presented on March 19, 2016, at the 10th ISMRC International Symposium on Minimal Residual Cancer: Liquid Biopsy in Cancer Diagnostics and Treatment held in Hamburg (Germany; http://ismrc2016.com). Image: The Parsortix system uses microfluidic technology in the form of a disposable cassette to capture and then harvest circulating tumor cells from blood (Photo courtesy of ANGLE plc).

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D-Dimer Efficacy Evaluated for Disseminated Intravascular Coagulation Diagnosis isseminated intravascular coagulation refers to an acquired syndrome characterized by procoagulant substances entering the general circulation and leading to a systemic thrombotic process, which may be derived from or causing microvascular system damage. D-dimer (D-D) was shown to be an important indicator for the diagnosis of overt disseminated intravascular coagulation (DIC) and non-overt DIC; however, its diagnostic cutoff value in the clinic is not clearly defined. The initiation of treatment in nonovert DIC leads to better outcome than in DIC and therefore, early diagnosis of non-overt DIC is pivotal for DIC prevention and treatment. Clinical scientists at the Nanjing Medical University (Suzhou, China; www.njmu.edu.cn) enrolled 40 male and 80 female cases in each group (DIC, non-overt DIC, and non-DIC control group). All 360 cases were collected in Suzhou Municipal

Hospital. The DIC group included patients clearly diagnosed with DIC who had been hospitalized in the intensive care unit (ICU); the non-overt DIC group comprised patients who were diagnosed later as DIC; and the non-DIC control group included patients who were convalescing after surgery, had normal liver and kidney function. D-D, fibrinogen degradation products (FDP), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fg), thrombin time (TT), antithrombin (AT), and blood platelet count (PLT) of 360 cases were used to assess the diagnostic efficacy of Innovance D-Dimer reagent (Siemens Healthcare Diagnostics, Erlangen, Germany; www.healthcare. siemens.com) for the diagnosis of DIC and non-overt DIC, compared to, or combined with, other DIC coagulation indicators. D-D was quantitatively analyzed using a Sysmex CA1500 automatic coagulation analyzer (Sysmex Corporation; Kobe, Japan; www.

sysmex.com) with an immunoturbidimetric method. The investigators found that when D-D was greater than 3.0 g/mL was used as the cutoff, the sum of diagnostic sensitivity and specificity reached maximum values for DIC and non-overt DIC, whereas the sum of misdiagnoses and missed diagnosis rate was minimal. Excluding D-D, AT, or Fg, but not TT, from the test combination reduced the diagnostic sensitivity of DIC or non-overt DIC by various degrees. The authors concluded that monitoring D-D and FDP levels is useful for early intervention and improving microcirculation disturbance caused by disease. They propose that a cutoff value of D-D of greater than 3.0 g/mL would be suitable for the InnovanceR D-D reagent in the laboratory; D-D in combination with FDP is meaningful for primary screening of non-overt DIC. The study was published on February 2, 2016, in the International Journal of Laboratory Hematology.

Combined Tests Improve Tuberculous Meningitis Diagnosis t present, there is no established laboratory test to diagnose early tuberculous meningitis and cerebrospinal fluid (CSF) culture sensitivity is low in developing countries and it usually takes several weeks to obtain results with this method. Tuberculous meningitis (TBM), the most severe form of tuberculosis (TB), accounts for 5% to 10% of extrapulmonary TB and 0.5% of systemic TB worldwide. Those who have contracted this disease have a mortality rate of 20% to 41% in developed countries and 44% to 69% in developing countries. Scientists at Huashan Hospital Fudan University (Shanghai, China; www.fudan.edu.cn) studied a total of 30 patients who were suspected of having TBM, of whom six were clinically diagnosed as having TBM and 24 as probably harboring the disease. These patients included 24 men and six women,

aged between 18 and 79 years, with a mean age of 45 years. The diagnostic criteria for TBM were positive acid-fast (AFS) results or positive CSF culture results for Mycobacterium tuberculosis. After the first admission of each study participant from the TBM and control patient to the hospital, a 1-mL CSF specimen from each via lumbar puncture was collected. The team also collected cerebrospinal fluid from 10 patients in the TBM group on initial visit and at four weeks, to observe changes. A total of 30 individuals with TBM and 39 control individuals without TBM participated in this study. IFN-γ-secreting T cells were detected by ELISPOT, an enzyme-linked immunospot (TSPOT.TB, Oxford Immunotec International, Abingdon, UK; www.oxfordimmunotec.com), and cerebrospinal fluid interferon-γ (cIFN-γ) was detected by enzyme-linked immunosorbent assay (ELISA).

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The sensitivity and specificity of peripheralblood T-SPOT.TB testing in the diagnosis of TBM were 70% and 87%, respectively. The area under the receiver operating characteristic (ROC) curve of cIFN-γ (greater than 81.36 pg/mL) for TBM diagnosis was 0.819, and the corresponding sensitivity and specificity were 83% and 85%, respectively. When T-SPOT.TB and cIFN-γ results were positive, the specificity and positive predictive value of TBM diagnosis reached 100%. The consistency is poor between peripheral-blood T-SPOT.TB and cIFNmethods probably due to the factors that could result in false-negative and false-positive results. However, this finding may partially confirm that the combination of these approaches can improve the efficiency of diagnosis of TBM. The study was published on January 4, 2016 in the journal Laboratory Medicine.

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PRODUCT NEWS ME TEST SYSTEM

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AUTOMATED MICROSCOPE

ELECTROLYTE ANALYZER

BioMérieux

Immuno Concepts

SFRI

The FilmArray Meningitis-Encephalitis (ME) panel tests CSF for the 14 most common pathogens responsible for meningitis or encephalitis. It offers sample prep, amplification, detection and analysis in one automated system, with a run time of about an hour, and two minutes of hands-on time.

The Image Navigator captures images of autoantibody indirect immunofluorescent slides and separates the images into controls, possible positives, possible negatives, and titers. It then presents these images on separate review screens for easy and quick confirmation and reporting.

The IONIX is designed for the direct determination of Na+, K+, Cl‚ Äê, Ca2+, and pH by ion selective electrodes in whole blood, serum, and aqueous QC material. It offers a choice between four possible combinations of seven different electrodes, and nine possible parameters.

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High Risk HPV Multiplex Assay Clinically Validated ersistent infection with at least one of the high-risk carcinogenic human papillomavirus (HPV) types is the primary risk factor for the development of cervical cancer and HPV is found in virtually all cases of cervical cancer and precursor lesions. Providing clear information about infected HPV genotypes in the stage of infection, clearance, and persistence is important to manage patient monitoring and treatment; however, conventional cytology tests do not determine HPV infection, but detect only cytological abnormality. Scientists at the Catholic University of Korea (Seoul, Republic of Korea; www.catholic.ac.kr) collected 1,137specimens from Korean women that were randomly selected from the liquid-based cervical specimens between January and June 2014. All specimens were collected with a cytobrush, and were placed in a Huro Path liquid-based cytologysampling device (CelltraZone; Seoul, Republic of Korea; www.celltrazone.com). They were stored at -70 °C until HPV testing. Each specimen was divided into two aliquots and then used for HPV detection tests. The cervical cytological examination was performed by experienced cytopathologists.

The investigators used the Anyplex II HPV HR detection kit (Seegene Inc.; Seoul, Republic of Korea; www.seegene.com) which is a new, multiplex, real-time polymerase chain reaction assay to detect individual 14 high-risk (HR) human papillomavirus (HPV) types in a single tube. For each sample, HPV detection and genotyping were performed using a CFX96 real-time thermocycler (Bio-Rad; Hercules, CA, USA; www.bio-rad.com). They compared the assay with the Hybrid Capture 2 (Qiagen; Valencia, CA; www.qiagen.com) using the non-inferiority score test in a routine cervical cancer screening setting. The intra laboratory and inter laboratory agreements of HPV HR were also evaluated. The scientists found that overall agreement between the two assays was 92.4% (1,051 of 1,137) with a value of 0.787. Clinical sensitivity of HPV HR for high-grade squamous intraepithelial lesions and cervical intraepithelial lesions grade 2 or worse was 94.4% and 92.5%, respectively. The respective values for Hybrid Capture 2 were 93.1% and 87.5%. Clinical sensitivity and specificity of HPV HR were not inferior to those of Hybrid Capture 2. The HPV HR showed good intra

laboratory and inter laboratory reproducibility at 98.0% and 97.4% respectively. The authors concluded that their data indicate that the HPV HR assay was highly comparable to HC2 for clinical equivalence and reproducibility based on international guidelines. The individual typing information for 14 hrHPV genotypes, including HPV-16 and HPV-18, provided by the HPV HR can be an important tool in patient management. The study was published in the March 2016 issue of the journal Archives of Pathology & Laboratory Medicine. Image: The CFX96 real-time thermocycler (Photo courtesy of Bio-Rad Laboratories).

Immunoassay Systems Evaluated for Detection of Antiphospholipid Antibodies ntiphospholipid syndrome or antiphospholipid antibody syndrome (APS or APLS), or also Hughes syndrome, is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. APS provokes blood clots (thrombosis) in arteries and veins as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, and severe preeclampsia. The diagnostic criteria require one clinical event, such as thrombosis or pregnancy complication, and two antibody blood tests spaced at least three months apart that confirm the presence of either lupus anticoagulant, or anti-β2-glycoprotein-I (since β2-glycoprotein-I (GpI) antibodies are a subset of an-

ti-cardiolipin antibodies (aCL), an anti-cardiolipin assay can be performed as a less specific proxy. Scientists at the Hospital Ordine Mauriziano (Torino, Italy; www.mauriziano.it) assayed aCL and a-β2GpI in serum samples from 30 healthy individuals, 77 patients with antiphospholipid syndrome (APS) diagnosed according to the Sydney criteria, 51 patients with autoimmune diseases, eight patients with previous thrombotic events, six patients with other diseases, and 18 patients with infectious diseases. The investigators used the enzyme-linked immunosorbent assay (ELISA, Inova Diagnostics; San Diego, CA, USA; www.inovadx.com); enzyme im-

munoassays (EliA) (Phadia Laboratory Systems; Freiburg im Breisgau, Germany; www.phadia.com) ; chemiluminescence enzyme immunoassay (CliA), (Zenit-RA, A.Menarini Diagnostics; Florence, Italy; www.menarinidiagnostics.com); and Inova Diagnostics’ CliA Bio-Flash to evaluate analytical and clinical performances of IgG and IgM anticardiolipin (aCL) antibodies and anti-β2-glycoprotein I (a-β2GpI) antibodies and upper limit reference ranges (99th percentiles) in comparison with manufacturer’s cutoff values with different commercial methods. The study was published on March 15, 2016, in the International Journal of Laboratory Hematology.

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Test Predicts Death In Patients with Serious Liver Disease cute-on-chronic liver failure (ACLF) is a sudden deterioration of the liver function in a patient with liver cirrhosis accompanied by failure of one or more organ systems and this liver disease has a serious prognosis and the four-week mortality rate is 20% to 30%. This condition is often triggered by an infection, bleeding or other stressful events and due to the severity of the disease it is important to develop a test to identify patients with the highest risk of developing this condition and thus the highest risk of a fatal outcome. Scientists at Aarhus University (Denmark; www.au.dk) screened patients at liver units in 29 university hospitals with a diagnosis of cirrhosis based on previous liver biopsy findings or a composite of clinical signs and findings provided by laboratory test results, endoscopy, and radiologic imaging. Eightysix cirrhosis patients had no ascites and no ACLF, 580 had ascites but no ACLF; 100, 66, and 19 had ACLF-grade-I (ACLF-I), ACLF-II, and ACLF-III, respectively. The scientists measured the circulating macrophage activation markers soluble sCD163 and mannose receptor (sMR) and related them to the short-(one to three months) and long-term (6 months) mortality in the cirrhosis patients. The plasma concentration of sCD163 was determined in duplicate in samples that had been frozen at -80 Â°C by an in-house sandwich enzyme-linked immunosorbent assay (ELISA) using a BEP-2000 ELISAanalyzer (Dade Behring, Deerfield, IL, USA; www.dadebehring.com). The team measured sMR by a newly developed inhouse ELISA assay. The investigators found a stepwise increase in median sCD163: 5.68; 8.26; 9.50; 15.68; 20.18 mg/L, and sMR: 0.60; 0.81; 1.17; 1.41mg/L with increasing grades of ACLF. Both sCD163 and sMR were independently associated with short and long-term mortality and showed equal or higher predictive accuracy than MELD, CLIF-C ACLF and CLIF-C AD scores. Addition of the macrophage markers to the clinical scores improved the prognostic efficacy. In ACLF patients sCD163 improved prediction of short-term mortality and in patients without ACLF sMR improved prediction of long-term mortality. The authors concluded that the severity related increase in sCD163 and sMR and close association with mortality suggest a primary importance of inflammatory activation of liver macrophages in the emergence and course of ACLF. The study was published in the April 2016 issue of the Journal of Hepatology.

Image: The BEP 2000 Advance System fully automated microtitration plate (MTP) analyzer (Photo courtesy of Siemens Healthcare).

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Elevated C-Reactive Protein Found in H7N9 Influenza Infection he avian influenza H7N9 virus can cause cytokine overproduction and result in severe pneumonia and acute respiratory distress syndrome; and many studies have focused on hypercytokinemia during avian influenza infection. C-reactive protein (CRP) is synthesized primarily by the liver and is one of the nonspecific acutephase proteins produced in response to most forms of infection inflammation, and tissue injury. This protein has been considered a nonspecific biomarker for early diagnosis and prognostic measurements. Infectious disease specialists at the Zhejiang University (Hangzhou, China; www.zju.edu.cn) recruited 82 patients with laboratory-confirmed H7N9 infections from April 2013 to February 2014, and 14 patients with H1N1 virus in Beijing from December 2012 to February 2013, as well as six healthy volunteers as controls. Plasma samples were collected within two days of admission. Patient sputum samples or pharyngeal swabs were collected on the same day. Viral load was detected by TaqMan real-time reverse transcription polymerase chain reaction (PCR) targeting the influenza A H7N9 virus subtype-specific H7 gene or influenza A H1N1 virus subtype-specific H1 and N1 genes using standard thermal cycling conditions. A Bio-Plex Pro Human 27-plex cytokine group I assay kit (Bio-Rad; Hercules, CA, USA; www. bio-rad.com) was used to measure the concentrations

of plasma cytokines. Samples were analyzed using a MAGPIX system (Luminex Corporation, Merck Millipore; Temecula, CA, USA; www.merckmillipore.com). Cytokine/chemokine values that were detected outside of the standard range were flagged as high or low out-of-range (OOR), and the highest or lowest value on the standard curve was used instead of the OOR measurement. Measurement of CRP in patient plasma was detected using a Beckman Coulter IMMAGE 800 Immunohistochemistry System and Beckman Coulter reagents (Beckman Coulter; Brea, CA, USA; www.beckmancoulter.com). The CRP levels were much higher in patients with H7N9 infection than in patients with H1N1 infection, 84.0 ± 65.2 mg/L compared to 11.37 ± 6.70 mg/L. The CRP concentration of the H1N1 group was significantly lower than those in the survivor and non-survivor H7N9 groups. Patients with H7N9 who died had much higher concentrations of CRP of 129.6 ± 63.9 mg/L. Several cytokines, including Macrophage inflammatory protein-1β (MIP-1β), Monocyte chemoattractant protein-1(MCP-1), Interferon gamma-induced protein 10 (IP-10), and interleukin-6 (IL-6), were observed to have significantly positive relationships with CRP levels, whereas IL-17A was negatively

associated with CRP levels. The authors concluded that CRP, as a conventional clinical indicator, could be a simple and convenient marker for the early prediction of potential cytokine storms, particularly when cytokine detection is unavailable. This marker will contribute to the early identification of high-risk cases, further assessment of cytokine profiles of severe cases, and the development of an appropriate therapeutic plan, such as anti-cytokine treatment. The study was published in the March 2016 edition of the International Journal of Infectious Disease. Image: The IMMAGE 800 immunochemistry system (Photo courtesy of Beckman Coulter).

DNA-Based Test Determines Degree Of Liver Fibrosis on-alcoholic fatty liver disease (NAFLD) accounts for the majority of liver disease burden in the Western world. Liver biopsy remains the gold standard test to accurately stage fibrosis in patients with NAFLD, but it is invasive and carries risks. A DNA-based test has been developed that determines the degree of fibrosis in the liver which could be a replacement for a liver biopsy and this new type of genetic blood test diagnoses scarring in the liver even before an individual may feel ill. Scientists at Newcastle University (Newcastle upon Tyne, UK; www. ncl.ac.uk) recruited 26 patients with biopsy-proven NAFLD and age-matched controls from the liver and gastroenterology clinics. Plasma cell-free circulating DNA methylation of peroxisome proliferator-activated receptor gamma (PPARγ) was quantitatively assessed by pyrosequencing. Liver DNA methylation was quantitatively assessed by pyrosequencing NAFLD explant tissue, subjected to laser capture microdissection (LCM). Patients with alcoholic liver disease (ALD) were also subjected to plasma DNA and LCM pyrosequencing.

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DNA was extracted from 200 L of plasma and DNA was also extracted from laser capture microdissected tissue (PALM MicroBeam, Zeiss, Jena, Germany; www.zeiss.com) using the QIAamp DNA micro kit (Qiagen, Venlo, Netherlands; www.qiagen.com). Quantitative plasma DNA methylation of PPARγ stratified patients into mild (Kleiner 1–2) and severe (Kleiner 3–4) fibrosis (CpG1: 63% versus 86%; CpG2: 51% versus 65%). Hypermethylation at the PPARγ promoter of plasma DNA correlated with changes in hepatocellular rather than myofibroblast DNA methylation. Similar results were demonstrated in patients with ALD cirrhosis. The authors concluded that differential DNA methylation at the PPARγ promoter can be detected within the pool of cell-free DNA of human plasma. With further validation, plasma DNA methylation of PPARγ could potentially be used to non-invasively stratify liver fibrosis severity in patients with NAFLD. Plasma DNA methylation signatures reflect the molecular pathology associated with fibrotic liver disease. The study was published on March 21, 2016 in the journal Gut. LabMedica International August-September/2016

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Group A Streptococcus Rapid Immunoassay Evaluated linical reasoning utilizing certain symptoms and scores has not proven to be a reliable decision-making tool to determine whether or not to suspect a group A Streptococcus (GAS) infection in the patient presenting with a sore throat. An excellent solution for this dilemma would be a bedside rapid antigen detection test (RADT) for GAS that provides a positive or negative result within five to 10 minutes, thus directly influencing the treatment decision. Such RADTs have been evaluated previously using throat culture as the gold standard and initially showed insufficient sensitivity and specificity. Scientists at North West Hospital and Health Service (Mount Isa, QLD, Australia; www.health.qld.gov.au) collected throat swab samples from patients attending the Mount Isa Hospital emergency department for a sore throat; these samples were compared to swab samples collected from healthy controls that did not have a sore throat and both groups were aged three to 15 years. None of these children had previously had rheumatic fever. The study team processed the swabs within 72 hours using the Alere Test Pack +Plus with OBC Strep A kit (Alere, Waltham, MA, USA; www.alere.com). This test kit had shown a 95% to 97% sensitivity and a specificity of 95% to 100% to detect GAS. In this study the outcomes were compared with the assumption that the sensitivity of the pointof-care test was 95% and with the assumption that the sensitivity was 97%. The treating clinician was blinded to the point-of-care test result. From June 30, 2014 to February 27, 2015, 248 throat swabs were collected and examined within 72 hours. Out of the 101 patients presenting with a sore throat, 26 (26%) tested positive for GAS. Only one (0.7%) of the 147 control patients had a positive test result. Statistical analysis showed both the positive and negative etiologic predictive value (EPV) to be high. The 95% confidence interval for positive EPV was 88% to 100% and for negative EPV was 97% to 99%, depending on assumptions made. The authors concluded that their study demonstrated that the point-of-care test

Image: The Test Pack +Plus with OBC Strep A kit (Photo courtesy of Alere).

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Alere Test Pack +Plus Strep A has a high positive predictive value and was able to rule in GAS infection as long as the proportion of carriers is low. Also the negative predictive value for ruling out GAS as the etiologic agent is very high irrespective of the carrier rate. Hence, this test is always useful to rule out GAS infection. The study was published in the April 2016 issue of the International Journal of Infectious Diseases (www.ijidonline.com).

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Radiometer

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The Sorvall BP 16 has a capacity of 16 x 500mL blood bags, and automatically adjusts run time to account for variations in acceleration. It features a bright, highly visible and glove-friendly display for simplified run set-up, making it suitable for highthroughput blood processing needs.

The ABL800 FLEX allows the user to automatically analyze up to three blood gas samples in succession, and measure a full panel of up to 18 STAT parameters on the same sample. Its Drop 'n' Go capability removes the need to wait for results, making it ideal for medium- to high-volume labs.

The CT-3180 is a three-part differential analyzer offers 18 parameters, and more than three histograms with two counting modes: whole blood and prediluted. It has a throughput of 60 tests per hour and consumes 25mL of diluent and 0.6mL of lyse (with 20uL of whole blood) per test.

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Novel Biochip Combines Antibody Binding and Electronic Counting to Simplify Diagnosis of HIV/AIDS recent paper described the construction of a microchip biosensor that uses immunocapture technology to detect sub-populations of immune leukocytes. Investigators at the University of Illinois (Urbana-Champaign, USA; www.illinois.edu) developed the small, disposable biochip in order to differentiate and count CD4+ and CD8+ T-cells, which is a key factor in diagnosing HIV/AIDS. The prototype biochip is built around a capture chamber coated with anti-CD4+ antibodies. In addition, it has separate ports for lysing reagents and quenching buffers that preserve the leukocytes for counting by co-planar platinum microfabricated electrodes. In practice, ten microliters of whole blood was infused into the biochip. The red cells were removed by lysis, and leukocytes were preserved using quenching buffers. The leukocytes were counted while passing over a counting device comprising

co-planar platinum microfabricated electrodes on the way into the capture chamber. CD4+ T-cells were captured as they interacted with specific antibodies in the capture chamber. Leukocytes that were not captured passed out of the capture chamber and were counted again with a second counter. The difference in the respective cell counts gave the number of cells captured. While this paper provided a comprehensive stepwise protocol to replicate the biosensor for CD4+ and CD8+ cell counts, the biochip could be adapted to enumerate other specific cell types such as somatic cells or cells from tissue or liquid biopsies. Capture of other specific cells would require immobilization of their corresponding antibodies within the capture chamber. In clinical trials, the differential immuno-capture biochip achieved more than 90% correlation with flow cytometry for both CD4+ and CD8+ T-cells using HIV infected blood samples.

Production of the prototype biochip required approximately 24 hours. A one-time optimization of the cell capture step took six to nine hours, and the final cell counting experiment required 30 minutes to complete. The biochip protocol was published in the March 10, 2016, online edition of the journal Nature Protocols. Image: A microfluidic biochip sensor for counting white blood cells from whole blood (Photo courtesy of John Dixon / The News-Gazette).

Early Stage Breast Cancer Recurrence Linked to High Leukocyte Ratio high ratio of two types of immune system cell is linked to an increased risk of disease recurrence after a diagnosis of early stage breast cancer and the findings might guide future treatment and monitoring strategies, if prospective studies confirm the link. Breast cancer is a commonly diagnosed malignancy and the leading cause of cancer death in women worldwide and despite the widespread adoption of adjuvant treatments having resulted in improved survival, nearly 20% of patients with breast cancer still suffer from recurrence of disease. Scientists at the Second University of Naples School of Medicine (Caserta, Italy; www.unina2. it) carried out a retrospective study of A total of 300 female patients with histologically proven early (T1–2, N0–1, non-metastatic) breast cancer treated from July 1999 to June 2015. The following data

were collected: age, menopausal status, histological tumor type, tumor size, tumor-node-metastasis stage, and degree of histological differentiation, expression of estrogen and/or progesterone receptor, human epidermal growth factor receptor (HER2) status, Ki67 levels, recurrence rate and distant metastasis–free survival (DMFS) rates. The ratio of neutrophils to lymphocytes (NLR) ranged from 0.21 to 30.00 (mean 2.67±2.52, median 2.09) in the 300 patients. A significant NLR increase was observed only with T2 stage cancer, and NLR had the ability to distinguish between relapsing and non-relapsing patients. On the basis of their blood counts taken after diagnosis, but before treatment, 134 of the women had a low NLR of 1.97 or lower and 166 had a high NLR above 1.97. After 15 years, cancer had returned in another part of the body in 37 (12%) of

the women. Women with a low NLR fared better at each of the subsequent check-ups at 1, 3, 6, 9, 12, and 15 years, with, respectively, 100%, 98.9%, 91.7%, 82.7%, 82.7%, and 82.7% of them free of recurrence. This compares with comparable figures of 99.4%, 94.3%, 84.5%, 69.2%, 66%, and 51.4% at the same time points in those with a high NLR. The authors concluded that despite looking apparently simple, the relationship between NLR and outcome in patients with cancer is probably a complex and multifactorial process that is still poorly understood. In simple terms, a high NLR may reflect the key role of systemic inflammation in enhancing angiogenesis (formation of new blood vessels), tumor growth, and development of metastasis. The study was published on March 7, 2016, in the journal ESMO Open. LabMedica International August-September/2016

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LabMedica International

Blood Test Evaluated for Suspected Obstructive Coronary Artery Disease oronary artery disease (CAD), also known as ischemic heart disease, is a very common heart condition in the USA, and one in seven deaths among Americans is caused by CAD. A common symptom is chest pain or discomfort, which may travel into the shoulder, arm, back, neck, or jaw. CAD can cause a narrowing or blockage of the coronary arteries which are the vessels to the heart that supply the heart with blood, oxygen, and nutrients, reducing blood flow to the heart muscle. This narrowing or blockage in the coronary arteries is often referred to as obstructive CAD, characterized by the presence of atherosclerosis, or plaque. In a collaborative trial, scientists at Duke University (Durham, NC, USA; www. duke.edu) utilized 2,370 non-diabetic patients from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial biobank repository. Almost half of the patients (1,137) in the sub-study were randomized to the computed tomography angiography (CTA) arm. In this group, 115 (10.1%) of patients were found to have obstructive CAD, and a Corus CAD score more than 15 was associated with increased obstructive CAD likelihood. Findings from the PROMISE Trial provide independent confirmation of the association between the Corus CAD test scores and the presence and extent of coronary artery disease in patients and the likelihood of obstructive CAD. The 1,312 patients with higher Corus CAD test scores (greater than 15) had higher event rates that were statistically different from 1,058 patients with lower Corus CAD test scores (1–15). Additionally, the results from the sub-study found that at 25-month median follow-up, the clinical event rates for patients with low Corus CAD scores (less than or equal to 15), were low and no different from negative or normal noninvasive test results using either cardiac stress testing or coronary CTA (3.2% vs. 2.6%). The Corus CAD blood test is produced by CardioDx, Inc. (Redwood City, CA, USA; www. cardiodx.com). The test incorporates age, sex and gene expression measurements into a single score that indicates the likelihood of obstructive CAD. Mark Monane, MD, FACP, Chief Medical Officer of CardioDx, said, “We note the finding that clinical outcomes among the patients with the low scores on the Corus CAD blood test (approximately 45% of the study patients) were no different from patients with normal cardiac stress testing or CT-angiography. Taken together, these three results highlight the characteristics of the Corus CAD test to safely and accurately help clinicians risk stratify symptomatic patients, so that patients can potentially avoid additional cardiac testing and procedures that may be potentially unnecessary.” The study was presented at the 65th American College of Cardiology Annual Scientific Meeting, on April 3, 2016, held in Chicago, IL, USA; https:// accscientificsession.acc.org).

Image: The Corus CAD gene expression test for the evaluation of patients presenting with typical and atypical symptoms suggestive of coronary artery disease (Photo courtesy of CardioDx).

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The CP3000 offers a throughput of up to 400 tests/hour, including chromogenic and immunoturbidimetric assays. It provides 14 clotting channels, and six chromogenic and immunoturbidimetric channels, with minimal interference from lipemia, icterus and hemolysis.

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Optical Device Rapidly Detects Biomarkers in Urine compact optical device has been developed that can rapidly and sensitively detect biomarkers in urine and has promise for developing simple point-of-care diagnostics of cancer and other diseases. Micro ribonucleic acids (miRNAs) are a newly discovered class of short, about 19 to 24 nucleotides in length, fragments of noncoding RNAs that are useful biomarkers for diagnosing various diseases, including cardiac disease and some cancers. Since they are surprisingly well preserved in fluids such as urine and blood, their detection is well suited to a rapid, point-of-care method. Bioengineers at the Agency for Science, Technology and Research (Singapore; www.a-star.edu.sg) have devised a silicon photonic biosensor that can detect tiny changes in the phase of a light beam caused by hybridization between an immobilized DNA probe and target miRNAs in a sample. A laser beam travels through a waveguide, which splits into two arms: a sensing arm in which the light interacts with the sample and a reference arm. The two light beams then rejoin each other. Binding between the DNA probe and the target miRNA alters the phase of the light traveling in the sensing arm,

whereas the phase in the reference arm remains unchanged. The amount of target miRNA in the sample can be determined by monitoring the variation in the intensity of the output beam. To demonstrate the system, the team used it to detect two types of miRNAs in urine samples from three patients with late-stage bladder cancer; the tests involved a single reaction and took 15 minutes. The microRNA levels of the patients differed markedly from those of two healthy subjects. Mach–Zehnder interferometer (MZI) biosensor was fabricated using standard complementary metal-oxide-semiconductor (CMOS) processes. For the optical characterization of the MZI sensor, the light coming from a TSL-510 tunable laser (Santec; Komaki, Japan; www.santec.com) at a wavelength 1,562 nm passes through a polarization controller and a fiber pigtailed collimator. Mi Kyoung Park, PhD, the principal investigator, said, “Existing methods to detect microRNAs are time consuming and require cumbersome machines, which limit their usefulness in clinical set-

tings. This inspired us to develop a simple and efficient point-of-care device for detecting microRNAs. The device is also highly sensitive and thus does not require labeling or amplification; it can deliver results within 15 minutes, eliminating the need for patients to return for their results; and it can potentially detect up to 16 targets in a single test.” The study was originally published in the September 2015 issue of the journal Biosensors and Bioelectronics. Image: A diagram of the MZI biosensor system for miRNA detection (Photo courtesy of Agency for Science, Technology and Research).

Blood Test Accurately Detects Idiopathic Pulmonary Fibrosis diopathic Pulmonary Fibrosis (IPF) is a chronic, progressive and lethal lung disease characterized by scarring and reduction in the lungs’ capacity to absorb oxygen. In the USA, around 100,000 people are currently affected by IPF, with approximately 30,000 to 40,000 new cases diagnosed each year. Diagnosis of IPF is based on a range of clinical, laboratory, radiological and pathological tests, often to exclude other conditions first. The key diagnostic test currently available is High Resolution Computed Tomography (HRCT), a costly procedure to which access is limited in many countries. The disease has a poor prognosis, with many patients sur-

viving only three to five years after diagnosis. Scientists at the Liège University Hospital (Belgium; www.chu.ulg.ac.be) carried out a clinical study of 78 subjects, 21 were non-treated patients with IPF, 27 patients had been treated for IPF, and 30 were healthy volunteers. Analysis of the preliminary data revealed that a single NuQ biomarker assay (VolitionRx; Namur, Belgium; www.volitionrx.com) detected 86% of the non-treated IPF patients (18 of 21) from the healthy subjects with only 6 false positives (80% specificity). Julien Guiot, MD, project coordinator from Liège University Hospital, said, “At present, relatively little is known about this deadly disease. An accurate, cost-effective diagnostic for IPF could

have a significant impact in assisting doctors in their efforts to understand the disease and develop a more viable treatment and potential cure.” Jake Micallef, PhD, MBA, Chief Scientific Officer at VolitionRx, said, “Some NuQ biomarker assays are particularly appropriate for the detection of inflammatory diseases such as IPF. To have achieved such impressive accuracy for detecting IPF using only a single such NuQ biomarker assay in this pilot study is very encouraging. Our next step will be to work on a larger study sample and to include additional NuQ biomarker assays to form a panel blood test that could have even greater accuracy.” LabMedica International August-September/2016

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Polymer-Based Rapid Test Visually Differentiates Tumor Cells polymer-based rapid test has been developed which visually differentiates tumor cells from healthy cells in a tissue section through the use of a simple microscope. Surgeons can already use the test in the operating room, which saves time and expenses. Antibodies combat viruses and bacteria and they also attach themselves to cancer cells in a typical, characteristic way. This property has been used to detect cancer cells in tissue samples and such rapid tests can already be applied by surgeons during operations, within a few minutes and without expensive equipment. Scientists at the Fraunhofer Institute for Applied Polymer Research (IAP; Potsdam, Germany; www.iap. fraunhofer.de) have developed a polymer-based rapid test which visually differentiates tumor cells from healthy cells in a tissue section through the use of a simple microscope. Surgeons can already use the test in the operating room. This

saves time and expenditures. Studies have shown that receptors sit on tumor cells, and certain specific antibodies attach to these receptors: for example, estrogen antibodies on breast carcinomas. Using this “immunodiagnostic” method, the surgeon only needs a few minutes to make sure that all the diseased tissue has been removed. Once placed on the tissue sample, the antibodies search independently for their counterpart, the receptors, which are distinctive for them. For reasons of reliability, a cross test characteristically dyes the healthy cells in the next step. Once neither of the two tests detects any more tumor cells, the surgeon can conclude the operation as he has cut out all of the diseased cells. The scientists are working to make the color contrasts between healthy and diseased tissue cells more clearly visible. Joachim Storsberg, PhD, head of department Functional Polymers for Medical Technology,

Hepatitis C Positive Antibody Test Leads to Molecular Assay onventional laboratory and medical practice for Hepatitis C virus infection involves referring a patient for a second office visit and blood draw if the initial antibody screening test produces a positive result. A hepatitis C screening test identifies viral antibodies while a molecular test identifies viral ribonucleic acid (RNA) when the infection is active. In some people, the immune system clears hepatitis C infection on its own, but antibodies may linger in the blood for decades. As a result, a positive antibody screening test can signify resolved or active infection, and as much as 3% of antibody screens produce a false positive. Quest Diagnostics (Madison, NJ, USA; www.questdiagnostics.com) will automatically perform molecular testing on all patient specimens whose antibody screening results indicate Hepatitis C virus infection, and remove standalone positive antibody screening as a test option. The change to the company’s service menu eliminates the prospect a patient may receive a positive screening result but fail to undergo additional molecular testing, as recommended by medical guidelines, to help con-

LabMedica International August-September/2016

firm a diagnosis of active hepatitis C infection, the cause of chronic hepatitis C. With the change to the Quest menu, any specimen that an antibody screening test indicates is positive will automatically reflex to molecular testing. Pricing for the screen and molecular tests are the same as before; positive screening results will reflex to molecular testing automatically and be charged the additional molecular test fee. Early diagnosis, through laboratory blood tests, and treatment can help prevent liver damage, cirrhosis, liver cancer and death. Rick L. Pesano, MD, PhD, vice president of development, science and innovation at Quest Diagnostics, said, “This change to Quest’s test offerings is medically responsible and appropriate. It closes a gap in current hepatitis C care by reducing the possibility a patient will undergo multiple office visits and blood draws or be inappropriately referred to specialists based on incomplete testing. With this change to our offering, we will help more people receive insights they can use to access effective treatment and ultimately lead healthier lives.”

said, “Locating tumors accurately in tissue sections is not easy. It’s easy to distinguish diseased from healthy tissue at the core of the cancerous ulcer, but not around the edges: tu-

mors spread out asymmetrically.” Image: A cell phone camera is sufficient to examine tissue samples for tumor cells (Photo courtesy of Fraunhofer IAP).

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Prostate Cancer Diagnosed from Urinary Ribonucleic Acid test for noncoding ribonucleic acid (RNA) molecules in urine may offer a way to detect prostate cancer that is more accurate and reliable than current methods using biomarkers such as prostate-specific antigen (PSA) and prostate cancer gene 3 (PCA3). A new study has identified a series of noncoding RNA molecules that could potentially be combined into a single urine test to detect prostate cancer. The test could offer greater sensitivity and specificity than the current biomarker tests and thus make population screening much more viable. The test with high sensitivity is good at ruling out disease when the result is negative, and a test with high specificity is good at ruling in disease when the result is positive. Scientists at the University of Leipzig (Germany; www.zv.uni-leipzig.de) and their colleagues took 64 prostate cancer tissue samples obtained from

biopsies and read 200 million sequences in genetic molecules from each sample. They found over 2,000 sequences that were significantly different in tumor samples than in healthy controls. Some of these sequences were for non-coding RNAs that showed better specificity and sensitivity than established prostate markers. The biomarkers were also found to be present in urine samples from cancer patients, and initial tests suggest they offer a precise way to detect the disease and a combination of biomarkers will give better specificity. One of the noncoding RNAs, called tumor-associated proliferation-inducing RNA (TAPIR), also showed significant promise in stopping cancer cell growth. However, the team says it is too soon to say whether this result will prove to be clinically useful. The team is now developing a highly specific and sensitive urine test for the early diagnosis of prostate cancer. The test will use a combination of

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biomarkers rather than just a single one. Manfred Wirth, MD, a professor of Urology, and one of the leaders of the study, said, “Given that our initial results show a high specificity for prostate cancer in urine tests, the prospects are good that we will be able to translate this into a better test for prostate cancer. We have several good candidate biomarkers; however, we are aiming to design a test, which utilizes a combination of biomarkers. This will give significantly better specificity than existing tests.” The study was presented at the European Association of Urology Congress (EAU16), held March 11–15, 2016, in Munich (Germany; https://uroweb.org).

Novel Method Detects Bacterial Infection in Preterm Infants new criterion has been proposed for diagnosis of bacterial infection in preterm infants and using this method could lead to early diagnosis and treatment for bacterial infection and improve the prognosis for preterm infants. Infants born prematurely do not have fully developed immune functions and compared to full-term infants, and if preterm infants suffer a bacterial infection there is a higher chance of fatality or negative impact on future growth and development. Scientists at Kobe University (Japan; www. kobe-u.ac.jp) examined 1,267 serums from 283 newborns at the neonatal intensive care unit in Kobe University Hospital between June and December 2014. The enrolled newborns were divided into three infant groups as follows: 37 preterm of less than 34 weeks’ gestational age (GA); 61 late preterm of 34 to 36 weeks’ GA, and 185 term infants equal to or greater than 37 weeks’ GA. Serum procalcitonin (PCT), was used as a marker used for early detection of bacterial infection in adults and children. Serum PCT measurement was performed using 30 L of serum, the serum PCT concentration was measured by electrochemical luminescence immunoassay using the COBAS 8000e analyzer (Roche Diagnostics, Basel, Switzerland; www.roche.com). The results demonstrated that PCT levels in full-term infants rose temporarily one day after birth, returning to the normal level for adults within five days (0.1ng/mL). However, for preterm infants it took nine days after birth for PCT to return to normal levels. Based on these results, the group plotted two reference curves: 50th percentile and 90th percentile values. The authors concluded that that the physiological feature in preterm infants was significantly different from that in late preterm infants, even in those less than 37 weeks’ gestational age. To detect lateonset bacterial infection and sepsis, an age-specific percentile-based reference curve may be useful in preterm infants. Ichiro Morioka, MD, a professor of pediatrics and senior author of the study said, “We could also potentially use this method to limit unnecessary use of antibacterial agents. Our next step is to verify the precision of diagnoses based on these reference curves.” The study was published on April 1, 2016, in the journal Scientific Reports.

LabMedica International August-September/2016

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Multiple STIs Could Be Detected with Single Rapid Test ne test that could detect four of the most common sexually transmitted infections (STIs) in 30 minutes and allow them to be rapidly treated is under development. A GBP150,000 grant has been awarded to develop the test that will detect STIs, including chlamydia and gonorrhea. Testing kits have been sent out by the UK National Chlamydia Screening Program aimed at those aged under 25 who did not have symptoms but wished to know they are clear of the infection. Their samples were then sent away for testing and those who tested positive for Chlamydia were offered the opportunity to trial the new technology. Chlamydia is the UK’s most common STI with about 100,000 cases diagnosed each year and people under 25 years old are most at risk. If untreated, it can have serious long-term health consequences, including infertility in women. In some areas, one in five people never get treatment for their infection and others wait a long time before coming back to a clinic. The test is being developed by scientists at St George’s, University of London (UK; www.sgul.ac.uk) and Atlas Genetics (Trowbridge, UK; http://atlasgenetics. com). The STI multiplex combines tests for four major nucleic acid targets, Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium, without the need for microscopy. The test is run on the Atlas Genetics’ io system which is a fully automated solution, requiring minimal hands-on time. Following the addition of an unprocessed patient specimen on to the io Cartridge, the Cartridge is then inserted in to the io Reader. Tariq Sadiq MD, chief investigator at St. George’s, leads the eSTI2 Consortium which has developed a new smartphone app which allows patients to access an electronic clinic, the eSexual Health Clinic, to get rapid online treatment for chlamydia infection once they were diagnosed. Using a secure National Health System (NHS) log in, the app included an online medical consultation, leading to an electronic prescription for antibiotics, which patients could collect at a high street pharmacy. The app also enabled the patients’ sexual partners to get treatment quickly and easily in the same way. A clinical helpline is available for patients who need advice or support. Eventually the eSexual Health Clinic will link to a hand held diagnostic device for STIs is also being developed by the scientists. This will mean that a urine or swab sample from patients would not have to be sent away for analysis, but can be analyzed at home so patients would receive their results within half an hour and then get their care online without ever needing to see a doctor face to face or attend a clinic.

Image: A disposable cartridge for testing for a sexually transmitted disease (Photo courtesy of Atlas Genetics).

LabMedica International August-September/2016

LabMedica International

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The CAPILLARYS 3 TERA offers a throughput up to 390 tests per hour for proteins and up to 210 tests per hour for HbA1c. Features include substantial sample/reagent capability, full RFID-based next-generation traceability, and cap-piercing technology for work with capped primary tubes.

The CL-1000i benchtop analyzer offers a throughput of 120 tests per hour and 25 reagent positions, with features such as continuous sample loading and off-loading. Its large reagent and sample capacity, and user-friendly operation interface makes it suitable for mid- to small-sized labs.

The cobas c 513 delivers up to 400 results per hour, and has a high test capacity on board of 14,000 determinations. It requires minimum operator intervention from sample registration to result delivery, and its closed tube sampling function delivers maximum safety to the operator.

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Noninvasive Method Determines Subclinical Childhood Celiac Disease new, simple and noninvasive method has been developed to determine whether a child aged two to four years of age suffers from celiac disease (CD) or not, without the necessity of a blood extraction. Silent celiac disease goes unnoticed to the eyes of the doctor because it presents minor symptoms, imperceptible even for the patient. Celiac disease is a systemic disease caused by a permanent intolerance to gluten, which can be found in wheat, barley and rye, and it affects people with genetic predisposition. The symptoms are intestinal malabsorption, abdominal distension, diarrhea, abdominal pain, and extra-digestive including skin problems, joint pain, cephalalgia. Scientists working in collaboration with those at the Virgen de las Nieves University Hospital (Granada, Spain; www.hospitalvirgendelasnieves.org) recruited 198 children aged two to four years, mean age 32.3 ± 9.2 months, and 53% were males. CD prevalence according to the serological tests was 3% (CI 95%, 1.4%–6.4%). Biopsies were used to

confirm the diagnosis in all suspected cases. Crosssectional study was carried in a sample population of children who were apparently healthy subjects from the same metropolitan area. The team collected clinical, anthropometric, analytical, and serological variables. They also tested for anti-gliadin immunoglobulin A (IgA) and antitransglutaminase IgG and IgA using a rapid immunochromatographic test CD1WB and CD2WB (Operon; Zaragoza, Spain; www.operon.es). The tests detected six celiac children among the 198 who participated in the study, which is a very high prevalence of 3%, higher than the European mean. All of them presented no symptoms at all, or minor imperceptible symptoms which did not make their parents consult a pediatrician. The sensitivity and negative predictive value of the CD2WB immunochromatographic test strip were 100% and 1, respectively. The sensitivity of CD1WB was 16.6% and its specificity was high at 89.1%. A positive outcome of the test will require

further confirmation via blood extraction and assessment of the disease antibodies via other methods, but a negative outcome will allow the dismissal, with certainty, of being affected by the disease. The method does not require experienced personnel, although it has to be interpreted by health professionals, is quick as it only takes10 minutes, economic at EUR 10 to 12 per device, and, most important of all in the case of infant population, this method is less invasive than a blood extraction. The study was published originally published in September 2015 in the journal Pediatric Research. Image: A Simple CD2WB immunochromatographic test for detection celiac disease in pediatric patients (Photo courtesy of Operon).

Diabetes Testing on High-Throughput Analyzer Files for FDA Approval he cobas c513 analyzer has been submitted to the US Food and Drug Administration (FDA) for approval as a dedicated, high-throughput HbA1c testing solution to help laboratories meet increasing testing needs for people with diabetes. The cobas c513 analyzer from Roche (Basil, Switzerland; www.roche.com) is based on the proven, trusted cobas technology developed in cooperation with Hitachi High-Technologies (HHT). The HbA1c test is a longer-term measurement of blood sugar levels used to determine if a person has or is at risk of developing diabetes. Set to run on the established Tina-Quant HbA1c A1cDx Gen.3 test, which is also used across the Roche laboratory HbA1c portfolio, the cobas c513 will ensure highquality results and comply with current guidelines and recommendations for HbA1c testing and measures A1c as defined by the IFCC.

cobas c513 features direct results reporting, thereby minimizing risk of result misinterpretation and eliminating the need to perform time-consuming, manual result interpretation. This feature will help save valuable time and laboratory resources, while ensuring high-quality results. Furthermore, cobas c513 will provide a higher on-board test capacity, enabling laboratories to load the analyzer with more tests at a time, save lab space, minimize resources, and ensure a smooth workflow. It offers closed tube sampling, which will reduce hands-on time, prevent sample contamination, and ensure operator safety for laboratory personnel. The prevalence of diabetes has increased, with estimates of as many as 566 million people with diabetes worldwide, of which 32% may still be undiagnosed. The total number of people with diabetes is anticipated to increase by 53% until 2035. Over

half of all cases are preventable. “As the prevalence and incidence of diabetes continues to grow, it’s estimated that by the end of this decade 15% of American adults – or roughly 39 million people will be affected. This staggering number is not only a major cause for concern for healthcare providers, but for healthcare organizations as well,” said Dr. Alan Wright, Chief Medical Officer, Roche Diagnostics Corporation. Upon receiving FDA clearance, Roche plans to replace its existing analyzer, the COBAS INTEGRA 800 CTS, which has been a successful and well-established solution. The cobas c513 analyzer will further increase efficiency by doubling the already market-leading throughput of the COBAS INTEGRA 800 CTS from 200 to 400 patient results per hour. cobas c513 will achieve this performance with the same space footprint. LabMedica International August-September/2016

Edited by Tahir Pillay MBChB, PhD, FRCPath(Lon), FCPath(SA) IFCC members may send news to: Tahir Pillay MBChB, PhD, Head, Dept of Chemical Pathology, Faculty of Health Sciences, University of Pretoria, Private Bag Bag x323, Arcadia, 0007, South Africa Tel: (27) 012-319-2114; Fax: (27) 012-328-3600; Email: enews@ifcc.org

NEWS

Shaping the Future of Laboratory Medicine Opportunities and Challenges for Laboratory Medicine Specialists in Modern Healthcare by Graham Beastall, Past President, IFCC, University of Glasgow; David Kinniburgh, Director, NAFCC, Alberta Centre for Toxicology, University of Calgary haping the Future of Laboratory Medicine” is an IFCC policy, which is being implemented by the IFCC Executive Board. This article, the first of two, is an opinion paper written by two members of the IFCC Executive Board. It is based on issues identified in laboratory medicine (LM) communities around the world. This article is an overview rather than a detailed scientific treatise. Seven topic areas have been identified. Three will be covered in this article with the remaining four addressed in the subsequent article. In each case there is a broad statement from which illustrative opportunities and challenges may be identified. A general comment is included for each area.

“S

Centrality of Laboratory Medicine to Healthcare: Statement. LM results influence a high percentage of all clinical decisions, meaning that LM is central to modern healthcare. However, this is not always recognised and LM is undervalued. Opportunities: Achieve LM input to multidisciplinary teams and clinical networks at local and national level; Establish interactive links with primary care centres and patient organisations; Provide clinical interpretation and advice on appropriate use of the laboratory to users and directly to patients. Challenges: To convince users that LM is a service provider, not a numbers factory or a commodity; To present LM as a coherent clinical specialty and not several separate sub-specialties. Comment. The centrality of LM in healthcare places a responsibility on laboratory specialists to understand the requirements of users and assist them to use the LM service for maximum clinical benefit. This will mean working outside as well as inside the laboratory.

New Technology and Locations for Delivery of Laboratory Medicine: Statement. Rapid advances in technology are leading to higher quality and a wider repertoire of LM services. Technology is also enabling LM services to be provided outside traditional clinical laboratories. Opportunities: Adopt new technology that facilitates the production of faster, higher quality results and positive clinical outcomes ; Adopt and be responsible for quality management of point of care testing (POCT) in a range of hospital and community based healthcare settings; Introduce informatics to facilitate new cont’d on page 28

IFCC OFFICE Via Carlo Farini 81, 20159 Milan, ITALY Tel: (39) 02-6680-9912 • Fax: (39) 02-6078-1846 E-mail: ifcc@ifcc.org • Web: www.ifcc.org Office Hours: 8.30-13.00 and 13.30-17.30 Staff Members: Paola Bramati, Silvia Cardinale, Silvia Colli-Lanzi

LabMedica International August-September/2016

Graham Beastall

David Kinniburgh

NEWS cont’d from page 27

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

Shaping the Future of Laboratory Medicine

ways for interpreting and delivering data. For example, analysing ‘big data’ and reporting results via smart phone apps. Challenges: To accommodate disruptive technologies that change testing strategies; To avoid the uncoordinated introduction of new technology outside the laboratory. Comment. Technological advance is at the core of LM in a modern healthcare system. That technology is likely to be used more frequently outside the laboratory, closer to the patient. LM specialists and their partners in the diagnostics industry should promote the benefits of integrated diagnostics, including effective connectivity.

Managing the Costs of Laboratory Medicine: Statement. Every country is struggling to manage the financial demands of modern healthcare. LM services are visible targets because our workload and costs can be measured. Opportunities: Strengthen business and management training for LM specialists; Present LM as part of the cost of patient investigation rather than an isolated cost; Engage positively with those responsible for reimbursement schedules; Lead projects aimed at appropriateness of testing (also known as laboratory utilisation); Consider service rationalisation and smarter ways

IFCC eAcademy: Aiming for Online Scientific Education and Training Worldwide by Peter Vervaart, Chair, IFCC Committee on the Internet and e-Learning; Janet Smith, Chair, IFCC Committee on Distance Learning n recent years distance learning has become a key initiative of the IFCC and is a strategic priority for the Executive Board. The Education and Management Division (EMD) Committee on Distance Learning (C-DL) and the Communications and Publications Division (CPD) Committee on the Internet and eLearning (C-IeL) were established to work together on the development of the IFCC eAcademy, which aims to make high quality educational modules available to its membership and will provide a resource for individuals in their training and CPD requirements as well as for those involved in the planning and organisation of educational programmes. The eAcademy is a Learning Management System using a curriculum based approach to catalogue and access educational material and contains linked presentations, webinars and other educational material managed through

the Umbraco content management system. There are 3 phases in its development, the first was launched in Paris in 2015. The second released in Madrid in 2016 and the third phase currently under development. Two approaches are being used to acquire novel high quality material for the eAcademy. The first is to identify interesting presentations at IFCC and National Society scientific meetings and courses for recording and inclusion in the eAcademy. Appropriate presentations are identified from the published programmes for upcoming events and we need the support and help of National Societies to work with us to arrange the recordings. The second approach, to which we are devoting most of our effort and resources, is to commission international experts to prepare single or series of short modules on specific topics for in-

of working to improve laboratory cost effectiveness. Challenges: To convince clinical users that laboratory costs are central to effective clinical care; To convince managers that appropriate use of LM can reduce overall healthcare costs ; To introduce new, improved services in an environment of financial restraint. Comment. Demonstrating cost effectiveness is a responsibility for LM specialists. Positive engagement with users and management at local and national levels should focus on LM costs as part of the patient pathway rather than being considered in isolation.

corporation into the eAcademy. Using the present.me software, PowerPoint slides can be coupled with author voiceover and even video to produce these modules. Each module includes keywords, searchable on the website and learning objectives. When the 3rd phase in the eAcademy, currently under development, is launched, a series of questions, designed to assess how well the learning objectives have been met, will be incorporated into each module. Several of these modules have already been published in the eAcademy, including a presentation on laboratory accreditation, prepared by IFCC Past President Dr Graham Beastall on behalf of IFCC and ILAC and two modules which will form a series on aspects of the laboratory assessment of thyroid function, authored and presented by Dr Carol Spencer. Others currently being prepared include a series of presentations on evidence-based laboratory medicine and one on immunoassay as well as more on a range of single analytes. In selecting topics for inclusion in the eAcademy we have taken note of those highlighted by National Societies as being priorities for distance learning requirements, as well as the need for material on basic clinical laboratory and management practice for those in training. Much high quality distance learning material is produced by other professional bodies and we are providing links to these from the eAcademy. We are particularly grateful to EFLM and the AACB for allowing us access to material on their websites. All material published on the

eAcademy or recommended by our committees is reviewed beforehand by members of the C-DL. It is through the generous financial support of Siemens that we are able to finance this approach. We have also just begun a project, under the direction of C-IeL member Eduardo Freggiaro, to translate much of the eAcademy material into Spanish utilising a subtitling online collaborative platform called Amara. Using Amara means that a large number of people work simultaneously in the translation of videos from English to Spanish. Each of those people are called collaborators. So, a small contribution in translating the video coupled with the contributions of other partners can achieve the enormous task of translating all the educational content. As such the IFCC is currently seeking volunteer translators to take part in the project and thus convert the educational material within the e Academy from English to Spanish (and potentially other languages in the future). We invite you to visit the IFCC website and access the eAcademy from there. Comments on ease of use and suggestions for future presentations are most welcome. Also, if you would be willing to prepare educational modules for inclusion in the eAcademy, or to help with the translation project, your contribution would be much appreciated. Contact should be made through Silva Colli-Lanzi in the IFCC Office (colli-lanzi@ifcc.org)

New IFCC App is Now Available for Download! he IFCC Communications and Publications Division (CPD) is pleased to announce the release of the IFCC app on both iOS and Android platforms. The app is free to download from iTunes or Google Play and is the latest communication tool for use by all IFCC officers, member society members, and other lab medicine professionals. The app is available for both Apple and android phones or tablets and provides: Direct access to the IFCC website The latest news from IFCC lFCC calendar of upcoming confer-

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ences and other events Access to the eAcademy eLearning modules Ability to browse the latest issues of the eNewsletter and eJournal, even when you are offline. Everything in one place, accessible with a single click. Search for the app in the Apple AppStore or Google Play using "ifcc" today! Apple Store (iOS), and Google Play (Android). by Khosrow Adeli, Chair, Communications and Publications Division (CPD) LabMedica International August-September/2016

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

NEWS

Achieving Compliance with QMS- and QC-Requirements in the Clinical Laboratory: What is the Best Strategy? by Egon Amann, Chair IFCC Committee on Analytical Quality (C-AQ); Sedef Yenice, Chair IFCC Committee on Clinical Laboratory Management (C-CLM) his was the title of an interactive workshop which took place at the IFCC General Conference held in Madrid on Sunday, March 20, 1216. The workshop was jointly conducted by Egon Amann, Chair of C-AQ and Sedef Yenice, Chair of C-CLM (the “moderators”). The goal of this interactive workshop (IW) was to enhance the participants’ understanding of strategies for dealing with important aspects of QC (Quality Control) before running patient tests and of key steps in establishing an effective QMS (Quality Management System). As an envisioned outcome, participants should be enabled to more effectively address the problems in the processes of implementing continuous quality improvement efforts in the clinical laboratory.

The Workshop The IW employed a “bottom-up” approach such that actual and “real” laboratory issues concerning QM, IQC, and EQA questions including aspects of regulatory requirements could be addressed by the participants. The IW was conducted three times in a row. Each workshop lasted for 45 minutes. After a short impulse lecture was given by the moderators, spontaneous groups formed. A questionnaire was handed out to the groups to structure their debate and to collect, in a standardized fashion, their experiences with QMSand QC-requirements in their countries’ clinical laboratories. After the groups’ discussions, each group leader presented their outcomes shortly to all workshop participants. The “most burning” top three issues were listed on flip charts by the group leaders and was subsequently collated by the moderators. In combination with the filled-in questionnaires, a comprehensive analysis (the “Post Implementation Review”) was compiled after the workshop by the moderators. At the end of the workshop, moderators asked the participants for comments on what aspects of the workshop were most useful and how future workshops might be improved. These were captured as well and are part of the Post Implementation Review document.

Workshop Statistics

15189) – 93% Overall grade on QMS is very good (Figure 1) – 43% The stage of implementations related to QMS is Phase 4 – 55% The top strategic objective for the laboratory in quality management- to improve patient safety is extremely important – 69% Overall grade on QC is excellent (Figure 2) – 42% Identified Areas for Improvement. The areas that showed potential for improvement with the highest average percent positive responses were: Areas with Potential for Improvement for Respondents: Accreditation not achieved – 7% Top challenges in achieving the strategic objective for QM: the lack of training support and guidance (strongly agree) – 25% the lack of executive support and commitment (agree) – 42% The main challenges in implementing QC: The lack of training support and guidance for IQC and the lack of budget to finance EQC materials (strongly agree) – 10% The lack of training support and guidance for EQC (agree) – 30% To illustrate identified areas for improvement, the following table shows answers (grouped according to QMS elements) provided to the question: "What aspects of your laboratory’s work (if any) should be improved as a result of effective QMS and QC?" in the questionnaire that are grouped in line with the quality system elements are as follows: Facilities and Safety: Inadequate space. Organization: Lack of leadership, lack of time. Personnel: Short of staff, staff limitation to adequately document details of lab operation, eg.reagent lots. etc., commitment of staff, lack of qualified personnel, education and training/competency assessment, lack of motivation, Quality Culture: not involved

Egon Amann

Sedef Yenice

in QM processes. Equipment: Inadequate resources . Purchasing and Inventory: High costs, lack of financial support for EQA, IQC. Process Management: Pre-analytical errors, making errors on handling specimens, training to prevent failure to follow SOP, analytical – verification of methods, verification of reference materials, operational procedures, establishment of processes in preanalytical, analytical and post-analytical phases. Information Management: Inefficient LIS. Assessment: Regulatory problems, inconsistency in performing the QMS, lack of communication, data presentation of QC performance with alerts or warnings showing failed and not performed, ISO 15189 too much focusing on technical details and very little on medical part, no QC run in histo- and cytopathology.

Workshop summary Most participants evaluated the IW as useful. Participants praised the fact that they had the chance to discuss laboratory-related quality topics and issues in a “round table discussion format”. Also, suggestions for future improvements for this kind of IW were obtained and put into the post-implementation report. Although the IW was low in total participant numbers, significant learnings of laboratory’s need in the participating countries revealed quite different aspects and suggestions. These learnings were compiled in the 16-page document: Post Implementation Review on the Interactive Workshop: What is the best strategy to achieve compliance with QMS- and QC-requirements in the clinical laboratory? The report is available upon request from the authors: Prof. Sedef Yenice Email: sedefyenice@gmail.com, Prof. Egon AMANN e-mail: egon.amann@hshl.de

A total of 14 respondents out of total 23 IW participants submitted data for the questionnaire (response rate was 60.9 percent). Workshop participants who responded to the questionnaire attended from: Argentina, Belgium, Germany, Guatemala, India, Indonesia, Iran, Malaysia, Nigeria, Russia, South Africa, United Kingdom, USA, and Uruguay. The top three respondent work areas were in Biochemistry/Clinical Chemistry (45 percent), General Laboratory (27 percent), and Immunology or Pathology or Quality Management (9 percent). The top three respondent staff positions were: Department Head (30 percent), Pathologist or NonPhysician Lab Director (20 percent), and Physician Lab Director or Professor/Instructor or Lab Technician (10 percent).

Workshop Results Identified Areas of Strength. The five areas of strength with the highest average percentage of positive responses were: Areas of Strength for Respondents: Accreditation achieved (mostly according to ISO

LabMedica International August-September/2016

Figure 1. Percentages of responses to overall grade on QMS

Figure 2. Percentages of responses to overall grade on QC

EFLM CORNER

European Federation of Clinical Chemistry and Laboratory Medicine

Editor: Harjit Pal Bhattoa, MD, PhD, EuSpLM

EFLM-WG Websites Reorganized

FOREWORD n the present issue of the EFLM Corner, MariaStella Graziani, the Chair of the EFLM Communication Committee introduces the New Look of the Working Groups webpages as presented on the EFLM website. Dr Ioana Brudasca, President of the Romanian Association of Laboratory Medicine presents the highlights of their first conference held in May of this year. Last but not least, an invitation to participate in the Preanalytics meeting in Amsterdam in 2017 is also included.

Harjit Pal Bhattoa, MD, PhD, EuSpLM

FLM is pleased to announce the overhaul of the EFLM Working Groups (WGs) pages on its website. Following a suggestion of the EFLM Secretary, Ana-Maria Simundic, the webpages dedicated to the WGs have been recently re-organized. The idea was to create a “resource centre” where people interested in the topic within the scope of the WG could search for information, news, announcements, published papers, assistance and knowledge. This will allow more insight into the work and activity of the EFLM WGs and more inter-

action with the professional audience. The platform would also assist in dissemination of WG recommendations, guidelines and opinions. The material transmitted by the various WGs has been screened for eligibility by the Communication Committee, with precious help from Merve Sibel Gungoren (member of the Committee) prior to upload. The innovation is almost complete and the WG webpages can be visited to learn about the EFLM WGs activities at www.eflm.eu. The different WGs are grouped under their respective Committees: An abbreviated site map is illustrated below. On each WG Homepage, along with images, the list of members and the terms of reference, there are additional links as follows: News about WG activities: here you can find news about the ongoing WG activities, current projects and future plans. Announcements of the upcoming surveys and links to surveys or invitations to participate in the survey can also be found here. Upcoming events: this page hosts information about upcoming scientific events (conferences, workshops, symposia, eseminars, etc.) related to topics within the scope of the WG activity o Resources: Articles: papers published by the WGs can be read here – PPT presentations: a list of (and access to) presentations given by the WG members can be found here – Posters: a list of (and access to) posters presented by the WG member can be found here – Useful tools: uploaded here are various tools created by the WG members such as checklists, charts, interactive Excel sheets for various calculations, risk assessment tables, questionnaires, knowledge tests, etc. These tools could be downloaded for free and used by individual colleagues, laboratories or even institutions Useful Links to external sites: links to some useful external websites related to the topic within the scope of the WG are listed here. Stay updated with the activities of the EFLM WGs: they cover an important number of topics of interest in the field of Laboratory Medicine!!

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EFLM CORNER

European Federation of Clinical Chemistry and Laboratory Medicine

Romanian Society’s First National Congress Is Held in Historic Transylvanian Capital by Assoc. Prof. dr. Ioana Brudașcă, RALM president he 1st Romanian Association of Laboratory Medicine (RALM) Conference was held between 18-21 May 2016 in Cluj Napoca. The conference was organized under the auspices of IFCC and EFLM and in collaboration with the Romanian Society of Microbiology, the Romanian Society of Hematology and the Universities of Medicine and Pharmacy in Cluj Napoca, Târgu Mureș, Iași, București., Timisoara. The congress was attended by over 530 participants. IFCC representative Dr. Janet Smith and EFLM representative Prof. Tomas Zima were invited to the congress. Other invited speakers from abroad were Prof. Laszlo Muszbek (University of Debrecen, Hungary), Prof. Eva Ajzner (president of the Hungarian Society of Laboratory Medicine), Prof. William Au (Shantou University Medical College, China). Many of the Romanian speakers were teachers at the medical faculties of Bucharest, Cluj Napoca, Târgu Mureș, Iași, who delivered state-ofthe art lectures according to their field of expertise. As our association is very interested in motivating young laboratory professionals, many communications were presented by young colleagues, most of them PhD fellows. Two awards were granted, one for the best poster, and one for professional activity. The scientific programme covered a large area of themes in laboratory medicine (clinical chemistry, microbi-

From the top left: Prof. Ioana Brudașcă (RALM President), Prof. Tomas Zima (EFLM Executive Board Representive), Prof. Eva Ajzner

ology, hematology, genetics, molecular biology), which were presented in 21 plenary reports, 25 oral presentations and 67 poster presentations. Many of the presentations focused on quality assessment, standardization, performance criteria of laboratory tests, laboratory errors and patient safety, showing the interest of the participants in the improvement of our professional activity. One session was dedicated to continuous medical education for laboratory professional, and included presentations addressing e-learning, scientific publishing, harmonization of the training of laboratory specialists.

During the discussions that followed the presentations, the participants had the opportunity to share their experience and to identify solutions for the scientific or technical issues they are confronted to in their everyday practice. Conference abstracts were published in a supplement of the Romanian Review of Laboratory Medicine (RRML). As our profession is in a permanent partnership with the clinical diagnostic industry, during the congress an exhibition of reagents, equipment, supplies, software was organized by IVD companies. There

were also 8 workshops organized by clinical diagnostic providers, which were an excellent opportunity for the development and transfer of technical innovations to clinical laboratory professionals. The scientific quality and the diversity of the presentations, the excellent organization, the appealing social programme, as well as the charm of the historical city of Cluj (former European Youth Capital in 2015, and one of the most important academic, cultural, industrial and business centres in Romania) fully contributed to the success of this scientific and professional event.

Invitation: 4th EFLM-BD European Conference on Preanalytical Phase (Amsterdam; March 24-25, 2017) fter meeting in Parma (2011), Zagreb (2013) and Porto (2015), with great pleasure, on behalf of the conference organizers, you are invited to the 4th EFLM-BD European Conference on Preanalytical Phase, to be held on 24-25 March 2017 in Amsterdam (NL). The conference is organized by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) and sponsored by BD Diagnostics, Preanalytical Systems. The focus of the conference is the quality of the preanalytical phase of the laboratory work. It is the largest such conference in Europe. The conference programme has been tailored by the scientific committee to deliver up-to-date knowledge in the field and create an open forum for interactive discussions. Your feedback during the previous meetings has guided us in the selection of the topics of this one. Our guiding principle was to be different, pragmatic, practical and interactive, to address challenges, to raise questions and offer answers. We will offer you an excellent programme, renowned speakers, lots of practical tools and tips. We therefore invite you to join us in Amsterdam. At the end of the day, it is you who will make this conference a great success. Please save the date and mark your calendars for this interesting scientific conference in the beautiful city of Amsterdam. We are looking forward to your attendance!

Ana-Maria Simundic, Conference Scientific and Organizing Committee, Chair LabMedica International August-September/2016

Industry News

LabCorp to Acquire Non-Invasive Prenatal Testing Pioneer aboratory Corporation of America (LabCorp; Burlington, NC, USA; www.labcorp. com), and Sequenom, Inc. (San Diego, CA, USA; www.sequenom.com), which is in the business of non-invasive prenatal testing (NIPT) for reproductive health, have entered into a definitive agreement and plan of merger. According to the terms of the agreement, LabCorp will acquire all of Sequenom’s outstanding shares in a cash tender offer of USD 302 million, representing a total enterprise value of approximately USD 371 million, including net indebtedness. “Sequenom’s market-leading NIPT

and genetic testing capabilities will advance LabCorp’s strategy to deliver world-class diagnostic solutions,” said David P. King, chairman and chief executive officer of LabCorp. “This is exactly the kind of strategic acquisition that LabCorp seeks: Sequenom was the first laboratory to offer a clinically validated NIPT test (MaterniT 21) and has performed more than 500,000 tests to date. Sequenom’s proven bestin-class technology and strong research complement LabCorp’s extensive women’s health offering, providing patients and physicians with one source for the most complete range of testing options in women’s health, including NIPT and reproductive genetics.”

Global Digital Pathology Market Worth Over USD 1 Billion by 2022 he global digital pathology market will reach USD 1.052 billion by 2022, driven by the growing popularity of virtual slides over physical slides, technological advancements, and cost-effective products, with North America accounting for the major share. According to a new Allied Market Research (Portland OR, USA; www. alliedmarketresearch.com) report, other factors such as workflow efficiency, analysis efficiency, improved productivity and patient care, and accuracy are also contributing to the market growth. However, lack of reimbursement policies, inadequate infrastructure, and pending product approvals are restraining the growth of the global digital pathology market. Digitalization of pathology, where

glass slides are converted into digital images for easy viewing, analysis, storage, and management of collected data, has resulted in automation of tests during diagnosis, thus saving cost and efforts. For instance, pathologists can now perform tests using a single digital instrument instead of five instruments required earlier. Based on product, the market is segmented into whole slide imaging (WSI), image analysis informatics, information management system storage & communication, and others. WSI is the major segment and is expected to grow at a CAGR of 14.8% from 2014 to 2022, due to its diversified use in surgical pathology, clinical diagnosis, consultation, and education, as well as in proficiency testing, which is a part of cytopathology.

Cardiac Biomarker Testing Market Reaches USD 2 Billion he market for tests using cardiac biomarkers, including cardiac markers for heart attack detection, and cholesterol and coagulation tests, surpassed $2 billion in 2015. These are the latest findings of Kalorama Information, (New York, NY, USA; www.kaloramainformation. com), an independent medical market research firm. Cardiovascular diseases (CVDs) are the number one cause of death globally and kill approximately 2.6 million people each year in France, Germany, Italy, Japan, Spain, U.K., and the U.S. Biomarkers are biological or bio-

LabMedica International August-September/2016

chemical molecules, or genetic changes, or other characteristics that can be measured, and that indicate or predict a condition, risk, or likely response. They can be used for predicting disease risk, diagnosis, predicting prognosis, identifying appropriate therapy for an individual, and monitoring disease or for return of a disease. Over the past few years, traditional markers such as CK-MB, troponin, and myoglobin used in acute care and tests such as those for cholesterol to evaluate risk have been replaced by tests for cardiac markers such as myeloperoxidase (MPO) brain natriuretic peptide (BNP) and proBNP.

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

International Calendar, LabMedica International P.O.Box 802214, Miami, FL 33280-2214, USA Fax: 1-954-893-0038 • E-mail: info@globetech.net

SEPTEMBER 2016 34th International ISBT – International Society Blood Transfusion Congress. Sep 38; Dubai, UAE; Web: www.isbtweb.org Eurotox 2016 – 52nd Congress of the European Societies of Toxicology. Sep 4-7; Istanbul, Turkey; Web: www.eurotox2016.com 55th Annual ESPE Meeting – European Society of Paediatric Endocrinology. Sep 1012; Paris, France; Web: www.espe2016.org 19th Annual Meeting of the ESCV – European Congress of Virology. Sep 14-17; Lisbon, Portugal; Web: www.escv.org ASCP 2016 – American Society for Clinical Pathology. Sep 14-17; Mandalay Bay, Las Vegas; Web: www.ascp.org 26th International CPOCT Symposium. Sep 21-24; Copenhagen, Denmark; Web: www.aacc.org 4th Joint EFLM-UEMS Congress Laboratory Medicine at the Clinical Interface. Sep 21-24; Warsaw, Poland; Web: www. ifcc.org/ifcc-congresses-and-conferences 15th International Congress on Antiphospholipid Antibodies. Sep 21-24; Istanbul, Turkey; Web: www.isbtweb.org ESP 2016 – 28th European Congress of Pathology. Sep 25-30; Cologne, Germany; Web: www.esp-pathology.org 42nd Annual Meeting of the American Society for Histocompatibility and Immunogenetics (ASHI). Sep 26-30; St. Louis, MO, USA; Web: www.ashi-hla.org 2nd German Congress of Laboratory Medicine. Sep 28-30; Mannheim, Germany; Web: http://laboratoriumsmedizin2016.de

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International Calendar mace Specifications for the Extra-Analytical Phases of Laboratory Testing”. Oct 27; Padova, Italy; Web: www.lccongressi.it/ laboratorymedicine2016

NOVEMBER 2016 EFLM Course on Test Evaluation, Developing medical tests that improve patient outcomes. Nov 9-11; Leiden, The Netherlands; Web: www.eflm-test-evaluation-course. eu Association for Molecular Pathology (AMP) Annual Meeting 2016. Nov 10-12; Charlotte, NC, USA; Web: www.amp.org MEDICA 2016. Nov 16-19; Dusseldorf, Germany; Web: www.medica.de 10th International Scientific Meeting of the Centre of Metrological Traceability in Laboratory Medicine (CIRME) “Ten Years After”. Nov 17-18; Milan, Italy; Web: http:// users.unimi.it/cirme/home WASPaLM 2016- 29th World Congress of Pathology. Nov 18-21; Las Vegas, NV, USA; Web: www.waspalm.org 14th Asia-Pacific Federation for Clinical Biochemistry and Laboratory Medicine Congress. Nov 26-29; Web: www. apfcbcongress2016.org

DECEMBER 2016 50e Journées de Biologie Praticienne. Dec 2-3; Paris, France; Web: http://eflm.eu

JANUARY 2017 The British Fertility Society (BFS) Annual Meeting. Jan 5-7; Edinburgh, UK; Web: http://fertilityconference.org CBRD 2017 - 4th Caribbean Biomedical Research Days. Jan 16-18; Gros Islet, Saint Lucia; Web: www.stress-and-behavior.com

FEBRUARY 2017 SLAS 2017 - Society of Laboratory Automation and Screening. Feb 4-8; Washington, DC, USA; Web: www.slas.org Labquality Days2017. Feb 9-10; Helsinki, Finland; Web: www.labquality.fi MARCH 2017 Pittcon Conference and Expo 2017. Mar 59; Atlanta, GA, USA; Web: http://pittcon.org KIMES 2017. Mar 16-19; Seoul, Korea; Web: www.kimes.kr ARABLAB 2017. Mar 20-23; Dubai, UAE; Web: www.arablab.com MEDLAB Asia Pacific 2017. Mar 29-31; Singapore; Web: www.medlabasia.com APRIL 2017 ENDO 2017 – Endocrine Society Annual Meeting. Apr 1-4; Orlando, FL, USA; Web: www.endocrine.org MEDICAL FAIR INDIA. Apr 6-8; New Delhi, India; Web: http://medicalfair-india.com ECCMID 2017. Apr 22-25; Vienna, Austria; Web: www.eccmid.org/eccmid_2017 MAY 2017 Biomarkers & Diagnostics World Congress 2017. May 2-4; Philadelphia, PA, USA; www.biomarkerworldcongress.com ISLH 2017 – International Society of Laboratory Hematology. May 4-6; Honolulu, HI, USA; Web: www.islh.org 19th European Congress of Endocrinology. May 20-23; Munich, Germany; Web: www.ese-hormones.org/meetings ESPID 2017- European Society for Paediatric Infectious Diseases. May 23-27; Madrid, Spain; Web: www.kenes.com/ espid_2017_lp ESHG 2017 - European Human Genetics Conference. May 27-30; Copenhagen, Denmark, Web: www.eshg.org

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