LabMedica International April 2018

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WORLD’S CLINICAL LABORATORY NEWS LEADER ISSN 1068-1760

Vol. 35 No.2 • 4/2018

DAILY CLINICAL LAB NEWS

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New Biomarkers Predict Outcome Of Cancer Immunotherapy elanoma and lung cancer can be combatted effectively through immunotherapy, which makes targeted use of the immune system’s normal function of regularly examining the body’s tissue for pathogens and damages.

Specific inhibitors are used to activate immune cells in a way that makes them identify cancer cells as foreign bodies and eliminate them.

This way, the immune system can boost its often weak immune response to allow it to even detect and destroy metastatic cancer cells.

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t is known that activated immune cells of patients with viral hepatitis destroy hepatocyte, but its regulatory mechanism has not yet been described. Regulatory T cells (Tregs) inhibit activation of other immune cells and thus are important for homeostasis of the immune system.

However, recent studies contradictorily show that immune inhibitory functions of regulatory T cells weaken in inflammatory conditions and the cells secrete inflammatory cytokines in response. Meanwhile, such a phenomenon was not observed in viral hepatitis including types A, B and C.

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Noninvasive Test Detects Bladder Cancer

Liquid Biopsy Test Detects Eight Types of Common Cancers

n Europe, bladder cancer represents the fourth most common cancer in men and the 15th most common cancer in women, with 151,000 people diagnosed with the condition in 2012. In order to make a bladder cancer diagnosis, experts currently recommend cystoscopy for all patients with hematuria, in conjunction with computed tomography (CT) urography (in selected high-risk patients) or renal and bladder ultrasound.

At the moment, cystoscopy cannot be replaced by cytology or

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ased on an assessment of levels of circulating proteins and mutations in cell-free DNA, the newly-developed CancerSEEK assay can detect eight common cancer types that account for more than 60% of cancer deaths, five of which currently have no screening alternative.

Image: Courtesy of University of Alberta

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new test allows simultaneous processing of any combination of four separate sexually transmitted infections: Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG), from one patient sample.

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Experts Recommend Fewer Tests for Hospitalized Patients

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Test Allows Simultaneous Processing of Four STDs

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Cellular Mechanism Identified For Severe Viral Hepatitis

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outine daily laboratory testing of hospitalized patients reflects a wasteful clinical practice that threatens the value of health care. Initiatives from numerous professional societies have identified repetitive laboratory testing in the face of clinical stability as low value care.

Excessive phlebotomy can lead to hospital-acquired anemia, increased costs, and unnecessary downstream testing and procedures. Efforts to reduce the frequency of laboratory orders can improve patient satisfaction and reduce cost without negatively affecting patient outcomes.

Clinical News . . . . 2-28 IFCC News . . . . . . . . 29 Product News . . . 6-28 Industry News . . . . .33 Events Calendar . . . 34 PUBLISHED IN COOPERATION WITH

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Biomarkers Predict Prognosis in Alcohol-Related Cancer Patients lcohol consumption has been identified as a modifiable risk factor for cancers such as gastric cancer. Alcohol consumption likely induces gastric carcinogenesis through deregulation of ribonucleic acid polymerase III (POLR3) III and oxidative damage.

A new report sheds light on how specific proteins interact with alcohol, and how that interplay impacts survival and response to platinumbased adjuvant chemotherapy in patients with gastric cancer who may or may not still be drinking.

Scientists at Anhui Medical University (Hefei, China; www. ahmu.ciss.org.cn) analyzed tumor tissue from 77 patients who had undergone surgery for primary gastric adenocarcinoma and 69 tissue samples taken from outside the tumor area. Among them, 66 patients received radical surgery and 57 patients received platinum-based adjuvant chemotherapy. All 77 patients were followed for an average of 18 months, during which time 94% (62/66) experienced disease recurrence. Patients remained free of disease for an average of 14 months (disease free survival, DFS) whereas the median overall survival (OS) was 20 months.

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The team found that transcription factor IIB-related factor 1(BRF1), breast cancer susceptibility gene 1/2 (BRCA1/2), and myeloperoxidase (MPO) were also helpful in predicting which patients would benefit more from platinum-based adjuvant chemotherapy. For example, DFS was extended two-fold or more in patients who underwent chemotherapy and showed negative or low BRCA1/2 expression. For those with negative or low BRCA1, the average disease-free interval was 18 months compared to nine months in the high-expression group. Patients with negative MPO also had a better outcome trend, although it was not statistically significant.

The investigators found that alcohol continued to have a detrimental effect in patients. High BRF1 expression and MPO-positive inflammatory cell infiltration were more frequent in gastric cancer patients with hazardous or harmful alcohol consumption habits. Abnormal changes in BRCA1 in tissues outside the tumors were more frequent in alcohol abusers. In previous studies, these investigators found similar correlations between BRF1 and alcohol consumption in breast and liver cancer patients.

Hua Wang, MD, PhD, the co-senior author of the study, said, â&#x20AC;&#x153;Alcohol consumption is a known risk factor for gastric cancer, which carries high morbidity and mortality in China. We found that DNA repair-related markers, BRF1, BRCA1/2, and MPO. have good prognostic value in gastric cancer patients with or without harmful alcohol consumption habits. Moreover, these proteins are also associated with how effective platinum-based adjuvant chemotherapy will be for gastric cancer patients.â&#x20AC;? The study was published on January 10, 2018, in The American Journal of Pathology.

Image: Human stomach adenocarcinoma stained with anti-myeloperoxidase (MPO) antibody (Photo courtesy of Roche Life Science).

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Noninvasive Test Detects Bladder Cancer

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any other noninvasive tests. Most bladder cancer diagnostic approaches have disadvantages; cystoscopy is an undignified, invasive, and uncomfortable procedure exposing patients to the risk of developing urinary tract infections (UTIs), which are known to occur in around 5% undergoing cystoscopy. Cytology is known to have a low sensitivity and its interpretation is dependent on the user, while CT urogram exposes patients to ionizing radiation.

Urologists at the Northern Institute for Cancer Research (Newcastle Upon Tyne, UK; www.ncl.ac.uk) carried out a prospective blinded study involving 577 hematuria patients in clinics at six centers across the UK between August 2016 and February 2017,who underwent the novel non-invasive testing, with results then compared with the current diagnostic benchmark of combined cystoscopy, ultrasound, and CT scanning.

The team used the ADXBLADDER test (Arquer Diagnostics Ltd, Sunderland, UK; https://arquerdx.com) that employs standard Enzyme Linked Immunosorbent assay (ELISA) methodology to measure levels of Minichromosome Maintenance Complex Component 5, (MCM5), which is a protein marker of replicating cells, or cells that have the capability to replicate. The test requires just 10 mL of urine and delivers definitive “yes/no” results within three hours.

The ADXBLADDER test received its CE Mark on October 11, 2017. The results of the study showed that 7.96% of the tests were positive for cancer and 92.1% negative. When

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

ADXBLADDER was compared to the gold standard the investigators found that the test correctly identified 95% of patients with highrisk cancers, and that the negative predictive value (the test’s ability to correctly identify patients without cancer) was 97%.

Stuart McCracken, MD, a Consultant Urological Surgeon and the principal investigator, said, “The ADXBLADDER test offers a real game changer in bladder cancer diagnosis.

The results of our new study, demonstrating fantastic accuracy, open the way for non- invasive bladder cancer testing to become widespread. This test undoubtedly has a role to play in helping identify women with bladder cancer early which could have a positive impact on survival.” The study was presented at the 37th Société Internationale d’Urologie (SIU) meeting, held October 19-22, 2017, in Lisbon, Portugal.

Image: The ADXBLADDER MCM5 ELISA kit for the diagnosis of bladder cancer (Photo courtesy of Arquer Diagnostics).

Test Allows Simultaneous Processing of Four STDs cont’d from cover

Trichomonas vaginalis is the most common non-viral sexually transmitted infection (STI) in the world and roughly 70% of people infected with TV do not have any symptoms.

Mycoplasma genitalium is a fastidious bacterium and has been associated with male and female urethritis, balanoposthitis, prostatitis, cervicitis, pelvic inflammatory disease, and male and female infertility.

The new test cobas TV/MG (Roche, Pleasanton, CA, USA; www.roche.com) is for use on the fully automated cobas 6800/8800 Systems that offer the fastest time to results, the highest throughput and the longest walkaway time available among automated molecular platforms, providing laboratories with improved operating efficiency and the flexibility to adapt to changing testing demands.

The cobas TV/MG offers laboratories the broadest set of specimen claims available in one test, including the ability to test for both TV and MG from one patient sample. This new flexibility can aid health care professionals in faster diagnosis and in reducing the test-

ing volume for labs, while enabling fewer sample collections from patients. The cobas TV/MG has been validated for use with the same, full set of female urogenital specimens available for use with cobas CT/NG. In addition, the test has been validated for use with male urine and is the first CE-IVD molecular test to receive a claim for combo TV/MG testing using a meatal swab specimen.

Uwe Oberlaender, PhD, Head of Roche Molecular Diagnostics, said, “We are pleased to continue our commitment to expanding our portfolio for the detection of sexually transmitted infections. By coupling cobas TV/MG with recently launched cobas CT/NG for the detection of Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG), laboratories now have the most flexible, high throughput testing solution on the market today. Laboratories can now simultaneously process, from a single patient sample, any combination of CT, NG, TV and MG, which provides clinicians the valuable information they need to properly diagnosis STIs and improve patient care.”

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ISSN 1068-1760 Vol.35 No.2. Published, under license, by Globetech Media LLC; Copyright © 2018. 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.

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Cellular Mechanism Identified For Severe Viral Hepatitis cont’d from cover

Medical scientists at The Korea Advanced Institute of Science and Technology (Daejeon, Republic of Korea; www.kaist.ac.kr) analyzed blood samples collected from 63 patients with acute hepatitis A (AHA) at the time of hospitalization (and some at later time points) and 19 healthy donors in South Korea. Liver tissues were collected from patients with fulminant AHA during liver transplantation. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and lymphocytes were isolated from liver tissues and analyzed by flow cytometry. Cytokine production from Treg cells (CD4+CD25+Foxp3+) was measured by immunofluorescence levels following stimulation with anti-CD3 and anti-CD28. Epigenetic stability of Treg cells was determined based on DNA methylation patterns.

The scientists found a higher proportion of CD4+CD25+Foxp3+ Treg cells from patients with AHA, compared with controls, and produced tumor necrosis factor (TNF) upon stimulation with anti-CD3 and anti-CD28 (11.2% versus 2.8%). DNA methylation analysis confirmed the identity of the Treg cells. TNF-producing Treg cells had features of T-helper 17 cells, including upregulation of RAR-related orphan receptor gamma (ROR t), which was required for TNF production. The Treg cells had reduced suppressive functions compared to Treg cells from controls. The frequency of TNF-producing Treg cells in AHA patients’ blood correlated with their serum level of alanine aminotransferase.

The authors concluded that Treg cells from patients with AHA have altered functions, compared with Treg cells from healthy individuals. Treg cells from patients with AHA produce higher levels of TNF, gain features of T-helper 17 cells, and have reduced suppressive activity. The presence of these cells is associated with severe liver injury in patients with AHA. EuiCheol Shin, MD, PhD, a professor and senior author of the study, said, “This is the first study on regulatory T cells that contributes to hepatocyte damage in viral hepatitis. It is significant for identifying the cells and the molecules that can be used as effective treatment targets for viral hepatitis in the future.” The study was originally published online on December 8, 2017, in the journal Gastroenterology.

Image: T regulatory cells (also known as Tregs or Regulatory T cells) are essential cells that suppress immune responses of other cells, designed to limit excessive reactions and prevent autoimmunity. Tregs are characterized by the expression of CD4+, CD25+,and Foxp3+, while lacking CD127 (Photo courtesy of BioLegend).

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Experts Recommend Fewer Tests for Hospitalized Patients cont’d from cover

Physicians at Johns Hopkins School of Medicine (Baltimore, MD, USA; www.hopkins medicine.org) along with experts from several other institutions across North America compiled and crafted an experience-based quality improvement blueprint to reduce repetitive laboratory testing for hospitalized patients.

Citing individual studies where front-line health care workers reduced the number of orders for laboratory tests by anywhere between 8% and 19%, the authors reported that cost savings have ranged from USD 600,000 to more than USD 2 million per year.

The experts recommended that it is necessary to design hospital-wide educational initiatives backed by data to collectively outline and standardize best practice. Establish target numbers by which to reduce laboratory test ordering and provide instant feedback to those ordering tests to show their personal ordering patterns, so they are aware of their own be-

havior with respect to agreed-upon standards.

Reprogram the electronic systems used to order tests to restrict the number of “pre-ordered” tests with an eye on having better reasons to order tests than just doing so daily.

To date, numerous interventions have been deployed across multiple institutions without a standardized approach. Health care professionals and administrative leaders should carefully strategize and optimize efforts to reduce daily laboratory testing. Published studies show that decreasing repetitive daily laboratory testing did not result in missed diagnoses or increase the number of readmissions to the hospital.

Kevin P. Eaton, MD, a third-year internal medicine resident and the lead author, said, “Excessive blood draws can deplete a patient’s hemoglobin count, which often leads to repeat testing. Others have estimated that nearly 20% of hospitalized patients can develop moderate to severe hospital-acquired anemia. This

spiral can generate additional unnecessary tests, interventions and costs for the patient.”

The study was published on October 16, 2017, in the journal JAMA Internal Medicine.

Image: Samples of human blood collected for testing; excessive testing may cause hospitalacquired anemia (Photo courtesy of Rebecca Zeffert).

Early Disease Detection Made Easier with Aptamer-Related Blood Test novel, highly sensitive blood test for a wide range of serum proteins combines aptamer-DNA capture molecules with nanopore-based single molecule sensing.

Nucleic acid aptamers are nucleic acid species that have been engineered through repeated rounds of in vitro selection to bind to various molecular targets such as small molecules, proteins, nucleic acids, and even cells, tissues, and organisms. Aptamers are useful in biotechnological and therapeutic applications as they offer molecular recognition properties that rival that of antibodies. In addition to their discriminate recognition, aptamers offer advantages over antibodies as they can be engineered completely in a test tube, are readily produced by chemical synthesis, possess desirable storage properties, and elicit little or no immunogenicity in therapeutic applications. Relative to monoclonal antibodies, DNA aptamers are small, stable, and non-immunogenic.

Investigators at Imperial College London (United Kingdom; www. imperial.ac.uk) recently described a fully flexible, scalable, and low-cost detection platform to sense multiple protein targets simultaneously by grafting specific aptamer sequences along the backbone of a doublestranded DNA carrier.

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Protein bound to the aptamer produced unique ionic current signatures, which facilitated accurate target recognition. This powerful approach enabled the investigators to differentiate individual protein sizes via characteristic changes in the sub-peak current. By using DNA carriers it was possible to perform single-molecule screening in human serum at ultra-low protein concentrations.

The investigators pointed out that the system could be expanded to more than five different aptamers, allowing simultaneous detection of multiple biomarkers. Furthermore, since the biomarkers were detected in human serum, preparation time was minimized and was less costly than traditional tests to detect these proteins.

Contributing author Dr. Alex Ivanov, research fellow in the department of chemistry at Imperial College London, said, “The detection of single molecules of biomarkers represents the ultimate in sensitivity for early diagnosis. We have now shown that this is possible to perform such measurements in real human samples, opening up the potential for meaningful early diagnosis.” The aptamer-based nanopore analytical method was described in the November 16, 2017, online edition of the journal Nature Communications.

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New Biomarkers Predict Outcome of Cancer Immunotherapy cont’d from cover

Scientists at the University of Zurich (Zurich, Switzerland; www.uzh.ch) and their colleagues examined biomarkers in 40 blood samples of 20 patients, both before and 12 weeks after immunotherapy.

For this, they used the high-dimensional “cytometry by time of flight” (Cy-TOF) cell analysis method, which analyzes cells for up to 50 different proteins one cell at a time. The team was able to differentiate every single cell and document its activation status and even nuanced differences between the patient samples were recorded in detail.

The investigators, observed that during therapy a clear response to immunotherapy in the T cell compartment. However, before com-

mencing therapy, a strong predictor of progression-free and overall survival in response to anti-PD-1 immunotherapy was the frequency of CD14+CD16-HLA-DRhi monocytes. They confirmed this by conventional flow cytometry in an independent, blinded validation cohort, and they propose that the frequency of monocytes in peripheral blood monocytes (PBMCs) may serve in clinical decision support.

For the finding to be easily verifiable the biomarkers should be easily detectable; indeed, the blood count was able to be validated using conventional methods in a second, independent cohort of more than 30 people. The study was published on January 8, 2018, in the journal Nature Medicine.

Liquid Biopsy Test Detects Eight Types of Cancer ancer researchers have developed a liquid biopsy blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. The CancerSEEK test screens for mutations in 16 genes that regularly arise in cancer cells and eight proteins that are often released. The assay was designed to detect the eight common cancer types that account for more than 60% of cancer deaths in the United States. Five of the cancers detected by CancerSEEK currently have no screening test.

Investigators at Johns Hopkins University (Baltimore, MD, USA; www. jhu.edu) tested the CancerSEEK liquid biopsy assay on 1,005 patients who had already been diagnosed with one of eight cancers: ovarian, liver, stomach, pancreatic, esophageal, colorectal, lung, or breast. Individuals whose cancer had metastasized were excluded, so the focus would be on early stages of the disease.

Results revealed that the effectiveness of CancerSEEK varied widely depending on the cancer: it detected 98% of ovarian cancers, but only 33% of breast cancer cases. It was able to pinpoint the organ in which the disease had taken root in about 63% of patients. Furthermore, the test performed better on later-stage cancers than on earlier ones, finding 78% of stage III disease versus 43% of stage I tumors.

Test sensitivities ranged from 69% to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for averagerisk individuals. The specificity of CancerSEEK was greater than 99%: only seven of 812 healthy controls scored positive.

“Many of the most promising cancer treatments we have today only benefit a small minority of cancer patients, and we consider them major breakthroughs. If we are going to make progress in early cancer detection, we have to begin looking at it in a more realistic way, recognizing that no test will detect all cancers,” said contributing author Dr. Bert Vogel-

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stein, professor of oncology at Johns Hopkins University. “This test represents the next step in changing the focus of cancer research from latestage disease to early disease, which I believe will be critical to reducing cancer deaths in the long term.” The CancerSEEK test was described in the January 18, 2018, online edition of the journal Science.

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The Assipettor allows for volume fixing by locking lever, and can be adjusted and fixed using one hand. It is maintenance-free without the need for readjustment and allows for easy replacement of capillaries and tips.

The Evidence for rapid multiplex testing combines the latest technological advances along with an innovative system design. It has a throughput of up to 3,960 tests per hour, a capacity of 180 samples and can screen up to 44 analytes per biochip.

The CLINITEK Novus combines urine chemistry technology and cassette test format to ensure maximum productivity and standardized testing with CLINITEK analyzers. It offers a full spectrum of tests and throughput of up to 240 samples/hr.

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New Genetic Risk Factors Identified for Peanut Allergy eanut allergy develops in early life and is rarely outgrown. Roughly 1% of Canadian adults and between 2% and 3% of Canadian children are affected, and the symptoms can be severe and even life threatening.

A new gene associated with peanut allergy has been revealed, offering further evidence that genes play a role in the development of food allergies and opening the door to future studies, improved diagnostics and new treatment options.

An international team of scientists collaborating with those at the University of British Columbia (Vancouver, BC, Canada; www. ubc.ca) scanned more than 7.5 million genetic locations in the DNA of 850 people with peanut allergy and nearly 1,000 people without it, through a genome-wide association study (GWAS), to search for markers that might be linked to food allergy. They recruited the peanut allergy participants from the Canadian Peanut Allergy Registry. The team also

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conducted a fresh analysis of results pooled from six other genetic studies of populations in North America, Australia, Germany, and the Netherlands. Genotyping of 1,974 individuals (987 cases, 987 controls) was conducted on the Illumina Omni 2.5M+Exome 8v1.1 chip (Illumina, San Diego, CA, USA; www.illumina. com).

The scientists reported that their study is the first to associate the EMSY, BRCA2 Interacting Transcriptional Repressor (EMSY) locus with food allergy, and these findings suggest that the gene plays an important role in the development of not just food allergy but also general allergic predisposition. The gene, called c11orf30/EMSY (EMSY), is already known to play a role in other allergy-related conditions, such as eczema, asthma, and allergic rhinitis.

The team also found evidence that five other genetic locations might be involved.

Denise Daley, PhD, an associate professor and senior author of the study, said, “Food allergy is the result of both genetic and environ-

mental factors, but there are surprisingly few data regarding the genetic basis of this condition. The discovery of this genetic link gives us a fuller picture of the causes of food allergies, and this could eventually help doctors identify children at risk.” The study was published on November 10, 2017, in the Journal of Allergy and Clinical Immunology.

Image: Whole genome genotyping arrays are an important tool for discovering variants that contribute to human disease (Photo courtesy of Megan Smolenyak, MBA).

Whole Genome Sequencing Identifies New Autism Signature urrent genetic tests for autism scan broad portions of the genome for DNA insertions or deletions that have previously been linked to autism. Other tests look for changes in the DNA building blocks of certain genes, but these tests flag only about 10% to 30% of cases. Autism has genetic roots, but most cases can not be explained by current genetic tests.An analysis of the complete genomes of 2,064 people reveals that multiple genetic variations could contribute to autism. The work suggests that scanning whole genomes may one day be useful for clinical diagnostics.

Scientists at the Howard Hughes Medical Institute (Seattle, WA, USA; www.hhmi.org) and their colleagues sequenced the genomes of 516 autistic children with no family history of autism, and no genetic anomalies detected by current tests. The team also sequenced the genomes of the children’s parents and an unaffected sibling equaling 2,064 people in total. They analyzed each family’s data, looking for ge-

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netic variations that occurred only in children with autism. Genomes were sequenced at the New York Genome Center (NYGC) using 1 g of DNA, an Illumina polymerase chain reaction (PCR)-free library protocol, and sequencing on the Illumina X Ten platform (Illumina, San Diego, CA, USA; www.illumina.com). The team used the Quick Change Lightning Multi Site-Directed Mutagenesis Kit (Agilent Technologies, Santa Clara, CA, USA; www.agilent.com).

The investigators identified genetic changes that disrupted gene function and led to altered protein production, and genetic deletions too small to see with current tests. They also found changes in areas of the genome that do not contain genes, but are responsible for turning genes on. They compared the number of variations in autistic children’s genomes with that of their unaffected siblings and found that children with autism were significantly more likely to have three or more different kinds of genetic variations. The study was published on September 28, 2017, in the journal Cell.

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Liquid Biopsy Test Outperforms Prostate Cancer PCA3 Test f the nearly two million prostate biopsies performed each year, less than a third find cancer. Most of these men could have avoided a painful and invasive prostate biopsy procedure, with its associated complications and costs.

Early diagnosis of clinically significant prostate cancer (PCa) is important to choose the optimal treatment plan. Current methods such as prostate-specific antigen (PSA) and multiparametric magnetic resonance imaging (mpMRI) are helpful, but do not provide information on the biology underlying the cancer.

Scientists at the Radboud University Medical Center (Nijmegen, the Netherlands; www.radboudumc.nl) performed a retrospective observational study using data from a validation study, in which urine was collected after digital rectal examination from men undergoing prostate biopsies. In total, 172 patients were included for analysis. A subset of these patients also underwent an mpMRI scan of the prostate. The indications for performing mpMRI were based on persistent clinical suspicion of PCa or local staging after PCa was found upon biopsy.

The non-invasive liquid biopsy test evaluated was the SelectMDx for Prostate Cancer (MDxHealth SA, Herstal, Belgium; www.mdxhealth.com).

One hundred (58%) patients had prostate cancer detected upon biopsy of which 52 (52%) had high-grade disease correlated with a significantly higher SelectMDx score. There was a statistically significant difference in the SelectMDx score between Prostate Imaging Reporting and Data System (PIRADS) 3 and 4 and between PI-RADS 4 and 5. The prostate cancer gene 3

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(PCA3) test showed contradictory results regarding the correlation between PCA3 and mpMRI. The scientists concluded that the SelectMDx risk score could guide clinicians in identifying patients at risk for significant prostate cancer and selecting patients for further mpMRI diagnostics to reduce unnecessary procedures.

Peter F.A. Mulders, MD, PhD, Chairman of the Department of Urology at Radboud University, and a co-author of the study said, â&#x20AC;&#x153;mpMRI has been a fast-growing technology for the detection of prostate cancer among the urology community worldwide. Studies have shown that negative predictive value of mpMRI varies between 67% and 85%. Like histopathology the interpretation and scoring of the scan heavily relies on the experience of the radiologist. The study was published on August 29, 2017, in the journal The Prostate.

Image: SelectMDx can be used to diagnose prostate cancer without doing a biopsy or an MRI scan (Photo courtesy of MDxHealth SA).

Technology Diagnoses Pneumonia Caused by Undetected Pathogens novel next-generation sequencing (NGS) test for respiratory infections has been launched. The test provides a new solution for thousands of physicians who currently experience difficulty in diagnosing and treating patients with pneumonia and other respiratory diseases.

A strategic partnership was developed and commercialized novel infectious disease testing using metagenomics. This hypothesis-free approach to infectious disease testing uses DNA and RNA analysis to quickly identify bacteria, viruses, fungi, and parasites in patient samples.

The test detects more than 200 common and rare bacterial, fungal, and viral respiratory pathogens with a single test. By providing more comprehensive and actionable information within a clinically relevant turnaround time, this testing can help reduce inappropriate antibiotic use, avoid sequential testing, and potentially shorten hospital stays.

Diagnosing patients, particularly critically ill, immunocompromised

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patients, with suspected pneumonia can potentially require more than a dozen tests (including test panels) to determine the culprit pathogen.

The novel test, known as Explify Respiratory, was developed by Arup Laboratories (Salt lake City, UT, USA; www.aruplab.com) and IDbyDNA, Inc (San Francisco, CA, USA; www.idbydna.com). The test is powered by IDbyDNAâ&#x20AC;&#x2122;s Taxonomer software, a DNA search engine that can rapidly identify any organism by its genetic material. In a study, Explify Respiratory identified pathogens missed by conventional laboratory tests in 44% of immunocompromised children treated in the intensive care unit (ICU) for pneumonia. In 67% of specimens, only one pathogen was detected. Pathogens included 13 bacteria; Klebsiella pneumoniae, Haemophilus influenzae, Staphylococcus aureus; seven fungi; Mucor spp., Fusarium spp., Pneumocystis jirovecii and viruses. The study was originally presented at the 2017 American Thoracic Society Annual Meeting, held May 19-24, 2017, in Washington, DC, USA. LabMedica International April/2018

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New Zika Serotypes Likely to Emerge in Future Brazilian researcher warns that Zika virus is mutating so fast in Brazilian patients that different serotypes could soon appear. This would hinder the production of a vaccine and impair the effectiveness of the diagnostic tests already developed.

The alarm was sounded by Edison Luiz Durigon, professor at University of São Paulo’s Biomedical Science Institute (ICB-USP; Sao Paulo, Brazil; https://ww2.icb.usp.br/ing), in the opening address to the 2017 Annual Meeting of the Federation of Brazilian Societies for Experimental Biology (FeSBE; September 3-6, Campos do Jordão, São Paulo State, Brazil).

“People become immune after being infected once, but the virus is constantly mutating, and I wouldn’t be surprised if we see Zika 2, 3, and 4 emerging before long,” Prof. Durigon told the Sao Paulo Research Foundation (FAPESP; Sao Paulo, Brazil; www.fapesp.br/en).

This assertion was based data from 3 asymptomatic patients – 2 men and 1 woman – monitored weekly in a study conducted under the auspices of the Zika Virus Research Network in São Paulo (Rede Zika), supported by FAPESP. The researchers collected blood, saliva, and urine, as well as semen from the men. Samples were sent for wholegenome sequencing of the virus in partnership with the US Army.

“Week by week, we examined the data to see what was different in the viral genome,” said Prof. Durigon, “In one patient, we found compartmentalized strains: the virus present in his semen was different from the virus in his urine. In all cases, the pathogen we found in the final stage of the infection wasn’t the same as the virus that entered the patient.”

Both male patients continued to excrete large amounts of Zika virus in their semen for up to 6 months; one had Zika in his saliva for 3 months.

“Using an electron microscope, we could see that the spermatozoa were formed already infected,” he said, “This means a conception could occur with infected sperm. We have no idea whether pregnancy progresses in such cases, and if so, what the consequences would be for the fetus.” “It’s no use testing only pregnant women to see if the virus is present,” he said, “while leaving men to go on with their lives as normal.”

According to Durigon, the scientific community’s swift response in São Paulo inspired other groups and funding agencies in Brazil, enabling the creation of a nationwide Zika network. Advances achieved include validation of a serological test that can be used also after the infectious stage is over. Validation included 800

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samples from patients in Salvador, Bahia. “If this test can identify Zika in Salvador, it can work anywhere in the world,” he said, “Bahia, Pernambuco, and Paraíba will probably have few cases for at least 4 years or so, until a significant proportion of the population is susceptible again. In São Paulo, we don’t yet know.”

Up to 80% of cases may be asymptomatic, so without the serological test it is impossible to know the real magnitude of the epidemic and percentage of the population that is still susceptible. The team that developed the serological assay also includes ICB-USP researchers Paolo Zanotto and Luís Carlos de Souza Ferreira.

A main concern today is children who “may have brain damage but not microcephaly, so they won’t be carefully monitored.

The problem won’t appear until later, when they start displaying motor or learning difficul-

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ties. We could have a generation of children with all kinds of complications.” All children born during the period should be tested. Positive results should be assessed with caution and confirmed by imaging.

Image: A drawing of the outside of one Zika virus particle, and a cross-section through another as it interacts with a cell (Photo courtesy of David Goodsell).

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PASTEUR PIPETTES

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BRAND

Caretium

The BW 50 allows for full control of precise fluidic delivery from the dripping of a simple squeeze bottle to the full force of pressure delivery systems. It can be pre-programmed and is suitable for EIA, FIA, RIA, DNA probe and cellular assays.

The Pasteur pipettes are disposable and offer very good reproducibility of the number of drops per milliliter. They can be filled and deep-frozen, or changed into a closed vessel by heat-sealing the tip, and are ideal for aliquots.

The NB-201 offers high reliability and anti-interference and allows up to 112 test profiles to be programmed. Other features include large LCD touch screen; memory for storing 3,200 sample results; reaction curve and QC graph printout.

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New 3D App Provides More Accurate Cancer Diagnosis ith further development of light-sheet microscopy based 3D imaging, researchers were able to examine tumor biopsy tissue in more detail than current 2D methods, resulting in improved intratumoral heterogeneity phenotyping and diagnosis of solid tumors.

Vast numbers of tumor tissue samples are examined by pathologists around the world, whose pronouncements inform the treatment patients are given. Mistakes can result in more suffering and sometimes death.

Current pathological examination methods for assessing tumors use twodimensional (2D) light microscopy, which can cause a major information gap in studying 3D objects.

“To be sure, the tumors can be divided into sections for individual study, but 3D structures such as the blood and lymph systems are very hard to study in this way,” said study lead investigator Per Uhlén, professor at Karolinska Institutet (Solna, Stockholm, Sweden; http://ki.se/en/startpage). To better study human tumor tissue, the researchers applied an imaging technique, currently being used in basic research, that involves making the tissue transparent (clearing) and then reproducing it in 3D in a light-sheet microscope.

For example, upon labeling with specific antibodies, certain proteins can be analyzed in more detail.

“Light-sheet microscopy has been used in basic research for a while, but it is only in recent years that it’s been refined so much that it can be used practically in hospitals,” said Prof. Uhlén, “It was an unforgettable experience to look inside a tumor from a patient for the first time.”

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Working with clinicians from Karolinska University Hospital, the researchers were able to study stored samples from patients with bladder cancer and then by 3D reproduction of, amongst other structures, the blood system feeding the tumors, they could find more information about how aggressive the tumors are. The new technique also enabled more accurate diagnosis of muscle-invasive tumors, which can be missed with 2D methods. The light-sheet microscope used for the study is one of only a few in Sweden and is housed at the core facility CLICK – the Center for Live Imaging of Cells at Karolinska Institutet. The study, by Tanaka N et al, was published October 2, 2017, in the journal Nature Biomedical Engineering.

Image: Three-dimensional images showing the complex vascular system in ovarian cancer (left) and bladder cancer (right). Thick vessels are colored red, thin vessels colored blue (Photo courtesy of Nobuyuki Tanaka / Karolinska Institutet).

Rapid Diagnostic Used in Sepsis Management ntil now, clinicians have had to trade off the speed and relative ease of use of conventional highly parallel individual assays, against the information richness, but complexity and unwieldiness of next generation sequencing (NGS).

A new diagnostic test will identify directly, without the need for culture, the microbial cause of bloodstream infection leading to sepsis. Fast and accurate identification of the infection can be a lifesaver. The test achieves this relatively quickly compared to at least a day for current tests that rely on a prior positive blood culture.

LiDia (DNA Electronics Ltd, Carlsbad, CA, USA; www.dnae.com) is a closed system that can be operated at the clinical point-of-need, with no laboratory services or specialist training required. It is able to deliver accurate results in less than three hours, direct from blood (or other sample material), providing treating physicians with valuable intelligence to help treat their patients. The genomic analysis platform, LiDia, is based on the invention of semiconductor DNA sequencing by serial technology.

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The first test available on the LiDia platform will be the LiDia bloodstream infection (BSI) test, a rapid blood-to-result diagnostic for use in the management of sepsis. LiDia BSI offers a significant reduction in time-to-result compared to the current standard of culture-based diagnosis, which requires a microbiology laboratory and generally several days to produce a result.

Nick McCooke, Chief Business Officer of DNAe, said, “Our use of semiconductor-based genomic analysis sets us apart from other molecular diagnostics companies by combining the analytical power of next generation sequencing (NGS) technologies with the speed of multiplexed polymerase chain reaction (PCR) platforms. This is critical to facilitating the integration of genomic technologies into the everyday workflow of physicians and hospitals, and will have a profound impact on how patients are treated.” The product was introduced at the BioCentury’s 24th Annual Newsmakers in the Biotech Industry meeting held September 8, 2017, in New York, NY, USA. LabMedica International April/2018

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RAPID TEST

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Certest Biotec

Coris BioConcept

Diagon

The VIASURE Flu Typing I is designed for the specific identification and differentiation of Influenza A (H1N1)pdm09 and H3N2 subtypes.

The RNA is extracted from specimens, amplified using RT-PCR and detected using fluorescent dye probes.

The RESIST-4 O.K.N.V. allows the identification of OXA-48-like, KPC, NDM and VIM carbapenemases from a single sample. Each kit can test three parameters without the need for any equipment and offers the shortest time-to-result.

The Coag-M ensures efficient, reliable results with built-in QC features. Its friendly graphical interface and connectivity to LIS support work and is ideal for small- and middle-sized laboratories performing routine and special assays.

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Diagnostic Performance of Blood Counts Compared he use of point-of-care testing is increasing, however many hematology analyzers can only determine granulocyte count without further differentiation into neutrophils, eosinophils and basophils.

The technology of morphological assessment and counting of blood cells has advanced over recent decades, particularly in the white cell lineage, with concomitant benefits in relation to diagnosis, prognosis and management of inflammatory and malignant conditions.

The full range of measurements is available on modern automated laboratory analyzers.

Laboratory scientists at the Leeds Institute of Health Science (Leeds, UK; https:// medhealth.leeds.ac.uk) conducted an analysis on a pseudonymised, retrospective database containing peripheral venous blood sample results between 1 January 2004 and 1 September 2013 from 21,020 patients, all of whom had received chemotherapy treatment. Blood

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counts were measured from EDTA venous whole blood samples obtained for the purposes of routine clinical care, and taken at any time in relation to chemotherapy delivery.

All samples were submitted for a full blood count analysis, including a five-part differential on a Siemens ADVIA 120 analyzer (Siemens Healthcare Diagnostics, Erlangen, Germany; www.healthcare.siemens.com) until August 2004 and subsequently on the Siemens ADVIA 2120 analyzer; both instruments employ the same method principles. Data of interest included the eosinophil, basophil and neutrophil counts, with the sum of these three parameters being taken as the granulocyte count and lymphocyte and monocyte results were also extracted for analysis.

The team found that granulocyte to neutrophil count correlation was 0.997. The accuracy for classification into neutropenia grades using the derived equivalent granulocyte

count ranges was 96.4%. Identification of results with a neutrophil count less than 1.5×109 cells/L using an equivalent granulocyte count of less than 1.69×109 cells/L resulted in sensitivity, specificity, positive and negative predictive values of 98.0%, 99.5%, 97.8% and 99.5%, respectively. The study was published on October 4, 2017, in the journal Practical Laboratory Medicine.

Image: The ADVIA 2120 hematology analyzer (Photo courtesy of Siemens Healthcare).

Genetic Decoding Improved for Neurodevelopmental Disorders LG2 gene study as a case in point that will help facilitate future diagnosis of children with neurodevelopmental disorders (NDDs), such as intellectual disability, autism, or early-onset symptoms of psychiatric diseases such as schizophrenia.

NDDs are a group of often severe pediatric conditions. The recent development of higher resolution genetic diagnostic tools has underlined the prevalence of genetic anomalies (e.g. gene copy-number variations) in children with NDDs. In the study, two patients at Queen Fabiola Children’s University Hospital (HUDERF; Brussels, Belgium; www.huderf.be/en/index.asp) with NDDs (here cognitive and behavioral symptoms) showed partial loss, by deletion, of the DLG2 gene, which plays an important role in the development, plasticity, and stability of synapses.

A research team led by Dr. Guillaume Smits, Dr. Nicolas Deconinck, and Dr. Catheline Vilain of HUDERF and Prof. Gianluca Bontempi of ULB collaborated through the Interuniversity Institute of Bioinformatics in Brussels (IB), a joint research institute at Free University of Brussels (ULB; Brussels, Belgium; www.ulb.ac.be/ulb/presentation/uk.html)

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and Vrije Universiteit Brussel (VUB; www.vub.ac.be/en). Together, they worked at integrating large genomic, epigenomic, transcriptomic, and clinical datasets. The computational experiments, performed

by Claudio Reggiani, a PhD student, pinpointed 2 novel DLG2 promoters and coding exons conserved in human and mouse and present in the fetal brain. The deletion of these new regions was found statistically associated with developmental delay and intellectual disability in 2 independent patient cohorts, supporting the pathogenic role of these new elements into the neurodevelopmental symptoms of both HUDERF patients. The findings are presented in a paper and summarized in a video.

From a medical perspective, the findings will help medical doctors in improving future diagnosing of children with NDDs. From a scientific point of view, this work shows how the in silico integration of multiple large datasets can bring knowledge about the genome. It also provides elegant progress into the molecular cause of NDDs and improves fundamental knowledge about the DLG2 gene. The study, by Reggiani C et al, was published July 19, 2017, in the journal Genome Medicine.

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LabMedica International

Tumor Microenvironment May Provide Biomarker for Women with TNBC esearchers found that the presence of tumor-infiltrating lymphocytes (TILs) varied significantly in the tumors of AfricanAmerican and European-American women with triple negative breast cancer (TNBC), suggesting that TILs counts may help determine prognosis. TNBC is a highly aggressive breast cancer subtype that afflicts African-American women at a higher rate than white women, and often involves a worse prognosis, said study lead author Nikita Wright, a PhD student at Georgia State University (Atlanta, GA, USA; www.gsu.edu).

TNBC does not express 3 of the proteins that cause other types of breast tumors to grow – estrogen receptor, progesterone receptor, or Her2/neu.

Therefore, there are no targeted therapies currently available for TNBC. Previous research has shown that African-American women tend to develop more aggressive subtypes of TNBC than European-American women, exacerbating the disparity in survival. “Thus, there is an urgent need to investigate robust, clinically applicable biomarkers that can help clinicians discern which patients are likely to have a more aggressive disease course and guide the personalized treatment of TNBC,” said Wright.

Previous research has also shown that higher counts of TILs are associated with better survival in TNBC patients. Further research would be required to explain the mechanisms, but one theory is that more aggressive tumors elicit stronger infiltration of lymphocytes into the tumor.

Wright and colleagues tested resection samples from 142 TNBC patients at Emory Hospital (Atlanta, GA, USA), and compared overall (stromal) TILs between patients of African-American and European-American descent. None of the patients had undergone neoadjuvant chemotherapy. The results showed that African-American patients harbored significantly more overall TILs than European-American patients. Significant differences were also observed among early-stage TNBC patients, but not among late-stage patients.

High peripheral TILs were associated with better 10-year survival among early stage African-American TNBC patients, after adjusting for age, Nottingham grade, and stage. A greater presence of overall and peripheral TILs were also associated with a lack of androgen receptor (AR) expression among early-stage African-American TNBC patients. The lack of AR reception classifies some TNBC cases as quadruple negative, and this subtype is more prevalent among African-American compared to European-American TNBC patients.

Among African-American patients with early-stage TNBC, high TIL counts were also associated with younger age at diagnosis, increased intramammary lymph node involvement, increased BRCA1-associated protein expression, and programmed cell death protein 1 expression.

Wright said the study’s main limitation is that it only included patients who did not receive neoadjuvant

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chemotherapy. Retrospective studies that examine racial disparities in TILs among patients who did receive neoadjuvant chemotherapy could help confirm the role of TILs in TNBC. The study was presented at the 10th AACR (American Association for Cancer Research) Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved (Atlanta, GA, USA, September 25-28, 2017).

Image: Micrograph showing tumor-infiltrating lymphocytes in colorectal carcinoma. H&E stain. Tumor-infiltrating lymphocytes (TILs) are suggestive of microsatellite instability (MSI) (Photo courtesy of Wikimedia).

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IFT SLIDE WASHER

IHC/ISH STAINER

Dymind Biotechnology

Euroimmun

Leica

The DH36 is a three-part auto analyzer featuring advanced operating system and alarm system. It offers simple operation, ultra-low blood consumption, stable quality, superior performance and low maintenance cost.

The MERGITE! offers parallel washing of up to 50 substrate fields in about 40 seconds. It achieves high reproducibility with standardized washing processes and prevents cross contamination by field-wise washing with directed liquid flows.

The BOND-III is up to 50% faster than previous stainers and requires virtually no maintenance. It offers superior Bond reagents and proven Covertile technology to ensure delivery of clear and accurate staining for diagnostic confidence.

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Immunochromatographic Rapid Tests Evaluated for Cholera holera remains a significant cause of morbidity and mortality worldwide, resulting in an estimated 2.8 million cases and 91,000 deaths annually. Prompt identification of cholera cases facilitates rapid outbreak responses in the short term, while providing reliable surveillance data to guide long-term policies and interventions.

Microbiological stool culture, the current recognized gold standard for the diagnosis of cholera has significant limitations. Culture to isolate and identify the causative bacterium, Vibrio cholerae, may take up to three days to complete and requires laboratory capacity that is often absent in underserved settings.

An international team of scientists led by those at Harvard Medical School (Boston, MA, USA; https://hms.harvard.edu) carried out a retrospective review of diarrheal disease surveillance records in the Enteric Diseases Laboratory at the study site in Haiti between May 1, 2014 and October 15, 2015. All specimens that underwent both rapid diagnostic testing (RDT) and culture for identification of V. cholerae and had complete records were included in the data collection and analysis.

Three different RDTs were performed, depending on availability, such that some specimens underwent testing with one, two, three, or none of the RDTs. The team compared the results of 511 Crystal VC dipsticks (Arkray Healthcare Pvt., Mumbai, Indi; www.arkray.co.in), 129 Artron Vibrio cholerae O139 and O1 Combo Tests (Artron Laboratories Inc., Burnaby, BC, Canada; www.artronlab.com) and 451 SD Bioline Cholera Ag O1/O139 RDT (Standard Diagnostics Inc., Yongin-si, Republic of Ko-

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rea; www.standardia.com) RDTs to bacterial culture as the gold standard.

The scientists found that of 905 cultures, 477 (52.7%) were positive for V. cholerae O1, of which 27.7% were serotype Inaba. No cultures grew V. cholerae O139.

Sensitivity and specificity of Crystal VC were 98.6% and 71.1% respectively. Artron demonstrated a sensitivity of 98.6% and specificity of 69.1%. SD Bioline demonstrated a sensitivity of 81.1% and specificity of 92.8%. Crystal VC and Artron frequently showed false positive O139 bands, whereas none were seen with SD Bioline.

The authors concluded that there is significant variation in the performance of different cholera diagnostic RDTs. Artron and Crystal VC RDTs have high sensitivity and low specificity, while SD Bioline RDT has low to moderate sensitivity and high specificity when performed by laboratory technicians in Haiti. The study was published on November 1, 2017, in the journal Public Library of Science ONE. Image: The SD BIOLINE Cholera Ag 01/0139 rapid diagnostic test (Photo courtesy of Alere).

Urine-Based Markers for Bladder Cancer Reviewed he advances in understanding bladder cancer at the molecular and genetic level have led to the identification of detectable and measurable alterations associated with the disease. Given the ease of obtaining voided urine and its direct contact with potentially malignant urothelium, numerous urine-based tumor marker tests have been generated. Cystoscopy remains the standard for detection and surveillance of bladder cancer, but it is an invasive and potentially costly procedure. With the knowledge of molecular alterations associated with bladder cancer numerous urine-based tumor markers have become commercially available.

Urologists at the University of Texas Southwestern Medical Center (Dallas, TX, USA; www.utsouthwestern.edu) have reviewed the role of urine markers for screening, detection, and surveillance of bladder cancer. The requirement for a biomarker to be valuable is that it needs to provide a benefit or improvement over the current standard evaluation.

As has previously been described, an ideal biomarker needs to be â&#x20AC;&#x153;easier, better, faster, cheaperâ&#x20AC;? than current standards.

Point-of-care tests like NMP22 BladderChek (Alere, Waltham, MA,

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USA; www.alere.com) and BTA STAT (Polymedco, Cortlandt Manor, NY, USA; www.polymedco.com) can provide information during an office visit that may allow timelier decision-making. However, the more sophisticated markers often require more time to perform. Cost is also an issue for markers that rely on more technical expertise. The increased sensitivity of many urine markers such as fluorescence in situ hybridization (FISH) and uCyt+ (Scimedx Inc., Denville, NJ, USA; www.scimedx.com) and the high specificity of cytology, studies have shown that the combined analysis of these two tests reaches a high sensitivity and specificity.

The evaluation of second-test reflex UroVysion FISH (Abbott Inc., Abbott Park, IL, USA; www.abbott.com) and uCty+ testing in those with atypical or negative cytology has led to a prospective evaluation and subsequent validation study that was performed and found a high sensitivity of the FISH assay to detect bladder cancer in patients with atypical cytology and an equivocal or negative cystoscopy. The study was published in the October 2017 edition of the Rambam Maimonides Medical Journal.

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LabMedica International

Biosensor System Developed For Blood Glucose Monitoring urrently, noninvasive glucose monitoring is not widely appreciated because of its uncertain measurement, accuracy, weak blood glucose correlation and inability to detect hyperglycemia/hypoglycemia during sleep.

Regulated and continuous glucose monitoring (CGM) of diabetes patients can provide better monitoring and control of blood glucose and prevent complications and glucose monitoring with commercially available products relies on invasive lancet approaches.

Scientists at the Tsinghua University (Beijing, China; www.tsinghua.edu.cn) fabricated a skin-like biosensor system for noninvasive, in situ, and highly accurate intravascular blood glucose monitoring. The system integrates an ultrathin skin-like biosensor with paper battery–powered electrochemical twin channels (ETCs). The designed subcutaneous ETCs drive intravascular blood glucose out of the vessel and transport it to the skin surface.

The ultrathin (~3 μm) nanostructured biosensor, with high sensitivity (130.4 μA/mM), fully absorbs and measures the glucose, owing to its extreme conformability. The ultrathin skin-like biosensors completely conform to the skin and measure the outward-transported glucose driven by ETCs. These biosensors are multilayered with “sand dune” nanostructures, which exhibit better electrochemical properties and higher sensitivity.

The team conducted in vivo human clinical trials. Invasive glucose measurement was done using a commercial glucometer (ACCU-CHEK

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Performa, Roche, Basel, Switzerland; www.roche.com) and vein-detained needles. The skin-like noninvasive blood glucose monitoring system measured the intravascular blood glucose and the glucose in interstitial fluid (ISF). The ETCs greatly improve the correlation between the noninvasive measurement results and the real blood glucose level. With proper calibration, the system is potentially suitable for medical-grade CGM and insulin therapy when working with micro-insulin pumps. The study was published on December 1, 2017, in the journal Science Advances.

Image: The skin-like biosensor system developed for noninvasive blood glucose monitoring (Photo courtesy of Tsinghua University).

Molecular Automation Is Changing Clinical Laboratories ost mid-career laboratory medicine professionals find it hard not to recall the days when DNA had to be extracted manually and polyacrylamide gels were mixed by hand without also reflecting on how fast things have changed.

Automation has come so far, in fact, that it is poised to disrupt the very structure of molecular diagnostics laboratories. New molecular automation systems are capable of connecting directly to clinical chemistry and immunoassay lines, potentially moving high-volume testing out of molecular diagnostics entirely.

Frederick S. Nolte, PhD, D(ABMM), F(AAM), the director of the clinical laboratories at the Medical University of South Carolina (Charleston, SC, USA; www.musc.edu) has explored the current situation as regards automation of molecular testing in the clinical laboratory. His laboratory uses the Abbott m2000 system (Abbott Molecular, Des Plaines, IL, USA; www.molecular.abbott) for molecular testing and also Abbott’s automation line. He wondered if he could take a single sample from hepatitis C virus (HCV) serological testing and also use it to perform molecular confirmatory testing. He conducted a study alternating

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HCV-positive samples with negative samples and found a very low level of cross-contamination in about 5% of samples. His laboratory went ahead with the new single-sample routine, but if the RNA result is below a certain threshold the staff asks for a new specimen.

The Cobas 6800 (Roche Molecular Diagnostics, Branchburg Township, NJ, USA; www.usdiagnostics.roche.com) with the right connection modules, already uses a single sample for serology and molecular testing. It also uses information technology to control the testing workflow and incorporates intelligent rules for reflex testing.

The TriCore Reference Laboratories (Albuquerque, NM, USA; www. tricore.org) performs about 75,000 to 80,000 tests per month, on their recently installed the Roche Cobas 6800. Karissa Culbreath, PhD, D(ABMM), the scientific director of infectious diseases, said, “We can do more because now I’m able to free up my extremely talented molecular scientists and molecular technologists to work on the next wave of clinical infectious disease tests. Automation is not new; it’s just new to clinical microbiology.” The study was published on December 1, 2017, in Clinical Laboratory News.

Accurate Tool Developed to Track New HIV Infections n effort is underway to develop a more accurate way to gauge the incidence of human immunodeficiency virus (HIV) infections in large populations, which will improve scientific studies and prevention strategies worldwide.

Accurate HIV-1 incidence estimation is critical to the success of HIV1 prevention strategies. Current assays are limited by high false recent rates (FRRs) in certain populations and a short mean duration of recent infection (MDRI).

A large team of scientists working with those at Duke University Medical Center (Durham, NC, USA; https://medschool.duke.edu) received for testing 132 well-characterized untreated specimens drawn within 800 days of estimated date of seroconversion (EDSC) (120 unique subjects) for MDRI estimation and 134 specimens (121 subjects) from untreated and 58 specimens (56 subjects) from treated longstanding infection for FRR estimation. Specimens were largely from subjects infected with subtypes B (56%) and C (43%).

The investigators profiled HIV-1–specific binding antibody responses

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in participant serum or plasma. They evaluated antibody binding to a unique and broad set of HIV-1 antigens that included gp120, gp140, and V1-V2 antigens of multiple subtypes (i.e., A, CRF01-AE, B, C, and CRF07-BC) from both sexes. Serum and plasma were diluted in binding antibody multiplex assays (BAMA) and detection performed on either a Bioplex 200 (Bio-Rad, Hercules, CA, USA; www.bio-rad.com) or Luminex FM3D machine (Luminex Corporation, Austin, TX, USA; www. luminexcorp.com).

The scientists found that discriminant function analysis identified an optimal set of measurements that were subsequently evaluated in a 324-specimen blinded biomarker validation panel. These biomarkers included clade C gp140 IgG3, transmitted/founder clade C gp140 IgG4 avidity, clade B gp140 IgG4 avidity, and gp41 immunodominant region IgG avidity. MDRI was estimated at 215 day or alternatively, 267 days. FRRs in untreated and treated subjects were 5.0% and 3.6%, respectively. The study was published on December 21, 2017, in the journal JCI Insight.

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Genrui Biotech

Medix Biochemica

The GB HER2 RealEx PCR kit utilizes onestep qRT-PCR technology to detect HER2 RNA expression in various types of human breast cancer tissues. It requires only 50ng total RNA with an operation time of 65 minutes.

The GE300 features a color touch screen and throughput of 60 samples per hour based on ISE. Other features include auto calibration, sampling and cleaning, accurate results, as well as maintenance-free and long-life electrodes.

The Actim PROM is the world’s first rapid test for reliably detecting premature rupture of fetal membranes (PROM) in all patients. It gives reliable results in minutes, even in the presence of blood or other interfering substances.

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Rapid POC Assay Detects Micronutrient Deficiencies technology that could transform the way nutritional deficiency testing is done worldwide is based on a novel 15-minute point-of-care assay system that enables determination of vitamin A, iron, and inflammation status.

Micronutrient deficiencies such as vitamin A and iron affect a third of the world’s population with consequences such as blindness, higher child mortality, anemia, poor pregnancy outcomes, and reduced work capacity.

Many efforts to prevent or treat these deficiencies are hampered by the lack of adequate, accessible, and affordable diagnostic methods that can enable better targeting of interventions.

To rectify this situation, investigators at Cornell University (Ithaca, NY, USA; www. cornell.edu) developed a rapid diagnostic test and mobile enabled platform for simultaneously quantifying iron (ferritin), vitamin A (retinol-binding protein), and inflammation (Creactive protein) status.

This method combines multiple florescent

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markers and immunoassay approaches in a single test, allowing accurate quantification in 15 minutes even though the physiological range of the markers of interest vary over five orders of magnitude. The investigators reported sensitivities of 88%, 100%, and 80% and specificities of 97%, 100%, and 97% for iron deficiency (ferritin), vitamin A deficiency (retinol-binding protein) and inflammation status (C-reactive protein), respectively.

The novel test system was deemed suitable for point-of-care use in both resource-rich and resource-limited settings and can be read either by a standard laptop computer or with the NutriPhone dedicated smartphone application.

“We must address the micronutrient problem at the individual level – which is a much easier task. The key to solving these micronutrient deficiency problems is early detection and early intervention,” said senior author Dr. David Erickson, professor of mechanical engineering at Cornell University. “Having information, we can change or supplement diets, if we know who is deficient – and we are more

likely to prevent complications, and keep children and women healthy.”

The rapid diagnostic system was described in the December 4, 2017, online edition of the journal Proceedings of the [U.S.] National Academy of Sciences.

Image: The NutriPhone is a mobile diagnostics platform for monitoring individual vitamin and micronutrient levels was adapted to work with a rapid point-of-care assay system (Photo courtesy of Cornell University).

Prenatal Reflex DNA Screens for Three Trisomies t present, women are offered screening for these three chromosome disorders at 10-14 weeks of pregnancy.

The test combines an ultrasound scan and a blood test, and if it shows that a woman is at an increased risk of having an affected pregnancy.

Women are offered a diagnostic test, an amniocentesis or chorionic villus sampling (CVS); these are invasive tests that involve inserting a needle through the mother’s abdomen into her womb to collect samples of fluid surrounding the fetus or tissue from the placenta.

Medical scientists at Queen Mary University of London (QMUL, UK; www.qmul.ac.uk)

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have demonstrated that it is possible to incorporate DNA analysis into antenatal screening for three serious chromosome disorders, including Down’s syndrome, in a way that is far more accurate than existing methods, and safer and less stressful for mothers. The new method, called antenatal “reflex DNA screening,” which screens for Down’s syndrome, Edwards syndrome and Patau syndrome, detected more affected pregnancies than the test it replaced, with far fewer false-positives. Reflex DNA screening combines conventional screening with new DNA testing. The method was implemented in five UK NHS maternity units, screening over 22,000 women between April 2015 and August 2016, and continues to be in use.

The scientists collected blood for the serum and plasma samples was collected in a plain tube and an anticoagulant tube between 11 and 13 completed weeks of pregnancy and three pregnancies were tested in the 10th completed week of pregnancy. The combined test was performed on the serum sample using Roche (Basel, Switzerland; www.roche.com) pregnancy-associated plasma protein A and free -human chorionic gonadotropin assays.

Combined test risks were calculated separately for trisomy 21, trisomy 18, and trisomy 13 using the lpha software (Logical Medical Systems, London, UK; www.lmsalpha.com).

The study was published on November 9, 2017, in the journal Genetics in Medicine.

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LabMedica International

MicroRNA-based Assay Proposed For Early Detection of Cancer ancer researchers have proposed using a network of circulating microRNAs to diagnose ovarian carcinoma at a stage earlier than currently possible.

MicroRNAs (miRNAs) are a family of noncoding 19- to 25-nucleotide RNAs that regulate gene expression by targeting messenger RNAs (mRNAs) in a sequence specific manner, inducing translational repression or mRNA degradation, depending on the degree of complementarity between miRNAs and their targets. Many miRNAs are conserved in sequence between distantly related organisms, suggesting that these molecules participate in essential processes. In fact, miRNAs have been shown to be involved in the regulation of gene expression during development, cell proliferation, apoptosis, glucose metabolism, stress resistance, and cancer.

Screening techniques are currently not available for early stage ovarian cancer, making it challenging to diagnose the disease. As recent studies have suggested a role for non-coding RNAs in epithelial ovarian cancer (EOC), investigators at Brigham and Women’s Hospital (Boston, MA, USA; www.brighamandwomens.org) and Dana-Farber Cancer Institute (Boston, MA, USA; www.dfci.harvard.edu) evaluated the diagnostic potential for a serum miRNA neural network for detection of ovarian cancer.

“The key is that this test is very unlikely to misdiagnose ovarian cancer and give a positive signal when there is no malignant tumor. This is the hallmark of an effective diagnostic test,” said senior author Dr. Di-

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panjan Chowdhury, chief of the division of radiation and genomic stability at Dana-Farber Cancer Institute. The miRNA test for early detection of ovarian cancer was described in the October 31, 2017, online edition of the journal eLife.

Image: A scanning electron micrograph (SEM) of an ovarian cancer cell (Photo courtesy of Steve Gschmeissner / SPL).

Next-Generation Immunoassay Developed for Chagas Diseases hagas disease, caused by the protozoan Trypanosoma cruzi, is a major health and economic problem in Latin America for which no vaccine or appropriate drugs for large-scale public health interventions are yet available.

Accurate diagnosis is essential for the early identification and follows up of vector-borne cases and to prevent transmission of the disease by way of blood transfusions and organ transplantation. Diagnosis is routinely performed using serological methods, some of which require the laborious production of parasite lysates, parasite antigenic fractions or purified recombinant antigens.

Medical parasitologists at the National University of General San Martín (Buenos Aires, Argentina; www.unsam.edu.ar) obtained human serum samples from T. cruzi-infected patients who were in the asymptomatic chronic stage of the disease without cardiac or gastrointestinal compromise (age range: 11 to 51 years old, median age: 20). Serum samples were collected from clotted blood obtained by venipuncture and analyzed for T. cruzi-specific antibodies with commercially available kits: enzyme-linked immunosorbent assay (ELISA) using total parasite homogenate (Wiener Lab, Santa Fe, Argentina; www.wiener-lab.com.ar) and indirect hemagglutination (IHA) (Polychaco, Buenos Aires, Argentina; www.lab-lemos.com.ar).

The team performed a serological assessment of 27 selected epitopes and of their use in a novel multipeptide-based diagnostic method. A combination of seven of these peptides was finally evaluated in ELISA format against a panel of 199 sera samples (Chagas-positive and negative, including sera from patients with leishmaniasis). The multipeptide formulation displayed a high diagnostic performance, with a sensitivity of 96.3% and a specificity of 99.2%.

The authors concluded that their results provided a novel, robust multi-epitope formulation as a basis for the development of improved peptidebased serodiagnosis for chagas disease. In contrast with chimeric DNA constructs that encode multiepitope recombinant proteins, the fact that this diagnostic reagent is based on the combination of short peptides that can be synthesized separately and easily formulated in a mix-and-match approach, means that it can be improved successively over time with only a reasonable effort. The study was published on October 9, 2017, in the journal Public Library of Science Neglected Tropical Diseases.

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PRODUCT NEWS MALARIA ASSAY TEST

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HEMATOLOGY SOLUTION

IMMUNOBLOT SYSTEM

NG Biotech

Radiometer

Sugentech

The NG-Test Malaria Pf/Pan (pLDH) in-vitro immunochromatographic assay uses human blood for the qualitative detection of malaria.

It can be used for the specific detection of P. falciparum and differentiation of the other malarial species.

The 1st Automatic ensures automatic positive patient identification by matching patient, sample and operator information directly at the bedside. Its automation increases patient and operator safety, while providing more time for patient care.

The ADVANSURE ALLOSTATION uses electronic automation from specimen injection to analysis. It uses a syringe pump for dispensing and suction of samples and a water surface detection system for sample recognition and injection function.

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High Plasma Glucose Raises Baby Heart-Defect Risk or many years, physicians have known that women with diabetes face an increased risk of giving birth to babies with heart defects and some studies have also suggested a link between nondiabetic mothers’ blood sugar levels and babies’ heart defect risk.

One challenge associated with conducting such studies was the fact that maternal blood glucose is not routinely measured in nondiabetic pregnant women. Instead, women typically receive an oral glucose tolerance test halfway through pregnancy to determine whether they have gestational diabetes, but this test is performed well after the fetal heart has formed.

A team of scientists mainly from Stanford University Medical Center (Stanford, CA, USA; www.med.stanford.edu) studied medical records from 19,107 pairs of mothers and their babies born between 2009 and 2015.

The records included details of the mothers’ prenatal care, including blood test results and any cardiac diagnoses made for the babies during pregnancy or after birth. The scientists analyzed blood glucose levels from any blood sample collected from the mothers between four weeks prior to the estimated date of conception and the end of the 14th gestational week, just after the completion of the first trimester of pregnancy. These early blood glucose measurements were available for 2,292, or 13%, of women in the

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study. They also looked at the results of oral glucose tolerance tests (OGTT) performed around 20 weeks of gestation, which were available for 9,511, or just under half, of the women in the study.

After excluding women who had diabetes before pregnancy or who developed it during pregnancy, the results showed that the risk of giving birth to a child with a congenital heart defect was elevated by 8% for every increase of 10 mg/dL in blood glucose levels in the early stages of pregnancy. The mean early glucose value was 96 mg/dL (5.3 mmol/L) in pregnancies without congenital heart disease (CHD) versus 107 mg/dL (6.0 mmol/L) in pregnancies with CHD. The respective mean 1-hour OGTT values were 117 mg/dL (6.5 mmol/L) and 122 mg/dL (6.8 mmol/L).

The findings demonstrate that higher random plasma glucose values measured during early pregnancy correlate with increased risk for congenital heart disease in offspring of mothers who do not have diabetes.

Furthermore, plasma glucose measured during early pregnancy was more associated with risk for congenital heart disease in offspring, compared with the OGTT which is often used to risk-stratify pregnancies for fetal-echocardiographic screening. The study was published on December 15, 2017, in The Journal of Pediatrics.

Urine Test Developed for Accurate TB Detection n accurate screening test for active pulmonary tuberculosis (TB) is urgently needed for patients who are not co-infected with human immunodeficiency virus (HIV). Worldwide, TB is one of the most prevalent bacterial infections, with the highest mortality in developing countries.

Ideally, such a test would use a noninvasive body fluid such as urine to facilitate utilization in a low-resource setting. This objective, at first, appears straightforward because the outer surface glycan lipoarabinomannan (LAM), a TB antigen shed into the urine during active TB, has been identified and well characterized.

An international team of scientists collaborating with those at George Mason University (Manassas, VA, USA; www.gmu.edu) applied a copper complex dye called RB221 within a hydrogel nanocage that captures LAM with very high affinity, displacing interfering urine proteins. The technology was applied to study pretreatment urine from 48 Peruvian patients, all negative for HIV, with microbiologically confirmed active pulmonary TB by auramine staining for acid-fast bacilli in sputum and microscopic-observation drug-susceptibility (MODS) assay. Patient urine samples were qualified before the analysis by urinary dipstick testing (Multistix GP, Siemens Healthcare Diagnostics, Eschborn, Germany, www.healthcare.siemens.de).

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The scientists found that the RB221 nanocages trapped LAM from urine, increasing detection sensitivity by 100- to 1,000-fold, all while excluding interfering compounds from the samples that could confound results. In 48 Peruvian HIV-negative tuberculosis patients who had not yet been treated, the new test detected infections with greater than 95% sensitivity and a specificity of greater than 80%. LAM was quantitatively measured in the urine in a concentration range of 14 to 2,000 pg/mL, as compared to non-TB, healthy and diseased, agematched controls.

Elevated LAM concentrations in urine correlated with increased amounts of bacteria and more severe disease (as measured by weight loss or cough). The team also created nanocages to trap and detect other hallmarks of infection including very low abundance molecules named the 6 kDa early secretory antigenic target (ESAT6) and the 10-kDa culture filtrate protein (CFP10). Sandwich and lateral flow immunoassay feasibility for testing clinical specimens was documented for ESAT6. According to the authors, their next steps are to compare urinary LAM in patients before and after therapy to evaluate potential treatment-induced changes. The study was published on December 13, 2017, in the journal Science Translational Medicine.

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LabMedica International

Whole Genome Sequencing Yields Clinical Information mong acutely ill neonatal intensive care unit (NICU) patients, rapid whole genome sequencing (WGS) offers clinically useful information and substantial cost savings in comparison to the current standard of care.

It has been demonstrated that early diagnosis changes acute care management and that rapid WGS improves clinical care. A new study built on prior work by scientists showing that rapid WGS in neonates led to reduced time to diagnosis and better rates of diagnosis than previous practice.

A team of experts at Rady Children’s Institute for Genomic Medicine (San Diego, CA, USA; www.rchsd.org) enrolled 98 NICU patients who were nominated by a treating physician and whose parents gave consent to participate. Enrolled infants had blood samples taken within 48-72 hours of NICU admission, with polymerase chain reaction-free WGS at 40-45X coverage performed on these samples within 3 to 7 days. The investigators translated into human phenotype ontology terms the phenotypic features of each baby and mapped them to potentially causative genetic diseases. They used commercial tools to align DNA sequences and identify variants. Board-certified geneticists curated all variants and clinicians confirmed all significant results.

In one-third of patients (34/98), rapid WGS yielded a genetic diagnosis, which led to changes in medical management in 28 neonates (80%). For example, unnecessary surgery may have been avoided, med-

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ications may have been changed to better target underlying diseases, or families may have been counseled about palliative care. Among the first 42 infants, the investigators calculated that rapid WGS led to USD 1.3 million in net cost savings in comparison to standard care the babies otherwise would have received.

The study was presented at the Annual Meeting of the American Society of Human Genetics held October 17, to October 21, 2017, in Orlando, Florida, USA. Image: A new study suggests early diagnosis changes acute care management and that rapid whole genome sequencing improves clinical care (Photo courtesy of Scientific American).

Serum Albumin Level Predicts Serious HIV Events erum albumin may be used to stratify human immunodeficiency virus (HIV)–infected persons with a high CD4+ T-cell count according to their risk of serious non-Acquired Immune Deficiency Syndrome (AIDS) endpoints.

Serum albumin is sampled in many clinical settings, and previous literature has suggested that low amounts of it are associated with HIV-related comorbidities like inflammation, liver disease and nephropathy and lower serum albumin levels are strongly predictive of mortality risk, particularly within one year.

Scientists at the University Hospital Rigshospitalet (Copenhagen, Denmark; www.rigshospitalet.dk) and their colleagues tested serum albumin as a disease marker, and assessed data from the Strategic Timing of Antiretroviral Treatment (START) study, which was conducted between 2009 and 2013. The team included baseline serum albumin measures from 4,576 patients, who represented 98% of START participants, and assessed treatment outcomes. Serious non-AIDS events were defined as cardiovascular disease, end-stage renal disease, liver disease,

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non-AIDS-defining cancer, death from any of those conditions, and death not related to AIDS, accident or violence.

The investigators found that in all, 71 patients had serious non-AIDS events, 63 had AIDS events and 788 were hospitalized. A higher baseline serum albumin level per 1 g/dL was associated with a decreased risk for serious non-AIDS events and for hospitalization. It was not associated with a risk for AIDS. Similar results were obtained in a time-updated model, after controlling for interleukin 6, and after excluding initial follow-up years. Serum albumin was independently associated with hospitalization but not with risk of AIDS. Andreas Ronit, MD, of the University of Copenhagen department of infectious diseases and the lead author of the study, said, “We found that lower serum albumin was a strong predictor of serious non-AIDS events and hospitalization in seemingly healthy HIV-infected persons, with high CD4 counts. These associations were independent of traditional risk factors and various laboratory measures.” The study was published on December 13, 2017, in The Journal of Infectious Diseases.

Handheld Device Developed for DNA Amplification and Detection method has been developed that combines electrochemical detection with recombinase polymerase amplification (RPA) on a portable device to improve detection of genetic material from multiple tuberculosis strains. The RPA reaction uses enzymes called recombinases that form complexes with oligonucleotide primers and pair the primers with homologous sequences in DNA. A single-stranded DNA binding protein binds to the displaced DNA strand and stabilizes the resulting loop. The primer then initiates DNA amplification by a polymerase, but only if the target DNA sequence is present.

Scientists from Harvard University (Boston, MA, USA; www. harvard.edu) and Diagnostics for All (Salem, MA, USA; http://dfa.org) used disposable, paper-based strips that integrate three screen-printed carbon electrodes and accomplish thermoregulation with +/-0.1 ºC temperature accuracy. To detect DNA, the team first prepares the paper test strip that includes the blood sample and primers, in addition to integrated electrodes that contain the reagents for RPA. The test strips allows the team to cut down on reaction volume, reducing reagent cost and blood sample size. After identifying a 213-bp region common to both Mycobacterium tuberculosis and Mycobacterium smegmatis, the

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team designed appropriate primers for the RPA assay to amplify the specific sequence. Performed at 65 ºC, the assay combined isothermal amplification with electrochemical readout of redox-active hexa-amine ruthenium (III) (Ru(NH3)6]3+) as an electroactive mediator for the electrochemical detection of DNA. The team also performed the reaction with varying levels of initial concentrations of the M. smegmatis target DNA in order to demonstrate the assay’s sensitivity. According to the study, the assay’s limit of detection is 0.04 ng/μL, equating to 11 colony forming units (CFU)/mL of M. tuberculosis. Because RPA assays do not need additional sample preparation time, the assay in the study required 20 minutes to identify the biosignal.

The scientists emphasized that the RPA assay could potentially identify the signal faster depending on the type of primer and target sequence. While the team used M. smegmatis as a surrogate strain for M. tuberculosis, the benchtop RPA assay they developed can detect up to 19 Mycobacterium species. In addition, the team also carried out experiments using samples spiked with M. tuberculosis DNA that highlights that the electrochemical method also works with the specific bacterial strain. The study was published in the February 2018 issue of the journal Analytical Biochemistry.

PRODUCT NEWS QUANTITATIVE ANALYZER

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URINE SEDIMENT ANALYZER

ROBOTIC CENTRIFUGE

Getein Biotechnology

77 Elektronika

Hettich

The Getein 1600 uses bar-coded, ready-touse strip cassettes to deliver accurate testing results in minutes. Its compact design, ease of use, and minimal maintenance allows it to be used in both routine and emergency testing situations.

The UriSed 3 PRO offers a uniquely advanced method of visualization and recognition of formed elements in urine samples. It is designed to increase reliability, improve workflow and decrease turnaround time.

The ROTANTA 460 Robotic can process a range of blood collection tubes, plates and racks for clinical chemistry or oncologic tests.

It is suitable for automated centrifugation prior to PCR, as well as prior to screening in drug development.

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Significant Disparities Found between Liquid Biopsy Providers iquid biopsy is a new and noninvasive alternative to tumor tissue sequencing, and it is intended to specifically detect and sequence tumor DNA circulating in patients’ blood. The results are used to help guide doctors to tailor the best treatment for patients at each point of their disease.

Patients may respond differently to cancer drugs depending on what kinds of gene mutations they have in their tumors. Oncologists use the results of a liquid biopsy to see if a patient is responding to treatment and to monitor tumors to see if they are progressing and may require a new or extra therapy. They may also use the results to select patients for clinical trials, if a specific mutation is found in their tumor’s DNA. Medical scientists at Johns Hopkins Medicine (Baltimore, MD, USA; www.hopkinsmedicine.org) collected blood samples from 40 metastatic prostate cancer patients from January 2007 and July 2017. The samples were shipped to two laboratories that were licensed by Clinical Laboratory Improvement Amendments, known as CLIA, and accredited by the College of American Pathologists, and report having high sensitivity (in this case, the ability to correctly identify mutations when they occur) and high specificity (the ability to correctly report as negative when

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those mutations are not present).

The two liquid biopsy panels compared were the Guardant360 (Guardant Health, Inc., Redwood City, CA, USA; www.guardanthealth. com) which sequenced at least part of the coding sequences of 73 genes, and the PlasmaSELECT panel (Personal Genome Diagnostics, Baltimore, MD, USA; www.personalgenome.com ) which sequenced coding segments of 64 genes. The two companies differ in which genes, and regions within each gene, are covered. Just 25 of the 40 patients in the study had at least one genetic mutation reported within the overlapping genetic sequences covered by both companies.

The team found that even when the companies were analyzing DNA from the same blood drawn, their results rarely matched each other. When comparing results within the overlapping genetic sequences, the results from both companies completely matched for all the mutations reported in only 3/40 patients (7.5%) of cases. In 6/ 40of the patients (15%), both companies’ results matched for at least one of the reported mutations. In 16/40 (40%) of the patients, no mutations reported that were potentially covered by both panels were detected by both companies. The study was published on December 14, 2017, in JAMA Oncology.

Genetic Test Recommended for Inherited Prostate Cancer o date, there have been few recommendations to guide physicians about when to offer men genetic consultation for prostate cancer risk. A subset of prostate cancers, about 10%-15% of all prostate cancer are inherited and that at least some of the genes that confer the inherited risk are known and testable.

Prostate cancer (PCA) is the third leading cause of cancer-related death in USA men, accounting for 26,730 deaths in 2017. Clinical practice including referrals, genetic counseling, genetic testing, and genetically informed management needs to encompass medical advances and increasingly available commercial genetic tests.

An international and inter-specialty panel of 71 experts convened at the Thomas Jefferson University (Philadelphia, PA, USA; www.jefferson.edu) and have developed a comprehensive set of recommendations to guide physicians about when to offer men genetic consultation for prostate cancer risk and this will help physicians and stakeholders make sense of a rapidly evolving field of practice. The goal of the consensus statement was to provide a comprehensive and balanced clinical approach to genetic referrals and testing relevant to clinical cancer genetics specialists, genetic counselors, urologists, oncologists, and primary care providers to provide men with an opportunity to make an informed decision regarding genetic testing, screening, and personalized treatment.

The group’s key findings and recommendations included that while

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current commercially available genetic tests specifically for inherited prostate cancer risk can cover anywhere from 10-14 genes (and even larger cancer gene panels are available), clinical actionability for prostate cancer screening and management are relevant for a subset of these genes. For example, men with prostate cancer with inherited mutations in the breast cancer 2 (BRCA2), breast cancer 1, early onset (BRCA1), and Ataxia Telangiectasia Mutated (ATM) genes may respond to polyadenosine diphosphate-ribose polymerase (PARP) inhibitors, especially if prostate cancer has progressed to metastasis and is resistant to initial treatments.

The following genes should be tested in males with PCA meeting criteria for the corresponding syndrome: HOXB13 (Syndrome: Hereditary pancreatitis [HPC]); BRCA1/BRCA2 (Syndrome: Hereditary breast and ovarian cancer [HBOC]), DNA mismatch repair (MMR) genes. Men with PCA with two or more close blood relatives on the same side of the family with a cancer should get tested. Others who may need testing are men with metastatic, hormone-sensitive PCA to identify germline mutations to inform potential future treatment options and cascade testing in families and men with tumor sequencing showing mutations in cancer-risk genes should be recommended for germline testing, particularly after factoring in additional personal history and specific family history. The study was published on December 13, 2017, in the Journal of Clinical Oncology.

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LabMedica International

Oral Microbiome Composition Reflects Risk for Esophageal Cancers sophageal cancer is the eighth most common cancer and the sixth leading cause of cancer death worldwide. Because the disease is often not discovered until it has reached an advanced stage, five-year survival rates range from about 15% to 25% worldwide.

Bacteria may play a role in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), although evidence is limited to cross-sectional studies. An analysis of bacteria present in the mouth showed that some types of bacteria that lead to periodontal disease were associated with higher risk of esophageal cancer.

Medical scientists at the NYU Langone School of Medicine (New York, NY, USA; www.nyulangone.org) and their colleagues collected oral wash samples from 122,000 participants in two large health studies. In 10 years of follow-up, 106 participants developed esophageal cancer. In a prospective case-control study, the investigators extracted DNA and sequenced oral wash samples, allowing the investigators to compare the oral microbiomes of the esophageal cancer cases and the cancer-free cases. Oral bacteria were assessed using 16S rRNA gene sequencing in pre-diagnostic mouthwash samples from n = 81/160 EAC and n = 25/50 ESCC cases/matched controls.

The team found that found the periodontal pathogen Tannerella forsythia was associated with a higher risk of EAC. Furthermore, they found that depletion of the commensal genus Neisseria and the species Streptococcus pneumoniae was associated with lower EAC risk. Bacterial biosynthesis of carotenoids was also associated with protection

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against EAC. Finally, the abundance of the periodontal pathogen Porphyromonas gingivalis trended with higher risk of ESCC. Overall, the findings have potential implications for the early detection and prevention of EAC and ESCC. The study was published in the December 2017 issue of the journal Cancer Research.

Image: A colored scanning electron micrograph (SEM) of the periodontal pathogen Porphyromonas gingivalis (Photo courtesy of the Forsyth Institute).

Immunoassay Quantifies Cancer Cell Loss During Treatment he quantification of cell loss in breast cancer during neoadjuvant treatment (NACT) can be assessed by serum thymidine kinase protein concentrations (sTK1). TK1 has a key function in DNA synthesis and repair responsible for maintaining the nucleoid pool balance by salvage and recycle thymidine from extracellular sources.

A new technology is based on patented methods to measure Thymidine Kinase 1 (TK1) protein levels in a blood sample. The TK 210 enzyme-linked immunosorbent assay (ELISA) test provides valuable information mainly about the condition of cancer patients. This may help clinicians to optimize treatment strategies and estimate the risk of recurrence of the tumor disease during the monitoring of the disease.

Scientists at AroCell AB (Uppsala, Sweden; www.arocell.com) quantified cell loss using the AroCell TK 210 ELISA kit to measure serum TK1 in serial samples from 145 breast cancer patients undergoing chemotherapy before surgery. Serum TK1 levels correlated to clinical/radiologically

determined tumor response after cycles 2, 4 and 6, as well as pathologically determined response and disease-free survival.

The investigators found that base-line sTK1 increases considerably 48 hours after treatment to plateau levels, but declines during the three weeks rest between courses. The level of sTK1 measured after treatment arrest periods correlated, after four cycles of treatment, significantly with clinical/radiological response during treatment and pathologic response at surgery. Surprisingly, the 48 hour plateau values are highest in pT0 (no evidence of breast tumor), followed by pT3 (tumor >50 mm in greatest dimension), pT2 (tumor >20 mm, but â&#x2030;¤50 mm in greatest dimension) and lowest in pT1 (Tumor â&#x2030;¤ 20 mm in greatest dimension).

Disease free survival (median follow-up 49 months) ranged between 29.7% in pT0 and 5.7% in pT1 and is significantly related to sTK1. The study was presented on November 18, 2017, at the European Society for Medical Oncology 2017 Congress held in Singapore.

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PRODUCT NEWS DIABETES/TB ANALYZER

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PRECISION DISPENSE PUMP

HEMATOLOGY ANALYZER

DxGen

The Lee Company

Abbott Diagnostics

The Epithod 616 system features 7-inch full color touch screen, thermal printer with full ITconnectivity. Key functions include PC dashboard control, automatic update, remote assistance, multi-lingual operation, operator and patient management.

The LPD series delivers consistent performance and significant cost savings in a compact package. Designed to be maintenancefree, the mini, chemically inert pumps are available in 50, 250, 1,000 and 3,000 microliter full dispense volumes.

The Alinity h-series solution integrates the Alinity hq with the Alinity hs slide maker and stainer module. The integrated system offers an intuitive user experience with iconography, color-coding and reporting features shared by all Alinity platforms.

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Multiple Myeloma Survival Associated with Enzyme Levels ultiple myeloma (MM) is the second most common blood cancer in the USA and 30% to 50% of multiple myeloma patients have extra copies of the gene that encodes the enzyme Adenosine Deaminase, RNA Specific (ADAR1).

ADAR1 is normally expressed during fetal development to help blood cells form. ADAR1 edits the sequence of RNA, a type of genetic material related to DNA. By swapping out just one RNA building block for another, ADAR1 alters the carefully orchestrated system cells use to control which genes are turned on or off at which times. Scientists at the University of California San Diego School of Medicine (La Jolla, CA, USA; https:// healthsciences.ucsd.edu) obtained bone marrow samples from MM patient and normal age-matched controls. Peripheral blood (PB) or bone marrow (BM) samples were processed by Ficoll density centrifugation and viable total mononuclear cells (MNC) were collected for further analyses and stored in liquid nitrogen. RNA editing site-specific quantitative real time polymerase chain reaction (RESSq-PCR) assay primer design was carried out for specific cancer and stem cell-associated loci. The team performed several other molecular procedures to confirm their results.

The scientists analyzed a database of nearly 800 multiple myeloma patient samples, and they discovered that 162 patients with low ADAR1 levels in their tumor cells survived significantly longer over a three-year

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period compared to 159 patients with high ADAR1 levels. While more than 90% of patients with low ADAR1 levels survived longer than two years after their initial diagnosis, fewer than 70% of patients with high ADAR1 levels were alive after the same period of time.

The team found that two events converge to activate ADAR1 in multiple myeloma, a genetic abnormality and inflammatory cues from the surrounding bone marrow tissue. Together, these signals activate ADAR1, which edits specific RNA in a way that stabilizes a gene that can make cancer stem cells more aggressive. They also found that silencing the ADAR1 gene in the xenograft model reduced multiple myeloma regeneration. Five to 10-fold fewer tumor cells were able to self-renew in mice lacking ADAR1, suggesting a new therapeutic target.

Catriona H. M. Jamieson, MD, PhD, professor of medicine and senior author of the study, said, “Several major advances in recent years have been good news for multiple myeloma patients, but those new drugs only target terminally differentiated cancer cells and thus can only reduce the bulk of the tumor. They don’t get to the root cause of disease development, progression and relapse, cancer stem cells, the way inhibiting ADAR1 does. I like to call our approach ‘precision regenerative medicine.” The study was published on December 4, 2017, in the journal Nature Communications.

Genetic Profile Identified for Dementia with Lewy Bodies (DLB) ementia with Lewy bodies has a unique genetic profile, distinct from those of Alzheimer’s disease or Parkinson’s disease, according to the first large-scale genetic study of this common type of dementia.

Dementia with Lewy bodies (DLB) is the second most common form of dementia in elderly people but has been overshadowed in the medical field, partly because of similarities between dementia with Lewy bodies, Parkinson’s disease, and Alzheimer’s disease.

An international team of 65 scientists from 11 countries collaborated with those at University College London (London, UK; www.ucl.ac.uk) collected samples from white participants of European ancestry who had been diagnosed with dementia with Lewy bodies according to established clinical or pathological criteria. Pathological samples were ascertained following autopsy in each individual brain bank, whereas clinical samples were collected after participant examination. The team genotyped 1,743 patients with dementia with Lewy bodies (DLB), including both clinical samples and 1,324 pathological samples assessed post-mortem, and 4,454 controls.

The investigators found that two of the genetic loci that were found

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to be significantly associated with DLB, Apolipoprotein E (APOE) and glucocerebrosidase (GBA), bore the same associations to DLB as they do to Alzheimer’s and Parkinson’s, respectively. Another one of the loci identified alpha-synuclein (SNCA), is also associated with Parkinson’s, but differently as the team found that a different part of the gene is linked to DLB. They also found preliminary evidence for a gene locus that had not been previously associated with DLB, but the results did not reach significance. The team also found that a few loci that are associated with Alzheimer’s and Parkinson’s do not appear to be associated with DLB. They were able to identify a heritability estimate of DLB for the first time, at 36%, which is similar to that of Parkinson’s. The heritability was particularly high for four specific chromosomes, suggesting that further studies could focus on those chromosomes to identify novel loci.

Rita Guerreiroa, PhD, a senior lecturer and the lead author of the study said, “As the gene loci that had previously been associated with DLB were also implicated in Alzheimer’s and Parkinson’s, it was unclear if DLB’s genetic roots were simply a combination of the other two diseases. We’ve confirmed that instead, it has its own unique genetic profile.” The study was published in the January 2018 edition of journal The Lancet Neurology.

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Low Serum Calcium Increases Risk of Sudden Cardiac Arrest udden cardiac arrest (SCA) is fatal for over 90% of patients, and more than half of men and close to 70% of women who die of SCA have no clinical history of heart disease prior to this cardiac event. It is one of the leading causes of death in the USA and kills more people than any single cancer.

Many patients who suffer SCA would not be considered high risk under current guidelines. These sobering facts drive the search for simple and relatively inexpensive ways to identify individuals at higher risk for SCA. Individuals with lower levels of calcium in the blood, which is easily monitored, are more likely to experience SCA than those with higher calcium levels.

A team of scientists working with those at the Cedars-Sinai Heart Institute (Los Angeles, CA, USA; www.cedars-sinai.edu) measured serum calcium levels during routine medical care of 267 SCA cases and 445 control subjects. All SCA cases had had serum calcium levels measured in the 90 days prior to their cardiac arrest. Each patient’s total serum calcium was corrected by their serum albumin level to estimate a more physiologically relevant corrected calcium level. Patients were included if their age was 18 years or older with available creatinine clearance (CrCl) and serum electrolyte levels for analyses to enable adjustment for renal function.

The scientists found that SCA cases had a significantly higher percentage of African Americans and patients with diabetes mellitus, chronic obstructive pulmonary disease, and chronic kidney disease compared to the control group.

Cases were also more likely than controls to be on hemodialysis. In addition, diuretics, especially loop diuretics, were prescribed more for cases than for controls with no differences in the rate of utilization of beta blockers. Blood calcium levels INTERACTIVE lower than 8.95 mg/dL were assoDIGITAL EDITION ciated with a 2.3-fold increase in odds of SCA as compared with levels higher than 9.55 mg/dL (odds ratio, 2.33).

Hirad Yarmohammadi, MD, MPH, a postdoctoral fellow at Cedars-Sinai and lead author of the study, said, “Our study showed that lower serum calcium levels, even within the normal range of values, may increase risk for sudden cardiac death. Although our findings may not be ready for routine clinical use in patients at this time, they are a step towards the goal of improving patient care by better prediction of risk.” The study was published on September 21, 2017, in the journal Mayo Clinic Proceedings.

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Image: Research shows individuals with lower levels of calcium in the blood are more likely to experience SCA than those with higher calcium levels (Photo courtesy of SPL).

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The ELx 50 offers a selection of wash programs by plate or strip. It features on-board software that allows for programmable aspiration time and final extra aspiration, and offers several wash options.

The HDL-EX (N) uses a homogenous method for the direct testing of HDL-C levels in serum and plasma. The assay consists of two steps and uses a well-characterized and specially selected surfactant.

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Single Cell Genomics Utilized for Evaluation of Prostate Cancer distinction between indolent and aggressive disease is a major challenge in diagnostics of prostate cancer. Histopathology of tissue biopsies is a standard method used for evaluating cancer risk. Many decades of experience have led to classification of the histological types correlated with clinical outcome.

A small-scale test of a new analytical method to improve the early detection of potentially lethal prostate cancer has been reported. The utility of single nucleus sequencing (SNS) to aid diagnosis has been explored and based on diagnostic biopsy samples; the method promises to more accurately diagnose men who need surgery from those who do not.

A team of scientists collaborating with those at Cold Spring Harbor Laboratory (CSHL, New York, NY, USA; www.cshl.edu) have described a small pilot study on eleven patients. In eight cases, they compared genomic pathology based on SNS to histopathology reports based on standard hematoxylin-eosin (H&E) staining of diagnostic needle core biopsies. They performed SNS on a total of 4,021 nuclei from 122 anatomical locations in 11 patients spanning a broad histological spectrum from benign prostatic epithelium to high grade prostatic intraepithelial neoplasia (HGPIN) and frank carcinoma (within and beyond the prostate) in both early and advanced stage disease.

The team isolated nuclei from frozen core biopsies and biopsy washings, processed and single nuclei were sorted by FACS using the SORP flow cytometer (BD Biosystems, San Jose, CA, USA; www.bdbiosciences.com).

Single nuclei were deposited into individual wells in a 96-well plate and amplified. Whole-genome amplification (WGA) was performed and after

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WGA DNA was sonicated using a Covaris focus acoustics system (Woburn, MA, USA; http://covaris.com). Multiple libraries were combined into pools ranging from 8-12 libraries to pools of 96 libraries for 76 bp singleread sequencing on single lanes of Illumina’s GAIIx and HiSeq flow cells (Illumina, San Diego, CA, USA; www.illumina.com), respectively.

The team sequences the genomes of several hundred single cells sampled from each patient’s biopsy cores. They searched for certain patterns, for the presence of DNA disturbances called copy-number variations (CNVs). Using computational methods to compare CNV patterns, the team looks for cells whose CNV profiles harbor the same irregularities. This is a sign of clonality, as cancerous tumors are composed of clonal cells, genetically aberrant cells that derive from a single wayward ancestor. The parameters all showed good correlation to the measure of prostatic malignancy, the Gleason score, derived from individual prostate biopsy tissue cores.

As the testing method yielded assessments of tumors that more closely matched the verdict of post-surgical pathological analysis (which reveal actual pathology) than the corresponding pre-surgical predictive biopsies, Alexander Krasnitz, PhD, an associate professor and a lead author of the study said, “This is important because treatment decisions in such cases depend on the pre-surgical biopsy, not the surgical specimen. We think single-cell analysis could potentially augment traditional biopsy-core histopathology, significantly improving risk assessment and informing treatment decisions, especially in borderline cases.” The study was published on November 27, 2017, in the journal Cancer Research.

Five New Genes Identified for ALS myotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is characterized by loss of motor neurons in the brain, brainstem and spinal cord, with concurrent muscle atrophy and is typically fatal within 2–5 years from diagnosis.

More than 30 genes have been linked to ALS, and mutations in the 11 genes that encode RNA binding proteins cause familial forms of ALS. These RNA binding proteins play a critical role in how genes encoded within the DNA in every cell are converted to the proteins that perform all the functions within a cell.

A team of scientists from the Barrow Neurological Institute (Phoenix, AZ, USA; www.barrowneuro.org) obtained ALS and nonneurologic disease control post-mortem tissue samples. Paraffin-embedded post-mortem tissue sections from spinal cords and cerebellum were used for immunohistochemistry. Sections were visualized using a Leica AperioScope microscope (Leica Biosystems Inc, Buffalo Grove, IL, USA; www.leicabiosystems.com), and analyzed using the Aperio eSlide man-

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ager image analysis. Laser-capture microscopy, RNA extraction and realtime polymerase chain reaction (PCR) analysis was also performed.

The team validated the top 10 RNA binding proteins using five different methods that included use of patient tissue samples and patient derived stem cells differentiated into motor neurons. They also examined a smaller set of RNA binding proteins near the bottom of the list to demonstrate that any changes detected in the top 10 were not observed for those at the bottom of the list, demonstrating the ability of Watson for Drug Discovery to correctly predict RNA binding proteins linked to ALS. Eight of the top 10 candidates were successfully validated and shown to be altered in ALS. Five of these genes had never been examined in ALS, indicating that IBM’s artificial intelligence platform could predict novel genes and proteins linked to this disease.

RNA binding proteins at the bottom of the list were not altered in ALS. The study was published on November 17, 2017, in the journal Acta Neuropathologica.

LabMedica International April/2018

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Blood Gas Analyzers for Point-of-Care Validated everal aspects of pH and blood gas analysis are unique in laboratory analysis, and furthermore, no other test results have such a great and immediate impact on patient care. In addition, it is now possible to carry out further vital biological assays on the same sample.

These results provide an overall picture of the patient’s state of health, which is especially important for patients admitted to adult and neonatal resuscitation wards (scalp pH), or in emergency medicine.

Blood gas analyzers are often integrated into point-of-care testing and this has been evaluated.

Clinical biochemists at the Clermont-Ferrand Teaching Hospital (Clermont-Ferrand, France; www.chu-clermontferrand.fr) installed and assessed 12 GEM PREMIER 4000 analyzers (Werfen, Le Pré-Saint-Gervais, France; www.werfen.com) for pH, pCO2, pO2, Na+, K+, Cl-, Ca2+, lactate, hemoglobin (Hb) and oxyhemoglobin (O2Hb). These instruments were distributed across 11 care sites in the hospital. Comparisons between GEM analyzers were performed on 30 samples and between GEM analyzers and the central laboratory for Na+, K+, Cl-, Ca2+ and hemoglobin on 30 to 50 samples. The GEM analyzers were compared with the automated analyzers of the central laboratory. Na+, K+, Cl- and lactate were assayed on a Vista-type analyzer (Siemens, SaintDenis, France; www.siemens.com). Ca2+ was assayed on a Siemens RAPIDPoint500 analyzer, and Hb was assayed on an XN analyzer (Sysmex, Villepinte, France; www.sysmex.fr).

The scientists obtained the results for the determination of [H+],

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pCO2, Na+, Cl-, K+, Ca2+, lactate and O2Hb that all complied with French Society of Clinical Biology (SFBC) recommendations, with corresponding coefficient of variation (CV) values below 1.5%, 3.8%, 0.8%, 1.2%, 1.2%, 1.2%, 3.8% and 3.8% respectively. These tests were carried out over the measurement ranges 6.80–7.58 for pH (100–22 nmol/L H+), 26–150 mmHg for pCO2, 33–203 mmHg for pO2, 125–163 mmol/L for Na+, 86–136 mmol/L for Cl-, 2.4–6.7 mmol/L for K+, 0.25–1.51 mmol/L for Ca2+, 0.8–19 mmol/L for lactate, 6.0–20.7 g/dL for Hb and 37.2–98.4% for O2Hb. The authors concluded that their results met standard requirements and the 12 analyzers were assessed as suitable for point-of-care testing in services of academic medical centers, as exemplified at Clermont-Ferrand hospital. The study was published on December 13, 2017, in the journal Practical Laboratory Medicine.

Image: The RAPIDPoint 500 analyzer (Photo courtesy of Siemens Healthineers).

Parental Screening Can Prevent Hydrops Fetalis in Fetus ydrops fetalis (fetal hydrops) is a serious fetal condition defined as abnormal accumulation of fluid in two or more fetal compartments, including ascites, pleural effusion, pericardial effusion, and skin edema.

Fetal anemia is often assumed to be due to red cell alloimmunization and Parvovirus infection, and can lead to hydrops fetalis and death in utero, while other causes, such as mutations of hemoglobin alpha, are less commonly considered.

Hematologists at Khon Kaen University (Khon Kaen, Thailand; www.kku.ac.th) reported on report seven cases with fetal anemia causing hydrops fetalis. They performed cordocentesis to find the cause of fetal anemia and check fetal hemoglobin for consideration of intrauterine infusion. Investigations for fetal anemia include complete blood count, blood morphology, and blood group of mother and fetus, reticulocyte counts, red cell indices, screening for thalassemia, hemoglobin typing, acid elution test, parvovirus B 19 serology, and TORCH titer (toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, human immun-

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odeficiency virus, and syphilis).

The seven cases with fetal anemia were prenatally diagnosed from gestational ages 20 to 34 weeks. Initial hematocrit in these cases varied from 9% to 17.2%. In each case, causes of anemia were determined using the investigations listed above. Intrauterine infusion, using irradiated prestorage filtered red cell with hematocrit level of 80%, is indicated if fetal hemoglobin is less than 10 g/dL. All cases underwent uneventfully up to three intrauterine transfusions.

The DNA study for thalassemia demonstrated homozygous Constant Spring (CS) in five cases, homozygous CS with heterozygous E in one case, and compound heterozygous CS and Pakse in one case. The perinatal outcomes were normal term in five cases, preterm in two cases. Low birth weight was determined in two cases. The screening for thalassemia major, including the osmotic fragility and dichlorophenol indophenol precipitation test (DCIP), was not helpful for detecting hemoglobin variants such as Constant Spring or Pakse. The study was published on December 12, 2017, in the Journal of Pediatric Hematology/Oncology.

Cartridge Developed to Detect Antibiotic-Resistant Bacteria diagnostic platform that exploits the phenomenon of linear dichroism (LD) for a number of uses including the detection of antibiotic resistance in infections is being developed. A key attribute of this technology is that it can measure multiple targets simultaneously in the same sample.

The technology is based on the arrangement of long, thin nanometer-sized molecules in a microfluidic chamber inside a test cartridge, which is self-contained, sterile, and holds all the reagents needed to perform a test. Scientists use a handheld external optical reader, to detect the molecules’ alignment in the chamber by shining polarized light from different angles into the cartridge.

The technology was created by Linear Diagnostics Ltd (Birmingham, UK; www.lineardiagnostics.com), which is a spin-off from the University of Birmingham (Birmingham, UK; www.birmingham.ac.uk). Scientists can modify the molecules with detection probes that bind to targets in solution. If bacteria are present in the sample, the probes bind to various bacterial targets, changing the alignment of the attached molecules in the microfluidic flow. The attached probes can be antibodies that can

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recognize specific bacterial cell surface markers, for instance, or short bits of DNA including genetic sequences that recognize specific bacterial transcripts or genes that code for antibiotic resistance.

The Linear Dx’s tests can be used with urine and whole blood samples, since they do not require previous sample preparation, although the scientists emphasized that the company will initially focus on urinary tract infections (UTIs). While technology such as easy, rapid dipstick tests can provide an indication of bacterial presence, they lack the information on antibiotic resistance that Linear Dx’s technology can provide. It is estimated the tests run on the platform will cost around USD 20 or GBP 15.

Matthew R. Hicks, DPhil, a cofounder and chief technical officer of the company, said, “Other molecular binding techniques need multiple processing steps like washing. In contrast, our platform is a single-step process, and can be adapted to a wide range of other applications in the future, including sexually transmitted infection (STIs) and tropical diseases. The reagents that we have developed enable us to use relatively low-cost hardware to give sufficient performance for the assays that we are developing.”

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The Lyser 3000 is a fully automated EIA and IFA processor for use in the clinical lab. Its 240-capacity sample deck reduces the number of daily interventions, while four independently operating probes provide fast turnaround time.

The XL 600 is designed to give quick returns without any compromise. The high-resolution diffraction grating ensures a high degree of photometric accuracy, while the bar coded reagents and sample identification minimizes programming time.

The PHOmo is designed to meet the requirements of microplate-based, photometric applications. It has a repetition rate of 5 seconds and a plate carrier system that can accommodate 96- and 48-well microplates without an additional adaptor.

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Dipstick Technology Could Revolutionize Disease Diagnosis ucleic acid amplification is a powerful molecular biology tool, although its use outside the modern laboratory environment is limited due to the relatively cumbersome methods required to extract nucleic acids from biological samples.

Cellulose-based DNA binding is ideal for molecular diagnostics as it is inexpensive, portable, disposable, and easily modified. A nucleic acid purification method using cellulose paper that does not require any complex fabrication or specialized equipment such as pipettes and centrifuges has been developed.

Scientists at the University of Queensland (St. Lucia, Australia; www.uq.edu.au) investigated a variety of materials for their suitability for nucleic acid capture and purification. The team found that untreated cellulose-based paper can rapidly capture nucleic acids within seconds and retain them during a single washing step, while contaminants present in complex biological samples are quickly removed. Building on this knowledge, they have successfully created an equipment-free nucleic acid extraction dipstick methodology that can obtain amplificationready DNA and RNA from plants, animals, and microbes from difficult biological samples such as blood in less than 30 seconds.

The investigators designed dipsticks made from Whatman No.1 with a

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small 8 mm2 DNA binding surface and a long water repellent handle made by impregnating the filter paper with Paraplast wax. Using these dipsticks, they developed an improved method in which all reagents can be prepared in advance and stored for a long period of time at room temperature. When needed, a nucleic acid extraction can be performed rapidly in three easy steps and less than 30 seconds without a pipette or any electrical device. To validate the newly developed nucleic acid purification method, they compared it with a popular commercial rapid paramagnetic bead DNA extraction method (AMPure, Beckman Coulter, Brea, CA, USA; www.beckmancoulter.com). They found that their method can purify amplifiable DNA significantly faster in less than 30 seconds for the new method versus 14.5 minutes for AMPure purification.

Jose Ramon Botella, PhD, a professor and senior author of the study said, “This technology will give people in developed and developing nations a new way of tackling a range of agricultural, health and environmental problems. Our dipsticks, combined with other technologies developed by our group, means the entire diagnostic process from sample collection to final result could be easily performed in a hospital, farm, hotel room or even a remote area such as a tropical jungle.” The study was published on November 21, 2017, in the journal Public Library of Science Biology.

Whole Exome Sequencing Offers Clinical Value in Diagnosing Chronic Kidney Disease hole exome sequencing was used to identify the genetic cause of chronic kidney disease in a population of patients, a finding that influenced subsequent treatment of the disease.

Whole exome sequencing (WES), is a transcriptomics technique for sequencing all of the protein-coding genes in a genome (known as the exome). It consists of two steps: the first step is to select only the subset of DNA that encodes proteins. These regions are known as exons – humans have about 180,000 exons, constituting about 1% of the human genome, or approximately 30 million base pairs. The second step is to sequence the exonic DNA using any high-throughput DNA sequencing technology.

The utility of WES for the diagnosis and management of adult-onset constitutional disorders has not been adequately studied. Investigators at Columbia University Medical Center (New York, NY, USA; www. cumc.columbia.edu) recently suggested that genetic diagnostics could be advantageous in adults with chronic kidney disease (CKD), in whom the cause of kidney failure often remained unknown.

Toward this end, the investigators performed whole exome sequencing on samples from 92 adults with kidney disease.

Results of whole-exome sequencing provided a diagnosis in 22 of 92 patients (24%), including nine patients with CKD of unknown cause

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and encompassing 13 distinct genetic disorders. Among these, loss-offunction mutations were identified in the PARN (Poly(A)-specific ribonuclease) gene in two patients with tubulointerstitial fibrosis. PARN mutations had been implicated previously in a short telomere syndrome characterized by lung, bone marrow, and liver fibrosis; the findings in the current study have extended the phenotype of PARN mutations to renal fibrosis.

“Because CKD is usually silent in the early stages, it may not be detected until an individual develops severe kidney problems,” said senior author Dr. Ali G. Gharavi, professor of medicine at Columbia University Medical Center. “At that stage, the patient may be sent to a variety of specialists in order to identify the type and cause of the disease and determine the best treatment. In this study, we hypothesized that genomic testing would help us answer these questions, without sending patients on a time-consuming and often frustrating diagnostic odyssey.”

“Our study, though small, demonstrates that whole exome sequencing may offer real clinical value in diagnosing and managing patients with kidney disease, especially those with a family history of kidney problems or those with an unknown cause of disease,” said Dr. Gharavi.

The study was published in the December 5, 2017, online edition of the journal Annals of Internal Medicine.

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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

New IFCC Unit to Facilitate Application of Diagnostic Advances Emerging Technologies Division (ETD) active as of January 2018

By Prof. Sergio Bernardini, IFCC ETD Chair, University Tor Vergata, Rome he IFCC is proud to announce the formation of a new Division, the Emerging Technologies Division (ETD).

The IFCC Executive Board has endorsed the creation of a new functional unit responsible for the translation of emerging and disruptive diagnostic and data analysis procedures from academic laboratories to clinical laboratories. The Emerging Technology Division (ETD) is fully functional from January 2018.

ETD Executive Committee members are: Sergio Bernardini (IT), Chair; Paolo Fortina (US), Vice-Chair; Ronda Greaves (AU), Secretary; Damien Gruson (BE), Member; Markus Roessler (Roche D. GmBH), Corporate Member; Peng Yin (Abbott D), Corporate Member; Larry Kricka (US), Consultant; Maurizio Ferrari, consultant (IT).

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ETD Responsibilities: The application of emerging technologies and methods including innovative mass spectrometry, highthroughput genotyping techniques and data analysis to clinical diagnos-

IFCC Curriculum Phase 1 Is Ready for Download

By Janet Smith, formerly C-DL Chair; Ronda Greaves, formerly C-DL member currently C-IDL consultants he IFCC Curriculum, phase 1, was developed as part of the IFCC eAcademy project by the Committee for Distance Learning.

Authors are: R. Greaves (AU, J. M. Smith (UK) and section authors are: R. Greaves, C Florkowski (NZ), L. Langman (US), J. Sheldon (UK).

The IFCC Curriculum is a guide for IFCC member societies in their development of syllabuses for postgraduate trainees in laboratory medicine, appropriate for use in their own countries. It is also intended to provide a resource for trainees in planning their private study in preparation for academic and professional qualifications which lead to formal recognition of expertise and status as experts and leaders in the field of laboratory medicine.

The IFCC Curriculum â&#x20AC;&#x201C; Phase 1, means to provide the laboratory medicine expert with a comprehensive knowledge of the science and medicine on which the specialty is based and is an help to use this knowledge to develop and provide a safe, effective, efficient and high quality service to its users. The curriculum is designed to provide a framework of learning both practical and theoretical components through which this expertise can be achieved. Other disciplines within laboratory medicine will follow in due course. IFCC Curriculum can be downloaded here: www.ifcc. org/media/477173/2017-ifcc-curriculum.pdf

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tic protocols focused on Precision Medicine; Defining for each emerging technology the clinical needs and criteria of education of specialists in Laboratory Medicine; Defining for each emerging technology and method the appropriate infrastructure and laboratory organization; Defining for each emerging technology and method pre-analytical, analytical and postanalytical processes necessary for clinical laboratory applications; Defining for each emerging technology and

NEWS method quality programs and certifications required to meet criteria for accreditation up to ISO15189 standard; Assess the clinical value of each test with regard to addressing unmet clinical need.

Four committees have been formed within the ETD: Committee-Advanced Paediatric Laboratory Medicine (C-APLM), Committee Oversight is Dr Ronda Greaves (AU); CommitteeHealthy Longevity Laboratory Medicine (CHLLM), Committee Oversight is Prof. Sergio Bernardini (IT); Committee-Omics Applications in Laboratory Medicine (C-OPLM), Committee Oversight is Prof. Paolo Fortina (US); Committee on Mobile Health and Bioengineering in Laboratory Medicine (C-MHBLM), Committee Oversight is Dr Damien Gruson (BE).

For more details and information on the IFCC Committee on Emerging Technologies, visit the website at: www.ifcc.org/ifcc-emerging -technologies-division

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

IFCC Working Group WG-GMECC Issues Report On Evaluation of Glucose Meters in Critical Care

By Dr. Cynthia Bowman, WG-GMECC Chair and Document editor, Baystate Health Department of Pathology, Springfield, MA, USA; Sean Cunningham, WG-GMECC member and Document Assistant editor, Consultant Clinical Biochemist (European Specialist Laboratory Medicine EuSpLM), Dublin, Ireland istration (FDA) issued its draft guidance on blood glucose test monitoring systems for “prescription” use and concerns about the accuracy and risks of using BGM for acutely ill patients were being widely raised.

The WG has been an inclusive one with 12 members, 10 corresponding members, 3 corporate members, and 6 advisors. It has been chaired

by Cynthia Bowman (US) who, along with Sean Cunningham (IE), Robbert Slingerland (NL), Dieter Mesotten (BE), Brad Karon (US) and James Nichols (US), authored the document. Input from all WG participants was broad-based, open, and active, including corporate members.

Time was taken to develop agreement on core principles and recommendations from all participants and to account for the evolution of recommendations, technology and perspectives in the field of BGM. The WG elected to cover the topic with some technical and clinical depth to allow readers and stakeholders NE to have a resource on principles of DES W IGN the technology and clinical issues that must be considered when evaluating BGM for critically ill and PHS patients.

The WG agreed that all users of BGM must be aware of their limiting WORLD’S MEDICAL PRODUCT MARKETPLACE technical and clinical factors, that evaluation and oversight of BGM must be practical and respect resource constraints, but that there must be a single international stanSIGN UP dard for BGM performance and FOR FREE! evaluation in critical care and PHS settings. At the current time, the WG does not recommend using capillary samples for BGM with critically ill or PHS patients, as described above.

Options for monitoring glucose levels in those patients include using alternative instruments or using arterial or venous samples with BGM cleared for those samples. However, the WG is aware that vendors and groups have data promoting the use of capillary samples for critically ill and PHS patients. An FDA public advisory committee meeting will receive testimony supporting that use on March 30, 2018.

The WG is hoping that the document will stimulate active multi-specialty discussion in many settings and will serve to foster collaborative awareness and best practices between laboratory, clinical, and corporate stakeholders for BGM. Many of Connecting Buyers with the principles included in the docuSuppliers Worldwide ment are general ones applying to good laboratory and clinical practice Reach new sources of supply for POCT in general. It is also hoped Identify latest products and technologies that this document and topic will be Send inquiries directly to suppliers an ongoing discussion in inter-society Receive latest product alerts meetings with an evolution of recomChat live with suppliers mendations and practices for current and future technologies. Using the principles of the document could proTradeMed provides a sophisticated yet easy-to-use global B2B platform for sourcing medical mote a good basis for ongoing partequipment. TradeMed connects buyers and sellers worldwide through a safe, secure and dynership with laboratory, clinical, and namic network. Solely dedicated to medical products, TradeMed is the premier choice for medcorporate stakeholders in dealing ical suppliers, hospital decisionmakers and buyers worldwide, regardless of size or budget. with other laboratory testing issues.

he IFCC Working Group on How should Glucose Meters be Evaluated in Critical Care (WG-GMECC), under the IFCC POCT Task Force, has completed a document on “How Should Glucose Meters Be Evaluated for Critical Care”. It addresses the clinical practice of using Blood Glucose Meters (BGM) and what requirements they must fulfill in order to be used in critically ill patients and in Professional Healthcare Settings (PHS) on patients in various states of health and receiving intensive medical intervention and therapy.

The document is already available on the IFCC website. A second document addressing quality management and training and competency recommendations for BGM is under development.

The WG was convened in 2014 after the US Food and Drugs Admin-

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

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How Can You Explain Traceability in Laboratory Medicine to Your Clinician Users?

by Dr Graham Beastall, on behalf of the Joint Committee for Traceability in Laboratory Medicine recent article by Graham Jones in his local hospital journal provides one approach to answer this question.

Clinicians who use laboratory medicine services take it for granted that the laboratory provides ‘the right result’. They believe that the result they get back from their laboratory is both accurate and capable of comparison with results obtained from other laboratories or retrieved from the medical/scientific literature. It comes as a shock to most clinicians to learn that for many results they receive there is significant between-method variability. In some cases, the variability may be such that clinical outcomes and even patient safety may be compromised if they compare the results that they get from their local laboratory with literature or clinical practice guideline results that were obtained using a different method.

Traceability in laboratory medicine (TLM) is the key to reducing between-method variability. IFCC is a founder member of the Joint Committee for Traceability in Laboratory Medicine (JCTLM), which “supports world-wide comparability, reliability and equivalence of measurement results in laboratory medicine, for the purpose of improving health care and facilitating national and international trade in in vitro diagnostic devices”. The website www.jctlm.org provides freely available resources to help laboratory medicine specialists to understand TLM and to train oth-

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ers to appreciate its importance. These resources take the form of webinars, PowerPoint presentations, symposia at scientific meetings and publications.

As part of the support provided to its users the clinical laboratory has a responsibility to alert clinicians to between-method variability and the pitfalls that could arise. At the same time clinicians can be reassured that there is a global effort to reduce the problem to make results more comparable.

The article by Graham Jones from St Vincent’s Hospital in Sydney, Australia provides an excellent template for communication with clinician users. Entitled ‘Chemical Pathology – Getting the Right Answer’ the article is written in non-technical language using examples that may be understood by clinicians and other healthcare professionals. Key references are included.

The article is published in the St Vincent’s Clinic, Proceedings (Sydney) Volume 25, 1 December 2017. It may be downloaded here. The article may be reproduced or modified for local use as long as an acknowledgement is provided to the original publication. The article provides you with an opportunity to educate and support your clinical users.

IFCC Task Force on Ethics: Results of Recent Survey

By Ann M. Gronowski, IFCC Task Force on Ethics Chair 2015-2017 he IFCC Task Force on Ethics (TF-E) focuses on ethical issues in laboratory medicine. The aims of the TF-E are: To increase awareness among Laboratory Medicine Professionals of ethical issues; To encourage the practice of Laboratory Medicine to the highest ethical standards; To develop guidance documents for member societies on ethics related issues; To provide a voice for Laboratory Medicine on ethical issues; To link Laboratory Medicine, ethics and the public interest.

In January 2018, the TF-E distributed an invitation to the national representatives from 93 Full IFCC member societies and 13 affiliate societies to complete an on-line survey. The survey was developed to allow the TFE to measure the level of interest in ethics-related issues and to develop new materials to help member societies.

Fifty-three responses were received. Most societies (87%) reported that their national society did not have an ethics task force or committee. Several societies indicated that their ethics committee met only when and if needed to deal with ethical issues if/when they arise. Other ethics committees served to create ethics-related documents and educational materials.

Twenty-one societies reported that they had a code of ethics (or professionalism), 9 reported a conflict of interest statement for society leadership to complete, and 6 have statements outlining proper interactions with industry. Importantly, of the societies that said they did not have any ethicsrelated documents, 95% said that they felt they would be useful.

The societies were asked if they had faced any issues that were ethical in nature. The results are as follows: Has your IFCC member national society faced any issues that were ethical in nature? (19 societies responded) 63% (12/19): Relationships with industry; 37% (7/19): Conflict of interest issues; 32% (6/19): Unprofessional conduct; 5% (1/19): Confidentiality.

The survey asked for ways in which the TF-E could help member soci-

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eties. The responses are as follows.

Ways in which the TF-E could help member society (41 societies responded) 68% (28/41): Sharing/developing general ethics guidelines; 22% (9/41): Sharing/developing Code of ethics; 10% (4/41): Sharing/developing Educational materials; 7% (3/41): Sharing/developing Industry guideline; 7% (3/41): Help to resolve cases of ethics-related issues.

Moving forward, the TF-E plans to create a tool box with examples of documents such as the ones in Table 2. The toolbox can be useful for member societies as examples to create their own unique documents appropriate for their society. As always the TF-E is open to suggestions and available to answer questions. Do not hesitate to contact Ann Gronowski (gronowski@wustl.edu.or) or Nilda Fink (NFink@fbpba.org.ar).

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

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

NEWS VIEWPOINT

Harnessing M-Health to Improve Diabetes Management

by Dr. Bernard Gouget Counselor for Public Health FHF; Chair-Human Health Care Committee-COFRAC; IFCC Chair-Nominations Committee; General Secretary of the International Francophone Federation Of Clinical Biology and Laboratory Medicine (FIFBCML) urrently 415 million people in the world are affected by diabetes.

This figure will increase to 642 million people by 2040 if nothing changes. Type 2 diabetes represents 90% of the diabetes encountered worldwide, or around 372 million people. 12% of global health costs concern diabetes. While these figures are impressive, many pre-diabetics are not even necessarily screened. Among the chronic diseases that are currently at the heart of health concerns, diabetes is at the head of the list.

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supported by mobile devices, such as mobile phones, patient monitoring devices, personal digital assistants (PDAs), and other wireless devices" offers new possibilities to improve monitoring of chronic diseases and permit patients to take a more active role in their management. It can also contribute to the development of the predictive and preventative dimension of medicine via patients who are experts in their disease and ultra-connected.

As shown by a study of the Fédération Francaise des Diabétiques [French Federation of Diabetics], 80% of diabetics are currently equipped with smartphones and tablets. While 25-34 year olds own most of them (63%), those above age 80 are not left behind. Twenty percent of them have both a tablet and a smartphone. Among this 80%, half of patients have already downloaded a mobile health application.

This is an impressive result if it is compared to that for all chronic diseases, which drops to 15%. Diabetics do not just download these applications. They use them! More than half of diabetics estimate today that these applications are vital for managing their disease.

Efforts by clinicians and laboratory medicine specialists are still ongoing to better understand the applications because only two out of 10 diabetics in France have a connected device. The connected blood glucose meter is the most popular. In diabetology, mobile health is already a reality. Many objects are forthcoming, such as the graphene and gold patch, a very strong and flexible sensor that is positioned on the skin for continuous monitoring of blood glucose levels. Google and Novartis are working on contact lenses using tears to measure blood glucose. We can also mention the artificial pancreas, comprised of a blood glucose sensor that sends data to a terminal that contains a complex algorithm in order to determine the best insulin dose to send to the connected pump. Data are sent at the same time to a monitoring service in order to improve long-term treatment.

Many applications can be found in the Apple or Google Play Store.

There are solutions to connect the blood glucose meter to your smartphone to send blood glucose values to the cloud. The data are then organized, prioritized and interpreted by healthcare professionals or patients themselves. Electronic blood glucose logbooks and rapid decision support systems are available to adjust the insulin dose. Connected digital scales, tensiometers, physical activity sensors, and nutritional programs complete the range.

Mixed telehealth type systems now encompass automated exchanges between a connected device and the patient, with telemonitoring by a telemedicine nurse, medical biologist and/or a physician. In terms of prevention, screening, and management, it is clearly "Medicine 3.0". Medical knowledge held by the entire human community is shared among its members via the Internet, especially the web applied to health, and all the new cutting-edge technologies, including telemedicine. In diabetes, m-Health does not substitute for the human relationship between the healthcare professional and the patient, but improves and simplifies the management of diabetic patients, allowing them to live in an optimal and independent manner. The more reliable, more systemic monitoring of diabetes parameters through m-Health is essential for more appropriate interventions by the healthcare professional.

Large companies, such as Novo Nordisk and Eli Lilly, are making investments for rapid innovation. Google, an expert in Big Data, and Sanofi, which has the knowhow in the field of medical treatment and devices, have already cemented their alliance via Onduo, a virtual clinic helping people with diabetes to live a fuller and healthier life by developing global solutions that combine devices, software, drugs, and professional healthcare to permit simple and smart management of the disease. Only a few sizeable pharmaceutical companies have not yet integrated Alphabet (Google)into their strategy.

Laboratory Medicine has become systemic, while conventional technology and the digital world have combined to generate interdisciplinary progress that revolutionizes healthcare. Faced with these trajectories, active reflection on m-Health and bioengineering becomes indispensable within the IFCC to anticipate the scientific, technical, and human disruption. New collaborations need to be established, not only with the GAFAM Big 5 giants, but also with the pharmaceutical, biomedical device, and IT industries, to address the new challenges and possibilities of digital health.

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Industry News

Siemens Healthineers IPO Seen to Enhance Future Expansion lobal technology powerhouse Siemens AG (Munich, Germany; www.siemens.com) (“Siemens”) and its separately managed healthcare business, Siemens Healthineers (Erlangen, Germany; www.healthcare.siemens.com) have announce that the planned IPO of Siemens Healthineers AG is expected to be completed in the first half of calendar year 2018, subject to capital market conditions.

The IPO will consist of a secondary offering of shares from the existing holdings of Siemens.

The target free float of a meaningful minority share is expected to create a liquid market for the shares of Siemens Healthineers. Siemens will retain a majority stake in Siemens Healthineers in the long-term. The public listing is planned on the Regulated Market (Prime Standard) of the Frankfurt Stock Exchange. While Siemens Healthineers will remain core to Siemens, the IPO will increase its entrepreneurial flexibility and lay the foundation for future growth.

Siemens Healthineers’ core markets of diagnostic and therapeutic imaging, laboratory diagnostics and molecular medicine are estimated to be worth more than Euro 50 billion per year. These core markets are expected to grow at an average rate of 3-5% annually, driven by favorable

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factors such as a growing and aging population, rise in chronic diseases, improved access to healthcare in the emerging markets and technologydriven transformation. As an independent company, Siemens Healthineers will benefit from increased agility and a strong capital structure, placing the company in an excellent position to capitalize on the medium- and long-term opportunities in its core markets.

“Siemens Healthineers is now ready for its market debut”, said Michael Sen, Chairman of the Supervisory Board of Siemens Healthineers and member of the Siemens Managing Board.

“Siemens Healthineers is a premium asset and we have worked hard to now list such an exciting franchise. We expect the business to capitalize on its strengths even more effectively after the listing.”

“We are in a powerful place to shape the future of healthcare. Becoming a listed company will give us the increased freedom that we need to continue expanding our global leadership,” said Bernd Montag, CEO of Siemens Healthineers. “With our Strategy 2025 we are ideally positioned to take advantage of the paradigm shifts in our industry and achieve even more growth.”

Molecular POC Market to Exceed Half Billion USD Mark by 2023 he molecular point-of-care market (POC), consisting of systems with molecular capability used in decentralized test environments, was worth an estimated USD 165 million in 2017 and is expected to continue growing in the double-digits to reach USD 510 million in 2023.

The key growth areas in molecular POC diagnostics are expected to be influenza testing, hospital-acquired infections and sexually transmitted diseases. Pricing remains a challenge for molecular systems, although the advantages they offer paint a bright long-term outlook for the market.

PCR or sequencing based systems in decentralized settings are expected to grow at the fastest pace, in terms of revenue, as compared to other IVD market categories. These are the latest findings of Kalorama Information, (New York, NY, USA; www.kaloramainformation.com), an independent medical market research firm.

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Beckman Parent Acquires Leader in Oligonucleotides for Molecular Biology anaher Corporation (Washington, D.C, USA; www.danaher. com), parent of Beckman Coulter Inc. (Brea, CA, USA; www. beckmancoulter.com) and other life sciences companies, has entered into a definitive agreement to acquire Integrated DNA Technologies (IDT) (Skokie, IL, USA; www.idtdna.com), a privately held provider of high-value consumables for genomics applications in molecular biology, qPCR, next generation sequencing, synthetic biology, gene editing and molecular diagnostics.

IDT develops, manufactures, and markets nucleic acid products for the life sciences industry in the areas of academic research, biotechnology, agriculture, medical diagnostics, and pharmaceutical development.

The company's primary business is the production of custom oligonucleotides for molecular biology applications. IDT has developed proprietary technologies for genomics applications such as next generation sequencing, CRISPR genome editing, qPCR, and RNA interference.

Through its GMP services, IDT manufactures products used in diagnostic tests for many forms of cancer and most inherited and infectious diseases. IDT will operate as a standalone operating company and brand within Danaher's Life Sciences platform.

"We are thrilled to have IDT join Danaher's Life Sciences platform," said Rainer Blair, Executive Vice President of Danaher's Life Sciences platform. "IDT expands our presence into the highly attractive genomics market and will help play a central role in accelerating our customers' research and time to market as they develop critical diagnostic tests and potential life-saving therapies. IDT's historical double-digit core revenue growth and strong margins are a testament to the team's commitment to the highest standards of quality, service, and technical expertise."

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Molecular point-of-care solutions now offer multiplexing capabilities, allowing an assay to detect multiple pathogenic targets for an infectious condition, in a single run. Multiplex assays for respiratory infections are more common, targeting multiple flu viruses and strains as well as respiratory syncytial virus, among others. Test panels are available for detecting multiple possible causes of gastrointestinal infection, sepsis, or even multiple tropical disease agents such as Ebola, Dengue, Chikungunya, malaria, and so on. It is also possible to design assays for targeting specific genes generally associated with non-infectious diseases such as cancer or Alzheimer's disease, or to determine a patient's sensitivity or resistance to pharmaceutical treatments.

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