LabMedica International September 2018 by Globetech

V I S I T

WORLD’S CLINICAL LABORATORY NEWS LEADER ISSN 1068-1760

Vol. 35 No.5 • 8-9/2018

DAILY CLINICAL LAB NEWS

Early Sepsis Indicator Alerts Emergency Clinicians epsis is an often-deadly condition that affects 26 million people worldwide every year and is increasing at a rate of 1.5% annually. Timely and accurate detection solutions in the acute-care setting are key components to stopping the progression of sepsis,

Cutting-Edge Technology Applied to Grading Cancer Tumors iopsy specimens are processed into formalin-fixedparaffin-embedded (FFPE) blocks and currently, hematoxylin and eosin (H + E) stained sections are widely used for the histopathological diagnosis of cancer and other pathologies.

Typically the sections are graded subjectively by eye, using disease-specific grading protocols. Histological grading of breast cancer currently varies widely across multiple institutions and practitioners, because it relies on subjective criteria. However an analysis

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Image: Courtesy of The Children’s Lyme Disease Network

Antigen Matching Advance Could Transform Transfusion Medicine

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new blood test for determination of prostate cancer risk was found to be more accurate than the current gold standard PSA (prostate specific antigen) test. Prostate-specific antigen, the current gold standard in prostate cancer detection, is distinct from virtually all other cancer biomarkers because of its almost exclusive specificity to the prostate, allowing

hronic infection with hepatitis C virus (HCV) is a major public health problem, estimated to infect 1.0% of the world’s population (71 million people) and to be responsible for 400, 000 annual deaths as a result of cirrhosis and liver cancer. A hand-held, portable device that weighs approximately 600 grams or a little more than 21 ounces has been validated as a Cont’d on page 6

Fully Automated System Simplifies Sample Prep and Analysis

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More Accurate Test for Prostate Cancer Risk

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Near-Patient Hepatitis C Assay Validated

ased on the application of advanced whole-genome sequencing techniques, antigen typing can enable more precise antigen matching of patients with blood donors, thus preventing complications of sensitization to antigens and materially improving transfusion outcomes.

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fully automated LC-MS/ MS system simplifies and accelerates the collection of high quality, reliable data by reducing the need to perform repeated runs, which gives clinical scientists increased confidence in the validity of results.

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SHERLOCK Diagnostic Platform Optimized for Rapid Viral Detection new technique enables the SHERLOCK diagnostic platform to detect a virus directly in bodily fluids, eliminating a step that required laboratory equipment and expanding the platform’s potential to quickly and cheaply track pathogens such as Zika

during an outbreak. The platform can now be used to detect viruses directly in clinical samples such as blood or saliva, eliminating a processing step that previously required a laboratory environment and professionally trained personnel. Cont’d on page 7

INSIDE Clinical News . . . . 2-26 IFCC News . . . . . . . . 27 Product News . . . 8-26 Industry News . . . . .33 Events Calendar . . . 34 PUBLISHED IN COOPERATION WITH

International Federation of Clinical Chemistry and Laboratory Medicine

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LabMedica International

New Test More Accurate for Determining Prostate Cancer Risk cont’d from cover

direct assessment of physiological conditions in the gland with a simple blood test. Unfortunately, PSA is tissue- but not cancer-specific, and over diagnosis and overtreatment of PSAdetected, biologically insignificant cancers are widely recognized as key limitations in its clinical utility. The IsoPSA test was developed to evaluate structural changes in the PSA isoforms that correlate with prostate cancer. This approach not only reduces the number of false positives, it also allows providers a window into the cancer grade before deciding on whether a biopsy is indicated. In a recent study, investigators at the Cleveland Clinic (OH, USA; www.clevelandclinic. org) conducted prospective validation of the clinical performance of IsoPSA, a novel structure-focused protein biomarker, to assess potential discrimination of high-grade prostate cancer (Gleason≥7) from benign or low-grade disease (Gleason=6). They found that more than 40% of biopsies could have been avoided in both the preliminary study (45.1%) and validation study (47%), suggesting that use of IsoPSA may substantially reduce the need for biopsy, and may thus lower the likelihood of over detection and

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

Published in cooperation with the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). HospiMedica International • HospiMedica en Español • HospiMedica China LabMedica International • LabMedica en Español • LabMedica China Medical Imaging International • Bio Research International • Medimaging.net HospiMedica.com • LabMedica.com • BiotechDaily.com • TradeMed.com

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overtreatment of nonlethal prostate cancer. The validation study was presented May 18, 2018, at the San Francisco, CA, USA, 13th Annual Meeting of the American Urological Association and was published in the April 2018 online edition of the Journal of Urology.

Raymond L Jacobson, PhD News Editor Gerald M Slutzky, PhD News Editor Andreas Rothstein News Editor Marcela Jensen Assistant Editor Brenda Silva New Products Editor Theresa Herman Regional Director Dr. Jutta Ciolek Regional Director Parker Xu Regional Director

Image: The IsoPSA is a new blood test for the accurate prediction of overall risk of malignant prostate cancer (Photo courtesy of the Cleveland Clinic).

Antigen Matching Advance Could Transform Transfusion Medicine here are more than 300 known red blood cell (RBC) antigens and 33 platelet antigens that differ between individuals. Sensitization to antigens is a serious complication that can occur in prenatal medicine and after blood transfusion, particularly for patients who require multiple transfusions. Although pre-transfusion compatibility testing largely relies on serological methods, reagents are not available for many antigens. Methods based on single-nucleotide polymorphism (SNP) arrays have been used, but typing for ABO and Rhesus, the most important blood groups, cannot be done with SNP typing alone. Scientists at Brigham and Women’s Hospital (Boston, MA, USA; www.brighamandwomens. org) and their colleagues created a database of molecular changes in red blood cell (RBC) and platelet antigens and developed an automated antigen-typing algorithm based on wholegenome sequencing (bloodTyper). This algorithm was iteratively improved to address cis–trans haplotype ambiguities and homologous gene alignments. Whole-genome sequencing data from 110 MedSeq participants (30 × depth) were used to initially validate bloodTyper through comparison with conventional serology and SNP methods for typing of 38 RBC antigens in 12 blood-group systems and 22 human platelet antigens. The bloodTyper was further validated with whole-genome sequencing data from 200 INTERVAL trial participants (15 × depth) with serological comparisons.

The scientists iteratively improved bloodTyper by comparing its typing results with conventional serological and SNP typing in three rounds of testing. The initial wholegenome sequencing typing algorithm was 99.5% concordant across the first 20 MedSeq genomes. Addressing discordances led to development of an improved algorithm that was 99.8% concordant for the remaining 90 MedSeq genomes. Additional modifications led to the final algorithm, which was 99.2% concordant across 200 INTERVAL genomes or 99.9% after adjustment for the lower depth of coverage. The authors concluded that by enabling more precise antigen-matching of patients with blood donors, antigen typing based on wholegenome sequencing provides a novel approach to improve transfusion outcomes with the potential to transform the practice of transfusion medicine. Connie M. Westhoff, PhD, from the New York Blood Center (New York, NY, USA; https://nybloodcenter.org) and co-first author of the study said, “This approach has the potential to be one of the first routine clinical uses of genomics for medical care for patients needing blood transfusion. It could prevent serious or even fatal complications because once patients are sensitized they have a life-long risk of hemolytic transfusion reactions if blood transfusion is needed in an emergency.” The study was published on May 17, 2018, in the journal The Lancet Haematology.

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ISSN 1068-1760 Vol.35 No.5. 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. Teknopress Yayıncılık ve Ticaret Ltd. Şti. adına İmtiyaz Sahibi: M. Geren • Yazı işleri Müdürü: Ersin Köklü Müşir Derviş İbrahim Sok. 5/4, Esentepe, 34394 Şişli, İstanbul P. K. 1, AVPIM, 34001 İstanbul • E-mail: Teknopress@yahoo.com Baskı: Postkom A.Ş. • İpkas Sanayi Sitesi 3. Etap C Blok • 34490 Başakşehir • İstanbul Yerel süreli yayındır. Yılda sekiz kere yayınlanır, ücretsiz dağıtılır.

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LabMedica International

Early Sepsis Indicator Alerts Emergency Department Clinicians contâ&#x20AC;&#x2122;d from cover

as patients with less severe sepsis can progress to severe sepsis or septic shock within 72 hours. Up to half of patients with sepsis die and in addition to the human toll, this global crisis places a significant clinical and

Fully Automated System Simplifies Sample Prep and Analysis contâ&#x20AC;&#x2122;d from cover

The new Thermo Fisher Scientific (Waltham, MA, USA; www. thermofisher.com) Cascadion clinical analyzer was designed to be a turnkey solution to enable clinical laboratories to easily adopt the power and capabilities of LC-MS/MS as the gold standard in screening and diagnostic testing. The instrument was made for clinical laboratory scientists lacking specialized technical knowledge in the field of LCMS/MS technology. The Cascadion system combines assays, software, accessories, consumables, support, and service in a standalone system designed to meet the regulatory requirements for routine and specialized clinical testing. The fully automated sample-in and result-out system incorporates advanced development features including: gold standard mass spectrometry technology, complete assay kits for standardized results, traceability of results to reagent lots, automated sample preparation, LIS connectivity to maximize productivity, a turnkey solution from one supplier for easy implementation, and random access workflow for fast turnaround times. The Cascadion system was designed and built using Thermo Fisher products and technologies combined with its industry-leading expertise in mass spectrometry. Tandem mass spectrometry, also known as MS/MS or MS2, involves multiple steps of mass spectrometry selection, with some form of fragmentation occurring in between the stages. In a tandem mass spectrometer, ions are formed in the ion source and separated by massto-charge ratio in the first stage of mass spectrometry (MS1). Ions of a particular mass-to-charge ratio (precursor ions) are selected and fragment ions (product ions) are created by collision-induced dissociation, ion-molecule reaction, photodissociation, or other process. The resulting ions are then separated and detected in a second stage of mass spectrometry (MS2). While sample preparation and analysis were once complex and timeconsuming tasks, the Cascadion system now delivers consistent, high quality results in the shortest possible timeframe. This instrument is IVD/CE-marked for marketing in Europe, but is not yet 510(k) cleared and therefore is not yet available for purchase in the United States.

LabMedica International August-September/2018

economic burden on the healthcare system. A clear link exists between the timeliness of treatment and the possibility of death. When antibiotics are administered early to patients with septic shock, the likelihood of death is decreased by 7.6% per hour. A hematology-based solution designed to alert emergency department clinicians to the possibility of sepsis or risk of developing sepsis has received the European CE Mark and has been designed to alert emergency department clinicians to the possibility of sepsis or risk of developing sepsis. The first early sepsis warning solution to be offered as part of a routine complete blood count (CBC) with differential test gives physicians a rapid and simple tool that can aid in the fight against sepsis. The Early Sepsis Indicator uses the DxH 900 hematology analyzer (Beckman Coulter, Brea, CA, USA; www.beckmancoulter.com), which characterizes cells in their near-native states. The systemâ&#x20AC;&#x2122;s powerful VCS 360 technology can uniquely detect morphological changes in monocytes, cells of the innate immune system that provide a first line of defense against infections. Monocytes play a role in the dysregulated immune response to sepsis, and identifying morphological changes provides insight into possible sepsis earlier than other indicators.

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Near-Patient Hepatitis C Assay Validated cont’d from cover

point-of-care molecular diagnostics system and assay for hepatitis C virus. A new study demonstrated proof of concept for a semi-quantitative assessment of HCV viral load using melting peak ratiometric analysis. A team of international scientists collaborating with those at the Institute Pasteur (Paris, France; www.pasteur.fr) tested 130 clinical plasma and serum samples across three instruments and four operators. Samples were collected from various African countries, including Ghana, Kenya, Mauritius, Mozambique, Nigeria, South Africa, Uganda, and Zimbabwe, as part of routine HCV diagnostic testing using the Abbott RealTime HCV Genotype II on the Abbott m2000 (Abbott Laboratories, Abbott Park, IL, USA; www.molecular.abbott). The team validated the Genedrive HCV point-of-care (POC) assay (Manchester, UK; www.genedriveplc.com) which is a two-step procedure requiring a plasma or serum preparation step, followed by a reverse transcription (RT) reaction to generate the complementary DNA (cDNA) from the target HCV RNA. This cDNA undergoes asymmetric polymerase chain reaction (PCR) to generate linear amplification of single

stranded products, followed by detection using a secondary hybridization probe and dissociation curve analysis. The point-of-care assay identified all major HCV genotypes, with a limit of detection of 2,362 IU/mL (95% CI 1966 to 2788). Using 422 patients chronically infected with HCV and 503 controls negative for antiHCV and HCV RNA, the Genedrive HCV assay showed 98.6% sensitivity (95% CI 96.9% to 99.5%) and 100% specificity (95% CI 99.3% to 100%) to detect HCV. In addition, melting peak ratiometric analysis demonstrated proof-of-principle for semi- quantification of HCV. The test was further validated in a real clinical setting in a resource-limited country. The authors concluded that they had provided proof of concept in a real-life clinical setting that the Genedrive HCV assay has great potential to provide an affordable and robust instrument for decentralized HCV Nucleic Acid Amplification Testing (NAAT). This highly sensitive and specific test has recently obtained CE-IVD certification and is positioned to enable real-time treatment management of patients with chronic HCV in any clinical setting. The study was published on April 3, 2018, in the journal BMJ Gut. Image: The Genedrive HCV ID kit is a qualitative assay providing results in 90 minutes in a decentralized environment (Photo courtesy of Genedrive). V

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LabMedica International

Diagnostic SHERLOCK Optimized for Rapid Viral Detection cont’d from cover

use in areas where special training and clinical laboratories can be challenging to access. Scientists at the Broad Institute of the Massachusetts Institute of Technology (MIT, www.broadinstitute.org) and Harvard Medical School (Cambridge, MA, USA; https://hms.harvard.edu) has also streamlined SHERLOCK’s (Specific High-sensitivity Enzymatic Reporter unLOCKing) capabilities to distinguish related viral species from one another and demonstrated the platform’s ability to identify clinically relevant mutations, such as a small mutation in Zika virus that has been associated with microcephaly. The SHERLOCK diagnostic platform uses a programmed Cas13 enzyme paired with reporter molecules to indicate the presence of a genetic target, such as a virus. Until now, a crucial preliminary step for SHERLOCK involved extracting and isolating nucleic acids from patient samples, which typically requires a laboratory and trained personnel, making it difficult to accomplish in the field. The team developed a simpler method that allows Cas13 to detect its target directly in bodily fluid samples such as saliva or blood. The process is called HUDSON, or Heating Unextracted Diagnostic Samples to Obliterate Nucleases. It consists of a rapid chemical and heat treatment used on the samples in order to inactivate certain enzymes that would otherwise degrade the genetic targets. The processed clinical samples can then be run through the SHERLOCK procedure, and the final detection results, positive or negative, can be easily viewed on the paper strip. The whole pipeline can be completed in less than two hours. By pairing HUDSON and SHERLOCK, the team was able to detect Dengue virus directly in patient samples of saliva and blood serum. The platform could also detect Zika virus particles that had been added to healthy blood and urine samples. Additionally, the team designed SHERLOCK reagents that make it even easier and faster to distinguish multiple related viral species (Zika, Dengue, West Nile, and yellow fever) from one another. These improvements are particularly useful when a patient has general symptoms, such as a fever, that could be caused by more than one virus. Pardis C. Sabeti, DPhil, MD, a professor and senior author of the study said, “Rapid and sensitive tools are critical for diagnosing, surveilling, and characterizing an infection. We’ve taken the SHERLOCK technology and optimized it in the context of these actual applied biological scenarios.” The study was published on April 27, 2018, in the journal Science.

LabMedica International August-September/2018

Image: A collection of SHERLOCK paper test strips: Unused paper strips (Left); Paper tests displaying a negative SHERLOCK readout (Middle); Paper tests displaying a positive SHERLOCK readout (Right) (Photo courtesy of Broad Institute of MIT and Harvard).

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PRODUCT NEWS CHEMISTRY ANALYZER

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CHEMISTRY ANALYZER

CELL CULTUREWARE

Erba Mannheim

Carolina Liquid Chemistries

Eppendorf

The XL 180 features a compact bench top design with a wide test menu. It offers reagent savings and comes with features such as auto dilution and auto rerun, and Levey Jennings program and QC rules.

The EasyRA now offers double the throughput, operating at a photometric rate of up to 240 tests per hour or up to 480 tests per hour with ISE. The test menu consists of 14 urine drugs of abuse tests and 35 general chemistry tests.

The ready-to-use surface with synthetic fibronectin-derived motifs supports cell attachment by mimicking native ECM proteins. The surface supports long-term expansion of hiPSCs over 25 passages and is suitable for hMSCs and other ECM-dependent cells.

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Cutting-Edge Technology Used to Grade Cancer Tumors cont’d from cover

of more than 24, 000 biopsies, graded by 732 breast cancer graders, found that they only agreed ~73% of the time on average. A team of scientists from Imperial College London (London, UK; www.imperial.ac.uk) carried out a double-blind clinical pilot trial using two adjacent slices taken from 75 breast cancer biopsies. The patients were all female with ages ranging from 30.4 to 83.7, mean age 58.7 at diagnosis. More than half of the samples were grade 2 tumors (54.3%). The majority were HER2 negative (90.0%). The first slice was graded by clinicians as usual, using the standard H+E protocol. It was also used to identify the so-called ‘region of interest’ (RoI), i.e. the part of the slice containing the tumor. The team used their new ‘Digistain’ technology addresses the problem of consensus among pathologists by using invisible mid-infrared light to photograph the tissue slices in a way that maps out the chemical changes that signal the onset of cancer. In particular, they measure the ‘nuclear-to-cytoplasmic-ratio’ (NCR): a recognized biological marker for a wide range of cancers. The team then used the Digistain imager to get a ‘Digistain index’ (DI) value averaged over the corresponding RoI on the other, unstained slice, and ran a statistical analysis on the results.

The DI measures the concentration ratios of phosphodiester to amide moieties, and because these are dominantly related to the amounts of nuclear and cytoplasmic material, respectively, The DI images can be regarded as 2D maps of the nuclear-to-cytoplasmic ratio, (NCR). The NCR factor that ‘Digistain’ measures is known to be common to a wide range of cancers, as it occurs when the reproductive cell cycle gets disrupted in the tumor and cell nuclei get distorted with rogue DNA. It is likely that in the long run, Digistain could help with the diagnosis of all different types of cancer. At a practical level, the team reported that the Digistain imaging technology can easily and cheaply be incorporated into existing hospital laboratories, and be used by their staff. Chris Phillips, PhD, a Professor of Experimental Solid State Physics and lead investigator of the study, said, “Our machine gives a quantitative ‘Digistain index’ (DI) score, corresponding to the NCR, and this study shows that it is an extremely reliable indicator of the degree of progression of the disease. Because it is based on a physical measurement, rather than a human judgement, it promises to remove the element of chance in cancer diagnosis.” The study was published on March 13, 2018, in the journal Convergent Science Physical Oncology.

Immunoassay Developed for Lassa Fever Virus assa fever is a type of viral hemorrhagic fever and is endemic in several West African countries. However, only few hospitals and laboratories in the region have the capacity to conduct molecular or serological Lassa fever diagnostics. The classical method for detection of Lassa virus-specific antibodies is the immunofluorescence assay (IFA) using virus-infected cells as antigen. However, IFA requires laboratories of biosafety level 4 for assay production and an experienced investigator to interpret the fluorescence signals. Scientists at the Bernhard Nocht Institute for Tropical Medicine (Hamburg, Germany; www.bnitm.de) and their West African colleagues chose a total of 576 sera from the diagnostic service of the Institute of Lassa Fever Research and Control. Of those, 270 sera tested positive by Lassa virus real-time polymerase chain reaction (RT-PCR) establishing the diagnosis of Lassa fever; 101 sera tested negative by Lassa virus RTPCR; and 23 had no RT-PCR result. From 47 RT-PCR confirmed Lassa fever patients, 182 (1–9 per patient) follow-up sera were available. From Lassa fever non-endemic areas, 199 samples collected between 2008 and 2011 from patients with suspected viral hemorrhagic fever or viral hepatitis in Ghana, all of whom tested negative by Lassa virus RT-PCR. Another 105 diagnostic leftover samples from German patients with various unknown diseases were included in the study.

The developed immunoglobulin M enzyme-linked immunosorbent assay (IgM ELISA) was based on capturing IgM antibodies using antiIgM, and the IgG ELISA is based on capturing IgG antibody–antigen complexes using rheumatoid factor or Fc gamma receptor CD32a. Analytical and clinical evaluation was performed with 880 sera from Lassa fever endemic (Nigeria) and non-endemic (Ghana and Germany) areas. The team used the IFA as the reference method, and observed 91.5% to 94.3% analytical accuracy of the ELISAs in detecting Lassa virus-specific antibodies. Evaluation of the ELISAs for diagnosis of Lassa fever on admission to hospital in an endemic area revealed a clinical sensitivity for the stand-alone IgM ELISA of 31% and for combined IgM/IgG detection of 26% compared to RT-PCR. In non-Lassa fever patients from non-endemic areas, the specificity of IgM and IgG ELISA was estimated at 96% and 100%, respectively. The authors concluded that the ELISAs are not equivalent to RT-PCR for early diagnosis of Lassa fever; however, they are of value in diagnosing patients at later stage. The IgG ELISA may be useful for epidemiological studies and clinical trials due its high specificity, and the higher throughput rate and easier operation compared to IFA. The established assays do not require expensive equipment; ELISA readers are available in many diagnostic laboratories in West Africa. The study was published on March 29, 2018, in the journal PloS Neglected Tropical Diseases. LabMedica International August-September/2018

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MULTIPARAMETER TEST

PROTEIN ANALYZER

Erba Mannheim

Euroimmun

Genrui Biotech

The Laura M urine analyzer features an evaluation time of 60 seconds and a capacity of 600 strips per hour. It also offers a memory capacity to save the last 2,000 measurements, making it ideal for use in clinical labs.

The EUROLINE DPA-Dx Pollen Southern Europe 1 detects and differentiates specific IgE antibodies against inhalation allergens. It identifies the allergy-causing proteins, distinguishing primary sensitizations from cross reactions and aids therapy decisions.

The PA120 uses latex Nephelometry and processes up to 60 samples every hour. It’s a fantastic upgrade for the semi-auto version protein analyzer that significantly increases efficiency while reduces the labor costs.

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CRP Levels May Indicate Schizophrenia Prognosis evels of C-reactive protein (CRP) indicating low-grade inflammation are associated with worsening scores on several psychometric scales and a poorer overall prognosis over a 1-year period in outpatients with stable schizophrenia. Schizophrenia is a mental disorder characterized by abnormal social behavior and failure to understand reality. Common symptoms include false beliefs, unclear or confused thinking, hearing voices that others do not, reduced social engagement and emotional expression, and a lack of motivation. Scientists at the University of Oviedo (Oviedo, Spain; www.uniovi.es) studied 50 stable outpatients of whom 62% were male, and the mean age was 31.1 years, who had been diagnosed with schizophrenia for fewer than 10 years. The team stratified subjects according to having low-grade inflammation, 14 who were defined with 3 to 10 mg/L CRP or 36 with normal CRP levels defined as equal to or less than 3mg/L CRP. The team excluded patients from the study who had greater than 10mg/L CRP, which represented

acute inflammation. During the course of the trial, the overall patient population demonstrated significantly improved scores from baseline. Scores after one year improved on the Positive and Negative Syndrome Scale-Positive, (PANSS) -General and -Total scale (range: 55.8 to 59.9); PANSS-General scale (range: 26.9 to 29.7); and the Clinical Assessment Interview for Negative Symptoms (CAINS)-Expression scale (range: 4.9 to 5.7). The team observed differences between the high versus normal CRP groups, however, in the duration of illness (6 versus 3.5 years; and in body mass index (BMI), 30.3 versus 26.5. Patients with low-grade inflammation and elevated levels of C-reactive protein (CRP), however, showed worsening scores during the year, which were represented by positive score values. These patients scores were poorer compared with those of patients with normal CRP levels on all PANSS scales; the PANSS Positive scale scores were 0.86 versus -1.3; PANSS Negative scores were 0.86 versus -1.2, the PANSS General scores were 0.93 versus -

4.2, and the PANSS Total scores were 2.6 versus -6.7 for patients with high versus normal CRP levels, respectively for all comparisons. The study was presented on March 5, 2018, at the 26th Congress of the European Psychiatric Association held in Nice, France. Image: Positron emission tomography (PET) imaging signal in healthy volunteers, high-risk subjects and patients with schizophrenia showing a stepwise elevation in microglial activity (orange) as severity of illness increases (Photo courtesy of MRC’s Clinical Sciences Centre).

Troponin I Levels Predict Coronary Artery Disease Severity lthough coronary artery disease (CAD) may be present early in life, its progression over time is highly unpredictable. Coronary atherosclerosis can progress at variable rates, ranging from a gradual increase in luminal narrowing to an abrupt progression to total luminal occlusion. Total luminal occlusion is often a result of disruption of a vulnerable non-stenotic plaque attributable to rupture or erosion and subsequent thrombosis. Consequently, CAD progression may be silent and gradual or sudden and catastrophic, leading to acute coronary syndrome or death. Medical scientists at Emory University School of Medicine (Atlanta, GA, USA; www.emory.edu) studied 3,087 patients (aged 63±12 years, 64% men) undergoing cardiac catheterization without evidence of acute myocardial infarction, the severity of CAD was calculated by the number of major coronary arteries with ≥50% stenosis and the Gensini

score. CAD progression was assessed in a subset of 717 patients who had undergone ≥2 coronary angiograms more than three months before enrollment. Fasting arterial blood samples were collected at cardiac catheterization and stored at −80 °C. High sensitivity troponin I (hsTnI) was measured using the Abbott ARCHITECT analyzer (Abbott Laboratories, North Chicago, IL, USA; www.abbott.com), which has a limit of detection of 1.2 pg/mL and an interassay coefficient of variation of <10% at 4.7 pg/mL. Serum high sensitivity C reactive protein (hs CRP) levels were determined in 2,127 patients using a particle enhanced immunoturbidimetric assay (FirstMark, a division of GenWay Biotech, San Diego, CA, USA; www.genwaybio.com) that has a lower limit of detection of 0.03 mg/L. The study was published on March 6, 2018, in the Journal of the American Heart Association. LabMedica International August-September/2018

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Amyloid Blood Biomarker Detects Alzheimer’s here is, as yet, no cure for Alzheimer’s disease. It is often argued that progress in drug research has been hampered by the fact that the disease can only be diagnosed when it is too late for an effective intervention. Alzheimer’s disease is thought to begin long before patients show typical symptoms like memory loss. Scientists have now developed a blood test for Alzheimer’s disease and found that it can detect early indicators of the disease long before the first symptoms appear in patients. The blood test would thus offer an opportunity to identify those at risk and may thereby open the door to new avenues in drug discovery. Scientists at Ruhr University Bochum (Bochum, Germany; www. ruhr-uni-bochum.de) measured the relative amounts of a pathological and a healthy form of amyloid-beta (Aβ) in the blood. The blood test developed uses a technology called immuno-infrared sensor to measure distribution of pathological and healthy structures of Aβ. The team developed an immuno infrared sensor that monitored the secondary structure change of Aβ peptides. The sensor is an antibody based (im-

muno) method to extract all Aβ peptides from CSF and blood samples and spectroscopically senses the secondary structure distribution of extracted soluble Aβ peptides in the infrared. The two structures absorb infrared light at a different frequency, allowing the blood test to determine the ratio of healthy to pathological amyloid-beta in the sample. The pathological form is a misfolded version of this molecule and known to initiate the formation of toxic plaques in the brain. Toxic Aβ molecules start accumulating in the patients’ body 15-20 years before disease onset. They first focused on patients in the early, so called prodromal stages of the disease from the Swedish BioFINDER cohort. They found that the test reliably detected Aβ alterations in the blood of participants with mild cognitive impairment that also showed abnormal amyloid deposits in brain scans. They then compared blood samples of 65 participants that were later in the follow-up studies diagnosed with Alzheimer’s disease with 809 controls. The assay was able to detect signs of the disease on average eight years before diagnosis in individuals without clinical symptoms. It correctly identified those with the disease in almost 70% of the cases, while about 9% of true negative subjects would wrongly be detected as positive. The authors suggest that their blood test serves as a cheap and simple option to pre-select individuals from the general population for further testing by these more invasive and costly methods to exclude the falsely positive subjects. The blood test will be extended to Parkinson disease by measuring another disease biomarker – alpha-synuclein – instead of amyloid-beta. The study was published on March 4, 2018, in the journal EMBO Molecular Medicine. Image: Determination of the amyloidbeta (Aß) secondary structure distribution in blood plasma by an immuno-IR-sensor correlates with PET scanning and CSF markers in Alzheimer’s disease (AD) patients, with potentials to be an accurate, simple, and minimally invasive biomarker for early AD detection (Photo courtesy of Ruhr University Bochum).

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LabMedica International August-September/2018

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PRODUCT NEWS UHPLC SYSTEM/ANALYZER

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BLOOD COLLECTION SET

ESR READER

Zivak Technologies

Greiner Bio-One

The Multitasker eliminates manual sample prep-related errors and allows you to turn your MS/MS into a walk-away analyzer. The VD-200 vitamin D2-D3 UHPLC analyzer prepares and injects the sample without any user intervention and gives results in six minutes.

The VACUETTE SAFETY Winged Set is equipped with a safety mechanism, which offers three different options for activating it immediately after blood collection. It is available both with and without a pre-assembled blood culture holder.

The ESR Reader (Item 836580) is fully automatic with an integrated printer for 100 tubes. It is non-sterile and runs on the G2S140BO software (version 1.4).

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Distinct Epigenetic Features Found in Alzheimer’s Brains ging is the strongest risk factor for Alzheimer’s disease (AD), although the underlying mechanisms remain unclear though AD tends to coincide with certain chromatin shifts in the aging brain. The chromatin state in particular through the chromatin histone acetylation mark H4K16ac, has been implicated in aging and thus may play a pivotal role in age-associated neurodegeneration. H4K16 is part what should now be a familiar group of lysines on the N-terminal tail of histone H4. Scientists at the University of Pennsylvania (Philadelphia, PA, USA; www.upenn.edu) used chromatin immunoprecipitation sequencing (ChIP-seq) targeting H4K16ac in post-mortem samples from the lateral temporal lobes of the brains of 12 individuals with AD who had a mean age of 68 years old. They did similar ChIP-seq-based profiling on samples from 10 older individuals with a mean age of 68 years old and nine somewhat younger individuals with a mean age of 52 years old. The team used the NextSeq 500 instrument (Illumina, San Diego, CA, USA; www.illumina.com) and detected that in the AD-affected brain samples, roughly 323,000 H4K16ac peaks by ChIP-seq, which was slightly fewer than the 349,000 or so peaks in the brain samples from older, unaffected individuals. Consistent with the histone mark’s ties to aging, the young brain samples had just 239,000 H4K16ac peaks. The H4K16ac mark distribution and overlap between the three groups, the scientists saw more pronounced overlap between the brain samples from older, healthy individuals and the AD sufferers. Around 183,000

H4K16ac peaks overlapped between those groups compared to a 153,000-peak overlap between samples from old and young controls and a 146,000-peak overlap in young controls and AD cases. Even so, the peaks were largely distinct in the younger, older, and AD groups. The study was published on March 5, 2018, in the journal Nature Neuroscience. Image: The NextSeq 500 benchtop sequencer delivers on-demand exome, transcriptome and whole-genome sequencing (Photo courtesy of Illumina).

Circulating Blood Markers Identified for Abnormal Heart Rhythms he irregular heart rhythm atrial fibrillation (AF) increases the risk of stroke and heart failure, but is often undiagnosed because of a lack of symptoms. AF increases the risk of developing strokes, heart failure, and even dementia. Four short lengths of RNA (miRNAs) have been identified that show increased expression in the circulating blood of AF patients. These miRNAs could be used as potential biomarkers to predict the onset of AF disease. MiRNAs control gene expression after the transcription stage, and have been suggested as possible markers for some cardiovascular diseases because of their stability in the bloodstream. A team of scientists at the Tokyo Medical and Dental University (Tokyo, Japan; www.tmd.ac.jp) recruited 60 AF patients and 55 controls for their study. The AF group comprised 30 patients with paroxysmal AF (PAF) and 30 with chronic AF (CAF). The control group consisted of 30 age-matched controls (AC) who had no AF-related symptoms, and 25

healthy young controls (YC). Of the total, 15 age-matched cases were selected for a comprehensive analysis of the miRNA and the remaining 100 subjects were enrolled for an individual miRNA expression analysis. Blood samples were collected from peripheral veins and serum was obtained by centrifugation at 1,600×g for 10 minutes, and stored at −80 until the RNA was isolated. The total RNA was extracted from the serum using mirVana PARIS Kit (Thermo Fisher Scientific, Santa Clara, CA, USA; www.thermofisher.com). The expression of individual miRNAs in serum was quantified by a quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Isolated total RNA samples (2 μL each) were reversely transcribed into cDNA and quantified using a Thermo Fisher Scientific TaqMan miR probe. PCR reactions were performed on a Thermo Fisher Scientific Step One Realtime PCR system. The authors also used a murine model. The study was released for publication on February 5, 2018, in the Circulation Journal. LabMedica International August-September/2018

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LabMedica International

Immune Signature Predicts Asthma Susceptibility sthma is a chronic inflammatory disease driven by the interplay of genetics, environmental factors and a diverse cast of immune cells. A subset of T cells has been identified whose frequency serves as early childhood immune signature that predicts the risk of developing asthma later on. Consistent with the “hygiene hypothesis,” which holds that increased microbial exposure in the first years of life is protective for asthma, the new findings also indicate that the presence of house dust components that stimulate the innate immune system decreases asthma risk. Scientists at La Jolla Institute for Allergy and Immunology (La Jolla, CA, USA; www.lji.org) followed 560 families from four disadvantaged urban areas who are at high risk for asthma to uncover potential risk factors that contribute to increased asthma rate in children growing up in impoverished neighborhoods. The team analyzed the frequency of different types of immune cells in blood collected from 110 one year-old study participants, the presence of immune-stimulatory components in the subjects’ house dust and asked whether any of the factors correlated with an increase of asthma at age seven. The team used peripheral blood from the participants to determine determined whether invariant natural killer T-cells (iNKT) or mucosalassociated invariant T-cells (MAIT) cell frequency at one year is correlated with the cytokine polarization of mainstream CD4+ T cells and/or the development of asthma by age seven years. Unlike conventional T cells, which belong to the adaptive arm of the immune response and take a few days before they are fully trained on a single, specific protein fragment or peptide antigen, MAIT and iNKT cells recognize molecular components common to many microbes. In addition dust samples from 300 houses were tested for iNKT cell antigenic activity. The investigators showed that a higher MAIT cell frequency at one year of age was associated with a decreased risk of asthma by age seven years. The frequency of MAIT cells was associated with increased production of interferon-gamma (IFN) by activated CD4+ T cells from the cohort. The iNKT cell antigenic activity in bedroom dust samples was associated with higher endotoxin concentration and also with reduced risk of asthma. Mitchell Kronenberg, PhD, president and chief scientific officer of La Jolla Institute and senior author of the study, said, “We found what I would consider very strong biomarkers for those children who are most likely to develop asthma as they get older. Children who, at the age of one, had a higher frequency of so called MAIT cells appear to be less likely to develop asthma by the age of seven.” The study was published on February 5, 2018, in the Journal of Immunology.

LabMedica International August-September/2018

Image: The frequency and activity of conventional T cells serves as an early childhood immune signature that predicts the development of asthma later on. The iNKT cells are shown in green, lung vasculature in red and cell nuclei in blue (Photo courtesy of Dr. Catherine Crosby, La Jolla Institute for Allergy and Immunology).

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PRODUCT NEWS OSMOMETER

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DIAGNOSTIC TEST SYSTEM

RAPID TEST

Advanced Instruments

BioFire Diagnostics

BIOKIT

The Advanced Model 3250 single-sample system is designed to provide fast, accurate results. It combines freezing point technology with the versatility of advanced sample processing in a device that is simple to operate and easy to maintain.

The FilmArray 2.0 manages up to eight instruments per computer and can test up to 175 samples a day. Its LIS-interfacing capabilities enable simplified test ordering, quicker turnarounds and increased accuracy by minimizing data entry.

The Bioblot reagents enable the detection of antibodies against specific antigens separated on a nitrocellulose strip. The product line is intended for us as a confirmation method for repeatedly reactive samples in screening tests.

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Tests Links Circulating Tumor DNA and Breast Cancer Survival ancer researchers used a liquid biopsy test for circulating tumor DNA (ctDNA) to profile cancer genomes from blood samples and predict survival outcomes for patients with metastatic triple negative breast cancer. Triple-negative breast cancer (TNBC) refers to any breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and Her2/neu. While TNBC represents just 10-15% of all breast cancer diagnoses, the disease is responsible for 35% of all breast cancer-related deaths. TNBC is characterized by few mutations but displays extensive somatic copy number alterations (SCNAs). However, little is known regarding SCNAs in metastatic TNBC. A team of investigators from several research institutes sought to evaluate SCNAs in metastatic TNBC exclusively via ctDNA and determine if ctDNA tumor fraction was associated with overall survival in metastatic TNBC. To this end, the investigators identified 164 patients with biopsy-proven metastatic TNBC at a single tertiary care institution who had received prior chemotherapy and performed low-coverage genome-wide sequencing of ctDNA from their plasma. Results revealed that without prior knowledge of tumor mutations, the investigators determined tumor fraction of ctDNA for 96.3% of patients and SCNAs for 63.9% of patients. Copy number profiles and percent genome altered were remarkably similar between metastatic and primary TNBCs. Certain SCNAs were more frequent in metastatic TNBCs relative to paired primary tumors and data for primary TNBCs published in publicly available data sets. Overall, 64% of patients had

more than 10% tumor DNA, and that this threshold of tumor DNA was correlated with poor survival outcomes in patients with metastatic TNBC. The study was published in the February 20, 2018, issue of the Journal of Clinical Oncology. Image: Circulating tumor DNA (ctDNA) is found in serum and plasma fractions from blood. The mechanism of ctDNA release is unknown, though apoptosis, necrosis, and active secretion from tumor cells have been hypothesized (Photo courtesy of Wikimedia Commons).

Bacteria Play Critical Role in Driving Colon Cancers atients with an inherited form of colon cancer harbor two bacterial species that collaborate to encourage development of the disease, and the same species have been found in people who develop a sporadic form of colon cancer. A process has been elucidated in which these bacteria invade the protective mucus layer of the colon and collude to create a microenvironment, complete with nutrients and everything the bacteria need to survive, that induces chronic inflammation and subsequent DNA damage that supports tumor formation. Scientists at Johns Hopkins Medicine (Baltimore, MD, USA; www. hopkinsmedicine.org) and their collaborators investigated the relationship between the bacteria-caused biofilms and cancer formation, by examining colon tissue removed from six familial adenomatous polyposis (FAP) patients. About 5% of colon cancers are caused by a hereditary

syndrome FAP, in which an inherited mutation launches a series of genetic changes that develop over time and eventually prompt the epithelial cells to turn malignant. The team identified patchy bacterial biofilms composed predominately of Escherichia coli and Bacteroides fragilis. Genes for colibactin (clbB) and Bacteroides fragilis toxin (bft), encoding secreted oncotoxins, were highly enriched in FAP patientsâ&#x20AC;&#x2122; colonic mucosa compared to healthy individuals. Bacteroides fragilis and Escherichia coli, a surprising finding since the colon contains at least 500 different types of bacteria. Tests on 25 additional colon samples from FAP patients showed that the B. fragilis strain was a subtype, called ETBF, which makes a toxin that triggers certain oncogenic, or cancer-promoting, pathways in colon epithelial cells and causes colon inflammation. The study was published on February 2, 2018, in the journal Science. LabMedica International August-September/2018

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PRODUCT NEWS BODY FLUID APPLICATION

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URINE LAB SYSTEM

MECHANICAL PIPETTE

CellaVision

77 Elektronika

Biosigma

The Body Fluid Application enables labs to automate, standardize and simplify exams of body fluid preparations. With analyzers and support software, it speeds up/simplifies the review process while delivering more standardized results.

The LabUMat 2, a high-throughput analyzer, and the UriSed 3, a sediment analyzer, combine to create a complete lab system. Both share well-designed hardware and software, and their efficiencies are maximized when used as one system.

The HPpette 2018 has an excellent grip, is easy to use and offers a range of volumes. Other features include volume reading window visible on the side, ejector button on the back for easy ejection and autoclavable tip cone.

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CTC Blood Test Detects Early Stage Colorectal Cancer olorectal cancer is among the most preventable cancers when detected early. Yet, it is the second leading cancer killer in the USA. Traditional methods like colonoscopies and stool-based tests are invasive or inconvenient and compliance with colorectal cancer screening remains low, leading to most colorectal cancers being detected in late stages, when survival rates are poor. Circulating tumor cells (CTCs) are cancer cells that detach from a primary tumor and circulate through the bloodstream and are a fundamental mechanism of metastasis. CTCs have long been known to be valuable in cancer detection, but most technologies using CTCs are only able to detect late-stage cancer. Scientists from Chang Gung Memorial Hospital (Taoyuan City, Taiwan; www.cgmh.org.tw) and their colleagues enrolled 620 people over the age of 20 who were either visiting the hospital for routine colonoscopies or had confirmed colorectal cancer. After a colonoscopy and biopsy, 438 people were found to have either adenomatous polyps (pre-cancerous growths) or early to late-stage colorectal cancer. The remaining study participants had no signs of pre-cancerous growths or colorectal cancer and were the comparison group. The investigators tested 2mL of peripheral whole blood were from each subject for CTC analysis through a routine blood draw. The blood samples were then processed through the CMx platform (CellMax Life, Sunnyvale, CA, USA; www.cellmaxlife.com). The results of these assays were then compared in a blinded analysis with the colonoscopy results. The study results showed that the test’s sensitivity ranged from 77% for detection of CTCs in pre-cancerous lesions to 87% for stage I-IV cancers. The accuracy of the results, taking into account both sensitivity and specificity, was high and ranged from 84% to 88% for pre-cancerous and can-

cerous samples. Additionally, the accuracy of this test was superior to that of fecal occult blood testing (FOBT), a guideline-recommended stool test for colorectal cancer screening. This blood test could potentially be offered between USD 100 and USD 150. Atul Sharan, MBA, MS, co-founder and CEO of CellMax Life, said, “Early detection is perhaps the only real cure for cancer. To be effective, tests for early cancer detection need to be non-invasive, easy, highly affordable and accurate, and our CTC blood test meets all of these requirements. Recent surveys reveal a preference for blood tests over stool-based screening tests in more than 80% of patients who did not undergo invasive colonoscopy screening. This test can be an option for these individuals and boost compliance.” The study was presented on January 20, 2018, at the ASCO Gastrointestinal Cancers Symposium held in San Francisco, CA, USA. Image: Depiction of circulating tumor cells detaching from a primary tumor and circulating through the bloodstream (Photo courtesy of CellMax Life).

Plasma Markers Predict Brain Amyloid Burden in AD ggregation and accumulation of beta-amyloid (Aβ), particularly Aβ42, is implicated in the pathogenesis of Alzheimer’s disease (AD) with overproduction in autosomal-dominant AD and impaired clearance in the presence of amyloidosis contributing to the cause of AD. Cerebrospinal fluid analysis and other measurements of amyloidosis, such as amyloid-binding positron emission tomography studies, are limited by cost and availability. There is a need for a more practical betaamyloid (Aβ) biomarker for central nervous system amyloid deposition. An international team of scientists working with the Japanese National Center for Geriatrics and Gerontology (Obu, Japan; www. ncgg.go.jp) used immunoprecipitation followed by matrix-assisted laser

desorption/ionization (MALDI) mass spectrometry to measure levels of the three markers, APP669-711, Aβ42, and Aβ40 in two cohorts, a discovery set consisting of 121 Japanese patients and a validation set consisting of 252 Australian patients. Both sets included a mix of cognitively normal individuals, subjects with mild cognitive impairment, and subjects with clinically diagnosed Alzheimer’s disease with dementia. All patients also had Aβ- positron-emission tomography (PET) imaging data, providing an assessment of their brain Aβ burdens. A subset of the Australian patients also had measurements taken of their cerebrospinal fluid Aβ levels. The study was published on January 31, 2018, in the journal Nature. LabMedica International August-September/2018

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PRODUCT NEWS IMMUNOASSAY SYSTEM

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HSTNI ASSAY

URINALYSIS CONTROL

MP Biomedicals

Beckman Coulter

Quantimetrix

The AutoBlot System 20 fully-automated, self-contained instrument performs immunoblot assays with next-gen software. It is fully programmable and can store up to 10 protocols, allowing for customization of assays for dispense, incubation and aspiration.

The Access hsTnI provides a reliable measurement of very low levels of cardiac troponin I, while also detecting small differences in cTnI levels over time. It is intended for use on the Access 2, DxI and the entire Access family of systems.

The Dipper single-use liquid control offers room temp stability of three months and three years refrigerated from the date of manufacture. Its stability exceeds all other urinalysis controls currently available, making it ideal for use in every testing environment.

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Microfluidic Device Captures Tumor-Specific Extracellular Vesicles microfluidic device has been developed that can capture glioblastoma-derived extracellular vesicles, with high specificity, using very small blood samples, which would be useful for pediatric patients. The microfluidic channels in the device contain a cocktail of antibodies that are specific for molecules found on glioblastoma-derived extracellular vesicles, meaning the vesicles are captured as they pass through the channels. Scientists at Massachusetts General Hospital (Charlestown, MA, USA; www.massgeneral.org) and their colleagues collected blood samples from a total of 13 brain cancer patients and six healthy donors were included in this study. Microfluidic devices consisted of 8-Channel herringbone structures were fabricated using standard photolithography and different strategies were tested for optimal configuration of capture antibodies on the surface of the microfluid device. Isolated extracellular vesicles (EVs) were quantified using a tunable resistive pulse sensing (TRPS) qNano instrument (Izon Science, Christchurch, New Zealand; www.izon.com). EV’s were isolated with immobilized with streptavidin-coated magnetic particles. The cyclic olefin copolymer (COC) The COC microfluidic device allowed direct imaging of captured EVs. Micrographs were captured with an LSM510 confocal microscope (Carl Zeiss, Peabody, MA, USA; www.zeiss.com) equipped with a ×63 Zeiss Plan-APOCHROMAT oil objective. RNA was isolated and quantified. Digital polymerase chain reaction, library preparation for RNA sequencing and RNA sequencing analysis was also performed. The team reported that the sensitive analytical microfluidic platform (EVHB-Chip) that enables tumor-specific EV-RNA isolation within three hours. Using the EVHB-Chip, They achieved 94% tumor-EV specificity,

a limit of detection of 100 EVs per L, and a 10-fold increase in tumor RNA enrichment in comparison to other methods. This approach allowed for the subsequent release of captured tumor EVs, enabling downstream characterization and functional studies. Processing serum and plasma samples from glioblastoma multiforme (GBM) patients, they detected the mutant Type III epidermal growth factor receptor (EGFRvIII) messenger RNA (mRNA). The study was published online on January 12, 2018, in the journal Nature Communications. Image: Extracellular vesicles (red) released from a patient’s tumor and captured on the surfaces of the EVHB-Chip (Photo courtesy of Professor Shannon Stott, PhD).

Urinary Gene-Based Test Detects Bladder Cancer redominantly of urothelial histology, invasive bladder cancer (BC) arises from non-invasive papillary or flat precursors, and many BC patients suffer multiple relapses prior to progression, providing ample lead-time for early detection and treatment prior to metastasis. Urine cytology is a non-invasive method for the detection of BC. Although it has value for the detection of high-grade BC, the test is unable to detect the vast majority of low-grade tumors. A test has been developed for urine, gathered during a routine procedure, to detect DNA mutations identified with urothelial cancers. A large team of international scientists collaborating with their colleagues at The Johns Hopkins Kimmel Cancer Center (Baltimore, MD, USA; www.hopkinsmedicine.org) collected urine samples prospectively

from patients in four participating institutions. A total of 892 urine samples were analyzed and composed of two types of samples. The first was residual urinary cells after processing with standard BD SurePath liquidbased cytology protocols (Becton Dickinson and Company; Franklin Lakes, NJ, USA; www.bd.com). Formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples from trans-urethral resections (TURB) or cystectomies were collected in 413 of the 892 cases. Nickolas Papadopoulos, PhD, a senior author of the study, said, “When you combine UroSEEK and cytology, you get better results. Side by side, UroSEEK has better sensitivity. There are some cases when cytology detects when UroSEEK doesn’t. Combining them produces the best results.” The study was published on March 20, 2018, in the journal eLife. LabMedica International August-September/2018

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LabMedica International

Low Total Testosterone Linked to Chronic Disease male’s total testosterone level may be linked to more than just sexual health and muscle mass preservation. Low amounts of the hormone could also be associated with chronic disease, even among men 40 years of age and younger. The prevalence of total testosterone (TT) deficiency in men increases with age, and is associated with several deleterious effects to the musculoskeletal system including osteopenia and sarcopenia, as well as with higher rates of all-cause mortality. Scientists from University of Michigan (Ann Arbor, MI, USA; https://umich.edu) evaluated the association between total testosterone (TT) deficiency and weakness on multimorbidity in men. Analyses were performed to examine the prevalence of multimorbidity among 2,399 young, middle-aged, and older men, with and without testosterone deficiency. Fasting and non-fasting measures of HDL-cholesterol, triglycerides, and glucose were measured. Non-fasting serum measures of glycated hemoglobin (HbA1c) were included as a diagnostic test for untreated diabetes, which reflects average plasma glucose for the previous ~three-months. TT levels were measured in serum using isotope dilution liquid chromatography tandem mass spectrometry. The investigators found that multimorbidity was more prevalent among men with testosterone deficiency, compared to normal TT in the entire group (36.6% versus 55.2%). However, differences were only seen within young (testosterone deficiency: 36.4%; normal TT: 13.5%; and older men (testosterone deficiency: 75.0%; normal TT: 61.5%). Low TT and weakness in men were independently associated with multimorbidity at all ages; however, multimorbidity was more prevalent among young and older men with testosterone deficiency. Prevalence of testosterone deficiency was 30.8% for the entire sample, and 22.6%, 35.8%, and 34.6% for young, middle-aged, and older men, respectively. The study was published on April 12, 2018, in the Journal Scientific Reports.

New Osteoarthritis Genes Discovered lmost nine million people in the UK suffer from osteoarthritis, a degenerative joint disease in which a person’s joints become damaged, stop moving freely and become painful. Osteoarthritis is the most prevalent musculoskeletal disease and a leading cause of disability worldwide. Osteoarthritis occurs when the cartilage that cushions the ends of bones in joints gradually deteriorates. Cartilage is a firm, slippery tissue that permits nearly frictionless joint motion. In osteoarthritis, the slick surface of the cartilage becomes rough. Eventually, if the cartilage wears down completely, all that is left is bone rubbing on bone. A large team of scientists collaborating with the Wellcome Trust Sanger Institute (Hinxton, UK; www.sanger.ac.uk) studied 16.5 million DNA variations from the UK Biobank resource. Following combined analysis in up to 30,727 people with osteoarthritis and nearly 300,000 people without osteoarthritis in total, scientists discovered nine new genes that were associated with osteoarthritis, a significant result for this disease. For three loci, they detected association with biologically relevant radiographic endophenotypes, and in five signals they identified genes that were differentially expressed in degraded compared with intact articular cartilage from patients with osteoarthritis. The team then investigated the role of the nine new genes in osteoarthritis, by studying both normal cartilage and diseased cartilage from individuals who had a joint replacement. The team looked for genes that were active in the progression of the disease by extracting the relevant cells from healthy and diseased tissue, studying the levels of proteins in the tissue and sequencing the RNA, the messenger that carries instructions from DNA for controlling the production of proteins. Of the nine genes associated with osteoarthritis, the investigators identified five genes in particular that differed significantly in their expression in healthy and diseased tissue. The study was published on March 20, 2018, in the journal

LabMedica International August-September/2018

Image: A liquid chromatography-tandem mass spectrometer (LCMS/MS) (Photo courtesy of University of Michigan). S TOR Y IBU APPL R T O DIS ED T IT INV

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PRODUCT NEWS COAGULATION MONITOR

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MODULAR LAB INSTRUMENT

STAND-ALONE ALIQUOTER

Roche Diagnostics

Sarstedt

The CoaguChek Vantus features built-in Bluetooth technology, allowing patients to send their results automatically via wireless connectivity. The hand-held device includes several additional features to help patients with their self-testing.

The BL 1200 ID can be used with any analytical platform and features a bulk loader that eliminates manual sorting and pre-racking. It accessions and sorts up to 1,200 tubes per hour without pre-racking for walk-away preanalytical processing.

The AL-Flex increases throughput by separating aliquoting from other prep and can process up to 380 primary tubes per hour. It can create as many secondary tubes as the sample volume allows and labels each tube with customer-specific data.

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Cancer Stem Cells Isolated Using Novel Method tem cells are in various tissues in the body, and unlike regular cells, which have a limited lifespan; they can divide and renew themselves for long periods of time. They are also unspecialized, meaning that when one of them divides, the resulting cells can transform into another cell type. Similarly, cancer stem cells (CSCs), believed to reside at the heart of tumors, fueling their growth, are also thought to be unspecialized and able to self-renew until they transform into new cancer cells. Most effective treatments for primary tumors leave cancer stem cells unscathed. Even if a primary tumor is successfully treated, secondary tumors can appear years later and are often more aggressive and harder to treat. Scientists at the University of Texas at Dallas (Richardson, TX, USA; www.utdallas.edu) have devised a new technique to isolate aggressive cells thought to form the root of many hard-to-treat metastasized cancers, a significant step toward developing new drugs that might target these cells. The team used a two-step process to sort through a library of 40,000 chemical compounds, looking for any that would selectively bind to breast cancer stem cells, isolating them from standard breast cancer cells. The screening process identified five compounds, called ligands that bind specifically to cancer stem cells and the investigators selected one of them for closer study. They incubated a mixture of both breast cancer stem cells and non-stem cancer cells together with 40,000 tiny plastic beads, each coated with multiple copies of this one ligand. The synthetic ligand (1) that specifically binds to CSCs over non-CSCs of breast cancer cells was identified for the first time via a cell-binding screening of a chemical library. The ligand 1 showed specific binding to CD24−/CD44+/ALDH+ CSC population of MCF-7 and MDA-MB-231.

The team demonstrated that 1-immobilized beads can be used as matrices for affinity isolation of 1-binding CSC population from breast cancer cells. The 1-binding population showed significantly increased expressions of stemness-associated transcription factors. Importantly, the 1-binding population demonstrated accelerated tumor growth in vivo, and the resulting tumor displayed an increased migratory activity and high expressions of CSC markers. The study was published on February 26, 2018, in the journal Chemistry - A European Journal. Image: A new technique to isolate cancer stem cells: 40,000 tiny plastic beads (blue),were used each coated with a unique chemical compound, to identify one compound that bound only to breast cancer stem cells (red) (Photo courtesy of the University of Texas at Dallas).

CO-Oximetry External QA Programme Launched o-oximetry is a methodology that measures the levels of the oxygen-carrying protein haemoglobin, which is the chief component of red blood cells and CO-oximetry is useful in defining the causes for hypoxemia, or hypoxia. Co-oximetry is a useful tool in that it helps determine the levels of various forms of haemoglobin and can be used to diagnose a variety of conditions related to oxygen content in blood. Oxygen content is an important indicator of oxygen transport within the body. The oxygen transport of arterial blood is used to evaluate the ability of transporting oxygen from the lungs to the tissue. A new CO-Oximetry programme to complement their existing Blood Gas programme has been launched by Randox

(Crumlin, UK; www.randox.com). The programme combines seven parameters in a user-friendly, liquid ready-to-use format, the new RIQAS CO-Oximetry External Quality Assessment (EQA) programme has been designed with consolidation and convenience in mind and it is even suitable for use in point-of-care testing. All samples are supplied in a liquid ready-to-use format ideal for both clinical and point-of-care testing. RIQAS is the world’s largest EQA scheme with 45,000 participants and 33 programmes ensuring peer groups are maximised. Lynsey Adams, BSc, the Quality Control Marketing Manager at Randox, said, “The launch of our new CO-Oximetry programme means we now offer a complete EQA solution for blood gas testing.” LabMedica International August-September/2018

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Epigenetic Signatures Show Promise for Diagnosing Neurodevelopmental Disorders enome-wide DNA methylation signatures have been discovered for several neurodevelopmental Mendelian disorders, which clinically could complement existing molecular tests. The so-called epi-signatures might be particularly useful in testing for several syndromes at once and to help classify variants of unknown significance. In addition to constitutional disorders, they might find applications in cancer diagnostics. Scientists at the Western University (London, ON, Canada; www.uwo.ca) and their collaborators analyzed peripheral blood DNA samples from nearly 300 patients with one of 14 Mendelian conditions, all neurodevelopmental syndromes that have been associated with defects in epigenetic regulation as well as from approximately 650 healthy controls. To generate the DNA methylation profiles, they used Illuminaâ&#x20AC;&#x2122;s HumanMethylation450 bead chip or their Infinium methylation EPIC arrays (Illumina, San Diego, CA, USA; www.illumina.com). The team demonstrated that specific but partially overlapping DNA methylation signatures are associated with many of these conditions. The degree of overlap among these episignatures is minimal, further suggesting that, consistent with the initial event, the downstream changes are unique to every syndrome. In addition, by combining these epi-signatures, they demonstrated that a machine learning tool can be built to concurrently screen for multiple syndromes with high sensitivity and specificity, and they highlight the utility of this tool in solving ambiguous case subjects presenting with variants of unknown significance, along with its ability to generate accurate predictions for subjects presenting with the overlapping clinical and molecular features associated with the disruption of the epigenetic machinery. Bekim Sadikovic, PhD, DABMGG, FACMG, an associate professor of pathology and laboratory medicine and the lead investigator of the study said, â&#x20AC;&#x153;Once we introduce this in a clinical setting and start generating larger and larger databases, with clinical information linked to them, much like what happened with microarray testing and now exome sequencing, we will uncover what other genes or conditions may have these epi-signatures. I think the best way forward, from a discovery standpoint, is to put methylation testing into routine clinical use in these patient populations that normally get genomic profiles and allow the data itself to give us additional utility.â&#x20AC;? The study was published on January 4, 2018, in the American Journal of Human Genetics.

LabMedica International August-September/2018

Image: The Infinium methylation EPIC arrays for epigenome-wide association studies (Photo courtesy of Illumina).

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POC Testing Evaluated For Fecal Calprotectin lcerative colitis (UC) and Crohn’s disease (CD) are the two most prevalent forms of inflammatory bowel disease (IBD), with the highest prevalence and incidence in Europe and North America. Fecal calprotectin (FC) is widely used to monitor the activity of IBD and to tailor medical treatment to disease activity. Laboratory testing of fecal samples may have a turnaround time of 1–2 weeks, whereas FC home testing allows results within hours and thus enables a rapid response to clinical deterioration. Clinical biochemists working at Copenhagen University Hospital Hvidovre (Hvidovre, Denmark; www.hvidovrehospital.dk) and their colleagues analyzed 55 stool samples. All stool samples were collected in plastic tubes by the patients and sent in by ordinary mail. The samples were immediately frozen at −20 °C upon receipt and analyzed within 1–2 days. The team investigated the correlation between FC measured by the BÜHLMANN home test kit, IBDoc (BÜHLMANN Laboratories AG, Schönenbuch, Switzerland; www.buhlmannlabs.ch) and BÜHLMANN immunoturbidimetric method fCAL turbo assay on a Roche Cobas 6000 c501 (Roche Diagnostics, Mannheim, Germany; www.cobas.com). The 55 samples included in the study, covered the clinically relevant concentrations in the range 38 μg/g to 796 μg/g (BÜHLMANN fCal turbo). The team found a strong correlation coefficient of 0.887 be-

tween FC measured on IBDoc and the laboratory assay BÜHLMANN fCAL turbo. Ten extractions of three fecal samples with low (< 50 μg/g), medium (50–200 μg/g) and high (> 200 μg/g) FC concentrations were performed in each assay, showing an intermediate imprecision in the range of 2.3%–5.5% (BÜHLMANN fCAL® turbo) and in the range of 4.8%–26.6% (IBDoc). The study will be published in the March 2018 issue of the journal Practical Laboratory Medicine. Image: Loading the IBDoc Calprotectin point of care test kit cassette (Photo courtesy of Calprotectin).

Rapid Salivary Test Developed for Zika Virus arly pathogen identification is necessary to combat the spread of newly emerging and re-emerging epidemics. Diagnosis can be accomplished with a generic platform and protocol designed to identify any pathogen by detection of the pathogen’s nucleic acid once its sequence is determined and its antigenic footprint identified. Blood samples are most often used to test for Zika virus (ZIKV) and are typically processed using a common diagnostic technique called realtime polymerase chain reaction (RT-PCR). Scientists at the New York University College of Dentistry (New York, NY, USA; https://dental.nyu.edu) and their colleagues developed a rapid Zika test that combines both nucleic acid and antibody assays using saliva, given that Zika virus and antibodies persist in saliva. A saliva test is also noninvasive, cost effective, and easier to collect than blood or urine. The team first optimized the reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay to detect ZIKV RNA using a benchtop isothermal amplification device and then adapted the assay to the CARD cartridge microfluidic device (Rheonix, Ithaca, NY, USA; http://rheonix.com).

The microfluidic Rheonix CARD cartridge is an integrated cassette that can provide both an immunological and nucleic acid (RT-LAMP) result from a single sample. It incorporates all the pumps, valves, micro channels, reactions, and reagent reservoirs on a disposable cartridge. The processing and analysis on the Rheonix CARD cartridge is controlled by the Encompass Optimum workstation developed to provide automated control of all sample preparation functions. The assay in a microfluidic device that will allow analyzing 24 samples simultaneously and automatically from sample introduction to detection by reverse dot-blot for detection (RDB) technique. Preliminary data using saliva samples spiked with ZIKV showed that the diagnostic system detects ZIKV RNA in saliva. The limit of detection of the RTLAMP assay on the Genie III instrument (OptiGene, Horsham, UK; www.optigene.co.uk) and Rheonix CARD cartridges is similar to other results reported using RT-LAMP and other isothermal assays. The study was published on February 5, 2018, in the journal Public Library of Science ONE. LabMedica International August-September/2018

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LabMedica International

Multigene Breast Cancer Recurrence Signatures Tests Compared comparison of commercially available signatures was “weaker” in assessing distant multigene breast cancer recurrence recurrence than in the node-negative setting. signatures suggests that some tests Therefore, using the combination of clinical may be better than others at assessing which and genomic signatures may be the best appatients are at risk for late distant recurrence, proach in the node-positive setting. which could be impacting oncologists’ ability The authors concluded that for women to guide appropriate treatment decisions for with node-negative disease, the ROR, BCI, patients. and EPclin were significantly more prognostic An accurate estimate of the risk of distant for overall and late distant recurrence. For recurrence helps discern whether a patient women with one to three positive nodes, limshould receive chemotherapy on top of enited independent information was available docrine therapy, while an accurate estimate of from any test. These data might help oncoloImage: The Oncotype-Dx 21-gene recurrence the risk of late distant recurrence helps detergists and patients to choose the most appropriscore for predicting risk for metastatic breast mine whether patients should receive extendate test when considering chemotherapy use cancer has been quickly adopted in clinical ed adjuvant endocrine therapy. More than and/or extended endocrine therapy. The practice, but which is currently going through consultation (Photo courtesy of Genomic 50% of women with estrogen receptor-positive study was published on February 15, 2018, in Health). (ER+) breast cancer experience recurrence afthe journal JAMA Oncology. ter five years. Scientists led by those at Queen Mary University London (UK, www. qmul.ac.uk) carried out a retrospective analysis of samples from nearly 800 postmenopausal women with ER-positive, HER2-negative breast cancer using five molecular test signatures. The samples came from patients enrolled in the Translational Study of Anastrozole or Tamoxifen Alone or Combined (TransATAC), PRINT MAGAZINE 591 of who were node-negative and 183 of who had node-positive breast cancer. Data were collected from January 2009 through April 2015. The team included the following assays in the study: Oncotype Dx recurrence score (Genomic Health, Inc. Redwood City, CA USA; www. genomichealth.com), PAM50-based INTERACTIVE Prosigna risk of recurrence (ROR, DIGITAL EDITION Seattle, WA, USA; www.prosigna. com), Breast Cancer Index (BCI, bioWEB PORTAL Theranostics Inc, San Diego, CA, USA; www.biotheranostics.com), EndoPredict (Epclin, Myriad Genetics, Salt Lake City, UT, USA; https:// myriad.com) MammaPrint Netherland Kanker Institute 70-gene signature (Agendia BV, Amsterdam, The Netherlands, www.agendia.com), Clinical NEW: RUSSIAN Treatment Score, and a 4-marker imEDITION munohistochemical (IHC-4) score. The team reported that all six signatures provided statistically significant prognostic value 10 years out from diagnosis in node-negative patients, though Prosigna, BCI, and EndoPredict proved to be statistically Website Editions: more prognostic than the other sigEnglish Spanish natures. The analysis found that these molecular signatures provided Chinese Russian significantly more prognostic information than the score based only on clinical features of the tumor, Oncotype DX, and IHC-4. In the node-positive setting, the performance of the

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Portable Olfactory Sensor Designed for Diagnosis of Bacteria portable electronic “nose” (eNose) has been designed to rapidly detect and identify the most common bacteria causing soft tissue infections. Rapid diagnosis of wound infections is based on bacterial stains, cultures, and polymerase chain reaction assays, and the results are available after several hours at the earliest, but more often not until after days of waiting. Therefore, antibiotic treatment is often administered empirically without a specific diagnosis. To rectify this situation, a team of Finish bioengineers developed eNose, a device able to produce “an olfactory profile” for each molecular compound in gaseous headspace created by bacterial infection. The profile was analyzed by a computer programmed to differentiate between different compounds. The investigators used the eNose system for a proof-of-concept study aimed at differentiating the most relevant bacteria causing wound infections. The study utilized a set of clinical bacterial cultures on identical blood culture dishes, and established bacterial lines from the gaseous headspace. Results revealed that the eNose system was capable of differentiating both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa, and Clostridium perfringens with an accuracy of 78% within minutes without prior sample preparation. Most importantly, the system was capable of differentiating MRSA from MSSA with a sensitivity of 83%, a specificity of 100%,

and an overall accuracy of 91%. “Our aim was to create a method for the rapid diagnosis of soft tissue infections. If we had such a method, treatment could be started in a timely manner and targeted to the relevant pathogen directly. This would reduce the need for empirical treatments and shorten diagnostic delays,” said first author Dr. Taavi Saviauk, a researcher in the faculty of medicine and life sciences at the University of Tampere (Finland; www.uta.fi). “The portable eNose device we used does not require laboratory conditions or special training, so it is well suited for outpatient use. The results of this study are a significant step towards our goal.” The eNose study was published in the January 2018 issue of the journal European Surgical Research. Image: Researchers developed the eNose to detect common bacteria such as MRSA (pictured) responsible for soft tissue infections (Photo courtesy of Shutterstock).

New Blood Draw Device Evaluated for Hemolysis emolysis, defined as the breakdown of red blood cells and the release of hemoglobin and intracellular contents into the plasma, is a frequent occurrence in blood samples submitted to clinical laboratories for testing. Blood collections from peripheral intravenous catheters offer several benefits to patients, including reduced needle punctures and patient discomfort, but they risk reducing the quality of blood specimens analyzed by the laboratory. The estimated prevalence of hemolyzed specimens is approximately 3% of routine samples and they make up approximately 60% of specimens classified as unsuitable for analysis. A team of medical laboratory scientists led by those at University Hospitals Cleveland Medical Center (Cleveland, OH, USA; www. uhhospitals.org), in an effort to balance analytical quality of test results with patient-centered care initiatives, a needle-less blood collection device called PIVO (Velano Vascular, San Francisco, CA, USA; www.velanovascular.com)

was evaluated at two institutions. The primary objective of this study was to assess the ability of the PIVO device to provide high-quality blood specimens for laboratory testing compared to current blood collection methods. The PIVO blood collection device was used for blood draws from a peripheral intravenous (IV) catheter (PIVC). Prior to the PIVO collection, the IV catheter was flushed with 5 mL normal saline. The PIVO device was attached to the needle-less valve and actuated through the IV catheter into the blood stream. Standard vacuum tubes or a syringe were used at the back end of the device to collect blood samples. The blood collections were typically performed with a tourniquet above the PIVC. A discard volume of 1 mL was collected through PIVO prior to the required specimen collection. After the PIVO collection the device was retracted, removed, and disposed of. The IV catheter was again flushed with 5 mL normal saline. The study was published on January 4, 2018, in the journal Practical Laboratory Medicine. LabMedica International August-September/2018

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; Email: enews@ifcc.org

Commutability Explained in Freely Available Resources by Dr. Graham H Beastall, IFCC Representative to the Executive of the Joint Committee for Traceability in Laboratory Medicine (JCTLM)

What is commutability? ne of the key considerations in improving the harmonisation of clinical laboratory results is that the reference materials (and calibrants) used in laboratory methods should behave in an identical fashion to the analyte being measured in the clinical sample. A commutable reference material achieves this desirable aim. Non-commutable reference materials may be a source of variability between different methods for the same analyte and can contribute to methods giving erroneous results, which may have clinical consequences for patient care. Commutability is also important in external quality assessment (EQA) for the same reason. For EQA results to be meaningful the EQA specimens distributed by the scheme organiser should be commutable, i.e. behave in an identical way to clinical specimens in the assay that is being assessed. The concept of commutability is easy to understand but more difficult to evaluate. At the basic level commutability is assessed by using two different methods for the same analyte to measure a panel of clinical samples and the reference materials / calibrants (or EQA specimens). For the clinical specimens there should be a straight-line relationship between the two methods. If the reference materials / calibrants (or EQA specimens) lie on the same straight line they are said to be commutable. Deviation from the straight-line relationship rendered the reference material / calibrant as non-commutable 1. Such a ‘black or white’ has long been regarded as unsatisfactory. To address the topic in a more scientific way the IFCC Scientific Division established the Working Group on Commutability (WGC), chaired by Greg Miller from the USA. The WG-C attracted a large and expert membership who examined commutability in a systematic and scientific way and employed statistics to define the extent to which a reference material is commutable, so helping to determine whether that reference material may be employed with confidence in a clinical laboratory method. The WG-C recently published three linked articles in Clinical Chemistry 2-4. These articles prompted an Editorial entitled ‘The enduring importance and challenge of commutability’ 5. Together, these publications provide the definitive explanation of commutability and should be of interest to all manufacturers of clinical laboratory diagnostics and to all laboratory medicine specialists.

JCTLM resources to aid the understanding of commutability The JCTLM is an international consortium that promotes the global standardisation of clinical laboratory test results, and provides information on reference materials, reference measurement methods and services that are available from around the world. The aim of JCTLM is to support world-wide comparability, reliability and equivalence of measurement results in laboratory med-

LabMedica International August-September/2018

NEWS

icine, for the purpose of improving health care and facilitating national and international trade in in vitro diagnostic devices, by: Promoting the concept of traceability of measurement results to the Système International d'Unités (SI) or, where necessary, to other internationally agreed references; Evaluating reference materials, reference measurement procedures and reference measurement services for laboratory medDr. Graham H Beastall icine with respect to conformity with appropriate international standards; Producing educational materials and activities promoting the value of traceability in laboratory medicine and raising awareness amongst stakeholders; Promoting close links between Reference Laboratories in Laboratory Cont’d on page 28

NEWS

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

IFCC-Roche Travel Scholarships Awarded For Conference in Rome Tor Vergata FCC and Roche are pleased to announce the IFCC-Roche Travel Scholarship Awardees. They were selected to attend the 1st IFCC, EFLM, AFCB Conference "Laboratory Medicine: Meeting the needs of Mediterranean Nations", held in Rome Tor Vergata (IT). Congratulations to: Khalil Ramy Samir Helmy Assaad (EG Aff), Ana Sofía Duarte Acuña (GT), Ashish Kumar Mohanbhai Agravatt (IN Aff), Swarnima Singh (IN Full), Dwy Yuniati Daulay (ID), Kamal Abu-Eisheh (JO), Caroline Wanjiku Njeru (KE), Nerxhivane Gerguri-Ratkoceri(XK), Sebbar El-houcine (MO), Mithileshwar Raut (NP Full), Adaeze Njideka Nwabuogo Onyekwena (NG), Suhanyah Mahathevan (LK), Manel Chaabane Ep Doghri (TU), Yevgenija Kryvenko (UA), Itai James Blessing Chitungo (ZW). IFCC Roche Travel Scholarship programme enables Young Scientists from emerging countries to attend major conferences of clinical chemistry and laboratory medicine.

Photo: IFCC Roche Travel Scholarship Recipients in Rome, Tor Vergata University, together with IFCC President, Prof. Howard Morris, IFCC Past President, Prof. Maurizio Ferrari, and Task Force for Young Scientists Chair, Dr Pradeep Dabla

Commutability Explained in Freely Available Resources Cont’d from page 27 Medicine and National Metrology Institutes; Facilitating the identification and prioritisation of measurands requiring international traceability and comparability and thereby encouraging appropriate organisations to accept responsibility for the development of suitable reference methods and measurement procedures and certified reference materials; Encouraging the in vitro diagnostic (IVD) industry to apply the agreed reference measurement systems; Encouraging EQAS organizers to apply the agreed reference measurement systems. Details of JCTLM may be found at www.jctlm.org. The JCTLM database of reference materials, reference measurement procedures, and reference measurement services is freely available at www.bipm.org/jctlm .

Commutability is of considerable importance to JCTLM and its members. The listing of reference materials on the JCTLM database requires evidence of commutability. Consequently, the JCTLM has produced educational resources, based on the IFCC WG-C publications, that are freely available to its members and to all interested parties – including IFCC Members and individual laboratory medicine specialists. There are two resources: A special report entitled ‘Commutability of certified reference materials’. This report, prepared by Greg Miller and Neil Greenberg (US) on behalf of the IFCC WG-C, was published as an addendum to the 2018 JCTLM Newsletter; Two webinars have been prepared by Vincent Delatour (FR), a member of the IFCC WG-C and a member of the JCTLM WG for Traceability, Education & Promotion (WG-TEP). These two webinars, each lasting ~20 minutes, have been published on the IFCC e-Academy together with learning points. Multi-choice questions to test the understanding gained from the webinars will be available shortly. The webinars may be freely accessed as follows: • Commutability: why it matters http://eacademy.ifcc.org/events/jctlm-webinars/?ctype=1154&cid=1857 • Commutability explained http://eacademy.ifcc.org/events/jctlm-webinars/?ctype=1154&cid=1858

Conclusion The recent work of the IFCC WG-C has led to definitive publications on the clinically important topic of commutability. The JCTLM has produced freely available educational resources to aid understanding of commutability and its importance. This short article aims to encourage laboratory medicine specialists to improve their own understanding of commutability and to encourage peers, trainees and students to do the same. By insisting on methods that contain commutable reference materials / calibrators and by using commutable EQA specimens laboratory medicine specialists can make an important contribution to harmonisation and patient safety. References: 1. Miller WG, Myers GL. Commutability Still Matters. Clin Chem 2013; 59: 1291-1293 2. Miller WG, Schimmel H, Rej, R, Greenberg N, Ceriotti F, Burns C, Budd JR, Weycamp C, Delatour V, Nilsson G, Mackenzie F, Panteghini, M, Keller T, Camara JE, Zegers I, Vesper HW. IFCC Working Group Recommendations for Assessing Commutability. Part 1: General Experimental Design. Clin Chem 2018; 64(3): 447-454 3. Nilsson G, Budd JR, Greenberg N, Delatour V, Rej R, Panteghini M, Ceriotti F, Schimmel H, Weycamp C, Keller T, Camara JE, Burns C, Vesper HW, Mackenzie F, Miller WG. IFCC Working Group Recommendations for Assessing Commutability. Part 2: Using the Difference in Bias between a Reference Material and Clinical Samples. Clin Chem 2018; 64(3): 455-464 4. Budd JR, Weycamp C, Rej R, Mackenzie F, Ceriotti F, Greenberg N, Camara JE, Schimmel H, Vesper HW, Keller T, Delatour V, Panteghini M, Burns C, Miller WG. IFCC Working Group Recommendations for Assessing Commutability. Part 3: Using the Calibration Effectiveness of a Reference Material. Clin Chem 2018; 64(3): 465-474 5. Young IS. The Enduring Importance and Challenge of Commutability. Clin Chem 2018; 64(3): 421-423 LabMedica International August-September/2018

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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IFCC DQCML Visit to Malawi: A Field Report by Egon Amann, Chair of DQCML he Malawi Association of Medical Laboratory Scientists (MAMLS) became a Full Member of IFCC during 2015. Shortly after joining IFCC, MAMLS expressed a wish for support from IFCC to help develop the quality of laboratory medicine in Malawi. A scoping visit by Graham Beastall took place in 2016, in which particular needs were identified and specified in a detailed report. In November 2017, after additional discussions at the occasion of the IFCC WORLDLAB Conference in Durban in October 2017 with the people concerned, MAMLS issued a request for an IFCC DQCML (Developing Quality Competence in Medical Laboratories) workshop in Malawi. Two major topics were listed in this application: Training of Medical laboratory professionals on quality process and practice. Helping the society plan and strategize on how to execute an EQA pilot project in Malawi. The application was approved by the EMD Executive Committee and DQCML started to prepare the visit and assessed how best IFCC may assist MAMLS. The program for the visit was discussed in advance with the following MAMLS’ members, who were our hosts and extremely helpful and open in the preparation and execution of this visit: Victor Makwinja, MAMLS Interim President, Elias Chipofya, National Representative, Humphries Malata, Training and Education Technical Advisor to MAMLS council, and Wakisa Kipandula, MAMLS project coordinator.

The workshops The visit to Malawi took place from 26 February to 1 March 2018. The visiting team consisted of Egon Amann, Graham Beastall, and Annette Thomas, each of whom covered special topics for two (identical) workshops held in Blantyre at the College of Medicine (Day 1) and Lilongwe, Malawi’s capital, at the Kamazu College of Nursing, part of the Medical Department (Day 3). Day 1 and Day 3 were devoted for presentations and workshops, divided into three sessions, including lectures on QC and EQA and a “Lessons Learnt” presentation given by Ronald Khunga who completed an IFCC-funded PMEP at the EQA scheme run by neighboring Zimbabwe (ZINQAP). For the interactive workshop “What is the best strategy to achieve compliance with QMS and QC requirements in the clinical laboratory?” the participants (38 in Blantyre and 16 in Lilongwe) were divided into groups to discuss and articulate the most burning issues of clinical laboratories in Malawi. An example is given for the results developed by the Blantyre workshop: Group 1: Quality monitoring inadequate, Too intensive Governmental control of labs, Missing freedom to act, Even National Labs not being accredited, Insufficient training of personnel. Group 2: Insufficient inventory management, Documentation and document control, Equipment maintenance not done properly, EQA National labs: not trustworthy. Group 3: Internal quality control not always correctly applied, EQA materials supply logistics inadequate, Trained staff have high workload and must do everything, No CAPA system in place, Missing instrument maintenance & servicing. Group 4: Knowledge gap from policy makers to labs workers, Insufficient supply of reagents and QC, Too ambitious government body plans – reality miss, No real interest and push for EQA from government, Bad commitment from lab staff / no reward system.

The Laboratory Visit Tour On Day 2, five public sector District Hospitals (Zomba, Machinga, Balaka, Ntcheu, and Dedza) were visited along the way from Blantyre to Lilongwe (The “Laboratory Visit Tour”), which allowed the visitors a deep and detailed insight into daily routines, practices and issues of these rural, hospital-associated clinical laboratories. We were welcomed in all laboratories and shown around. Questions were openly answered. Instead of describing the impressions of each laboratory separately, a selection of common themes (examples) and situations are summarized: Laboratories are very small in size, variety and number of assays and endowment. Personnel number is small and varies between 5-8 staff. Laboratories primarily serve the hospitals in-patients, and also (in smaller percentage) out-patients.

LabMedica International August-September/2018

Photo: Visit to Ntcheu District Hospital Laboratory. Left to right: Next to Annette Thomas is Ronald Khunga (Laboratory Manager for Thyolo District Hospital Lab), Alice Kamwamba (Lab Manager for Ntcheu District Hospital Lab), Symon Naype (Laboratory Manager for College of Medicine Pvt Clinic) and lastly Daniel Lawadi Banda (Senior Lecturer in Medical Microbiology, College of Medicine, University of Malawi). Graham Beastall, IFCC past President Egon Amann, DQCML Chair, complete the group.

Phlebotomy areas were very small and not always in good shape and hygienic standards. No laboratory displayed a fully developed LIMS system. Some labs used a four-digit system to assign and identify patients’ samples. Most labs just used the patient’s name as ID. Instrument maintenance and servicing is poor: we saw often signs reading “Out of order since…” Blood-group matching (in transfusion medicine) could often not be done, because fridges and freezers were not in operation. The labs often experience power outages. Few have generators, and in case they have, diesel may not be available. Some labs have large battery packs, which allow to bridge power outages for instruments affected for approximately four hours. Tests of major public health importance are: Malaria, HIV, and TB. The three major test (some of which are POC tests / Test strips) are sponsored by international organizations such as US Aid, the Bill Gates foundation, the CDC, amongst others. For those tests, some labs employ EQA schemes. Only one Lab performed blood glucose tests (by POCT). No glomerular filtration rates are measured. Often QC/EQA could not be done since QC materials did not arrive on time.

Visit Summary This visit of IFCC officers by request of MAMLS was extremely useful. MAMLS expressed their thanks and explained that the two workshops have raised their attention towards improved IQC and, even more importantly, towards implementing EQA schemes for all tests being performed in Malawi. So far, EQA is done by the National EQA institute only for Malaria, HIV and TB. MAMLS should intensify their activities to the Ministry of Health towards country-wide, general EQA schemes. In brief, such activities should include, but are not limited to the following strategic plan: Develop an EQA establishment work place. Establish an EQA technical Working Group. Inform (and involve where necessary and appropriate) all labs and MAMLS members accordingly. Raise attention to the EQA schemes by workshops or seminars. MAMLS must influence the education curriculum by highlighting the meaning of IQC and EQA. MAMLS should influence the education curriculum by raising attention to risk management tool, e.g. FMEA. MAMLS should develop programs to enable labs to “move up the Quality ladder” by applying SLIPTA, SLMTA schemes. The final goal must be to achieve accreditation according to ISO 15189. The IFCC visitors would like to express their thanks to MAMLS for this invitation to come to Malawi. We wish you all the best in working towards (and reaching) these ambitious goals in the medium term.

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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IFCC WG-PCT: Towards Standardization of Procalcitonin Assays by Vincent Delatour, Amandine Boeuf; Laboratoire National de Métrologie et d'Essais (LNE), 75015 Paris, France arly identification diagnosis and appropriate therapy of severe sepsis remains a real challenge in intensive care units. Despite new therapies and guidelines developed over the past decade, sepsis incidence and mortality remain high. Severe sepsis is the first cause of death in the non-coronary intensive care unit where the mortality rate generally ranges from 30% to 60%. Every year in the US, severe sepsis strikes about 750,000 people resulting in 100,000 deaths, making it the tenth-leading cause of death in the US. Due to the aging of the population, the increasing number of immunocompromised patients, the use of invasive procedures and the use of antibiotics which encourages the growth of drug resistant microorganisms, the incidence of severe sepsis in the US is expected to rise and reach close to one million in the upcoming years. Thus, early recognition of sepsis and timely initiation of appropriate therapy are key steps for survival faced with these potentially devastating conditions. In addition to the medical consequences on patient, it also places an enormous strain on the healthcare system. The annual cost of treating sepsis is a staggering $16.7 billion in the US and 5 billion Euros in Germany (Angus et al. Crit Care Med. 2001;29(7):130310). Therefore, both the medical and the health-economic problems of sepsis are in the focus of the medical community. The intensive care specialists took the challenge to overcome the current situation and to reduce significantly sepsis mortality by implementing evidence-based clinical standards for diagnosis and treatment of sepsis worldwide. Subsequently, Procalcitonin (PCT) has demonstrated its major utility in medical and emergency medicine practice (Assicot et al. Lancet. 1993;341(8844):515-8). According to its selectivity and specificity of severe bacterial/parasitic infections (sensitivity 93%, specificity 96%), PCT is increasingly recognized as the most promising early biomarker for risk stratification of progression to severe sepsis or septic shock. Since PCT concentration does not increase during non-infectious inflammatory reactions contrary to C-reactive protein (CRP), its diagnostic relevance is superior to that of CRP. Indeed, high PCT levels allow the early identification of patients prone to develop severe sepsis or septic shock. The medical area application of PCT is rather broad as its measurement not only includes discrimination between inflammatory disease and infectious complication or between bacterial/parasitic and viral infection, but also allows assessing antibiotic treatment efficiency. Based on more than 500 trials, PCT obtained a valuation according to the criteria of evidence-based medicine. Particularly, some interventional trials showed the possibility of guiding antibiotic treatment with PCT measurements in patients with infections of the lower respiratory tract. Lower respiratory tract infections account for almost 10% of the worldwide burden of morbidity and mortality. About 75% of all antibiotic doses are prescribed for acute respiratory-tract infections, despite their mainly viral cause (Macfarlane et al Lancet. 1993;341(8844):511-4.). This inappropriate use of antibiotics is believed to be a main cause of the spread of antibiotic-resistant bacteria (Wenzel et al. Clin Infect Dis. 1999;28(5):1126-7). Thus, PCT measurements have a key role to play in the reduction of the excessive use of antibiotics and is essential to combat the increase of antibiotic-resistant microorganisms (JAMA. 1999; 28;281(16):1512-9, Clin Infect Dis. 2001;33(4):542-7). In 2004, a clinical trial involving more than 200 patients with suspected infections of the lower respiratory tract (e.g. pneumonia, chronic obstructive pulmonary disease, Bronchitis) and utilizing PCT as a decision biomaker allowed to reduce by 50% the antibi-

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otic prescriptions (Christ-Crain et al. Lancet. 2004;363(9409):600-7). In another interventional trial including more than 200 patients with community acquired pneumonia (CAP) and guiding the antibiotic treatment with PCT measurements allowed to shorten the duration of antibiotic treatment from 13 days to 5 days (Christ-Crain et al. Am J Respir Crit Care Med. 2006;174(1):84-93). Since the cost of daily PCT measurement is about 10 times lower than that of a broad-spectrum antibiotherapy (10€ vs. 115€), the use of PCT obviously leads to substantial savings. When an antibiotic-based treatment is needed, PCT demonstrated its interest to monitor its efficiency and adapt posology since sepsis-related raised PCT levels are closely linked to the magnitude of host systemic inflammatory response to microbial invasion. A 50% reduction of PCT concentration per day over several days has been shown to be an indication for success of therapeutic intervention (surgery, antibiotic treatment). Persisting high or further increasing PCT levels, indication for non-controlled infectious process, justify a re-assessment of therapeutic strategy. Overall, having reliable PCT measurements is of major interest for the accurate identification of bacterial infections in patients presenting at the emergency department to allow early and rational antibiotic treatment. The first PCT assays were based on manual immunochemistry methods (Brahms PCT LIA). These assays have been replaced by fully automated immunochemistry methods (Brahms Kryptor, Diasorin Liaison, Biomerieux Vidas, Siemens Advia, Roche Cobas, Abbott Architect, Beckman AU, Radiometer AQT90 FLEX). Although results provided by most of these methods are traceable to the Kryptor designated reference method, results of different EQA schemes suggest that method comparability is quite poor (eg. 2015 French Mandatory EQAS in which a 1720% between–methods RSD was observed). In the absence of any higher order reference method or reference material for PCT measurements, this situation can only worsen with the inevitable onset of new techniques in response to the increasing demand for PCT testing in the intensive care unit environment. However, other studies come to the opposite conclusion (Dipalo et al. Pract Lab Med. 2015;2:22-28), suggesting that commutability of EQA materials could be questionable. To address this issue, IFCC WG-PCT will address the following objectives: (1) Develop and validate a reference measurement procedure for PCT absolute quantification by isotope dilution mass spectrometry (IDMS) in order to establish metrological traceability of results to the SI Units: Agreement on measurand(s) Produce and characterize a primary calibrator for PCT; Develop separation methods to purify PCT in biological samples; Assess recombinant PCT and/or synthetic peptides as possible primary calibrators; Develop and validate a candidate reference measurement procedure for absolute quantification of PCT by IDMS. (2) Document and understand the variability of results provided by the different commercially available PCT assays : Produce candidate EQA materials consisting in various matrices; Organize a commutability study aiming at assessing suitability of various EQA materials to assess comparability of results provided by the different PCT assays; Organize an EQA scheme relying on commutable EQA materials to document the state of the art on the results provided from the different PCT assays used in clinical practice; Investigate the sources of variability between PCT assays; Make a decision whether standardization is needed or not. (3) Evaluate the feasibility for standardization of PCT assays through common calibration with commutable calibrators value assigned with the SIDMS reference measurement procedure; (4) If standardization of PCT assays appears desirable and feasible: Produce commutable calibrators value assigned with the IDMS reference measurement procedure; In cooperation with assays manufacturers, effectively recalibrate PCT assays; Using commutable EQA materials, assess accuracy and comparability of PCT assays before and after recalibration with commutable calibrators; Evaluate the impact of assays recalibration and the need to revise clinical decision limits that are currently used in clinical practice. LabMedica International August-September/2018

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

NEWS

Romanian Society Holds 2nd National Congress in Bucharest by Assoc. Prof. Dr. Ioana Brudașcă, RALM president Photo: (From left to right) Prof Evi Lianidou, Prof Janos Kappelmayer, Prof Mauro Panteghini, RALM pres-

he 2nd Romanian Association of Laborato- ident Ioana Brudasca ry Medicine (RALM) Congress was held Four applications were submitted, which were reagents, supplies, software was organized by between on 9-12 May 2018 in Bucharest. The evaluated by experts, and the winner of the com- 20 companies. There were also 13 workshops congress was organized under the auspices of petition (dr. Adina Hutanu from the University of organized by IVD providers, which were an exIFCC and EFLM and in collaboration with the Medicine and Pharmacy of Târgu Mureș) was cellent opportunity for the development and Romanian Society of Microbiology, the Romantransfer of technical innovations to clinical labannounced at the General Assembly. ian Society of Hematology and the Universities Conference abstracts were published in a oratory professionals. of Medicine and Pharmacy of Bucharest, Târgu The scientific quality and the diversity of the supplement of Romanian Journal of LaboratoMures, Cluj Napoca, Iași, Timisoara. presentations, the excellent organization, as ry Medicine. The congress was attended by over 650 parAs our profession is in a permanent partner- well as the attracting social programme fully ticipants (medical doctors, scientists and lab ship with the clinical diagnostic industry, during contributed to the success of this scientific and technicians working in medical laboratories). the congress an exhibition of equipment, professional event. Four speakers from abroad were invited to the congress: Prof. Mauro Panteghini (Italy), Prof. Evi Lianidou (Greece), Prof. Janos Kappelmayer NE DES W (Hungary) and Prof. William Au (ChiIGN na). Most of the Romanian speakers were teachers at the medical faculties of Bucharest, Cluj Napoca, Târgu Mureș, Timisoara, Iași. The lectures of the keynote speakers proWORLD’S MEDICAL PRODUCT MARKETPLACE vided up-to-date information about various aspects (high sensitivity troponin, liquid biopsy, laboratory monitoring of direct oral anticoagulants, clinical value of genetic testing, inSIGN UP flammatory cytokines, etc). FOR FREE! As in Romania laboratory medicine encompasses a large area of subspecialties, the scientific programme covered themes in clinical chemistry, microbiology, haematology, genetics, molecular biology, immunology, presented in 41 posters, 17 short oral communications and 22 plenary reports. The posters and the slides for the oral presentations were written in English. Many of the presentations focussed on continuous professional development for laboratory professionals, quality assessment, standardization, technology, instrumentation and method evaluation, performance criteria of laboratory tests, showing the interest of the participants in the improvement of our professional activity. During the discussions that followed the presentations, the participants had the opportunity to share their experience and to identify soConnecting Buyers with lutions for the scientific or technical issues they are confronted to in Suppliers Worldwide their everyday practice. Reach new sources of supply As our RALM is very interested Identify latest products and technologies in motivating young laboratory proSend inquiries directly to suppliers fessionals, many communications Receive latest product alerts and posters were presented by Chat live with suppliers young colleagues, most of them PhD fellows. Two awards were granted, one for the best poster, TradeMed provides a sophisticated yet easy-to-use global B2B platform for sourcing medical and one for professional activity. equipment. TradeMed connects buyers and sellers worldwide through a safe, secure and dyRALM also initiated this year an innamic network. Solely dedicated to medical products, TradeMed is the premier choice for medternal grant competition for young ical suppliers, hospital decisionmakers and buyers worldwide, regardless of size or budget. scientists, consisting in 3000 euros.

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VIEWPOINT

Making the Link: Migrants, Refugees and Lab Medicine by Dr. Bernard Gouget Counselor for Public Health FHF; Chair-IFCC Committee on Mobile Health and Bioengineering in Laboratory Medicine (C-MHBLM), SFBC-International Committee; General Secretary of the International Francophone Federation of Clinical Biology and Laboratory Medicine (FIFBCML), Chair-Human Health Care Committee-COFRAC

ore than ever before, people are on the move. According to the Hellenic Centre for Disease Control and Prevention (HCDCP), a migrant is described as someone who makes a conscious, voluntary choice to leave his/her country of origin and who, voluntarily, can return home in safety. A refugee is defined as the person who does not have this option and is formally owed protection, including access to health services, from the first country of registration of asylum, where the asylum claim has been accepted. An asylum seeker is the person whose claim for refuge is under consideration. Immigration is reshaping societies and it is one of the great challenges of the globalized world. People fleeing conflict and poverty in Africa and the Middle East are still making the dangerous journey by land or by sea to Europe. Two years after sparking an unprecedented humanitarian and political crisis, the largest influx of refugees and migrants into Europe since World War II, seems to be slowing down, according to the International Organization for Migration (IOM). 172,000 people, mostly escaping from conflict in the African and Mediterranean region, crossed the Mediterranean into Italy, Greece, Cyprus and Spain in 2017, compared to more than 363,000 in 2016. Also decreasing is the number of deaths in the Mediterranean significantly from 5,143 to 3,118. If major policies have partially successfully stemmed the flow of migrants into Europe, this has been nothing short of controversial. A slowdown in the European migrant crisis is undoubtedly a relief, especially for host countries. But numbers do not show the whole picture. Migration is still deadly for too many, and for those who survive, it is no better than the unbearable conditions they fled from. However, too much remains to be done to reach the ultimate goal which is to facilitate orderly, safe, regular and responsible migration and mobility of people, including through the implementation of planned and well-managed migration policies, according to one of the targets of Sustainable Development Goal 10 by the United Nations, which aims to reduce inequality. Nicole Scholz from the European Parliamentary Research Service considers that migration itself does not count as a risk factor for health

eJIFCC Vol 29 n°2: Laboratory Investigation of Vitamin D and Bone Metabolism Markers The second issue of eJIFCC for 2018 is now available. Guest edited by Dr Harjit Pal Bhattoa (Department of Laboratory Medicine, University of Debrecen, HU), it focuses on Laboratory Investigation of Vitamin D and Bone Metabolism Markers. Given the pandemic of vitamin D insufficiency experienced on a global scale it is important to understand the laboratory implications pertaining to the determination of this not so easily measured analyte. The articles in the current issue consider the many aspects related to Vitamin D. Three further articles complete the edition.

IFCC Handbook 2018-2020 Released We are happy to announce that the 2018 - 2020 edition of the IFCC Handbook is now available. A valuable resource, the Handbook contains comprehensive information about the function and operation of IFCC, including IFCC Regional Organizations, Divisions, Committees and Working Groups; Full Members, Corporate Members and Affiliate Members; contact details; and Statutes and Rules of the IFCC. Read all the updated information about the function and operation of IFCC in a single online publication!

as migrants are often comparatively healthy. But the circumstances of migration are often associated with physical, mental and social health disorders. Throughout the process of migration, several aspects may have a negative influence on the health of migrants: predeparture traumas due to suffering from war, conflict, violence, torture, etc.; and during the journey due to the travel mode, and its duration. The most commonly reported problems are hypothermia, gynaecological and obstetric complications, gastrointestinal and respiratory illnesses, dermatological, cardiovascular events, metabolic problems and mental and psychosocial illness as well as accidental injuries, small wounds, burns, dehydration and musculoskeletal problems. Once in host countries, the migrants are often met with substandard or inhumane conditions, uncertainty and instability. Women and young people are vulnerable to sexual violence. They are living on the margins of society because of an inadequate reception system and harmful border policies. This situation combined with language and administrative barriers, makes it extremely difficult for them to access social services and health care, as well as the basics, such as potable water, food and electricity. The poor hygienic conditions increase the risk of communicable diseases such as water- and food-borne diseases (salmonellosis, hepatitis A, Cholera). Crowded settings can lead to a higher risk of infections transmitted by the bite of infected arthropods (mosquitoes, sandflies, lice, ticks, fleas, etc.), such as malaria, leishmaniasis, relapsing fever, rickettsial diseases and typhus. The poor living conditions in crowded refugee centres are associated with respiratory infections: influenza, respiratory syncytial virus, adenovirus. WHO is supporting provision of influenza vaccine to risk groups, irrespective of legal status. The risk for acquiring tuberculosis or being infected depends on factors such as the incidence in their own countries. The risk of HIV importation is low but some migrants acquire HIV after their arrival. Sub-saharan Africans have the highest sero-prevalence of chronic HBV. The health of those who are suffering from chronic diseases such as cardiovascular diseases, diabetes, or cancers can increase the vulnerability because of the loss of medication and of psychological strain. Mental aid is important, many of them have endured physical and emotional trauma and torture. Children, pregnant women and the elderly are particularly susceptible. There is an urgent need to address the public health consequences and this therefore requires an adequate response from the health players and from the governments. Prof Sergio Bernardini, President SIBioC (Italy) organized on July 24, with the IFCC, EFLM, AFCB and FIFBCML representatives the first conference on ”Meeting the needs of Mediterranean countries” at the Tor Vergata University-Roma. This event attracted over 270 attendees and 85 Posters. During two days, it was possible to highlight the value of lab medicine for a greater effectiveness in access to healthcare for the migrants. This conference was “the” place of scientific exchange of knowledge, information and good practices where progress can be made related to priority aspects of migrant health, as well as emphasizing the positive impact of the medical laboratory in the management and their follow up. Initiatives from medical biologists colleagues, who collaboratively developed locally relevant projects addressing migrant and refugee health in Italy, Greece, Syria, Lebanon, Jordan, Algeria, Tunisia, Morocco, were welcomed and encouraged. The right of everyone to enjoy the highest attainable standard of physical and mental health is established in the WHO Constitution of 1948. Our understanding of fundamental freedoms and human rights, our concept of what it means to be human; all these things know no borders, whether these are borders of countries or continents. In this sense, we also bear responsibility for what happens in the rest of the world. The scale of the migratory challenge requires collaborative actions between states, international organizations and cooperation between different disciplines and health sectors. The desire to emigrate is today so strong that the reality of migration represents the future of our new world. It is a global challenge that requires a strong response from the international community. That is precisely why a second edition of this type of conference is important to connect between migrants, refugees, lab medicine and healthcare needs. It is essential to help build healthier communities and tackle health inequalities. LabMedica International August-September/2018

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Industry News

DIAsource in Alliance with ZenTech for RIA Products IAsource Immunoassays (Brabant Wallon, Belgium; www. diasource.be), a BioVendor group company, has entered into a strategic agreement with ZenTech (Angleur, Belgium; www.zentech.be) under which ZenTech will transfer its portfolio of radioimmunoassays (RIA) products to DIAsource, securing their continued production and sales. DIAsource ImmunoAssays is a diagnostics company specialized in the development, manufacturing, and sales and distribution of immunoassay tests and open instrumentation solutions for clinical diagnostics. It delivers manual RIA and ELISA kits and open automation solutions to the international markets, and has a portfolio of over 190 ELISA and 140 RIA assays. ZenTech specializes in the development, production and commercialization of solutions for clinical diagnostics of early life stage diseases and newborn screening. It has a broad portfolio of

products in prenatal, neonatal and pediatric screening and offers complete and flexible solutions to set up the screening activity. Both the companies have long standing collaborations for more than 15 years, with DIAsource already successfully managing a part of the commercialization of the ZenTech portfolio. The current transfer of RIA products from ZenTech to DIAsource is in line with their strategies. The portfolio to be transferred includes the complete line of special RIAs with thyroid markers and markers for fertility and salt balance. Effective July 24, 2018, DIAsource Immunoassays has assumed commercial ownership of ZenTech’s RIA product portfolio and will service clients from order to shipment, while ZenTech will remain the manufacturer during the transition period in which the production will be transferred to DIAsource. The transfer of production will be done in close collaboration and in phases to be concluded by September 30, 2019.

Global Critical Care Diagnostics Market Foreseen at USD 1.3 Billion by 2024 he global critical care diagnostics (CCD) market is estimated to have been valued at USD 837.6 million in 2015 and is expected to reach USD 1.3 billion by 2024, driven by increasing awareness among physicians, patients’ requirements for cost-efficient, rapid, and accurate diagnostic tests, and technological advancements. However, the high costs of these tests and scarcity of skilled labor for handling new platforms pose a challenge to the market growth. These are the latest findings of Grand View Research, Inc. (San Francisco, CA, USA; www.grandviewresearch.com), a market research and consulting company. CCD tests deal with the specialized care and diagnosis of life-threatening diseases occurring in patients. Being cost-effective and easy-to-use with rapid and accurate diagnosis, they are used in emergency rooms, operating

Infectious Diseases to Continue Driving Diagnostic Testing he global market for infectious disease products is expected to record a 60% higher growth than the overall world market for in vitro diagnostics, with tests for infectious diseases representing more than one-fourth of the entire testing market. These are the latest findings of Kalorama Information, (New York, NY, USA; www. kaloramainformation.com), an independent medical market research firm. Currently, almost one-third of the revenue earned from clinical testing products come from products that detect infectious diseases. Influenza, molecular HPV, emerging infectious disease testing and mycology are the fastest growth segments. Other key segments include TB, HIV, hepatitis, Strep A, malaria, blood screening, STDs, ID/AST, rapids, HAI and other test products. Governments across the world are according the highest priority to infectious diseases in their healthcare provision. Public health officials have realized that infectious diseases are no longer a problem of just the developing countries, but also affect the social and economic welfare of industrialized countries. The globalized world market exposes far-apart populations to infectious diseases and exacerbates disease outbreaks. The potential for re-introduction of eradicated or controlled infectious diseases is at an all-time high and pathogen drug resistance is a problem being faced across the world that calls for a global response. Meanwhile, payers in industrialized countries are being encouraged and have become receptive to expanding the coverage of infectious disease testing and screening. Although preventive testing services are traditionally associated with “lifestyle” or non-communicable diseases, infectious disease tests can also be considered under preventive services. Latent or asymptomatic diseases can progress into severe chronic conditions, creating challenges in healthcare funding and contributing significantly to national healthcare spending. As a result, increasingly sensitive and accurate infectious disease diagnostics are vital for implementing therapy at an earlier stage during infection to control rising treatment costs.

LabMedica International August-September/2018

rooms, and intensive care units (ICUs) around the world. The CCD segment accounts for a share of 2-3% of the in-vitro diagnostic market. The demand for CCD tests has been increasing due to growing awareness among patients about better healthcare options and increasing knowledge of target therapy among physicians. Based on type, the CCD market is being driven mainly by the clinical chemistry, flow cytometry tests, and coagulation tests segments. The immunoproteins segment is estimated to account for the largest share of the CCD market, in terms of value, due to a rise in the demand for rapid and accurate early diagnosis as well as the ability to reduce the recovery time of patients. However, microbiology and infectious tests along with immunoproteins assays are estimated to drive the CCD market, by type, during the forecast period.

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SEPTEMBER 2018 Eurotox 2018 – 54th Congress of the European Societies of Toxicology. Sep 2-5; Brussels, Belgium; Web: www.eurotox-congress.com ESP 2018 – 30th European Congress of Pathology. Sep 9-12; Bilbao, Spain; Web: www.esp-pathology.org MSACL 2018 EU – 5th Annual European Congress & Exhibits for Clinical Mass Spectrometry. Sep 11-13; Salzburg, Austria; Web: www.msacl.org ESCV 2018 – 21th Annual Meeting of the European Congress of Virology. Sep 23-26; Athens, Greece; Web: www.escv.org ESPE 2018 – 57th Annual Meeting of European Society of Paediatric Endocrinology. Sep 27-29; Athens, Greece; Web: www.espe2016.org BSACI 2018 – British Society of Allergy & Clinical Immunology Annual Meeting. Sep 30-Oct 2; Telford, UK; Web: www.bsaci.org OCTOBER 2018 ASHI 2018 – 44th Annual Meeting of the American Society for Histocompatibility and Immunogenetics. Oct 15; Baltimore, MD, USA; Web: www. ashi-hla.org ASCP 2018 – American Society for Clinical Pathology. Oct 3-5; Baltimore, MD, USA; Web: www.ascp.org BCLF 2018 – Meeting of Balkan Clinical Laboratory Federation. Oct 3-5; Skoplje, Macedonia; Web: www.bclf.info 5th Joint EFLM-UEMS Congress Lab-

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Events Calendar date 2019. Feb 11-15; Kohala Coast, HI, USA; Web: ce.mayo.edu 14th Annual Biomarkers Congress. Feb 21-22; Manchester, UK; Web: www.biomarkers-congress.com CHINALAB 2019. Feb 26-28; Guangzhou, China; Web: www.chinalabexpo. com

MARCH 2019 ARABLAB 2019. Mar 12-14. Dubai, UAE; Web: www.arablab.com KIMES 2019. Mar 14-17; Seoul, Korea; Web: www.kimes.kr PITTCON 2019. March 17-21; Philadelphia, PA, USA; Web: pittcon.org 5th EFLM-BD European Conference on Preanalytical Phase. Mar 22-23; Zagreb, Croatia; Web: www.preanalytical-phase.org ENDO 2019 – Endocrine Society. March 23-26; New Orleans, LA, USA; Web: www.endocrine.org MEDLAB Asia Pacific. March 27-29; Singapore; Web: www.medlabasia.com ExpoMED Eurasia 2019. Mar 28-30; Istanbul, Turkey; Web: expomedistanbul.com APRIL 2019 AIUM Annual Convention 2019 – American Institute of Ultrasound in Medicine. Apr 6-10; Orlando, FL, USA; Web: www.aium.org ECCMID 2019 – 29th European Congress of Clinical Microbiology and Infectious Diseases. April 13-16; Amsterdam, Netherlands; Web: www. eccmid.org World Vaccine Congress 2019. Apr 14-17; Washington, DC, USA; Web: www.terrapinn.com KoreaLab 2019. Apr16-19; Seoul, Korea; Web: www.korealab.org AACE 2019 – 28th Annual Meeting & Clinical Congress of the American Association of Clinical Endocrinolo-

gists. Apr 24-28; Los Angeles, CA, USA; Web: www.aace.com

MAY 2019 International Cytology Congress 2019. May 5-9; Sydney, Australia; Web: www.cytology-iac.org ISLH 2019 – International Society of Laboratory Hematology. May 9-11; Vancouver, Canada; Web: www.islh.org AAI Immunology 2019 – American Association of Immunologists. May 9-13; San Diego, CA, USA; Web: www. aai.org CMEF Spring 2019 – China International Medical Equipment Fair. May 14-17; Shanghai, China; Web: www. cmef.com.cn ECE 2019 – 21st European Congress of Endocrinology. May 18-21; Lyon, France; Web: www.ese-hormones.org 23rd IFCC/EFLM EuroMedLab. May 19-23; Barcelona, Spain; Web: www. euromedlab2019barcelona.org Hospitalar 2019. May 21-24; Sao Paulo, Brazil; Web: www.hospitalar.com JUNE 2019 EAACI Congress 2019 – European Academy of Allergy & Clinical Immunology. Jun 1-5; Lisbon, Portugal; Web: www.eaaci.org BIO International Cnvention 2019. Jun 3-6; Philadelphia, PA, USA; Web: http://convention.bio.org ESGH 2019 – European Human Genetics Conference. Jun 15-18; Gothenburg, Sweden; Web: www.eshg.org FOCIS 2019 – Annual Meeting of the Federation of Clinical Immunology Societies. Jun 18-21; Boston, MA, USA; Web: www.focisnet.org ESHRE 2019 – 35th Annual Meeting of the European Society of Human Reproduction and Embryology. Jun 2326; Vienna, Austria; Web: www.eshre.eu

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