LabMedica International May 2019 by Globetech

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WORLD’S CLINICAL LABORATORY NEWS LEADER ISSN 1068-1760

Vol. 36 No.3 • 5/2019

DAILY CLINICAL LAB NEWS

Blood Test Detects Severe Transplant Rejection ung transplant recipients have the shortest survival rates among patients who get solid organ transplantation of any kind, as only about half live past five years. Lung transplant recipients face a high incidence of chronic rejection, which occurs when the

Inflammatory Bowel Disease Linked to Prostate Cancer bout one million men have inflammatory bowel disease in the USA, a common chronic condition that includes Crohn’s disease and ulcerative colitis. Epidemiologic studies have noted an association between chronic inflammation and prostate cancer.

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Prostate cancer is cancer that occurs in the prostate, a small walnut-shaped gland in men that produces the seminal fluid that nourishes and transports sperm. Prostate cancer is one of the most common types of cancer in men. Usually prostate cancer grows Cont’d on page 16

Blood Test Detects Alzheimer’s Before Symptoms Appear

Image: Courtesy of iQ Group Global

n international team of researchers identiA fied ten protein features

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Simple Inexpensive Test For Esophageal Cancer ancer of the esophagus claims more than 400,000 lives around the world each year. With no efficient, reliable method of screening for the disease, by the time symptoms become apparent, it’s often too late to save the patient. In 2016, the USA saw nearly 17,000 new cases diagnosed and about 16,000 deaths from cancer of the esophagus. Those numbers

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Bile Acid Blood Test Predicts Stillbirth Risk

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Newborn Cytomegalovirus Test Cleared for Marketing

INSIDE

ytomegalovirus or CMV is a common virus that infects people of all ages. In the USA, nearly one in three children are already infected with CMV by age five and over half of adults by age 40

Clinical News . . . . . . 4-42 IFCC Annual Report . . 19 IFCC News . . . . . . . . . . 43 Product News . . . . . 6-42 Industry News . . . . . . 49 Events Calendar . . . . . 50

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Cancer-Associated Circular RNAs Catalogued Across Tumors

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ntrahepatic cholestasis of pregnancy (ICP) is caused by a build-up of bile acids in the blood, and symptoms include pruritus. ICP is a liver disorder affecting approximately 5,300 pregnancies annually in the UK, more than 14 every day. ICP is diagnosed in women with gestational pruritus and increased serum bile acids, and can be complicated by preterm labor,

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to form a biomarker panel for Alzheimer's Disease before the appearance of any symptoms. By differentiating future Alzheimer's patients from among cognitively unimpaired individuals, such a blood test would be of key benefit toward coping with the disease.

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ircular RNA is a type of RNA which, unlike the better known linear RNA, forms a covalently closed continuous loop, i.e., in circular RNA the 3’ and 5’ ends normally present in an RNA molecule have been joined together. Circular ribonucleic acids (cir-

cRNAs) are an intriguing class of RNA due to their covalently closed structure, high stability, and implicated roles in gene regulation. Scientists have begun to catalogue and have started characterizing circRNAs found across cancer types, including proposed circRNA Cont’d on page 4

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Bacterial Pathogen Discovered in Brains of Alzheimer’s Patients lzheimer’s disease (AD) patients exhibit neuroinflammation consistent with infection, including microglial activation, inflammasome activation, complement activation, and altered cytokine profiles. Infectious agents have been found in the brain and postulated to be involved with AD, but robust evidence of causation has not been established. The recent characterization of amyloid-β (Aβ) as an antimicrobial peptide has renewed interest in identifying a possible infectious cause of AD. An international team of scientists including those from the University of Louisville School of Dentistry (Louisville, KY, USA; www.louisville.edu) investigated the prevalence of Porphyromonas gingivalis in the AD brain and to elucidate possible P. gingivalis–dependent mechanisms of action for neurodegeneration and AD pathology. P. gingivalis is mainly found during gingival and periodontal infections; however, it can also be found at low levels in 25% of healthy individuals with no oral disease. The team obtained human postmortem brain tissues and independent pathological analysis confirmed that any amyloid pathology was deemed normal for age in the control cases selected for this study. Human brain tissue microarrays (TMAs) comprised a total of 58 2-mm-diameter core samples, 29 from dementia-free control individuals and 29 from AD cases, each on two arrays. Gingipain antibodies were optimized initially on formalin-

fixed paraffin-embedded sections of gingival tissue collected from periodontal disease patients. Histological analysis was performed on an Olympus BX61 motorized microscope (Olympus, Tokyo, Japan; www.olympus lifescience.com). Several molecular techniques were used to identify other factors in the study. The study team found the organism’s toxic enzymes, or gingipains, in the neurons of patients with AD. Gingipains are secreted and transported to outer bacterial membrane surfaces and have been shown to mediate the toxicity of P. gingivalis in a variety of cells. The team correlated the gingipain levels with pathology related to two markers: tau, a protein needed for normal neuronal function, and ubiquitin, a small protein tag that marks damaged proteins. In animal models, oral P. gingivalis infection led to brain colonization and increased production of amyloid beta (Aβ), a component of the amyloid plaques commonly associated with AD. In preclinical studies the scientists demonstrated that by inhibiting the compound COR388, there was reduced bacterial load of an established P. gingivalis brain infection, blocked Aβ42 production, reduced neuroinflammation and protected neurons in the hippocampus, the part of the brain that mediates memory and frequently atrophies early in the development of AD. The study was published on January 23, 2019, in the journal Science Advances.

Cancer-Associated Circular RNAs Catalogued Across Tumors cont’d from cover

markers in the urine of prostate cancer patients. A team of scientists from the University of Michigan (Ann Arbor, MI, USA; https:// umich.edu) used exome capture and RNA sequencing to profile circRNAs in more than 800 tumors, cell line, or pooled normal samples assessed for the Michigan Oncology Sequencing Center (MI-ONCOSEQ) program. The analyses led to nearly 129,000 circRNAs in 40 cancer types, which they compared to more than 60,000 circRNAs previously compiled in the CircBase database. Along with circRNA expression data for more than two dozen matched tumor-normal pairs, the team’s cancer-associated circRNA collection known as MiOncoCirc, helped the team focus in on circRNAs associated with metastatic castration-resistant prostate cancer or aggressive neuroendocrine prostate cancer cases, as well as potential circRNA biomarkers found in urine samples from prostate cancer patients in general. The team used Agilent SureSelect exon capture probes (Agilent Technologies, Santa Clara, CA, USA; www.agilent.com) to target

nearly 21,000 genes and more than 334,000 exons in cDNA from 868 clinical samples, cell lines, and pooled normal tissue samples, following by sequencing with Illumina technology and identifying candidate circRNAs with an analytical pipeline called CIRCexplorer. When the team compared and validated this method against established Ribo-Zero sequencing and exoribonuclease RNase R-based enrichment approaches in a prostate cancer cell line, it found that the exome capture approach appeared to pick up some circRNAs missed by Ribo-Zero, while maintaining “circular-to-linear ratios” that cannot be gleaned with the RNase R method. The investigators used MiOncoCirc and identified candidate circRNAs to serve as biomarkers for prostate cancer and were able to detect circRNAs in urine. They further detected a novel class of circular transcripts, termed readthrough circRNAs that involved exons originating from different genes. MiOncoCirc will serve as a valuable resource for the development of circRNAs as diagnostic or therapeutic targets across cancer types. The study was published on February 7, 2019, in the journal Cell.

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ISSN 1068-1760 Vol.36 No.3. Published, under license, by Globetech Media LLC; Copyright © 2019. 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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Blood Test Detects Alzheimer’s Before Symptoms Appear blood-based assessment of preclinical disease would have huge potential in the enrichment of participants for Alzheimer’s disease (AD) therapeutic trials. Much effort has been dedicated to the discovery of single- and multianalyte protein markers to differentiate AD from agematched cognitively unimpaired individuals. Ultrasensitive immunoassay and immunoprecipitation mass spectrometry (MS) methods have recently reported plasma amyloid β (Aβ) ratios as being able to predict Aβ positron emission tomography (PET). However, there has been limited investigation using untargeted methods in the discovery of novel blood markers that could reflect Aβ burden. A large international team of scientists led by the group from King’s College London (London, UK; www.kcl.ac.uk) started by measuring protein group levels in blood samples from 238 (cognitively unimpaired) people participating in two Australian-based biomarker and aging studies. All of the donors had previously undergone PET scans to determine their Aβ status. The team then built a computer model to classify proteins and then analyzed data from participants in one of the biomarker and aging study groups with a machine-learning algorithm designed to learn to identify markers indicating preclinical Alzheimer’s disease. Then they tested the system on data from the second group of study participants. Some of the methodology used by the scientist included immunodepletion, enzymatic digestion, and tandem mass tag peptide labeling. Albumin and immunoglobulin G immuno-depletion was achieved by a commercially available ProteoPrep immunoaffinity column (Sigma-Aldrich, St. Louis, MO, USA; www.sigmaaldrich.com). Peptide separation was achieved using the 3100 OFFGEL Fractionator (Agilent Technologies, Santa Clara, CA, USA; www.agilent.com) with a 24-well setup. Liquid chromatography–tandem MS (LC-MS/MS) analysis, chromatographic separation and mass spectra acquisition was performed using the LTQ Orbitrap Velos Pro, (Thermo Fisher Scientific, Waltham, MA, USA; www. thermofisher.com). The team reported that preliminary testing showed the technique to be 90% accurate in matching results obtained from PET scan testing. They report also that their system found 10 protein features that together represent a biomarker, two of which had been identified as possibilities previously. The serine protease prothrombin (a precursor to thrombin) was the highest ranked feature in the cognitively unimpaired cohort. At the univariate level, prothrombin (or coagulation factor II) was shown to be decreased in Aβ+ individuals but had a modest effect size. Two protein groups were specifically associated with Aβ burden in cognitively unimpaired individuals (GPR115 and RPS6KA3). GPR115 was the second most important feature, after prothrombin, offering it as a potential

LabMedica International May/2019

marker of early Aβ deposition. The authors concluded that using an unbiased MS approach, they found and replicated with high accuracy, specificity, and sensitivity a plasma protein classifier reflecting Aβ burden in a cognitively unimpaired cohort. These predictive panels highlighted novel and established markers for AD. The study was published on February 6, 2019, in the journal Science Advances. Image: The 3100 OFFGEL Fractionator (Photo courtesy of Agilent Technologies).

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HBA1C TEST

IMMUNOASSAY ANALYZER

Erba Mannheim

Veda Lab

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Bile Acid Blood Test Predicts Stillbirth Risk cont’d from cover

fetal asphyxia, meconium-stained amniotic fluid, and stillbirth. It was previously thought that small increases in bile acid concentration are associated with higher risks of stillbirth. Pregnant women showing symptoms of ICP, therefore, are often offered early induction of labor at around 37 weeks in order to prevent stillbirth. A large team of international scientists collaborating with Kings College London (London, UK; www.kcl.ac.uk) analyzed more than 170,000 pregnancies from 40 international studies to understand the link between ICP, bile acid levels and stillbirth. The results of the study show that for the majority of women with ICP, who have bile acid concentration below 100 μmol/, the risk of stillbirth is not significantly greater than that of pregnant women without ICP. This means they need no further treatment other than regular bile acid blood tests for the remainder of their pregnancy. The scientists reported that stillbirth occurred in 45/4,936 (0.83%) of intrahepatic cholestasis of pregnancy cases and 519/163,947 (0.32%) of control pregnancies (odds ratio [OR] 1.46). In singleton pregnancies, still-

birth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve [ROC AUC] 0.83), but not alanine aminotransferase (ROC AUC 0·46). For singleton pregnancies, the prevalence of stillbirth was 3/2,310 (0.13%) of intrahepatic cholestasis of pregnancy cases in women with serum total bile acids of less than 40 μmol/L versus 4/1,412 (0.28%) of cases with total bile acids of 40–99 μmol/L (hazard ratio [HR] 2.35), and versus 18/524 (3.44%) of cases for bile acids of 100 mol/L or more (HR 30.5). Caroline Ovadia, BCh, a Clinical Lecturer and first author of the study, said, “This marks a real step forward in the diagnosis and management of liver disorders during pregnancy. Being able to measure the risks to women and their babies by simple tests allows doctors to concentrate treatment on those who really need it. It also means that women will not have to be offered preterm birth unnecessarily which comes with associated risks to their babies including admission to neonatal units, breathing problems and jaundice.” The study was published on February 14, 2019, in the journal The Lancet.

Blood Tests for Tuberculosis Could accelerate Diagnosis uberculosis (TB) is a bacterial infection affecting the lungs, causing cough, weight loss and fevers, and is spread through droplets from coughs and sneezes from infected patients. Diagnosing and treating the condition early is essential for the health of the patient as well as for preventing the spread of TB to others. There is therefore a need for rapid, convenient tests to rule out a TB diagnosis in suspected cases based on a blood sample. While laboratory cultures of patient samples, such as sputum or invasive biopsies, are used to confirm the presence of the bacterium, the cultures can take several weeks. A negative result does not rule out a diagnosis of TB, as the bacteria cannot be cultured from samples in a large proportion of TB patients. A team of British scientists working with the Imperial College London (London, UK; www.imperial.ac.uk) carried out a prospective study comparing existing commercially available interferon-gamma release-assays (IGRA) against new generation tests in 845 patients with suspected TB in 10 NHS hospitals in England. Patient blood samples were analyzed using both sets of tests, the results of which benchmarked against a confirmed diagnoses based on positive culture results. Patients were tested for Mycobacterium tuberculosis infection at baseline with commercially available assays: T-SPOT. TB (Oxford Immunotec, Abingdon, UK; www.oxfordimmunotec.com) and QuantiFERON-TB Gold In-Tube (Qiagen, Hilden, Germany; www.quantiferon.com)

and second-generation IGRAs incorporating novel M tuberculosis antigens, and followed up for six to12 months to establish definitive diagnoses. These new antigens are used in the generic ELISpot (enzyme-linked immunospot) platform technology on which the commercial T-SPOT.TB test is based. Sensitivity, specificity, positive and negative likelihood ratios, and predictive values of the tests were determined. Analysis of the rapid test results revealed that the second-generation test has a diagnostic sensitivity of 94% in patients with confirmed TB meaning it gives a positive result for 94% of patients with infection, significantly and substantially higher than either of the existing commercially available IGRA tests, which range from 67.3% and 81.4%. The findings indicate the test would be much more accurate at ruling out TB infection in suspected cases of TB, so saving time and resources and enabling patients to receive treatment more rapidly. Ajit Lalvani, DM, a professor of Infectious Diseases and a co-author of the study, said, “Tens of thousands of patients undergo diagnostic assessment for symptoms suggestive of TB, resulting in over 5,000 cases of TB diagnosed each year. Stopping the use of the existing, inadequate tests could save the NHS a lot of money. In contrast, the new, more accurate rapid blood test will improve and accelerate diagnostic assessment of patients with suspected TB.” The study was published on January 14, 2019, in the journal Lancet Infectious Diseases. LabMedica International May/2019

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LabMedica International

Simple Inexpensive Test Screens for Esophageal Cancer cont’d from cover

have increased sharply in recent years. The five-year survival rate for people with cancer confined to the esophagus is 43%. When it spreads to nearby tissues or organs, that rate falls to 23%, and esophageal cancer that spreads to distant parts of the body offers a five-year survival rate of only 5%. Scientists from Johns Hopkins University School of Medicine (Baltimore, MD, USA; www.hopkinsmedicine.org) and their associates sought to develop a Barrett’s esophagus (BE) detection method based on methylation status in cytology samples captured by EsophaCap (Capnostics LLC, Doylestown, PA, USA; www.capnostics.com) using a streamlined sensitive technique, known as methylation on beads (MOB). The principle behind the EsophaCap is simple. The patient swallows a small capsule that has a long string attached to it. After the capsule makes its way down the esophagus and into the stomach, a process that takes only a minute or so the gelatin coating on the capsule begins to dissolve. From that capsule emerges a 2-centimeter polyurethane sponge, still attached to the string, much of which still hangs from the patient’s mouth. The screener gently pulls the string and the sponge begins its return journey, out of the stomach, into the esophagus and, finally, out of the patient’s mouth. The team administered the EsophaCap test to 94 people over the course of the study. Eighty-five percent of subjects were able to swallow the capsule, with 100% successful sponge retrieval. Endoscopic evaluation of the patients after EsophaCap administration and showed no evidence of bleeding, pain, trauma or other adverse reactions to the test. The scientists employed methylation on beads (MOB) to extract and bisulfite-convert DNA, followed by quantitative Methylation-Specific polymerase chain reaction (qMSP) to assess methylation levels of eight previously selected candidate markers. The authors reported that in the training set, five of eight candidate methylation biomarkers (p16, HPP1, NELL1, TAC1, and AKAP12) were significantly higher in BE patients than in controls. They built a 4-biomarker-plus-age lasso regression model for BE diagnosis. The AUC was 0.894, with sensitivity 94.4% and specificity 62.2% in the training set. This model also performed with high accuracy for BE diagnosis in an independent test set: AUC= 0.929 with sensitivity of 78.6% and specificity of 92.8%. The authors concluded that EsophaCap, in combination with an epigenetic biomarker panel and the MOB method, is a promising, well-tolerated, low-cost esophageal sampling strategy for BE diagnosis. Stephen J. Meltzer, a gastroenterologist and a professor of medicine and oncology and senior author of the study, said, “It’s actually possible to miss early cancerous cells using endoscopy with

LabMedica International May/2019

biopsy and most patients with Barrett’s don’t ever undergo endoscopy. Right now, we’re confident that we have the tools to identify this type of cancer. But we previously lacked a way to collect enough genetic material to confidently determine a patient’s diagnosis. We believe that EsophaCap now provides a solution to this serious problem.” The study was published on January 22, 2019, in the Clinical Cancer Research. Image: The EsophaCap is packed into a gelatin capsule that dissolves in a patient’s stomach exposing the sponge, which gently collects cells from the whole surface of the esophagus when withdrawn. Cellular material will be examined using cytological, immunohistochemical and genomic methods (Photo courtesy of Capnostics).

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FLOW CYTOMETRY SYSTEM

FLOCKED SWABS

Erba Mannheim

Beckman Coulter

Puritan Medical

The LAURA Smart features a throughput of 60-240 tests per hour, and offers evaluation of 12 clinically significant parameters. It’s designed as an effective solution for small labs, ambulances of general practitioners, family doctors or specialists.

The ClearLLab 10C covers lymphoid and myeloid lineages, without extensive validation and relevant samples. It includes the first 10-color CEIVD panels of immunophenotyping reagents, and Kaluza C analysis software for data analysis/reporting.

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Blood Test Detects Severe Transplant Rejection cont’d from cover

body’s immune system attacks the transplanted organ. Existing tools for detecting signs of rejection, such as biopsy, either require the removal of small amounts of lung tissue or are not sensitive enough to discern the severity of the rejection. Scientists have developed a simple blood test that can detect when a newly transplanted lung is being rejected by a patient, even when no outward signs of the rejection are evident. A large team of scientists working with the National Heart, Lung and Blood Institute (Bethesda, MD, USA; www.nhlbi.nih.gov) enrolled and monitored 106 lung transplant recipients. Blood samples collected in the first three months after transplantation underwent the testing procedure. Genomic DNA isolated from donor and recipient pre-transplant blood was genotyped, and the data for the two samples were compared to identify single-nucleotide polymorphisms (SNPs). Following the transplant, cell-free DNA (cfDNA) was isolated from plasma samples to generate a DNA library for shotgun sequencing. The cfDNA sequence reads were then surveyed for the presence of donor and recipient SNPs and % of donor-derived cell-free DNA (ddcfDNA) was calculated as the percentage of donor SNPs to total (recipient and donor) SNPs.

The results showed that those with higher levels of the donor-derived DNA fragments (ddcfDNA) in the first three months of transplantation were six times more likely to subsequently develop transplant organ failure or die during the study follow-up period than those with lower donor-derived DNA levels. The team found that more than half of the high-risk subjects showed no outward signs of clinical complications during this period. The authors concluded that lung transplant patients with early unresolving allograft injury measured via %ddcfDNA are at risk of subsequent allograft injury, which is often clinically silent, and progresses to allograft failure. Hannah Valantine, MD, a professor of cardiovascular medicine and a co-leader of the study, said, “We showed for the first time that donor-derived DNA is a predictive marker for chronic lung rejection and death, and could provide critical time-points to intervene, perhaps preventing these outcomes. Once rejection is detected early via this test, doctors would then have the option to increase the dosages of anti-rejection drugs, add new agents that reduce tissue inflammation, or take other measures to prevent or slow the progression.” The study was published on January 26, 2019, in the journal EBioMedicine.

Hypersegmented Neutrophils Associated with Reduced Lung Function eutrophils are phagocytic innate immune cells, which patrol the blood vessels and become activated in response to inflammatory triggers. Activation results in neutrophil migration to the site of infection, where pathogens can be eliminated by phagocytosis or NETosis. Inflammation characterized by airway neutrophilia is reported in many cases of chronic obstructive airway disease. This includes 20% to 30% cases of asthma, more than 40% cases of chronic obstructive pulmonary disease (COPD), and 70% cases of non-cystic fibrosis (CF) bronchiectasis. Scientists at the University of Newcastle (Callaghan, Australia; www. newcastle.edu.au) and their associates recruited adults who were undergoing bronchoscopy either for medical purposes or were undergoing a surgical procedure that involved endotracheal intubation and had spirometry results. Participants included 78 adults with obstructive airway disease comprised of 39 with stable asthma, 20 with COPD and 19 diagnosed as bronchiectasis and 20 healthy controls. Spirometry was performed using an Easy One Spirometer, (ndd Medical Technologies, Andover, MA, USA; www.nddmed.com). Flexible bronchoscopy was performed and a fraction of the bronchial lavage (BL) was sent for microbial detection while the rest was processed. The BL was centrifuged and the cell pellet was resuspended in phosphate buffered saline to the concentration of 1×106/mL and cellular cytospins

were prepared. The cytospins were stained with May-Grünwald Giemsa (Beckman Coulter, Brea, CA, USA; www.beckmancoulter.com) and a differential cell count of 400 non-squamous cells was performed. The team reported that the numbers of hypersegmented neutrophils were significantly elevated in participants with airway disease compared with healthy controls. Both the number and the proportion of hypersegmented neutrophils were highest in COPD participants (median (Q1–Q3) of 1,073.6 (258.8–2,742) × 102/mL and 24.5 (14.0–46.5) %, respectively). An increased proportion of hypersegmented neutrophils in airway disease participants was significantly associated with lower forced expiratory volume in 1 s/forced vital capacity percent. In participants with COPD, the proportion of hypersegmented neutrophils was positively associated with proportion of eosinophils and negatively associated with cell viability. The authors concluded that the presence of three morphologically different subsets of neutrophils in the airways of healthy and obstructive airway disease participants, that is, asthma, COPD and bronchiectasis. The increased proportion of hypersegmented neutrophils in the airways of obstructive airway disease participants was associated with reduced lung function of these participants. The proportion of hypersegmented neutrophils was highest in COPD participants in comparison to all other groups. The study was published on January 28, 2019, in the journal BMJ OPEN. LabMedica International May/2019

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HEMATOLOGY ANALYZER

URINE CHEMISTRY ANALYZER

Erba Mannheim

Analyticon Biotechnologies

Beckman Coulter

The H560 offers a full 5 part differential report with 32 parameters, 3 histograms, and flow cytometry scattergrams with just 15 µL of blood. It also features a color touch screen, responsive user interface and RFID reagent management system.

The Hemolyzer 3 NG has a user interface designed for smart micro fluidic analysis, low sample volume requirement, and small footprint. Its connectivity tools and data management allow for state-of-the-art result reporting and instrument analysis.

The AUTION MAX AX-4030 generates accurate and reliable urine chemistry results without interruption. It increases workflow efficiency with a high throughput of up to 225 samples per hour, and continuous loading of up to 100 samples.

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Cell-Free DNA Sequencing Test for Infectious Disease Analyzed number of clinical collaborators testing a cell-free DNA sequencing test for infectious disease reported interim study results and anecdotal evidence of the assay. Karius (Redwood City, CA, USA; www.kariusdx.com) has been developing technology to isolate cell-free pathogen DNA from blood. It is aiming its technology in particular at finding the cause of sepsis and for diagnosing infection in immunocompromised patients. Investigator at St. Jude Children’s Research Hospital (Memphis, TN, USA; www.stjude.org) enrolled patients who had refractory or relapsed acute Lymphatic Leukemia (ALL) or Acute myeloid leukemia (AML). For patients who developed bloodstream infections, standard culturebased diagnostics were carried out, but the Karius test was also run on any samples that were available up to seven days before a diagnosis was made up through seven days after the diagnosis. The goal was to determine whether the Karius test could identify the pathogen before a diagnosis was made by culture. The Karius test was able to identify the pathogen that was ultimately diagnosed by culture in nine out of 11 cas-

es. In 10 of the cases, the scientists also had blood samples from the three days prior to culture diagnosis and the Karius test was able to identify the pathogen in eight of those samples. The team also analyzed samples from 16 patients without infections and while the Karius test did identify bacteria and fungi in three of those cases, none of those organisms were associated with bloodstream infections. Kathryn Goggin, MD, a clinical investigator and senior study author, said, “That in a number of cases Karius identified other microbes aside from the causative pathogen, and said that those findings had “unclear clinical significance.” Those cases, she noted, could be polymicrobial infections, contamination, or even a phenomena known as gut bacterial translocation, where indigenous intestinal bacteria invade other tissues and organs and can lead to bloodstream infection. The condition is more common in immunocompromised individuals. The study was presented at the Infectious Diseases Society of America’s annual IDWeek conference held October 3-7, 2018, in San Francisco, CA, USA. Image: The Karius test is a comprehensive next-generation sequencing (NGS) assay performed by the CLIA-certified and CAP-accredited Karius laboratory to identify and quantify microbial cell-free DNA in plasma from more than 1,000 bacteria, DNA viruses, fungi, molds, and protozoa (Photo courtesy of Karius).

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LabMedica International May/2019

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LabMedica International

Tumor Sequencing Finds Mutations Caused By Blood Disorder linical sequencing assays aim to identify somatic mutations in cancer cells for accurate diagnosis and treatment. However, most clinical-grade implementations lack patient-matched germline DNA, and supplemental analyses are needed to infer the mutational status of variants. A new analysis suggests that a subset of patients with solid tumors may also suffer from blood conditions that introduce additional mutations into tumor sequencing data via infiltrating hematopoietic cells, particularly when matched germline sequencing data are not available. Scientists at Rutgers University (New Brunswick, NJ, USA; www.rutgers.edu) studied clinical sequencing data for 2,030 individuals with solid tumors who were tested between late 2012 and last fall. In the process, they narrowed in on eight patients initially suspected of carrying myeloproliferative neoplasm (MPN)-associated JAK2 mutations in their solid tumors. The team found that the allele frequencies for these activating JAK2V617F mutations did not line up with tumor purity estimates. They used a combination of clinical records and sequencing data from targeted gene panels of tumor samples from three of the JAK2 mutation-positive patients, the investigators determined that at least four of the individuals with JAK2-V617F mutations had both cancer and MPNs such as polycythemia vera, essential thrombocythemia, and myelofibrosis. In two of the patients with newly sequenced samples, for example, the team saw enhanced frequencies for the JAK2-V617F allele in samples with greater lymphocyte white blood cell content compared with samples containing higher tumor tissue levels. Likewise, the available targeted sequence data turned up additional clonal hematopoiesis of indeterminate potential-related mutations in genes such as U2AF1, TET2, or DNINTERACTIVE MT3A in JAK2-V617F-positive cases, DIGITAL EDITION again enriched in lymphocyte-enriched portions of patient samples relative to the tumor tissue on hand. The authors concluded that when MPN-associated mutations are observed in solid tumor sequencing data, caution is necessary for proper patient treatment, and a hematologic workup should be considered in the appropriate clinical context. Their analysis suggests that although both of these results are possible, detection of JAK2-V617F may instead be associated with a coexistent MPN. The study was published on January 3, 2018, in the journal JAMA Oncology.

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Image: Bone marrow biopsy from a patient with polycythemia vera showing a hypercellular marrow as a result of an increase of myeloid, erythroid and megakaryocytic elements (Photo courtesy of Karl Theil MD).

LabMedica International May/2019

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QM SOFTWARE

DENGUE TEST

Maccura Biotechology

Instrumentation Lab

LumiQuick Diagnostics

The GeneReader provides a one-stop solution for clinical research and application. It quickly and accurately identifies genetic markers associated with approved therapies, leading professional guidelines and active clinical trials.

The iQM2 quality management software provides intelligent analyzing and automated QA with every sample in real-time. The error detection time is reduced from hours to minutes and errors are automatically corrected and documented.

The QuickProfile Dengue Test is for the simultaneous detection of IgG and IgM antibodies to Dengue virus in human whole blood, serum or plasma. It is also used as an aid for differential diagnosis of primary and secondary infections.

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Potential Screening for Tailoring Treatment of Aute Myeloid Leukemia cute Myeloid Leukemia (AML) is a serious disorder of certain blood-forming cells. In this disease, certain early precursor cells in the bone marrow that usually develop into white blood cells do not mature properly. They remain frozen as primitive cells called blasts, unable to further differentiate and mature. Leukemia stem cells (LSC), the progenitors for the immature cancerous blood cells, propagate AML, and also play a role in the cancer returning after treatment. Cancer scientists are interested in how genes are expressed in this cell population, because this data may hold clues to resistance to standard therapies and answers to why some patients relapse. A multidisciplinary team of scientists at the University of Washington Health Sciences (Seattle, WA, USA; www.washington.edu) and their colleagues obtained samples from patients with AML. LSCs were isolated by fluorescence-activated cell sorting (FACS) and the blast population enriched to more than 90% using immunomagnetic beads from blood samples from five patients with AML. A sixth AML patient sample was used for NOD/SCID IL2R γc−/− engraftment, in order to compare characteristics of pre- and post-engraftment subclones. The CLIA approved custom assay includes 153 drugs and targeted agents, both FDA approved and investigational, with additional drug combinations. High throughput screens (HTS) were conducted with enriched cells adherent to matrix protein in 384 well plates with eight concentrations of each drug spanning four logs. Viability was assessed with CellTiterGlo (Promega Corporation, Madison, WI, USA; www.promega.com).

HTS were performed on LSCs, blasts and pre- as well as post-engraftment AML subclones from the xenograft. Dose-response curves were generated to calibrate drug resistance patterns. Mutation analysis by NGS for a panel of 194 recurrently mutated genes in AML (MyAML, Invivoscribe, San Diego, CA, USA; www.invivoscribe.com) including 37 translocations was also conducted for the LSC and blast populations. The study was presented at the 60th Annual Meeting of the American Society of Hematology held December 1-4, 2018, in San Diego, CA, USA. Image: The CellTiter-Glo 3D cell viability assay (Photo courtesy of Promega).

Alzheimer’s Risk Alleles Profiled in Latino Populations he apolipoprotein E (APOE) gene encodes three common isoforms known as ε2, ε3, and ε4. These are determined by two single nucleotide polymorphisms (SNPs) that result in amino acid substitutions and associated functional changes in the protein. The APOε4 isoform is associated with increased circulating levels of total cholesterol and low-density lipoprotein (LDL), cardiovascular risk, Alzheimer’s disease (AD), and related dementias (ADRD); whereas APOε2 is associated with cognitive resilience and extended longevity. A team of scientists collaborating with the University of Texas Health Science Center (Houston, TX, USA; www.uth.edu) used a custom array to genotype APOE in nearly 10,900 individuals with diverse Latino ancestry from four metropolitan areas in the USA. The genotyped participants included representatives from Central American, Cuban, Dominican, Mexi-

can, Puerto Rican, and South American populations, and had an average age of just over 41 years and slightly more than half of the target population (50.4%) was female. Genome-wide SNP genotyping was performed on the participants using a custom Illumina array consisting of the HumanOmni2.5–8v1–1 array (Illumina, San Diego, CA, USA; www.illumina.com) content along with a panel of ∼150,000 investigator-chosen SNPs. The authors concluded that the APOE allele and genotype frequency distributions in a large and diverse sample of Latinos with well-characterized ancestry background. These data provide valuable information in this understudied ethnic group and provide the basis for future studies of the association of APOE with ADRD in this fast-growing segment of the US population. The study was published on December 13, 2018, in the journal Scientific Reports. LabMedica International May/2019

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PRODUCT NEWS COAGULATION ANALYZER

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DiaSys Diagnostic Systems

CellaVision

The CA51 comes with an electronic pipette and requires only a small sample and reagent volume. Features include disposable cuvettes and automatic start at reagent addition, making it ideal for small labs/clinics.

The BioMajesty JCA-BM6010/C features 43 reagent and 84 sample positions, and a throughput of 1,200 tests per hour. The system requires small sample volumes, and is for small to mid-sized IVD labs.

The CellaVision DC-1 is designed to meet the specific needs of smaller low-volume hematology labs. It allows these labs to perform blood cell differentials that many large labs today regard as standard practice.

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Less-Invasive Biosensor Created for Breast Cancer Diagnosis reast cancer is the most common form of cancer among women. Usually, diagnosis of the disease involves a mammogram or ultrasound followed by an invasive needle biopsy, where specific biomarkers are identified to determine the type of breast cancer type and develop a treatment plan. Results from a biopsy examination take up to two weeks. HER2-positive breast cancer is a breast cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. In about one of every five breast cancers, the cancer cells have a gene mutation that makes an excess of the HER2 protein. HER2-positive breast cancers tend to be more aggressive than other types of breast cancer. Bioengineers at the University of Hartford (West Hartford, CT, USA; www.hartford.edu) and their colleagues have devised a new biosensor to diagnose breast cancer less invasively compared to the existing needle biopsy approach. The device combines microfluidic technology and diagnostics, the device was partly built using an inkjet printer. The printed chip, consisting of an array of electrodes, was deposited into a prefabricated microfluidic device that regulates fluids to flow in a controlled manner.

During the test process, a patient’s blood sample flows through the microfluidic device and the biosensor chip coated with antibodies, which then captures and immobilizes HER-2 proteins present in the sample. Abnormal levels of HER-2 are considered to be an indicator of a specific type of breast cancer, and its detection is expected to enable treatment strategies. The device is designed to identify the breast cancer biomarker HER-2 in the blood within 15 minutes. The team believes that demonstrating monitoring of blood HER-2 levels as a potential biomarker of disease progression status during and after therapy. The scientist also believes that the advancement of biosensors could facilitate non-invasive breast cancer testing. They are working towards reducing the new biosensor chip size by using printed circuit boards to construct a portable electrochemical unit. Seila Selimovic, PhD, from the National Institute of Biomedical Imaging and Bioengineering (Bethesda, MD, USA; www.nibib.nih.gov) said, “Less invasive, more accessible, and faster diagnostic tools like this biosensor are essential to improving healthcare. As biosensors continue to progress it is important to keep in mind diagnostic tools are only helpful when accurate. This biosensor works in the clinically relevant range and has one of the lowest reported HER-2 detection limits, so fewer false positives and negatives will occur.” Image: An ink-jet printer layers gold nanoparticle ink constructing a batch of biosensors that could detect a breast cancer protein in the blood (Photo courtesy of Colleen E. Krause, PhD).

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Persistent Fatigue Induced by Interferon-Alpha hronic fatigue syndrome (CFS), or myalgic encephalomyelitis (ME), is a mysterious condition. The main symptom of CFS is extreme and often unrelenting fatigue; others include muscle and joint pain, sleep issues, and flu-like symptoms. There is some evidence implicating the immune system in the pathogenesis of CFS, but the exact role of immune mechanisms in this condition, especially at its onset, have yet to be established. Genetic polymorphisms in immune genes are associated with CFS as well as other disease-related fatigue. A large multidisciplinary team of scientists working with King’s College (London, UK; www.kcl.ac.uk) has presented a study of interferon-alpha (IFN-α)-induced persistent fatigue as a model of CFS. IFN-α, which is used in the treatment of chronic Hepatitis C Virus (HCV) infection, induces a persistent fatigue in some individuals, which does not abate post-treatment, that is, once there is no longer immune activation. Fifty-five patients undergoing IFN-α treatment for chronic HCV were assessed at baseline, during the 6–12 months of IFN-α treatment, and at six-month post-treatment. Measures of fatigue, cytokines and kynurenine pathway metabolites were obtained. Cytokines were measured using MSD V-PLEX sandwich immunoassays (Meso Scale Discovery, Rockville, MD, USA; www.mesoscale.com) and plates read on an MSD QuickPlex SQ 120. MSD Pro-inflammatory Panel 1 (human) kits were used for the measurement of IFN-γ, IL-1β, IL-2, IL-4, IL6, IL-8, IL-10, IL-12p70, IL-13, and TNF-α, and a custom Cytokine Panel 1 (human) kit was used for the measurement of IL-7, IL-17 A and VEGF. To assess kynurenine pathway metabolites plasma aliquots were analyzed chromatographic system was composed of a Waters Acquity UPLC separations module connected to a Xevo TQ MS triple-quadrupole mass spectrometer, equipped with a Z-spray ESI ion source (Waters Corp, Milford, MA, USA; www.waters.com). The team reported that 18 patients undergoing IFN-α treatment (33%) were subsequently defined as having ‘persistent fatigue’ (the proposed model for CFS), if their levels of fatigue were higher six-months post-treatment than at baseline; the other 67% were considered ‘resolved fatigue’. There was a trend towards increased baseline interleukin (IL)-6, and significantly higher baseline IL-10 levels, as well as higher levels of these cytokines in response to IFN-α treatment, along-

LabMedica International May/2019

side concurrent increases in fatigue. Levels increased to more than double those of the other patients by Treatment Week 4. There were changes in kynurenine metabolites in response to IFN-α, there was no association with persistent fatigue. CFS patients had lower levels of the ratio of kynurenine to tryptophan and 3hydroxykynurenine than controls. Alice Russell, PhD, the lead author of the study, said, “Our findings suggest that people who have an exaggerated immune response to a trigger may be more at risk of developing CFS.” Interestingly, once the CFS-like illness developed, there were no longer any detectable differences between the immune systems of those who developed the symptoms and those who did not. The study was published on December 17, 2018, in the journal Psychoneuroendocrinology.

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Image: The QuickPlex SQ120 utilizes MSD’s proprietary multi-array technology to provide significantly increased sensitivity and dynamic range over standard ELISA with the added benefit of multiplexing (Photo courtesy of Meso Scale Discovery).

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PRODUCT NEWS HEMATOLOGY ANALYZER

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RAPID TESTS

BLOOD CELL COUNTER

Beckman Coulter

MedMira

Karl Hecht

The Coulter LH-780 is equipped with automated nucleated NRBC enumeration, random access capabilities and AccuCount Technology. It is designed to improve productivity, while increasing user confidence.

The Miriad rapid tests detect HIV-1/2, hepatitis B and hepatitis C and provides instant results. It offers a simple procedure, a built-in procedural and reagent control line, and can be stored at room temperature.

The AC-15 PC is designed for the microscopic analysis of differential blood count. It enables continuous monitoring of the image, while resulting figures are recorded blindfolded and can be connected to a PC.

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Inflammatory Bowel Disease Linked to Prostate Cancer contâ&#x20AC;&#x2122;d from cover

slowly and is initially confined to the prostate gland, where it may not cause serious harm. However, while some types of prostate cancer grow slowly and may need minimal or even no treatment, other types are aggressive and can spread quickly. A team of urologists and physicians working with the Northwestern University (Evanston, IL, USA; www.northwestern.edu) investigated 1,033 men with inflammatory bowel disease (IBD) and a control group of 9,306 men without the disease. They followed the two groups of men for 18 years and found those with IBD were much more likely to have prostate cancer and higher prostate specific antigen (PSA) levels. Follow-up time for all patients was the duration between a patientâ&#x20AC;&#x2122;s first PSA test and last physician encounter. The median age of both case and control groups at first PSA measurement was 53 years, and 74% were white. The scientists reported that the 5- and 10-year incidences of any prostate cancer (PCa) were 2.8% and 4.4% for cases and 0.25% and 0.65% for controls, respectively. The crude incidences of any PCa were 715 cases in patients with IBD and 167 cases among controls per 100 000 person-years. The incidences of clinically significant PCa were 462 cases in patients with IBD and 115 cases among controls per 100,000 person-years. A total of 27, 221 PSA measurements were assessed for men without IBD and 3,357 for men with IBD. There was a slight trend toward a higher number of PSA tests and higher PSA values among patients with IBD. While PSA estimates were similar in younger patients,

age-specific PSA values were significantly higher in patients with IBD in older age, starting at approximately age 60. The authors concluded that in a retrospective matched-cohort study, men with IBD who underwent PSA-based PCa screening had higher rates of any and clinically significant PCa when compared with age- and race-matched men without IBD. These findings warrant future prospective investigation to better understand the relationship between IBD and PCa. The study was published on December 4, 2018, in the journal European Urology. Image: Patients with inflammatory bowel disease who have an elevated PSA, may be at risk for prostate cancer (Photo courtesy of Harvard University).

Colorectal Cancer Risk Linked to Common and Rare Variants olorectal cancer (CRC), also known as bowel cancer and colon cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Screening, by one of a number of methods, is recommended starting from the age of 50 to 75. Most colorectal cancers are due to old age and lifestyle factors, with only a small number of cases due to underlying genetic disorders. An international team has identified a combination of rare and common genetic variants coinciding with colorectal cancer (CRC) susceptibility. The international team led by investigators at the Fred Hutchinson Cancer Research Center (Seattle, WA, USA; www.fredhutch.org) performed whole-genome sequencing on more than 2,100 CRC cases and controls, using variants imputed from these and other data in a two-stage genomewide association study that included nearly 125,500 individuals with or

without CRC. This revealed 40 previously undocumented CRC-associated variants and 55 variants implicated in CRC risk in prior studies. The team used HiSeq 2500 paired-end sequencing (Illumina, San Diego, CA, USA; www.illumina.com), and did whole-genome sequencing on 1,439 individuals with CRC and 720 unaffected controls. Using sequence data covering each genome to 3.8- to 8.6-fold coverage, on average, and population reference sequence data from the Haplotype Reference Consortium, they got haplotype phasing information for 31.8 million variants, including rare variants. A subset of participants were genotyped using a custom Illumina array that included known cancerrelated loci as well as suspicious variants found in the first phase of the association study. The study was published on December 3, 2018, in the journal Nature Genetics. LabMedica International May/2019

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LabMedica International

Urinary Biomarkers Associated With Kidney Disease Risk Factors he improved life expectancy among treated human immunodeficiency virus (HIV)-positive patients has been tempered by the excess burden of age-related non-infectious co-morbidities, including chronic kidney disease (CKD). In this HIV-positive population, CKD results not only from traditional risk factors, such as diabetes and hypertension, but also from HIV-related risk factors, including uncontrolled viremia, chronic coinfection with hepatitis C virus (HCV), and exposure to potentially nephrotoxic antiretroviral (ART) medications. Scientists at the San Francisco Veterans Affairs Medical Center (San Francisco, CA, USA; www.sanfrancisco.va.gov) and their colleagues carried out a cross-sectional study of HIV-positive persons in the Multicenter AIDS Cohort Study and the Women’s Interagency HIV Study. Of the 198 participants, one third were on HAART and virally suppressed. The team evaluated associations of known CKD risk factors with urine biomarkers using separate multivariable adjusted models for each biomarker. The scientists measured levels of 14 urine biomarkers in clean catch urine specimens that were collected prospectively, refrigerated immediately after collection, and subsequently centrifuged. Each hypothesized urine biomarker was to indicate a distinct dimension of kidney injury and dysfunction. All urine biomarkers were measured using multiplex immunoassays from Meso Scale Discovery (MSD, Rockville, MD, USA; www.mesoscale.com), except urine creatinine which was measured using the Roche enzymatic creatinine assay (Roche Diagnostics, Indianapolis, IN, USA; www. roche.com) and α1-microglobulin (α1m), which was measured using a commercial assay (BN II Nephelometer, Munich, Germany; www. healthcare.siemens.com). The team reported that the vast majority (95%) had preserved kidney function as assessed by serum creatinine, with a median eGFR of 103 mL/min/1.73 m2. In the multivariable analyses, the associations of each CKD risk factor with urinary biomarker levels varied in magnitude. For example, HIV viral load was predominantly associated with elevations in interleukin (IL)18, and albuminuria, while higher CD4 levels were associated with lower monocyte chemoattractant protein-1 (MCP-1) and β2-microglobulin. In contrast, older age was significantly associated with elevations in α1-microglobulin, kidney injury marker-1, clusterin, MCP-1, and chitinase-3-like protein-1 levels, as well as lower epidermal growth factor, and uromodulin levels. The study was published on January 3, 2019, in the journal BMC Nephrology.

LabMedica International May/2019

Image: The BN II Nephelometer System is an easy-to-use, reliable nephelometric analyzer that offers a broad range of protein assays (Photo courtesy of Siemens Healthcare).

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PRODUCT NEWS PCR KITS

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OSMOMETER

IMMUNOASSAY TEST

Streck Laboratories

ELITech Group

Fujirebio

The Streck ARM-D kits detect beta-lactamases in existing/emerging strains of bacteria exhibiting MDR. The kit includes a premixed 2X master mix requiring a single step, along with validated positive internal controls.

The VAPRO features auto-calibration, self-cleaning, self-diagnostics, statistical analysis, and print capabilities. Its small sample requirement allows users to assay hard-to-get or expensive samples.

The INNO-LiPA HPV Genotyping Extra II (20T) line immunoassay is intended for the individual identification of 32 HPV genotypes. It comes with easy and ready-to-use master mix, along with Taq DNA polymerase.

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Newborn Cytomegalovirus Test Cleared for Marketing cont’d from cover

have been infected with CMV. Most people infected with CMV show no signs or symptoms. That is because a healthy person’s immune system usually keeps the virus from causing illness. However, CMV infection can cause serious health problems for people with weakened immune systems and for unborn babies. Only about one in five babies with congenital CMV infection will be sick from the virus or have long-term health problems. The US Food and Drug Administration (FDA, Silver Springs, MD, USA; www.fda.gov) announced that it has completed the de novo premarket review and cleared for marketing Meridian Bioscience’s (Cincin-

nati, OH, USA; www.meridianbioscience.com) cytomegalovirus assay for newborns called the Alethia CMV Assay Test System. A prospective clinical study showed the Alethia test correctly identified 1,472 out of 1,475 CMV negative samples. There were three false positive tests, and five saliva specimens correctly identified as positive. Meanwhile 34 archived positive specimens were also correctly identified. The Alethia CMV test system enables detection of CMV DNA from saliva swabs of newborn babies who are less than 21 days old. The FDA specified that test results must be used in conjunction with the results of other diagnostic tests and clinical information.

Genetic Marker Predicts Early Relapse in Pediatric ALL cute lymphoblastic leukemia (ALL) is the most common childhood cancer; however, treatment has improved dramatically due to the ability to stratify patients into groups based on risk factors and genetic analysis. About 15% to 20% of ALL patients who have reached complete remission eventually relapse. ALL relapse is considered one of the major cancer-related causes of death among childhood malignancies. Relapse can occur even in patients with favorable prognostic factors at diagnosis.

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Scientists at the Nova Southeastern University (Fort Lauderdale, FL, USA; www.nova.edu) and their associates discovered that by testing the level of nucleotide excision repair (NER) gene expression, pediatric oncologists can determine the likelihood of early relapse (less than three years) in their acute lymphoblastic leukemia (ALL) patients. This study included two matched diagnosis-relapse paired gene expression datasets of pediatric ALL. The Staal dataset included 41 patients diagnosed with both precursor-B-ALL (n = 27) and T-ALL (n = 14) and treated. The Hogan dataset included 49 treated patients with precursor-B-ALL. The Affymetrix Human Genome U133 plus 2 array (Affymetrix, Santa Clara, CA, USA; www.affymetrix.com) was used to generate both datasets. Data on 51 probes representing 20 NER canonical genes were extracted. Expression data on multiple probes for a single gene were averaged. The expression of the canonical 20 NER genes was examined in matched pediatric samples at the time of diagnosis and relapse of only precursor-B-ALL patients from both datasets. The team classified patients based on the time of recurrence as either early (less than 36 months) or late (equal to or more than 36 month) relapsers, regardless of other prognostic variables. The scientists reported that gene expression of the NER pathway was significantly increased upon relapse in patients that took three years or greater to relapse, whereas no such change was evident in patients that relapsed in less than three years. Moreover, at diagnosis, the NER gene expression of the early relapsing subpopulation was already significantly elevated over that of the late relapsing group. This pattern was validated by an ‘NER score’ established by averaging the relative expression of the 20 canonical NER genes. The NER score at diagnosis was found to be significantly associated with disease-free survival in precursor-BALL. The study was published on October 30, 2018, in the journal BMC Medical Genomics. LabMedica International May/2019

International Federation of Clinical Chemistry and Laboratory Medicine

2018 ANNUAL REPORT HIGHLIGHTS OF THE YEAR IFCC General Conference – Budapest, Hungary, November 2018 (www.ifcc.org/ifcc-congresses-and-conferences /ifcc-general-conference-budapest-hungary) 1st IFCC, EFLM, AFCB, FIFBCML Conference “Laboratory Medicine: Meeting the Needs of the Mediterranean Nations” – Rome, Italy, July 2018 IFCC VLP Programme Supported by Abbott (www.ifcc.org/ifcc-education-division/emd-special-projects) IFCC Speakers’ Bureau (www.ifcc.org/ifcc-education-division/speaker-s-bureau)

e-Academy, Open Educational Resources (http://eacademy.ifcc.org) Increased Frequency of eNewsletter to Monthly (www.ifcc.org/ifcc-communications-publications-division-cpd/ ifcc-publications/enewsletter/enews-volumes) IFCC ejIFCC Fully Indexed in PMC (www.ifcc.org/ifcc-communications-publications-division-cpd/ ifcc-publications/ejifcc-journal www.ncbi.nlm.nih.gov/pmc/journals/2920)

Roche/IFCC Travel Scholarships

IFCC Handbook 2018-2020 www.ifcc.org/executive-board-and-council/ifcc-handbook-2018-2020/

IFCC Professional Scientific Programmes (PSEP/PMEP)

IFCC App – Release on Both Android and iOS Platforms

IFCC FEN - Foundation for Emerging Nations (www.ifccfoundation.org)

IFCC on Instagram (www.instagram.com/ifclinchem)

New Division on Emerging Technologies (ETD) Established (www.ifcc.org/ifcc-emerging-technologies-division)

IFCC Flow Cytometry Courses (www.ifcc.org/ifcc-education-division/working-groups-special-projects/ httpifccorghostinginsoftdkmedia46789217_phd_course_program_bpdf)

Webinars and Distance Learning Modules (www.ifcc.org/ifcc-education-division/webinars/ifcc-webinars) Task Force Young Scientists (TF-YS) Webinars (www.ifcc.org/task-force-young-scientists-web-pages/tf-ys-webinars) IFCC Expert Database (www.ifcc.org/ifcc-education-division/experts) The IFCC Curriculum, Phase 1 Released (www.ifcc.org/media/477266/ejifcc2018vol29no1pp055-093.pdf)

9th Beginners’ Course in Molecular Diagnostics (www.ifcc.org/media/477209/2018-c-cmbc-slovakia-course.pdf) DQCML Projects in Malawi and Nepal (www.ifcc.org/ifcc-education-division/working-groups-special-projects/ developing-quality-competence-in-medical-laboratories-dqcml) Implement Cooperation and Agreements with IFCC Regional Federations

PRESIDENT’S MESSAGE he IFCC mission ‘Advancing excellence in laboratory medicine for better healthcare worldwide’ has been the guiding principle for our work in 2018, my first year as President. It is a great privilege and honour to serve in this role with the opportunity to meet and learn from so many of our learned, skilled and experienced clinical laboratory specialists internationally. Their devotion of time and energy to voluntarily undertake our numerous projects is most inspiring. Significant developments have been undertaken including the new Executive Board with representation of each of the Regional Federations, the development of our 2018-2020 Strategic Plan and the General Conference in Budapest in November 2018. It is a great pleasure to report on the success of the new Executive Board. All members have experienced the benefits of this significant change to IFCC leadership whether it be the availability of specific issues or conditions within the regions or information or resources available through the international standing of IFCC to national societies and regional federations. The IFCC has indeed benefited greatly from this constitutional change to our governance. The 2018-2020 strategic plan supports the principle of maintaining the IFCC as the as the most respected international resource of expertise for the improvement of patient care through laboratory medicine. In preparation for and following the General Conference we conducted surveys of our national representatives. The Executive Board is most grateful to all who have responded. They provided vital information on the major issues facing our national societies. These include funding for laboratory medicine, involving the recognition of the value of laboratory medicine and reimbursement; maintaining membership, involving continuing professional development and ongoing career development; and finally quality clinical laboratory performance and specifications. Our strategic plan aims to address these issues. The establishment of the EMD Committee for the Value Proposition in Laboratory Medicine (CVPLM) is undertaking research to assess methods for estimating the value of medical tests within the healthcare system in terms of financial impact and patient outcomes. This committee is also charged with assembling a compendium of tools such that all clinical laboratory specialists will be capable of undertaking such projects within their own environments and to use their data to negotiate with clinical, financial and administrative officers in their institutions or health jurisdictions. The CPD eAcademy continues to be developed to provide a quality, comprehensive curriculum in laboratory medicine via 20 to 40 minute we-

by Howard Morris, IFCC President

binars, with learning points and a certifiable assessment. Coordinators have been enlisted to assist presenters easily and uniformly record and deposit their presentations on the website. Currently these are largely available in English although collaborations are underway to increase the Spanish language presentations. These are available for all interested individuals to access and expand their skill set. Perhaps more importantly is utilization of the eAcademy by national societies or perhaps local area branches of national societies. These webinars are an excellent tool to bring together younger or trainee clinical laboratory specialists with one or two more experienced practitioners to listen to the presentation, discuss the learning points and then individually undertake the assessment. Learning together is always a more enjoyable experience. The excellent work of the Scientific Division in collaboration with the Joint Committee for Traceability in Laboratory Medicine (JCTLM) and the International Consortium for Harmonization of Clinical Laboratory Results (ICHCLR) and other metrology and reference material manufacturers continues to expand the standardization and harmonization of clinical laboratory assays. This is a key strategy to ensure accuracy or at least harmonization of results of medical tests for optimal medical practice. During the next period the IFCC will be working with metrology institutes, both regional and national, to enhance collaboration and avoid duplication of the preparation of certified reference materials. This has been identified as the current requirement for the profession to take the next steps in this long-term strategy. The 2-day General Conference was attended by some 210 delegates who reported overwhelmingly on the usefulness and benefits of this time of intense activity. We are very appreciative of the strong contingent from our Corporate Members. There was strong support for the scientific program and I am very appreciative of the extensive work contributed by all members of the program committee. Importantly, on the question of the most appreciated presentation, there was strong support across the whole program indicating that it met the needs across the broad spectrum of delegates. As well we are very grateful to our colleagues of the Hungarian Society of Laboratory Medicine who assisted the organization of this important event for the IFCC. I thank all IFCC officers for their invaluable service throughout 2018 as described in their specific reports below. I am extremely thankful for the excellent work of the EB in 2018 especially my predecessor Professor Maurizio Ferrari for all his support and advice and to Professor Dave Kinniburgh for the production of this Annual Report and his work throughout 2018. My sincere thanks also to the member organizations: full, associate and corporate members, for their continued support of the IFCC and for the individuals that they nominate to the IFCC functional groups. I wish to thank the IFCC Office Staff, Paola Bramati, Silvia Cardinale and Silvia Colli-Lanzi for their dedicated efforts in managing the day to day business of the IFCC, and for their personal assistance to me as President.

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2018 Annual Report EXECUTIVE BOARD (EB)

The IFCC Executive Board held three meetings during 2018. The first meeting was held in Milan on February 17-19; the second EB meeting was held in Frascati, Rome, in conjunction with Laboratory Medicine: Meeting the Needs of Mediterranean Nations on July 5-6; and the third EB meeting was held in Budapest in conjunction with the IFCC General Conference on November 8-9. The IFCC General Conference was held in Budapest on November 10-11, with the theme, Laboratory Medicine: Preparing for the 2020’s. The meeting was well attended, with 266 delegates from 71 countries. The format for this year’s General Conference was reduced to 2 days and presentations focused on issues in Clinical Chemistry and Laboratory Medicine that were of major importance to members. The post conference survey of delegates indicated major satisfaction for the GC, overall, and supported the revised format. A pre-conference survey identified issues of major importance to delegates, many of which are currently part of the EB Strategic Plan and others that are being considered. The IFCC membership, as of December 31, 2018, included 91 Full Members, 16 Affiliate Members and 44 Corporate Members. During 2018, three new Affiliate Members joined: Kazakhstan Public Association – Federation of Laboratory Medicine, French National Network of Accredited Laboratories of Medical Biology, and the Serbian Society for Clinical Laboratory Medicine and Science. A letter was sent to National Societies Full and Affiliate members, and to the Divisions requesting their annual reports. All reports will be included in the IFCC Annual report for 2018 which will be available on the IFCC Website (www.ifcc.org). The new EB format includes representation from each of the Federations and I urge members, and individuals, to contact their EB representatives, or the EB directly, with any issues so that the EB may better understand the issues and concerns that are important to members. Finally, 2018 was the first year of my term as Secretary of the IFCC and I would like to thank all the IFCC officers and colleagues who I have worked

IFCC

with for their cooperation and assistance. It has been my pleasure to meet many of the IFCC “family” this past year and I look forward to meeting more over the next 2 years. Special thanks to President Howard Morris, and the other EB members for their support and diligent efforts, and thanks to the staff of Emmezeta-MZ Congressi in Milan (Paola Bramati, Silvia Cardinale and Silvia-Colli-Lanzi). David Kinniburgh - Executive Board Secretary

TREASURER’S REPORT During the first year of my second term as the IFCC treasurer, with the valuable help and assistance of the IFCC office, the annual dues of Full, Affiliate and Corporate Members were received, the adherence of IFCC operating units to their allocated budgeted were monitored and detailed records of all transactions were kept, reimbursements were processed within two days after the receipt of the claims from the IFCC office. Close collaboration was achieved with the IFCC investment bank (Credit Swiss) to optimise the financial return on IFCC investments. The annual accounts and financial actions were reviewed by an external independent auditor in order to finalize the actual income and expenses at 31st December 2018. 1. COMPARISON OF 2018 PROPOSED BUDGET WITH ACTUALS AT 31ST DECEMBER 2018. The 2018 budget was expected to be closed with a deficit of CHF -1.100 107. Instead, it was closed with a deficit of CHF 315.861 (Fig. 1). The main reason for this difference was the high amount of new sponsorship funds and less expenditure. 2. TOTAL OPERATIONAL REVENUES AND FINANCIAL INCOME. The actual total operational revenues and financial income were CHF 953.007 (Fig. 2). 3. IFCC MEMBERSHIP DUES: Below is a diagram showing the percentage of the major income of IFCC from the annual dues of Full, Affiliate and Corporate Members collected during 2018 (Fig. 3). Thanks all member Soci-

Figure 4. IFCC meetings income.

Figure 1. 2018 proposed budget versus to actual at 31st December 2018.

Figure 5. IFCC GENERAL EXPENSES-2018

Figure 2. INCOME at 31st December 2018: CHF 953.007.

Figure 3. IFCC membership dues collected in 2018.

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eties and Corporate members that supported IFCC throughout the years. Their continuous contributions have made possible the accomplishment of numerous IFCC tasks and projects. IFCC is grateful to the IVD industry for their support and active participation in the IFCC scientific events. We also thank the members for their loyalty and attention in paying dues at the start of the year, which helps the cash flow. 4. IFCC MEETINGS INCOME PARTITION. IFCC meetings’ revenues are not a regular yearly income. The average yearly income of IFCC arising from the meetings can be calculated by dividing the total revenue by the frequency of the event. The yearly income of IFCC from the recent meetings (EuroMedLab 2017 Athens and WorldLab 2017 Durban and shares from the regional federations’ meetings) subdivided per year is indicated below (Fig. 4). The income of IFCC from the membership dues and annual meetings income (excluding sponsorships and other revenues) in 2018: CHF 458.738 (dues) + CHF 386.577 (annual meeting income) = CHF 845.315 5. SPONSORSHIP. Divisions and some Functional Units raise some sponsorships funds which give them a certain flexibility in conducting projects. These sponsorships are used for the specific projects in due time. The unspent sponsorship funds are carried over to the next years. The total amount of sponsorships available for specific projects at 31 December 2018 to be carried to 2019 is CHF 689 326. 6. TOTAL OPERATIONAL COSTS AND FINANCIAL CHARGES. The actual total operational costs and financial charges in 2018 were CHF 1.268.868 (Fig.5). 7. IFCC INVESTMENT AT CREDIT SUISSE IN 2018. The important issues of the agreement with Credit Suisse are outlined as below: • Investment strategy: Income oriented • Risk Profile: Moderate • Risk Budget: Moderate • Reporting currency: CHF (with investments in three currencies: CHF, EUR, USD) • Ticket fee model: 0.20% for the safekeeping fee (no investment fee). Tomris Ozben, Treasurer

CORPORATE MEMBERS Rolf Hinzmann, MD, PhD (Roche), Corporate Representative at IFCC Executive Board (2nd term 2018-2020) In 2018 IFCC was pleased to welcome Timedico and ET Healthcare as new Corporate Members. Regrettably, 2 companies left IFCC in 2018: Guangzhou Wondfo Biotech, and Analis. By the end of 2018, the total number of IFCC's Corporate Members was 42, providing the IFCC with annual fees of CHF ~280.000 which was approximately 60 % of IFCC's total direct annual income from its members (which comprise National Societies and Affiliate Member Societies as well). On top of this, IFCC received sponsorship for scientific or educational projects, awards, travel of students and lecturers, and congresses. Over the past years, IFCC has been seeing an erosion in corporate membership: Between 2014 and 2018 6 companies joined IFCC while 24 left (and 2 were lost due to mergers). The reasons are only partly understood; however, important contributors seem to be: Companies that had joined primarily to receive the lucrative discount on the exhibition fee at conferences dropped out again once they did no longer exhibit. Other companies see limited value in return for their annual fee. Although progress has been made to better address the needs of the Corporate Members, it is still necessary to further enhance the value of IFCC for its Corporate Members, e.g. by: • Better serving the needs of the Corporate Members instead of regarding Corporate Members mainly as a source of income, • Making it easier for employees of Corporate Members to actively participate in IFCC working groups and committees (and not only as corresponding members), • Collaborating better with clinical societies to harmonise guidelines and support medical claims leading to reimbursement for lab tests, • Aligning more strongly with others (CLSI, FDA, clinical societies, etc.) to avoid inconsistency and duplication of regulatory guidelines and recommendations, • Pursuing the opportunities of data analytics in laboratory diagnostics. One important step in this direction is a better representation of the Corporate Members within IFCC. For this reason, a New Task Force Corporate Members is currently being established to facilitate discussions among Corporate Members, identify common topics, and directly interact with / report to the Executive Board. The Task Force will define its own scope and goals. Selection of members is currently ongoing, and the task force will kick off during EuroMedLab in Barcelona in May 2019. The following suggestions for topics have already been received: • Suggestions on frequency and locations of IFCC conferences • Alternative funding structure for IFCC by Corporate Members • Collaboration of IFCC with Clinical Societies and Regulators on guidelines • Promotion of the value provided by lab testing The recently established Emerging Technologies Division provides multiple opportunities for Corporate Members. It has been agreed that each working group or committee will accept at least one full member from a Corporate Member company. The Corporate Members make several important contributions to IFCC activities: Numerous delegates from Corporate Members are actively en-

gaged in most of the working groups and committees in all IFCC divisions and in their Executive Committees, either as full members or as corresponding members, as well as in the Congresses & Conferences Committee. Here is the contact information for Corporate Representatives who were / are members of the Executive Committees of IFCC's 4 divisions and the Congresses & Conferences Committee. Please feel free to reach out to them in case you have questions: • Scientific Division: James Pierson-Perry (Siemens) (2nd term 20182020), • Emerging Technologies Division: This newly established division has two Corporate Representatives: Peng Yin (Abbott) (1st term 2018-2020) and Markus Roessler (Roche) (1st term 2018-2020), • Education & Management Division: André Ziegler (Roche) (1st term 2017-2019), • Communications & Publications Division: Peter Bialk (Roche) (1st term 2017-2019), • Congresses & Conferences Committee: Cheryl Jackson (Beckman Coulter) (1st term 2018-2020). The following persons are Corporate Members of the respective Congress Organizing Committees (COCs): • IFCC / EuroMedLab 2019, Barcelona, Spain: Jaime Vives (Roche) • IFCC / WorldLab 2020, Seoul, South Korea: Douglas Chung (Abbott) • IFCC / EuroMedLab 2011, Munich, Germany: Katja Schwarzer (Abbott) Since January 1, 2018 the transition period of certain MedTech Europe Code regulations has expired, and new rules have become effective: • For third-party organised conferences (main programme): Companies may not directly support a healthcare professional, neither as a delegate, nor as a speaker. • For company-organised events in the framework of third-party organised conferences (e.g. satellite symposia): Companies may directly support speakers (i.e. their consultants) but not delegates. • Educational grants are still possible. They can only be provided to legal entities but never to individuals. • Companies will be able to define the type of recipients who should be eligible for the grant but will not be able to identify individual recipients. • Companies must have an internal and independent process based on objective criteria to assess grant requests. For more information please check out the MedTech Europe website. Similar codes are expected to come into place in various other regions of the world. EuroMedLab in Barcelona will be the first major event for IFCC that is falling under the new rules. In spite of these strict regulations, interest of the IVD companies to sponsor the event is very high. As of March 2019, the following sponsorship arrangements have been made: 5 platinum, 4 gold, 5 silver, 5 bronze, 50 additional exhibitors. Several companies have confirmed that they have made arrangements regarding educational grants according to the new rules so that we can hopefully expect a large number of delegates at this event. The next Corporate Members Meetings will be held during EuroMedLab in Barcelona on May 20, 2019 and during AACC in Anaheim on August 6, 2019. I would like to encourage all members to take part in the meeting. The respective meeting details will be communicated soon. Rolf Hinzmann, Corporate Members Representative

COMMITTEE ON CONGRESSES AND CONFERENCES (C-CC) The thirty-fifth (35th) meeting of the IFCC Executive Board Committee on Congresses and Conferences (C-CC) was held on November 9, 2018 in Budapest, Hungary. There were several C-CC membership changes as of January1, 2018. Full Member J. Lopez was replaced by M. Blanes González who transitioned from Corresponding Member. Corresponding Member changes included the departure of A. Hedhili and the addition of W. Fang, E. Frank and H. Martin. C. Jackson (Beckman Coulter) replaced P. Yin (Abbott) as the Corporate Member. International Congresses of Clinical Chemistry & Laboratory Medicine (ICCCLM) IFCC ICCCLM (WorldLab) Seoul, Korea 2020 (May 24-28) Congress President: Prof. Won-Ki Min; Congress Chair: Prof. Junghan Song Planning for this Congress is on schedule. H. Martin joined the COC this year as the C-CC representative. Prof. Min reported on the Congress at the IFCC General Conference in Budapest. IFCC ICCCLM (WorldLab) Rome, Italy 2023 (May 21-25) Congress Chair: Prof. Sergio Bernardini Committee is being assembled and the first meeting is expected to take place in 2019. IFCC President Morris will serve as the IFCC EB representative and will be replaced by the incoming IFCC President Elect in 2020. James Wesenberg will serve as the C-CC representative. MZ Congressi will serve as the PCO. Regional Congresses of Clinical Biochemistry and Laboratory Medicine APFCB, Jaipur, India, 2019 (November 17-20) Congress Chair: Prof. Praveen Sharma Prof. Sharma presented a detailed report at the C-CC meeting in Budapest. Planning for the Congress is on target. EuroMedLab, Barcelona, Spain, 2019 (May 18 - 23) Congress President: Dra. Imma Caballé; COC Chair: Prof. Maurizio Ferrari The latest meeting of the COC was held on November 19, 2018. Planning for this Congress is on schedule. EuroMedLab, Munich, Germany, 2021 (May 16 – 20) Congress President: Dr. Karl Lackner Dr. Lackner was recently selected as the Congress Chair by the DGKL. Pre-

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liminary planning has gone well. The membership of the COC is being finalized and the first meeting will take place in 2019. COLABIOCLI, Panama City, Panama, 2019 (September 10-13) Congress Chair: Lizbeth Campillo, Jovanna Borace Planning for this Congress is well underway. AFCB, Ramallah, Palestine, 2018 Congress Chairs: Dr. M H Kamil and Dr. Osama Najjar Osama Najjar presented a detailed report at the C-CC meeting in Budapest. Overall, this was a highly successful Congress AFCB, Beirut, Lebanon, 2021 Congress Chair: Dr. Christian Haddad Osama Najjar reported only the above details in announcing the next AFCB Congress. AFCC, Marrakech, Morocco, 2019 Prof. Erasmus reported during the C-CC meeting in Budapest that the sixth (6th) AFCC Congress is to be held from 26 – 28 September, 2019 in Marrakech, Morocco. IFCC Specialized Conferences 16th Roche Diagnostics Bergmeyer Conference 2018 This conference has not been held since 2016 because of concerns related to the MedTech Europe Code of Ethical Business Practice. President Morris indicates that there are ongoing discussions within Roche and between the IFCC and Roche in terms of reactivating this conference. Congress Guidelines and Other Documents Review of the C-CC documents was not required in 2018. Many of the C-CC documents will be due for review and updating as required in 2019. IFCC General Conference A successful two-day IFCC GC was held in Budapest, Hungary on November 10 – 11, 2018. Congresses with IFCC Auspices: 76 events Other Business As determined at the C-CC meeting in Durban in 2017, the C-CC has worked with MZ Congressi in the development of a post-Congress survey for WorldLab and EuroMedLab delegates. The hope is that the survey will be approved by the IFCC and EFLM Executive Boards in time for EuroMedLab 2019 Barcelona. James Wesenberg, C-CC Chair

IFCC

further involvement of ICSH in JCTLM activities. A list of action items was developed. December 2018 ICSH made application to JCTLM to become a member organization of the JCTLM Executive Committee. Having met all the requirements for membership, ICSH was approved as the newest organizational member of the JCTLM Executive Committee. 1. JCTLM National and Regional Membership Applications. The Executive Committee approved the following applications in 2018 for JCTLM National and Regional Membership: • Greek Society of Clinical Chemistry - Clinical Biochemistry (GSCC-CB) • D.I. Mendeleyev Institute for Metrology, Rosstandart (VNIIM), Russian Federation • Canadian Society of Clinical Chemists (CSCC) / Societé Canadienne de Clinico-Chimistes (SCCC) 1. JCTLM Stakeholder Membership Application. The Executive Committee approved the following applications in 2017 for JCTLM Stakeholder Membership: • National External Quality Assessment Scheme for Clinical Chemistry in Greece (ESEAP) • International Consortium for Harmonization of Clinical Laboratory Tests (ICHCLR) • Institute for Quality Management in Healthcare (IQMH), Canada • UK National External Quality Assessment Scheme for Immunology. Immunochemistry & Allergy (UK NEQAS IIA) JCTLM Database: 1. Database Content as of March 2018: • 296 available certified reference materials; • 194 reference measurement methods or procedures • 176 reference measurement services delivered by 17 reference laboratories. 2. The JCTLM 2018 nomination cycle for certified reference materials, reference measurement procedures and calibration laboratories that provide reference measurement services for laboratory medicine and clinical chemistry closed May 30, 2018. The various Review Teams completed their respective reviews of the nominations in their areas of responsibility and the results were reviewed for approved at a meeting of the JCTLM Database WG on 4 December, 2018 at BIPM. Table 1 lists the results of the WG reviews and deliberations.

SCIENTIFIC DIVISION (SD) During 2018, the following members served on the SD Executive Committee: Philippe Gillery (FR) (Chair), Christa Cobbaert (NL) (Vice-Chair), Joseph Passarelli (US) (Secretary), Barnali Das (IN) – second half, Konstantinos Makris (GR), Tsutomu Nobori (JP) – first half, Mario Plebani (IT) (members) and James Pierson-Perry (US) (corporate representative). Five representatives of International Organizations are invited to attend the SD meetings as consultants or observers: Gary Myers (JCTLM), Heinz Schimmel (JRC), Karen Phinney (NIST), Chris Burns (NIBSC) and Youchun Wang (NIFDC). Two meetings were held during 2018: May 25 - 26 (Milano, Italy at the IFCC office) and November 8 - 9 (Budapest, Hungary in conjunction with the IFCC General Conference). Relationship with International Organizations The SD continues to pursue the expansion of its activities to partner with international organizations to promote the implementation of the concept of traceability in laboratory medicine and the implementation of reference measurement systems. • Joint Committee on Traceability in Laboratory Medicine (JCTLM) The JCTLM continues its work which is available for review on its database at www.bipm.org/jctlm. The following annual report summarizes 2018 activities of the JCTLM. Governance: Dr. Gary Myers completed his second and final term as Chair, JCTLM Executive Committee. Dr. Ian Young was nominated by IFCC and approved by the Executive Committee to serve a 2 year (2019-2020) as the new Chair of the JCTLM Executive Committee. Dr. Myers was appointed by IFCC to replace Dr. Graham Beastall as a representative from IFCC to the JCTLM Executive Committee. Dr. Myers joins Dr. Anja Kessler (Referenzinstitut für Bioanalytik) as the two appointed representatives from the IFCC to the JCTLM Executive Committee. JCTLM Membership: 1. JCTLM Executive Committee Organizations. The JCTLM Executive Committee continued its efforts to engage the International Council for Standardization in Hematology (ICSH) in collaborative programing activities in traceability. A joint leadership meeting with the ICSH and JCTLM was held 14-15 May, 2018 at BIPM, France. Members of the JCTLM Executive Committee and leaders from ICSH met to better understand the current status of standardization in the field of hematology and to facilitate further interaction between the ICSH and the JCTLM. The meeting discussion focused on the technical aspects and current developments for reference measurement systems for Blood Cell Counting and total Hemoglobin in blood samples. This meeting also provided the opportunity to look at the possibility to strengthen the working relationship between the ICSH and JCTLM and investigate possible options for

Table 1: Recommendation from Review Teams for 2018 Cycle 15 (Materials and Methods) and Cycle 13 (Services) JCTLM WG on Traceability Education and Promotion: JCTLM Newsletter. This fifth issue of the Newsletter was released in April 2018 and can be downloaded from the following link: http://www.bipm.org/ utils/common/pdf/JCTLM/JCTLM-Newsletter-2018.pdf • Meetings/presentations under the auspices of the JCTLM 1. JCTLM co-sponsored the 2018: Protein and Peptide Therapeutics and Diagnostics: Research and Quality Assurance International Workshop (PPTD-2018) in Chengdu, China. The theme of this workshop was “Measurement and Standards, Quality and Safety”. The output of this first meeting will be a discussion paper, which interested parties will be asked to comment on. 2. Dr. Graham Beastall delivered a JCTLM lecture entitled ‘Traceability in laboratory medicine: what is it and why is it important for patients?’ to three audiences at three different conferences. 3. 14 November, 2018: Dr. Graham Beastall delivered a JCTLM lecture entitled ‘Traceability in laboratory medicine: a driver for accurate patient results’ to the Conférence Générale des Poids et Mesures (CGPM) in Versailles, France. 4. 29 November, 2018: 12th International Scientific Meeting of the Centre of Metrological Traceability in Laboratory Medicine (CIRME) “Every day is patient safety day”. Milano, Italy. Working Group 1 (GUM): The circulation for review of the first Committee Draft of the document JCGM 103, Guide to the expression of uncertainty in measurement — Developing and using measurement models has been initiated. This document has been prepared by the Joint Committee for Guides in Metrology, of which the IFCC is a member, specifically by Working Group 1. This document is now being circulated for review amongst the eight mem-

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ber organizations (BIPM, IEC, IFCC, ILAC, ISO, IUPAC, IUPAP and OIML), and to the Directors of National Metrology Institutes. Working Group 2 (VIM): The number of members of JCGM-WG2 has expanded since the last JCGM meeting by 3, from 12 to 15, with new representatives from IUPAP (1), OIML (1), and IUPAC (2), and one representative leaving (ILAC). The main technical activity of JCGM-WG2 in the period May 2017 – November 2018 has been to develop a ‘minimum change’ version of a first “committee draft” (CD) of the fourth edition of the VIM that more fully incorporates entries on nominal properties and, to a much lesser extent, ordinal properties. The definitions of ‘measurement’ and ‘measurement unit’ have been given careful consideration in this regard. A longer-term ‘evolutionary’ version of the VIM4 CD has also been under development. Status of these two versions of these VIM4 CDs were presented at the 3 December 2018 JCGM meeting. Also to be discussed are publishing options of the VIM4 (e.g., electronic, hard copy, structure, languages). • Joint Research Center (JRC – formerly the Institute for Reference Materials and Measurements (IRMM)) Close collaboration with JRC continues through a number of joint ventures involving SD Committees and Working Groups. Reference materials are still a key area of focus of the JRC. The status of specific JRC reference materials activity is mostly covered under the respective Cs and WGs. • Clinical and Laboratory Standards Institute (CLSI) (Formerly NCCLS) An updated list of joint CLSI/IFCC documents is available on the IFCC web site at: http://www.ifcc.org/index.asp?cat=Publications&scat=CLSI_(Clin_ Lab_Stand_Inst)_-_IFCC_Joint_Projects&rif=6&dove=1. A project proposal was accepted by the CLSI Consensus Council for the update to EP28 (guidance document on Reference Ranges). This has direct implications to the Committee on Reference Intervals and Decision Limits (C-RIDL). As such, it is highly likely that Prof. Yeşim Özarda (chair of CRIDL) will co-chair the CLSI Document Development Committee (DDC) for the revision to EP28. • National Institute of Standards and Technology (NIST) NIST continues to undertake a large number of projects, many of which are of considerable interest to IFCC. The NIST website (www.nist.gov) can provide information on materials and services available today. The most relevant projects to the IFCC and SD are: • Renewal of Troponin • Vitamin D • Albumin in urine • National Institute of Biological Standards and Control (NIBSC) NIBSC successfully established 11 new WHO International Standards potentially of interest to the SD, including the first cell counting standard for CD4 enumeration. In addition, proposed 5 new standards projects to be endorsed by WHO. • European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) The EFLM Science Committee and SD leadership once again agreed there should be close liaison and communication between the two groups. Professor Eric Kilpatrick is the EFLM SC chair. The Science Committee is responsible for scientific matters within EFLM and projects which further the scientific development of EFLM. Activities of the Committee particularly focus on promotion of research that translates the scientific results of clinical chemistry and laboratory medicine to clinical applications and improves patient outcomes through the appropriate use and interpretation of laboratory data in clinical practice. Within the EFLM SC there are working groups on cardiac biomarkers, biological variation, test evaluation, personalized laboratory medicine and a number of others but the general consensus of the SD is that these activities do not overlap with the IFCC SD. Professor Philippe Gillery (SD chair) has been in contact with the chair of the EFLM SC. Approaches to avoid overlap and work collaboratively continue to be discussed and explored. World Health Organization (WHO) The WHO meeting occurs each autumn. Professor Philippe Gillery attends and participates as the liaison from the SD. Dr. Chris Burns is also a full member of the WHO Expert Committee on Biological Standardization (ECBS) and attended the 2018 meeting. Much of the focus was on public health and emerging pathogens (Zika, Ebola, polio containment). Much of the activities of ECBS are not relevant to the IFCC. The WHO has a different perspective with respect to metrology and as a result, commutability of some of the reference materials needs to be carefully considered. Congresses (WorldLab, Regional and other congresses) There were no congresses during 2018. The SD will next present at EuroMedLab 2019 in Barcelona, Spain. Activities of Committees and Working Groups The Committees (Cs), which are theme-oriented, carry out much of the scientific and professional activities of the SD. Their work is often in close collaboration with other international organizations. For more specific tasks, the activities are usually accomplished through Working Groups (WGs). Committees • C-Nomenclature, Properties and Units (C-NPU); in collaboration with International Union of Pure and Applied Chemistry (IUPAC) Chair: Karin Toska (NO) As a reminder, in 2014 a formal agreement between IFCC and IUPAC was put in place. Wikipedia presence for the NPU was created 2015 (edited by the chair with input from many NPU members). The Wikipedia entry is a use-

ful introduction: (https://en.wikipedia.org/wiki/NPU_terminology) and the NPU Website is performing well. The C has written a manuscript entitled: “Recommendation on measurement units - why and how” intended for submission in the electronic Journal of the International Federation of Clinical Chemistry and Laboratory Medicine. In a current C-NPU activity, an online manual of NPU terminology is under development. The goal is to have a sort of encyclopedia for medical laboratory terminology that is accessible for any medical laboratorians. The project is funded by IUPAC (https://iupac.org/projects/project-details/?project_nr=2016-044-2-700). The project is in an iterative stage of establishing, reviewing and revising homepages. The C plans to meet in Barcelona in conjunction with EuroMedLab 2019 and at the IUPAC meeting in Paris in July. • C-Molecular Diagnostics (C-MD), Chair: Deborah Payne (US) During 2018 ongoing progress towards C-MD’s terms of reference included: Term of Reference 1. To Foster dynamic exchanges between IFCC and molecular diagnostic laboratories and industry. Accomplishments Include: 1. Updated website to include Nomenclature page; 2. Proposed symposium to COLABIOCLI entitled “Quality Considerations for Molecular Diagnostics” was approved; 3. Contacted two companies: Promega (https://www. promega.com/) and Oxford Gene Technology (https://www.ogt.com/) regarding harmonization and standardization projects for lower income countries; 4. Communicated with chair of Nomenclature committee regarding CMD efforts; 5. Added additional webpage for Nomenclature to IFCC C-MD. Term of Reference 2. To produce guidelines on clinical validation of tests, conduct and report on molecular diagnostic tests. Accomplishments Include: 1. Completed survey on reporting aspects of Molecular Diagnostics; 2. Submitted paper and paper was accepted on harmonization of reports; 3. Models for pre-emptive Pharmacogenetics in process; 4. Opinion or research paper on Alternate Assessment and EQA in consideration Term of Reference 3. Creation of a network of locus-specific IFCC Molecular Diagnostics Centres. Accomplishments Include: 1. Changed acceptance criteria for Expert laboratories; 2. Implemented better monitoring and follow-up method for assessing participation of expert and network laboratories; 3. Approved laboratories in Argentina, Austria, Canada, Germany, Iran, Japan, Mexico, Uruguay and USA as IFCC Expert Centers; 4. Added additional expert laboratories to separate page of website. • C-Traceability in Laboratory Medicine (C-TLM), Chair: Anja Kessler (DE) During 2018 ongoing progress towards C-TLM terms of reference included: Term of Reference 1. To Support activities regarding Traceability in Laboratory Medicine, permitting IFCC to continue its international role in this area and providing an operating link between the SD and the WGs of the Joint Committee on Traceability in Laboratory Medicine (JCTLM), concerning identification of reference measurement procedures, reference materials and reference laboratories. Accomplishments include: The “Protein and Peptide Therapeutics and Diagnostics Workshop” (PPTD-2018) that was held at October 10-12, 2018 in Chengdu China under the auspices of the JCTLM. A series of lectures presented the elements of traceable reference systems. The chair of the C-TLM participated with a lecture on reference methods according to ISO 15193. It was also noteworthy that the results of RELA were cited in various lectures and act as support for the arguments of the speakers in terms of traceability. Term of Reference 2. RELA - External Quality Assessment Scheme for Reference Laboratories. The C-TLM supports reference laboratories in the context of complete reference systems (accepted reference measurement procedures of higher order, reference materials, and reference laboratories) by establishing an External Quality Assessment Scheme (EQAS) for reference laboratories in order to monitor their competence. Accomplishments include: The results of RELA2017 have been evaluated and published (http://www.dgklrfb.de:81). The number of published results increased from 343 (RELA2016) to 412 (RELA2017). Especially laboratories from Europe and China are active in the project. The survey RELA2018 has been announced. The shipment of samples has been arranged at the beginning of November. About 515 orders from 53 laboratories are registered. The committee discussed how to extend the RELA portfolio. Term of Reference 3. To promote establishment and maintenance of IFCC reference laboratory networks for clinically relevant measurands. Accomplishments include: HbA1c Network. It is standard for the IFCC Network to organize two intercomparison studies a year. This was also done in 2018 with participation of all approved network laboratories and the designated comparison method networks in the US (NGSP/DCCT), Japan (JDS) and Sweden (MonoS). This year there were no candidate reference laboratories. The Master Equations between the IFCC Reference Measurement Procedure and the designated comparison methods were confirmed again. In July there was a network meeting during the AACC in Chicago. The next meetings will be in Barcelona (EuroMedLab May 2019) and Seoul (WorldLab May 2020). Another topic was the criterion for approval of the network laboratories. • C-Reference Intervals and Decision Limits (C-RIDL), Chair: Yesim Ozarda (TR) During 2018 ongoing progress towards C-RIDL terms of reference included: Term of Reference 1. Review current concepts of establishing reference intervals (RIs) and decision limits and to prepare state-of-the-art position statements regarding new avenues. Accomplishments include: Two publications were realized (see Publications section): 1. Indirect methods for reference interval determination – review and recommendations: the indirect reference interval study in Turkey was completed to compare alternative approaches (comparing conventional and big data) for the determination of reference intervals with data obtained from the global study; 2. Distinguishing

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reference intervals and clinical decision limits: review the current concepts of clinical decision limits. The attempts for updating the CLSI document EP28-28-A3 guideline was initiated as a CLSI-IFCC joint project to reflect these recent published works of C-RIDL. The chair of C-RIDL, Dr. Yesim Ozarda, has been appointed as the vice chairholder for the EP28 revision to ensure alignment. Term of Reference 2. To make available reference intervals and decision limits that respects the requirements of international directives such as the European IVD Directive 98/79, and relevant ISO standards. Accomplishments include: The results of Global Reference Intervals Study performed by C-RIDL were previously downloaded on the web-page: "A global multicenter study on reference values" Part 1: Assessment of methods for derivation and comparison of reference intervals, Part 2: Exploration of sources of variation across the countries. The country-specific reference intervals were derived for China, Japan, Turkey, Russia, UK, USA, Saudi Arabia, Argentina, India, Philippines, South Africa, and Pakistan. Term of Reference 3. To determine priority list of measurands (analytes) for which reference intervals and/or decision limits have to be developed, considering various factors, such as age, gender, ethnicity, and for which the greatest improvements in medical decision making are anticipated. Accomplishments include: The previous studies performed by C-RIDL were on the most commonly used tests in the clinical laboratories for the adult age group in females and males. The main age was 18-65 years, although older healthy individuals were also included. The list of analytes were published by CCA and age-related changes in the reference values were nearly consistent across the participating 12 countries. Term of Reference 4. To monitor and evaluate currently proposed reference intervals for selected measurands (analytes) in the light of the concept of traceability and of the identification of the uncertainty. Accomplishments include: No action was taken on this Term of Reference. Term of Reference 5. Establish transferability protocols of reference intervals and decision limits, which take into consideration inter-routine laboratory method variations and achieve better applicability in clinical practice. Accomplishments include: The chair, Yesim Ozarda published an opinion paper with Khosrow Adeli titled Verification of reference intervals in routine clinical laboratories: practical challenges and recommendations, which the transference and verification protocols of reference intervals were discussed and taken into consideration with respect to inter-routine laboratory method variations to achieve better applicability in clinical practice. • C-Standardization of Thyroid Function Tests (C-STFT), Chair: Hubert Vesper (US) During 2018 ongoing progress towards C-STFT terms of reference included: Term of Reference 1. Establish a system to maintain traceability of free thyroid hormone and TSH measurements. Accomplishments include: 1. Samples locations were consolidated by moving those at Solomon Research Park to NIBSC. At NIBSC different sets for the follow-up panels were consolidated; 2. The UGent assessed the ruggedness of the free T4 RMP by validating modifications to the design of the equilibrium dialysis cells and the membranes; 3. A network of FT4 reference laboratories is being established that includes four labs in Japan, the Netherlands, Belgium and the USA. The first method comparison was completed. The results can be summarized as followed: The correlation of the 4 lab results to the overall mean is very good, the RMP SOP can be reproduced in different labs. The mean bias of labs is within ±2.5% bias, but there is room for improvement. Labs show consistent bias across the concentration range, and this indicates calibration differences rather than sample related issues. Term of Reference 2. Coordinate programs to evaluate free thyroid and TSH assays with regards to their analytical performance. Accomplishments include: C-STFT worked with the CDC Clinical Standardization Programs to ensure that reference measurements performed at CDC are in line with those at IFCC. Term of Reference 3. Develop reference intervals for free thyroid hormones and TSH. Accomplishments include: 1. A project to develop Japanese reference intervals was discussed and a decision on the design of the study was made; 2. Possible collaborations with other groups or organizations to develop regional reference ranges (i.e., EUThyroid, US NHANES) was explored Term of Reference 4. Liaise with key stakeholders to promote the use of the standardized assays in routine clinical practice and public health, to ensure analytical performance requirements meet clinical needs, and to help with developing and establishing reference intervals. Accomplishments include: 1. Presentations were given at the AACC Annual Scientific Meeting & Clinical Lab Expo in Chicago, IL July 29 – August 2, 2018 – the work of the C-STFT was presented in the scientific session on Accurate Measurement of Thyroid Hormones in Disease and Pregnancy held on August 1 2018; 2. A workshop was given at the same AACC meeting to manufacturers and stakeholders; 3. Information about the IFCC C-STFT was shared and coordinated with the educational activities conducted by the CDC. • C-Harmonization of Autoantibody Test (C-HAT), Chair: Joanna Sheldon (UK) During 2018 ongoing progress towards C-HAT terms of reference included: Term of Reference 1. To evaluate what are the main causes of variability for a number of diagnostically critical autoantibodies. Accomplishments include: The C-HAT working with the JRC have sent samples to Dr. Ulrich Specks from the Mayo Clinic for epitope mapping studies of the reactivity of ERM DA 476/IFCC and ERM DA 483/IFCC. The preliminary report suggests that both reference preparations have reactivity against the major epitopes of the relevant antigens. Further details of the epitope mapping studies are expected and we hope to report them at the C-HAT meeting in Barcelona in May 2019. Term of Reference 2. To identify autoantibodies where a common calibra-

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tor could reduce the inter-assay variability. Accomplishments include: IgG anti glomerular basement membrane is the next antibody where the C is planning to prepare a certified reference preparation. The committee is currently trying to source additional raw material for the reference material. IgG and IgA anti TTG antibodies are generally considered to be the next important antigens where a common reference material would be beneficial. Term of Reference 3. To identify or produce commutable materials that could be used as interim calibration material for autoantibody assays. Accomplishments include: A further commutability study for B2GP1 candidate reference material has given some challenging results and a suitable way forward is unclear. It may not be possible to assign values in mg/L of IgG against B2 glycoprotein 1 and may need an alternative approach. Currently, C-HAT is exploring the possibility of working with the WHO (or their agents e.g. NIBSC) to assign values in arbitrary or international units. Term of Reference 4. To produce well-characterized pure antibody preparations with known concentration and identity and use these to transfer values to a matrix preparation. Accomplishments include: The preparation of pure antibody preparations with known concentrations embedded in the value assignment process. Term of Reference 5. To evaluate the impact of new reference material on the variability of autoantibody tests and identify areas where further harmonization would improve diagnostic accuracy. Accomplishments include: The C is in discussion with UKNEQAS and the Royal College of Pathologists of Australasia Quality Assurance Programs. Working Groups • WG - Standardization of Hemoglobin A2 (WG-SHbA2), Chair: Andrea Mosca (IT) During 2018 ongoing progress towards WG-HbA2 terms of reference included: Term of Reference 1. Definition of a reference measurement procedure for haemoglobin A2. Accomplishments include: A paper describing the principle of the RMP based on isotopic dilution and mass spectrometry and its preliminary validation has been published in Clin Chim Acta. (See Publications Section) Term of Reference 2. Development of a secondary certified reference material (CRM) for hemoglobin A2 (in cooperation with the JRC). Accomplishments include: The JRC approved the start of this project and has recently nominated a project responsible person (Dr. Guy Auclair). A first conference call has been held in December. • WG - Standardization of Carbohydrate-Deficient Transferrin (WG-SCDT), Chair: Jean Deenmamode (UK) During 2018 ongoing progress towards WG-CDT terms of reference included: Term of Reference 1. Promoting the use of the HPLC reference measurement procedure (RMP) as the accuracy base for CDT test standardization. Accomplishments include: Some members of the WG have been in contact with other groups in Europe, with a focus on CDT, to participate as network laboratories by using the HPLC RMP. Term of Reference 2. Maintaining sustainability of an international network of laboratories Accomplishments include: Sustainability and performance of network laboratories and participating commercial manufacturers are assessed by the yearly distribution of IFCC calibrators, controls and blind samples from Dr. Weykamp’s laboratory. Laboratory performance is assessed on a pass/fail criterion and HPLC RMP performance is assessed in further detail by Dr. Schellenberg. Term of Reference 3. Supporting the worldwide standardization of commercial methods against the RMP. Accomplishments include: Most participating commercial CDT manufacturers have achieved positive results towards CDTIFCC and have launched respective assays. Term of Reference 4. Offering consultation concerning use of biomarkers of alcoholism towards national and international agencies. Accomplishments include: Generally, a local or extended activity initiated primarily by a member of the WG. The process has been in place with better success in Sweden and the Netherlands. • WG-Standardization of Albumin Assay in Urine (WG-SAU) (a joint committee with the Laboratory Working Group (LWG) of the National Kidney Disease Education Program (NKDEP), USA); Chair: Lorin Bachmann (US) During 2018 ongoing progress towards WG-SAU terms of reference included: Terms of Reference 1. Status of harmonization among commercial immunoassays for UA (funded by NKDEP). Accomplishments include: A freeze-thaw study was performed using 66 pairs of unfrozen and frozen freshly collected, native urine samples to determine the effects of a single freeze-thaw cycle on urine albumin results. Median bias for frozen vs. nonfrozen samples was < 1.2% for all methods tested suggesting that frozen samples may be used for the commutability studies. However, outlier samples were observed with biases that exceeded 10%. Formal statistical analysis is in process. Terms of Reference 2. Reference measurement procedure for UA (funded by NKDEP and NIST). Accomplishments include: Candidate isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) reference measurement procedures for UA are under development by the Mayo Clinic Renal Testing Laboratory, University of Minnesota Advanced Research Diagnostic Laboratory and NIST. NIST and Mayo have performed multiple comparison studies between the two candidate reference measurement procedures. There were some unexplained discrepancies that are under investigation. Univ of Minnesota and Mayo are developing a publically available refer-

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ence measurement procedure with the goal of submitting the reference measurement procedure to JCTLM and making reference measurement procedure services available to IVD manufacturers for metrological traceability of clinical laboratory measurement procedures. Term of Reference 3. Reference materials for UA and urine creatinine. Accomplishments include: SRM 2925 Human Serum Albumin from NIST is a primary certified reference material for use with higher order reference measurement procedures for albumin. To facilitate standardization of routine methods, NIST SRM 3666 is currently being developed based on the specifications recommended by the WG-SAU and the LWG of the NKDEP. • WG - Standardization of Pregnancy-associated Plasma Protein A (WG-PAPP A), Chair: Saara Wittfooth (UK) During 2018 ongoing progress towards WG-PAPPA terms of reference included: Term of Reference 1: To develop a reference system for standardization of PAPP-A measurement employed as marker for prenatal screening. Accomplishments include: 1. Pregnancy serum-based materials diluted in different diluent matrices were tested by various assay systems of the participating companies; 2. Both 2nd trimester and 3rd trimester serum pools were found suitable as reference materials to provide better agreement among the commercial assays; 3. Calf serum, human serum and company-specific diluent were shown preliminarily suitable as the diluent; 4. The commercial assays were confirmed to detect similarly endogenous PAPP-A in different forms. • WG - Growth Hormone (WG-GH), Chair: Eef Lentjes (NL) The overall goal of the WG-GH is to achieve standardization of growth hormone through secondary reference materials and a reference measurement procedure. To achieve this goal a harmonization study was done, in which several pooled serum samples were tested for commutability. In this study different calibrators were made by pooling samples from apparently healthy persons, or patients (adults or children) to asses for commutability. In addition, IS 98/574 was diluted in GH deficient serum. All calibrators were prepared in two different concentrations: about 10 and 40 mU/L or 3.3 and 13.3 ng/mL respectively. Measurements by LCMSMS are still unavailable. However, results from all immunoassay methods were processed and have been sent to the members of the working group together with a proposal for the future direction of investigation. Future directions: The most important change of approach will be the use of more fresh samples, in order to keep the native forms of GH preserved in the samples. A commutability study will be repeated with 30 patient samples and two IS 98/574 and five healthy donor calibrators. All available methods that are in use for routine GH measurements will be included in the study - at a minimum: Immulite 1000 (Siemens Healthcare), Cobas E411 (Roche), DXi (Beckman), Liaison (DiaSorin), and iSYS (IDL). • WG - Standardization of Insulin Assays (WG-SIA), Chair: Amy Saenger (US) During 2018 ongoing progress towards WG-SIA terms of reference included: Term of Reference 1. To improve the standardization of assays for insulin by the development of a candidate reference method and materials. Accomplishments include: 1. Ongoing development and validation of MS/MS method for intact insulin at University of Minnesota. A method has been established and undergoing minor modifications to ensure appropriate analytical sensitivity; 2. Continued discussions and collaborations with other laboratories developing insulin methods by mass spectrometry (Quest Diagnostics, Mayo Clinic). The WG plans to sustain these efforts to evolve potential additional reference method procedures in these laboratories; 3. In collaboration with the College of American Pathologists (CAP), established criteria for ongoing accuracy based evaluation of serum pools for testing of insulin, C-peptide, and glucose. This accuracy based survey can be sent globally and utilized to demonstrate ongoing state of harmonization and standardization of insulin assays (as well as C-peptide assays). Term of Reference 2. Establish availability of pure recombinant human insulin as a Reference Material (RM) for insulin assays and have the RM listed by JCTLM. Accomplishments include: A new reference material is available from the NIBSC. Continue collaboration with Dr. Chris Burns, Dr. Gwen Wark, and colleagues at NIBSC to evaluate and assist with validation of new recombinant insulin candidate reference material. Term of Reference 3. Continue a program to collect serum samples (and serum pools) as needed for assignment of IDMS values and a biobank which could be utilized collaboratively by the WG-SIA and C-peptide Standardization Group. These materials will sustain the program to harmonize results from manufacturers of insulin assays. Accomplishments include: Serum samples are bio-banked in -80C freezers at the University of Minnesota. Specimens were used to compare between a few existing insulin and C-peptide LC-MS/MS methods. • WG - Standardization of Troponin I (WG-TNI), Chair: Robert Christenson (US) During 2018 ongoing progress towards WG-TNI terms of reference included: Term of Reference 1: Development of a candidate secondary reference measurement procedure for cardiac troponin I. Accomplishments include: 1. The commutable set of Reference Materials (RM) for cardiac troponin I (TnI) has been coined RM 2922. At this stage of technology development, the material will be a RM rather than a Standardized RM (SRM) because the mass spectrometry methodology/technology for appropriate assignment of values to RM 2922 does not yet have the sensitivity and characteristics required; 2. The Workgroup has finalized the protocol for collecting the ‘raw materials” for RM 2922 samples from patients with myocardial infarction having appropriate TnI concentrations; 3. The WG-TNI will continue to work with NIST and worldwide metrology groups, academic experts and industry part-

ners toward development of the commutable secondary standard material. Term of Reference 2: Development of a candidate secondary reference material for cardiac troponin I Accomplishments include: 1. Initiated collection of patient samples for use in developing a commutable secondary standard using the WG-TnI developed protocol; 2. WG-TNI is working together to finalize arrangements with the contractor for blending the material and aliquoting the four (4) RM concentrations into 0.5 mL vials each; 3. RM 2922 will be distributed by NIST. Term of Reference 3: Conduct a round robin study to assess cTnI standardization and initiate validation among commercial cTnI assays. Accomplishments include: 1. The WG is in the process of designing a Round Robin Study for high sensitivity (hs)cTnI methods using common pools of commutable samples; 2. All manufacturers with hsTnI assays will be invited to participate; 3. A primary objective will be to reflect the relationships between the hsTnI methods. • WG - Parathyroid Hormone (WG-PTH), Chair: Cathie Sturgeon (UK) During 2018 the ongoing progress towards WG-PTH terms of reference included: The WG continues to work on developing a reference system for PTH. Currently, activities are focused in three areas: Term of Reference 1. Collaborative educational effort to encourage worldwide implementation of PTH IS 95/646 and to assess the effect of this on between-method agreement. Accomplishments include: The importance of establishing whether PTH IS 95/646 is commutable and improving betweenmethod agreement has been highlighted to audiences at several national and international conferences. A protocol for the planned commutability study has been circulated to supporters of the Working Group. Arrangements for specimen collection and processing are being made. Term of Reference 2. Definition of inclusion/exclusion requirements for an appropriate panel of sera and plasma with which to establish reference intervals and establishment of such a panel with support from the clinical community and diagnostics manufacturers. Accomplishments include: Requirements for the reference panel are expected to be similar to those for the commutability study. Term of Reference 3. Development of a reference measurement procedure for PTH(1-84) to a standard that would enable its adoption by the IFCC reference laboratory network. Accomplishments include: Considerable progress was made in 2018 to increase the analytical sensitivity of the candidate reference measurement procedure for PTH(1-84) that is being developed at the CDC laboratory in Atlanta under the direction of Dr Hubert Vesper. Analytical sensitivity of the candidate RMP now approaches that of immunoassay methods. Preliminary results with the method show promise for the accurate and reliable quantification of intact PTH and related fragments without enzymatic digestion. The latter represents a major step toward improving understanding of what is being measured as “PTH”. • WG - CSF Proteins (WG-CSF), Chair: Johan Gobom (SE) During 2018 ongoing progress towards WG-CSF terms of reference included: Term of Reference 1. 1. Collaborative effort to develop RMPs and CRMs of CSF biomarkers to enable harmonization across analytical platforms; 2. Development of new CSF biomarkers. Accomplishments include: 1. Planning of Round Robin study of candidate RMPs for CSF amyloid beta 1-40; 2. Planning of Round Robin study of candidate RMPs for CSF tau; 3. Planning of Round Robin study of candidate RMPs for CSF tau Term of Reference 2: CSF NFL Method/RMP collaborative project. Accomplishments include: Still to be done. • WG - Standardization of Bone Marker Assays (WG-SBMA), Chair: Etienne Cavalier (BE) This is a joint activity with the International Osteoporosis Foundation. During 2018 ongoing progress towards WG-SBMA terms of reference include: Term of Reference 1: Standardize or harmonize (as technically feasible or appropriate at this time) clinical assays available for routine and research use for the serum assay for C-telopeptide fragments of collagen type I α1 chains containing the epitope Glu-Lys-Ala-His-Asp-s-Gly-Gly-Arg in an isomerised form (also known as serum Crosslaps (CTx). Accomplishments include: A manuscript has been written and submitted to IFCC, IOF and IVD partners. Term of Reference 2: Standardize or harmonize (as technically feasible or appropriate at this time) clinical assays available for routine and research and the serum assay for N-terminal Propeptide of Type I Procollagen (P1NP). Accomplishments include: The comparability study of the two major clinical assays for PINP has been completed at four European centres including data on the effects of serum or plasma specimen, fasting or nonfasting subjects and males and females presenting to osteoporosis clinics on the comparability of the results of assays from two manufacturers used by clinical laboratories. A draft manuscript is to be prepared. Additional Information: The activities of this WG will be taken in charge by the formation of a new Committee “Bone Markers” (C-BM) that will be initiated in 2019. This will also include the WGs –PTH and Vit D. • WG - Commutability (WG-C). Chair: Greg Miller (US) During 2018 ongoing progress towards WG-C terms of reference included: Term of Reference 1: Establish operating procedures for the formal assessment of the commutability of a reference material intended for use as a calibrator, trueness control or EQA sample, taking into account different measurement procedure properties and categories of traceability described in ISO 17511. Accomplishments include: Three papers were published in Clinical Chemistry (see publications section). A proposed revision to the VIM definition of commutability was submitted to the JCGM WG2 via Gunnar Nordin who represents IFCC on JCGM WG2. Term of Reference 2: Establish procedures to correct for bias in a metrological traceability hierarchy caused by non-commutability, or by bias that

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meets a commutability criterion, of a reference material. Accomplishments include: Described in term of reference #1 and will be addresses in publication #4. Term of Reference 3: Establish how to define the criterion for acceptable commutability that is required for a given reference material, taking into account its intended use and the intended use of the measurand. Accomplishments include: Included in the part 1, 2 and 3 papers published in Clin Chem and in part 4 to be published in 2019. Term of Reference 4: Advise IFCC Committees and Working Groups on how to assess the commutability of materials on which they are working. Accomplishments include: No requests for advice were received in 2018. • Immunosuppressive Drugs (WG-ID), Chair: Christoph Seger (CH) During 2018 ongoing progress towards WG-FIT terms of reference included: Term of Reference 1. Regulatory framework for submission of methods and materials to JCTLM. Accomplishments include: During the first meeting the design outline for possible JCTLM submission were discussed. Term of Reference 2. Measurement comparison initiative. Accomplishments include: During the first meeting the design outline for comparative measurements were discussed. The RfB of the DGKL may serve as distributor (frozen blood only). Term of Reference 3. Production of reference materials. Accomplishments include: Not started yet. Term of Reference 4. Establishment of reference methods. Accomplishments include: Not started yet. Term of Reference 5. Establishment of reference procedures. Accomplishments include: Not started yet. Can only start when #3 and #4 is fulfilled. • WG - Apolipoproteins by Mass Spectrometry (WG-APO MS), Chair: Christa Cobbaert (NL) During 2018 ongoing progress towards WG-APO MS terms of reference included: Term of Reference 1: To achieve standardization of a panel of clinically relevant serum apolipoproteins (apo) A-I, B, C-I, C-II, C-III, E and apo (a) (including qualitative phenotyping where needed). Standardization is done in such a way that measurement results are traceable to SI as outlined in ISO 17511. Other traceability chains will be used in cases where traceability to SI cannot be achieved. Accomplishments include: 1. Reference measurement procedure. In 2018, the WG determined common LC-MS transitions for the apolipoprotein-derived peptides. Using these common transitions and synthetic peptides, an instrument comparison study was performed to see whether all three mass spectrometers (each from different vendors) perform similarly. The WG is currently finalizing the data evaluation towards the end of 2018; so far, only marginal differences in performance were observed between the three instruments and locations. It is currently investigated whether a common data evaluation strategy using open-source software is needed. Moreover, the WG has evaluated the optimal digestion conditions for serum apolipoproteins to ensure maximum recovery. For 5 out of the 7 apolipoproteins, this was achieved. For the other two, further optimization is needed. An SOP for the harmonized MS-based method is under development and will be finalized early 2019; 2. Reference materials. It was decided to use a step-up approach in the development of reference materials. First, reference materials for apo(a) will be developed, followed by apoA-I and apoB. Reference materials for apoC-I, C-II, C-III and E will follow last. During 2018, the WG obtained pig EDTA plasma with human apo(a) with a specified number of kringles. A first evaluation of the suitability of this material was performed. Term of Reference 2: To evaluate clinical performance and clinical utility of serum apolipoprotein panel(s) for CVD risk stratification and treatment, in comparison to or together with contemporary blood lipids. Accomplishments include: Several studies were initiated at the LUMC, which have resulted in two publications and a submitted manuscript. (see Publications section). • WG - Pancreatic Enzymes (WG-PE), Chair: Denis Grote-Koska (DE) During 2018 ongoing progress towards WG-PE terms of reference included: Term of Reference 1: To develop a primary reference method for pancreatic Amylase in Serum. Accomplishments include: In the calibration laboratory in Hannover different experiments were performed giving the proof of principle of the measurement procedure. Namely: determination of inhibition coefficients; recovery of experimental vs. calculated results; linearity of absorbance kinetics; glucosidase inhibition; correlation to lipase and total amylase; Term of Reference 2: To develop a primary reference method for pancreatic Lipase in Serum. Accomplishments include: Further investigation and development have been performed by Shigeru Ueda (Japan). Term of Reference 3: To support EC-JRC (Joint Research Centre, Directorate F – Health, Consumers and Reference Materials, formerly IRMM) in case of studies and certification of reference materials for enzymes. Accomplishments include: A commutability study of an ERM for amylase was published. This was not positioned in WG-PE, however, F. Ceriotti, J. Gella and D. Grote-Koska from WG-PE were involved. • WG - Fecal Immunochemical Testing (WG-FIT), Chair: Sally Benton (UK) During 2018 ongoing progress towards WG-FIT terms of reference included: Term of Reference 1. To harmonize and/or standardize analysis of haemoglobin in faecal samples by immunochemistry (FIT). Accomplishments include: 4 candidate reference materials have been identified. These reference materials are being tested on 4 different quantitative FIT laboratory analysers at the Cancer Screening Lab in Guildford with collaboration from the JRC reference laboratory in Geel. Preliminary analysis has been carried

IFCC

out which was presented at the FIT-WG meeting in October in Vienna. Term of Reference 2. To standardize the pre-analytical phase. Accomplishments include: A review was completed by Natasha Djedovic of the pre-analytical variables of FIT. This was discussed at the FIT-WG. Term of Reference 3. To establish EQA and 3rd party IQC programmes. Accomplishments include: A review of available EQA schemes available globally was completed. There are currently no 3rd party IQC materials available Term of Reference 4. To determine impact of assay interference of Hb variants and other factors. Accomplishments include: A paper investigating impact of Hb variants on FIT detection has been published by one of the group members team and this was discussed at a FIT-WG. • Cell free DNA and related circulating biomarkers (WG-cfDNA), Chair: Ron van Schaik (NL) The activities of the WG have only recently started. The WG has reached out for corporate member sponsorships to enable face-to-face meetings. Terms of Reference: To identify and provide guidance on preanalytical and analytical aspects for obtaining good and reproducible results for cfDNA and related circulating biomarkers for clinical use, and to guide the correct clinical implementation of these biomarkers; Current projects: 1. Defining pre-analytical aspects / drafting guideline; 2. Defining minimal analytical performance; 3. Setting up proficiency testing for cfDNA; 4. Organizing international workshops; 5. Defining grant proposals to address unmet needs. The chair and WG have prepared a paper about the pre-analytical aspects and the paper is currently being reviewed by the WG. The chair believes the WG members will provide expertise in lung cancer, organ rejection, and other broad areas (such as exosomes). The WG also plans to be involved early on with NMIs. • Standardization of Procalcitonin assays (WG-PCT), Chair Vincent Delatour (FR) During 2018 ongoing progress towards WG-PCT terms of reference included: Term of Reference 1. Develop and validate a reference measurement procedure for PCT absolute quantification by Stable Isotope Dilution Mass Spectrometry. Accomplishments include: 1. Different primary calibrators have been produced. Their purity is being characterized by high resolution mass spectrometry and PCT concentration in calibration solutions is being determined by Amino Acid Analysis (AAA); 3. Different separation methods to purify PCT in biological samples are under development with the objective to validate a candidate reference measurement procedure for absolute quantification of PCT by IDMS Term of Reference 2. Document and understand the variability of results provided by the different commercially available PCT assays. Accomplishments include: 1. Agreement and correlation between the different PCT assays will be evaluated through an interlaboratory comparison coupled with a commutability study involving the most popular PCT assays. Discussions on the design of the study have started. Term of Reference 3. Evaluate the need for standardization of PCT assays. Accomplishments include: The ICHCLR identified PCT standardization as high priority with high clinical impact. Consultation with IVD manufacturers revealed that the need and demand for standardization of PCT assays differs in the 2 following situations: a. BRAHMS licensed assays are all calibrated with the Kryptor method. Assay manufacturers feel that recalibration of BRAHMS PCT assays is not a priority and possibly appears undesirable because introducing a new reference system based on IDMS could potentially result in the need to revise clinical decision limits, which could create confusion in the clinical community; b. For PCT assays other than BRAHMS PCT assays, there is currently no internationally agreed reference system and there is a need for assay standardization. All WG members agree that commutable EQA materials are needed to accurately estimate betweenmethod agreement. Term of Reference 4. Evaluate the feasibility for standardization of PCT assays. Accomplishments include: Feasibility for standardization of PCT assays will be evaluated after activities planned within ToR 1 and 2 have been completed. Term of Reference 5: Perform standardization of PCT assays, if needed and feasible. Accomplishments include: The need and feasibility for standardization of PCT assays first need to be evaluated. • Vitamin D Standardization Program (WG-Vit D), Chair: Christopher Sempos (US) During 2018 ongoing progress towards WG-Vit D terms of reference included: Term of Reference 1. Re-evaluate current Vitamin D Standardization Program (VDSP) performance guidelines for serum total 25-hydroxyvitamin D measurement, i.e. CV≤10% and Mean Bias ±5% (Clin Chem Acta 2009;408:8-13). Accomplishments include: The first meeting of WG-Vit D was in July 2018 at the AACC meeting in Chicago. WG-Vit D members from universities, IVD manufacturers, Clinical and Commercial Laboratories, and PT/EQA attended the meeting. The meeting included a detailed presentation and discussion of the: (1) Overview of the Vitamin D Standardization Program (VDSP), its goals and objectives; (2) VDSP Performance Criteria – for routine laboratories, i.e. CV≤10% and Mean Bias ±5%; (3) The Problems with the current VDSP performance criteria – especially Mean Bias; (4) Terms of Reference for WG-Vit D. IVD manufacturers’ representatives were concerned that tightening the VDSP Performance Criteria could lead to lack of participation in efforts to standardize the measurement of serum total 25hydroxyvitamin D. It was suggested that WG-Vit D consider developing three sets of criteria for meeting or passing VDSP performance guidelines. There was some concern raised by Members about developing performance criteria for 3-epi-25(OH)D3 and 24,25(OH)2D3. Moreover, the ratio of 25(OH)D to 24,25(OH)2D3 is beginning to be used clinically and hence the need to develop performance criteria in order to promote a standardized re-

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search database. NIST provided updates on development of RMPs for 1,25(OH)2D3, and Vitamin D Binding Protein and PTH. Data analyses for the VDSP 2 Interlaboratory Comparison Study are nearly complete. In this study the performance characteristics of 10 immunoassays were measured vs. NIST RMP target values on 50 single donor serum samples. These data will be central to the re-evaluation of the VDSP performance criteria. A manuscript is in preparation. Data analyses for the VDSP 2 Commutability Study of NIST SRMs 972a and 2973 and CAP and DEQAS serum materials are nearly complete. Data analyses of replicate measures of serum total 25(OH)D in nearly 2,000 participants in the US National Health and Nutrition Examination Study are being re-analysed to estimate biological variation (within-person variation). Those analyses will be central to the re-evaluation of the VDSP performance criteria. PUBLICATIONS BY COMMITTEES AND WORKING GROUPS: C-NPU: Wikipedia page for the NPU Terminology: https://en.wikipedia.org/wiki/NPU_terminology C-TLM: The results of RELA2017 (http://www.dgklrfb.de:81).

has

been

evaluated

and

published

C-RIDL: 1) Yesim Ozarda, Ken Sikaris, Thomas Streichert, Joseph Macri & on behalf of IFCC Committee on Reference intervals and Decision Limits (C-RIDL) Distinguishing reference intervals and clinical decision limits – A review by the IFCC Committee on Reference Intervals and Decision Limits. Critical Reviews in Clinical Laboratory Sciences 2018, Vol 55 (6), 420-31. 2) Graham R.D. Jones, Rainer Haeckel, Tze Ping Loh, Ken Sikaris, Thomas Streichert, Alex Katayev, Julian H. Barth, Yesim Ozarda & on behalf of the IFCC Committee on Reference Intervals and Decision Limits. Indirect methods for reference interval determination – review and recommendations. Clin Chem Lab Med. 2018 Dec 19;57(1):20-29. doi: 10.1515/cclm2018-0073. Other articles directly related to the C-RIDL projects 1) Yesim Ozarda, Victoria Higgins and Khosrow Adeli. Verification of reference intervals in routine clinical laboratories: practical challenges and recommendations. Opinion Paper, Clin Chem Lab Med 2018, 57(1),doi: 10.1515/cclm-2018-0059. C-STFT: 1. Yoshihara A, Noh JY, Watanabe N, Iwaku K, Kunii Y, Ohye H, Suzuki M, Matsumoto M, Suzuki N, Sugino K, Thienpont LM, Hishinuma A, Ito K. Seasonal Changes in Serum Thyrotropin Concentrations Observed from Big Data Obtained During Six Consecutive Years from 2010 to 2015 at a Single Hospital in Japan. Thyroid. 2018 Apr;28(4):429-436. doi: 10.1089/thy.2017.0600. Epub 2018 Apr 2. C- HAT: Journal: CCLM Authors: Evanthia Monogioudi; Ingrid Zegers; Dana P Hutu; Joanna Sheldon; Heinz Schimmel; Pier Luigi Meroni; Title: Certified Reference Material against PR3 ANCA IgG autoantibodies. From development to certification Accepted for publication. Abstract submitted to Euromedlab Barcelona. Monogioudi Evi, Sheldon Joanna, Meroni Pier Luigi, Zegers Ingrid. On the lookout for the best candidate material to develop a Certified Reference Material for PR3 ANCA IgG antibodies: A commutability story WG-SHbA2: Paleari R, Ceriotti F, Harteveld CL, Strollo M, Bakker-Verweij G, ter Huurne J, Bisoen S, Mosca A. Calibration by commutable control materials is able to reduce inter-method differences of current high-performance methods for HbA2. Clin Chim Acta 2018; 477:60-5. Arsene CG, Kaiser P, Paleari R, Henrion A, Spannagl M, Mosca A, on behalf of the IFCC Working Group on Standardisation of Hemoglobin A2 (WGHbA2). Determination of HbA2 by quantitative bottom-up proteomics and isotope dilution mass spectrometry. Clinica Chimica Acta 2018;487:318-24. WG-SCDT: International standardization of CDT measurement and interpretation improves its use as biomarker for chronic excessive alcohol consumption. Jos Wielders eNews IFCC November-december 2017 WG-SAU: Seegmiller JC, Miller WG, Bachmann LM. Moving towards standardization of urine albumin measurements. eJIFCC 2017;28:258-67. Miller WG, Bachmann LM, Fleming JK, Delanghe JR, Parsa A, Narva AS; Laboratory Working Group of the National Kidney Disease Education Program and the IFCC Working Group for Standardization of Albumin in Urine. Recommendations for Reporting Low and High Values for Urine Albumin and Total Protein. Clin Chem. 2018 Nov 20. pii: clinchem.2018.297861. doi 10.1373/clinchem.2018.297861. [Epub ahead of print] WG-TNI: The following recommendation was made in the clinical practice guidelines promulgated by the AACC academy and IFCC TFCACB in 2018. Recommendation 8: Commutable materials should be developed for use

in harmonizing and standardizing cTn. This recommendation resulted was discussed in a section of the Clinical Practice Guidelines titled ‘Harmonizing and Standardizing’, and serves to highlight the importance of our work in developing RM 2922. Wu AHB, Christenson RH, Greene DN, Jaffe AS, Kavsak PA, OrdonezLlanos J, Apple FS. Clinical laboratory practice recommendations for the use of cardiac troponin in acute coronary syndrome: expert opinion from the academy of the American Association for Clinical Chemistry and the Task Force on Clinical Applications of Cardiac Bio-Markers of the International Federation of Clinical Chemistry and Laboratory Medicine. Clin Chem 2018;64:645-655. WG-cMSP: Clinical Mass spectrometry proteomics (cMSP) for medical laboratory: what could be the future? By Sylvain Lehmann, Cato Brede, Pierre Lescuyer, José A Cocho, Jérôme Vialaret, Pauline Bros, Vincent Delatour, Christophe Hirtz and the IFFCC WG-cMSP is currently submitted for publication in CCA (Editor P Gillery). WG-PTH: Members and supporters of the IFCC PTH Working Group were asked to provide the Chair with details of any publications and/or presentations highlighting activities of the Working Group during 2018 for inclusion in this Annual Report but no information has as yet been received. WG-C: W. Greg Miller, Heinz Schimmel, Robert Rej, Neil Greenberg, Ferruccio Ceriotti, Chris Burns, Jeffrey R. Budd, Cas Weykamp, Vincent Delatour, Goran Nilsson, Finlay MacKenzie, Mauro Panteghini, Thomas Keller, Johanna E. Camara, Ingrid Zegers, Hubert W. Vesper, for the IFCC Working Group on Commutability. IFCC working group recommendations for assessing commutability part 1: general experimental design. Clin Chem 2018;64: 447-54. Goran Nilsson, Jeffrey R. Budd, Neil Greenberg, Vincent Delatour, Robert Rej, Mauro Panteghini, Ferruccio Ceriotti, Heinz Schimmel, Cas Weykamp, Thomas Keller, Johanna E. Camara, Chris Burns, Hubert W. Vesper, Finlay MacKenzie, W. Greg Miller, for the IFCC Working Group on Commutability. IFCC working group recommendations for assessing commutability part 2: using the difference in bias between a reference material and clinical samples. Clin Chem 2018;64:455-64. This paper includes a worked example as supplemental information. Jeffrey R. Budd, Cas Weykamp, Robert Rej, Finlay MacKenzie, Ferruccio Ceriotti, Neil Greenberg, Johanna E. Camara, Heinz Schimmel, Hubert W. Vesper, Thomas Keller, Vincent Delatour, Mauro Panteghini, Chris Burns, W. Greg Miller, for the IFCC Working Group on Commutability. IFCC working group recommendations for assessing commutability part 3: based on the calibration effectiveness of a reference material. Clin Chem 2018;64:465-74. This paper includes additional example data and statistical tools as supplemental information. WG-APO MS: The WG is working on the outline of its independent publication strategy. Several publications were prepared with contributions of WG members: 1. Bodde MC, Hermans MPJ, Jukema JW, et al. Apolipoproteins A1, B, and apoB/apoA1 ratio are associated with first ST-segment elevation myocardial infarction but not with recurrent events during long-term follow-up. Clin Res Cardiol 2018 2018/10/10. DOI: 10.1007/s00392-018-1381-5. 2. Delatour V, Clouet-Foraison N, Gaie-Levrel F, et al. Comparability of Lipoprotein Particle Number Concentrations Across ES-DMA, NMR, LC-MS/MS, Immunonephelometry, and VAP: In Search of a Candidate Reference Measurement Procedure for apoB and non-HDL-P Standardization. Clin Chem 2018; 64: 1485-1495. 2018/08/09. DOI: 10.1373/clinchem.2018.288746. 3. Ruhaak LR, Smit NPM, Suchiman HED, et al. MS-based proteomics: a metrological sound and robust alternative for apolipoprotein E phenotyping in a multiplexed test. Clinical chemistry and laboratory medicine: CCLM / FESCC 2018 2018/09/22. DOI: 10.1515/cclm-2018-0782. 4. Ruhaak LR, Smit NPM, Romijn F, et al. Robust and Accurate 2-Year Performance of a Quantitative Mass Spectrometry-Based Apolipoprotein Test in a Clinical Chemistry Laboratory. Clin Chem 2018; 64: 747-749. 2018/01/31. DOI: 10.1373/clinchem.2017.285098. 5. Dittrich J, Adam M, Maas H, et al. Targeted On-line SPE-LC-MS/MS Assay for the Quantitation of 12 Apolipoproteins from Human Blood. Proteomics 2018; 18 2017/12/28. DOI: 10.1002/pmic.201700279. WG-PE: Deprez L, Toussaint B, Zegers I, Schimmel H, Grote-Koska D, Klauke R, Gella FJ, Orth M, Lessinger JM, Trenti T, Nilsson G, Ceriotti F. (2018). Commutability Assessment of Candidate Reference Materials for Pancreatic αAmylase, Clin. Chem. 64: 1193-1202. This was not positioned in IFCC-WG-PE, however, F. Ceriotti, J. Gella and D. Grote-Koska from WG-PE were involved in this EC-JRC publication. Philippe Gillery, SD Chair and Joseph Passarelli, SD Secretary

EDUCATION AND MANAGEMENT DIVISION (EMD) Prof Nader Rifai was appointed to the EMD EC vacancy for a first three year term in January 2018. Prof Nader was also appointed the Chair of the IFCCAbbott VLP in 2018. Prof Vanessa Steenkamp was appointed to the EMD EC vacancy for a first term beginning in July 2018 until the end of December 2020. The EMD EC met on 18 and 19 January 2018 in Milan to plan the strategic direction of the EMD for the three year period 2018 till 2020, and this has

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been accepted by all Chairs of EMD committees, working groups and special projects with discussion and amendments. In January 2018, four Task Forces (Chronic Kidney Disease, Clinical Applications of Cardiac Biomarkers, Point of Care Testing and Proficiency Testing) previously under the IFCC EB became committees of the Education and Management Division. A new EMD committee, Value Proposition for Laboratory Medicine, was established on 1 January 2018. The Committee for Distance Learning under the EMD and the Committee for Internet and eLearning under the Communications and Publications Division were merged to form a new committee called Committee for Internet and Distance Learning (C-IDL) on 1 January 2018 with two Co-Chairs, one from the EMD and the other from CPD. The Mentoring Programme (a Special Project) became a Working Group for Personal Support on 1 January 2018. COMMITTEES activities: • Clinical Molecular Biology Curriculum (C-CMBC) – Chair: Evi Lianidou 1. The 2018 C-CMBC course took place in Martin, Slovakia from 18 to 24 Feb 2018. Dr. Katarina Baluchova, Lecturer and Research Fellow, Division of Oncology, Biomedical Center Martin (BioMed), in Martin, Slovakia, was assigned as a trainee by the Slovakian Society of Laboratory Medicine and underwent training at Mannheim at the beginning of January 2018. 2. Responding to a request from the Chair of the EMD Committee on Proficiency Testing (C-PT) and with the technical support of ESEAP (the nonprofit EQA scheme of the Greek Society of Clinical Chemistry-Clinical Biochemistry) an EQA programme for the detection of EGFR mutations in human plasma liquid biopsy was implemented. 3. Publication: Ntzifa A, Kroupis C, Haliassos A, Lianidou E. A pilot plasmactDNA ring trial, for the Cobas® EGFR Mutation Test in clinical diagnostic laboratories. Clin Chem Lab Med. 2018, Sep 29. pii:/j/cclm.ahead-ofprint/cclm-2018-0676/cclm-2018-0676.xml. doi:10.1515/cclm-2018-0676. [Epub ahead of print] PubMed PMID: 30267626. • Analytical Quality (C-AQ) – Chair: Annette Thomas (UK) 1. The Resource table for EQA database was updated in 2018. This database is now a live document. 2. Presentations on Principles of EQA, Principles of IQC and EQA Planning already exist on the C-AQ website. It is planned to improve the existing presentations on line with the IFCC eAcademy and develop additional presentations on IQC Planning and Risk Management. A large number of presentations have been reviewed by the Committee and approval has been obtained from the authors. The Committee is working with Dr Langman and Eduardo Feggiaro to finalise the three presentations already forwarded to them. Further topics are to be mapped to the quality ladder concept. 3. Annette Thomas conducted two workshops in Malawi between 26 Feb and 1 March 2018 in collaboration with the DQCML Committee. A one and a half day workshop was organised in Kathmandu, Nepal between 28 and 31 May 2018, again in collaboration with the DQCML Committee. 4. Development of a Quality Ladder: a) Based on the feedback from the workshop held in South Africa in February 2017 on Quality and Markers for Diabetes for Developing Countries it was identified that existing resources on quality available on the IFCC website such as Quality of Management and Quality of Analysis were not used by the attendees. It was identified that “bite size” educational material such as the EQA checklist and quality outline presented at the meeting would be more suitable; b) The plan for 2018 was to develop a series of monographs covering the basic concepts of quality that can be used by developing countries. A scoping document has been developed, topics agreed and content/authors have been identified. It was agreed to stratify the topic areas into Basic, Intermediate and Advanced. 5. The Committee agreed to support a Moving Averages project proposed by Tony Badrick. An initial meeting of this project group was held on 25th October 2018. The aim of the group is to support laboratories‘ implementation of patient-based real time quality control (PBRTQC) with simple understandable help tools, engage with middleware suppliers to assist development of simple, harmonised software and to develop network/collaboration between users/societies/suppliers to investigate newer data approaches.

IFCC

be completed by April 2019 2. Aye Aye Khine communicated with corresponding members requesting assistance with pilot questions regarding various learning tools. This task was conducted through the webpage of C-CLM on 1 March 2018 to 31 August 2018. http://www.ifcc.org/ifcc-education-division/emd-committees/c-clm/6-c-clm-clinical-laboratory-management-toolbox/ 3. Development of a Laboratory Leadership Training Certificate Programme led by Ed Randell: C-CLM issued a survey questionnaire to all National Societies to circulate to their members regarding learning needs assessment to aid in developing the programme. Responses were analysed and submitted for publication in the IFCC eNews on 28 September 2018. The primary assignments for the Laboratory Leadership Programme were allocated on 11 February 2018. The work on content development will continue through 2018 and 2019. The final programme content will consist of reading materials, live/recorded workshop presentations, and a quiz covering session content. C-CLM plans to issue a certificate of accomplishment to programme participants who complete all of the learning objectives and course content. 4. An online survey (using SurveyMonkey) to determine interest and knowledge gaps on selected topics to be discussed in the Laboratory Leadership Training Certificate Programme was conducted by Ed Randell in early February 2018. The survey comprised 24 questions (mainly multiple choice questions) and was completed on 28 February 2018. 5. A Training Manual on Leadership Basics for Clinical Laboratory Professionals was completed and sent to the IFCC office on 22 December 2018. This manual is now on the IFCC website. A Joint Monograph with C-AQ is being prepared and will be completed in 2019. 6. The C-CLM Clinical Laboratory Management Toolbox was created and the case scenarios were uploaded under the subsection of "Interactive Case Scenarios - Approach to Common Problems in the Medical Laboratory". http://www.ifcc.org/ifcc-education-division/emd-committees/c-clm/6-c-clmclinical-laboratory-management-toolbox/ 7. C-CLM conducted the following workshops in 2018: a) Pre-Congress Satellite Educational Workshop on "Leadership Essentials for Laboratory Professionals" Date: 16 August 2018 - Venue: PATHCAPE 2018, Cape Town, South Africa - Duration: 180 min. Speakers: Sedef Yenice, Matthias Orth, Aye Aye Khine b) Interactive workshop on "What is the Role of Innovation and Leadership for the Clinical Laboratory?" at the IFCC General Conference in Budapest on 11th November 2018 conducted by Sedef Yenice and Ed Randell. c) Pre-Congress Satellite Educational Workshop; Duration: 25 – 26 October 2018 - Venue: National Annual Congress of Turkish Biochemical Society, Bodrum, Turkey. Title or workshop: Westgard Rules, QC and Six Sigma. Speakers: Sten Westgard, Sedef Yenice 8. Sedef Yenice delivered a talk on "Policies for standardisation of clinical laboratory management in Mediterranean Countries: Differences from EU members" on 3 July 2018 at the 1st IFCC-EFLM-AFCB Conference on Laboratory Medicine, Rome, Italy. 9. Symposia conducted by C-CLM. a). Date: 17 August 2018 - Venue: PATHCAPE 2018, Cape Town, South Africa. Title of symposium: Accreditation and Quality Management - Speakers: Sedef Yenice, Matthias Orth; b). Date: 27 October 2018 - Venue: National Annual Congress of Turkish Biochemical Society, Bodrum, Turkey - Title of symposium: Verification of Laboratory Test Results in the Core Lab: Exploring effectiveness from the ground up? Speakers: Sedef Yenice, Matthias Orth, Ed Randell https://doi.org/10.1080/10408363.2018.1540536. 10. Publications: a) Ed Randell and Sedef Yenice. Delta Checks in the Clinical Laboratory, Critical Reviews in Clinical Laboratory Sciences, published online on 11 Jan 2019. https://doi.org/10.1080/10408363.2018.1540536 b) Two short articles were published in the October issue of the IFCC eNews The titles of these articles are as follows: • C-CLM Educational workshop on leadership and management in the PathCape 2018 • C-CLM Survey Results on Laboratory Leadership

• Evidence-Based Laboratory Medicine (C-EBLM) – Chair: Annalise Zemlin (ZA) 1. Continuation of Guidelines reviews using AGREE II instrument. These and previous findings will be used for publication in eJIFCC in 2019. 2. A workshop on EBLM was conducted at the CSCC meeting in Ottawa in June 2018 by A. Don Wauchope and K. Rodriguez Capote. 3. Talks on EBLM and audits were presented under auspices of C-EBLM at quality workshops in Ethiopia, Kenya and Zambia by A Zemlin in 2018. 4. Talks by A Don Wauchope, K Rodriguez-Capote and A Zemlin are being finalised for submission to the IFCC e-Academy. 5. Publication: Nuria Gimenez was first author on a manuscript on PSA.published in Spanish. Gimenez N, Filella X, Gavagnach M, Allue JA, Pedrazas D, Ferrer F. Cribado del cancer de prostata mediante antigeno prostatico especifico: perspectiva del medico en atencion primaria y en el laboratorio clinic. Medicinia de Familia, Semergen 2018; 44(6): 409-419. IFCC C-EBLM is stated in the affiliation.

• Internet and Distance Learning (C-IDL) – Co-Chair: Loralie Langman (US) 1. Topics outlined in the curricula that do not have presentations already in the eAcademy have been identified. 2. Potential speakers or source content for these topics are being identified. A call has been sent to IFCC member societies asking for volunteers and a positive response has been obtained from many societies. 3. eAcademy Coordinators have been recruited: Paul Hamilton, David Armbruster, Frank Quinn, and Rojeet Shrestha. 4. Knovio account to facilitate recordings for the eAcademy has been established. 5. The eAcademy has 70 webinars and 51 linked presentations. There are, in addition, 5 broken AACB links which need to be fixed. There are 5 Vietnamese presentations pending English versions and 15 ICPLM presentations uploaded but have not been finalised. Hence, there are a total of 20 webinars pending. On the occasion of the IFCC General Conference held in Madrid, IFCC obtained permission from Prof. Gronowski to insert links to three AACC webinars: http://eacademy.ifcc.org/events/aacc-pearls-of-laboratory-medicine/

• Clinical Laboratory Management (C-CLM) – Chair: Sedef Yenice (TR) 1. The first draft of a monograph entitled “Basic Problem Solving Tools” or “Basic Tools for Quality Improvement” was ready in August 2018. This will

• Education in the Use of Biomarkers in Diabetes (C-EUBD) – Chair: Garry John (UK) 1. The committee is working with WHO to finalise the Diabetes Laboratory

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Handbook. Following recent discussions with collaborators at WHO, this document is undergoing a final write up. There will need to be a meeting with collaborators at WHO to finalise the wording and format. 2. Following the very successful HbA1c European EQA study the next phase is being planned which will include laboratories in Korea with the potential to include laboratories in Indonesia. 3. The committee is continuing to work with colleagues from the IDF on a project looking at the diagnostic cut points for T2DM. Data gathering has been completed and is in the process of being reviewed. The project has been expanded to include additional laboratory measurements. 4. The committee is working with the Chinese Diabetes Society (CDS) to develop a joint IFCC-CDS committee to look at diabetes services within China. Dr Emma English and Prof Garry John were invited to give presentations at the Annual Chinese Diabetes Society (CDS) meeting, 29 November till 2 December 2018. 5. The committee is continuing to provide a scientific/clinical steer to the IFCC HbA1c Reference Laboratory Network. The IFCC HbA1c Reference Laboratory Network report was presented to the C-EUBD during its annual meeting in Chicago during AACC 2018. The Network continues to perform to a high scientific and clinical standard. 6. A lecture was delivered by Prof Garry John on HbA1c standardisation at the 5th EFLM-UEMS European Joint Congress, 10-13 October 2018 in Antalya, Turkey. 7. Following a C-EUBD presentation at the NGSP–IFCC-Manufacturer Forum there has been a tremendous response from manufacturers offering support for educational events and invitations to help them develop their own educational agenda (e.g. webinars). Representatives from these companies will be contacted and initiatives followed up. 8. Rolf Hinzmann proposed during the C-EUBD meeting in Chicago during AACC 2018 that the committee investigates Traceability of Continuous Glucose Monitors (CGM). Garry John will write a proposal to go to EMD and SD for consideration. 9. During the AACC 2018 meeting in Chicago, the C-EUBD participated in: NGSP Steering Committee, 29 July 2018; NGSP IFCC Manufacturer Forum, 30 July 2018; IFCC HbA1c Network Meeting, 31 July 2018. 10.Publications: a) English E, Weykamp C, Ji L, Siebelder C, Shan Z, Wang Y, Li H, John WG. The global impact of the International Federation of Clinical Chemistry and Laboratory Medicine, Education and Management Division: engaging stakeholders and assessing HbA1c quality in a multicentre study across China. Clin Chem Lab Med. 2018, Jul 25. pii: /j/cclm.ahead-of-print/cclm-2018-0434/cclm-2018-0434.xml. doi: 10.1515/cclm-2018-0434. [Epub ahead of print] PubMed PMID: 30044761. b) EurA1c Trial Group. EurA1c: The European HbA1c Trial to Investigate the Performance of HbA1c Assays in 2166 Laboratories across 17 Countries and 24 Manufacturers by Use of the IFCC Model for Quality Targets. Clin Chem. 2018; 64(8): 1183-1192. doi: 10.1373/clinchem.2018.288795. Epub on 19 June 2018. PubMed PMID: 29921723. c) English E, Lenters-Westra E. HbA1c method performance: The great success story of global standardization. Crit Rev Clin Lab Sci. 2018; 55(6): 408-419. doi: 10.1080/10408363.2018.1480591. Epub 12 July 2018. PubMed PMID: 30001673. d) Lenters-Westra E, English E. Evaluation of Four HbA1c Point-of-Care Devices Using International Quality Targets: Are They Fit for the Purpose? J Diabetes Sci Technol. 2018;;12(4): 762-770. doi: 10.1177/1932296818785612. Epub 19 June 2018. PubMed PMID: 29921132; PubMed Central PMCID: PMC6134306. • Cardiac Biomarkers (C-CB), Chair: Fred Apple (US) 1. The committee has developed educational materials for a) high-sensitivity, contemporary and point of care cardiac troponin assays and b) natriuretic peptide assays used in clinical practice and will continue to distribute educational posters and mouse-pads, as well as pocket-cards, addressing high sensitivity cardiac troponin and natriuretic peptide assays at IFCC (laboratory medicine) and clinical society meetings. a) Approximately 1300 educational posters based on high sensitivity cardiac troponin assays were distributed by the IFCC booth at the 2018 Chicago AACC meeting. b) An educational poster and pocket card guide are in development for natriuretic peptide assays, with the goal for distribution at the May 2019 Barcelona EUROMEDLAB meeting. Educational topic videos are being discussed. 2. A joint educational workshop of the ‘C-CB’ and ‘Academy of the AACC’ was held at the 2018 AACC meeting in Chicago (1 August 2018) that was co-sponsored by numerous industries supporting of the C-CB: Title: Clinical Laboratory Practice Recommendations for the Use of Cardiac Troponin in Acute Coronary Syndrome: Expert Opinion from the Academy of the American Association for Clinical Chemistry and the Task Force on Clinical Applications of Cardiac Bio-Markers of the International Federation of Clinical Chemistry and Laboratory Medicine. It was a great success with over 400 participants. 3. The C-CB determined at their last committee meeting that the website for both cardiac troponin and natriuretic peptide assays will be updated quarterly, in partnership with manufacturers. The latest update occurred on 23 September 2018 and new updated tables are being submitted on 28 January 2019. 4. Development of a searchable App that will be the educational tool for cardiac biomarker assays used in clinical practice by clinicians and laboratorians is still in the developmental stage and will be the primary focus of the C-CB to finalise in 2019. This will require collaborative work with App

developer, IFCC office, and industry/corporate members. This activity was brain-stormed for 3 hours at the 1 December 2018 C-CB meeting in Boston; with two writing/content sessions addressing both hs-cTn and NP assays, focusing on educational laboratory medicine content and influence on clinical use. Apple and Ortisi, et. al., hope to meet with IFCC IT contact in Milan in February 2019. 5. Development of a study model to define a ‘clinical scorecard’ for high sensitivity cardiac troponin assays. After one year of careful planning, this activity [official title and acronym are: ‘Clinical Scorecard Based on Comparison Of High-Sensitivity (hs) Cardiac Troponin (cTn) I and T Assays for Ruling Out AcutE MyocarDial Infarction’ (SCORED)] is on track to start in February 2019. Contracts and invoices with 7 companies are in the final stages. Specimens are in place for analysis, with the goal to complete measurements of specimens by the end of April 2019, with statistical analysis completed in May 2019. The corporate funding awarded to IFCC to support this study is USD 184,800. 6. Corporate members have initiated a second round of education contributions to C-CB through the IFCC office to assist in workshop planning, App development, and full day committee meetings. 7. Publications: a) Wu AHB, Christenson RH, Greene DN, Jaffe AS, Kavsak PA, OrdonezLlanos J, Apple FS. Clinical Laboratory Practice Recommendations for the Use of Cardiac Troponin in Acute Coronary Syndrome: Expert Opinion from the Academy of the American Association for Clinical Chemistry and the Task Force on Clinical Applications of Cardiac BioMarkers of the International Federation of Clinical Chemistry and Laboratory Medicine. Clin Chem 2018; 64: 545-655. b) Amy K. Saenger, Allan S. Jaffe, Richard Body, Paul O. Collinson, Peter A. Kavsak, Carolyn S. P. Lam, Guillaume Lefèvre, Tobjørn Omland, Jordi Ordóñez-Llanos, Kari Pulkki, Fred S. Apple. Cardiac Troponin and Natriuretic Peptide Analytical Interferences from Hemolysis and Biotin: Educational Aids From the IFCC Committee on Cardiac Biomarkers (IFCC C-CB), Clin Chem Lab Med (In Press, posted online). https://doi.org/10.1515/cclm-2018-0905. c) Paul O.Collinson, Amy K.Saenger and Fred S. Apple, on behalf of the IFCC C-CB. High sensitivity contemporary and point-of-care cardiac troponin assays: educational aids developed by the IFCC Committee on Clinical Application of Cardiac Bio-Markers, Clin Chem Lab Med (In Press, posted online). https://doi.org/10.1515/cclm-2018-). d) An IFCC eNews article was published in 2018 describing C-CB activities. e) An educational document based on natriuretic peptide assays and their clinical implications in practice (primary authors: Drs Lam and Kavsak) was finalised at the 1 December 2018 C-CB full day meeting in Boston, and will be submitted to Clinical Biochemistry for publication. • Chronic Kidney Disease (C-CKD), Chair: Flavio Alcantara (BR) 1. The objectives of the C-CKD were discussed during the IFCC General Conference in Budapest and members agreed to the suggestion of the EMD Executive Committee to encompass “Acute Kidney Disease” along with chronic kidney disease. 2. Portuguese and Croatian members have undertaken surveys on CKD practices in their home countries. A survey on CKD assays in different countries using a standardised format is currently underway. 3. A review on uses of CKD assays for risk stratification of cardiovascular diseases in hypertensive patients is being prepared. • Point of Care Testing (C-POCT), Chair: Rosy Tirimacco (AU) 1. GMECC WG presented their blood gas document both at the AACC 2018 annual meeting and at CPOCT meeting in September 2018. The document is a high calibre education tool citing many useful references. This document is being reviewed by a third party before final formatting and release. 2. The committee plans to present blood gas education as a webcast in consultation with CPD. The completed document will be placed on the IFCC website. 3. Publications: a) In preparation: Bowman C., Cunningham S., Slingerland IER, Mesotten D., Karon BS, Nichols J. on behalf of the IFCC Working Group. How should glucose meters be evaluated in critical care? b) How should glucose meters be evaluated for critical care? (by WGGMECC). Article published in IFCC eNews, April 2018 • Proficiency Testing (C-PT), Chair: Alexander Haliassos (GR) 1. In order to develop and implement the Analytes section of the Proficiency Testing Database (PTDB) a document was produced describing all the fields required for the creation of an Analyte record and documenting the procedure for creating the analyte section of the database. The committee members started with biomarkers of neurodegenerative diseases. This document describing the neopterin was finalised during the IFCC General Conference (Budapest, November 2018). 2. The revision of all changes on the webpage of C-PT reflecting the change from TF-PT to C-PT has been completed. 3. All the changes to the PTDB have been documented in order to comply with the change from TF-PT to C-PT, and these changes are implemented by InSoft, the IT provider of IFCC and developer of the PT DataBase. 4. In cooperation with C-AQ, the webpage of C-AQ has been updated to point to the PTDB. 5. The Chair of C-PT participated in the EQALM EB meeting (Zagreb, October 18th & 19th, 2018), where the next steps of the participation and the contribution of the EQALM members for the implementation, updating and

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maintenance of the C-PT database were discussed, as well as the planning of a symposium to be held at the EuroMedLab Congress in Barcelona 2019. 6. Responding to a request from the Chair of the EMD Committee on Clinical Molecular Biology Curriculum (C-CMBC) and with the technical support of ESEAP (the non-profit EQA-PT scheme of the Greek Society of Clinical Chemistry - Clinical Biochemistry) the committee members designed and implemented an EQA programme for the detection of EGFR mutations in human plasma liquid biopsy. This scheme validates the companion diagnostics test of detection of EGFR mutations. This test is a prerequisite for the administration of innovative, personalised, anti-cancer therapy. In February 2018, after a very successful pilot run ISO/IEC 17043 accreditation was applied for. The final inspection visit of the accreditation body was in early October 2018 and there were no non-conformances. The certificate for ISO 17043 is awaited. 7. Invited talks by the Chair of C-PT: a) “Inter-laboratory comparisons and EQA in the Mediterranean area” at the first IFCC, EFLM, AFCB Conference, "Laboratory Medicine: Meeting the needs of Mediterranean Nations" on 2 - 4 July 2018, Rome, Italy. The Chair presented the work of the committee, including the PTDB online database and web app. b) “Creation of an external quality assessment scheme for companion diagnostics” at the 2018 Moroccan Congress of Clinical Chemistry, Casablanca, 27 – 29 September 2018. The Chair delivered this lecture in French and presented the combined work of C-CMBC and C-PT. 8. Publications: a) Ntzifa A, Kroupis C, Haliassos A, Lianidou E. A pilot plasma-ctDNA ring trial, for the Cobas® EGFR Mutation Test in clinical diagnostic laboratories. Clin Chem Lab Med. 2018, Sep 29. pii:/j/cclm.ahead-ofprint/cclm-2018-0676/cclm-2018-0676.xml. doi:10.1515/cclm-20180676. [Epub ahead of print] PubMed PMID: 30267626. b) Haliassos A. Inter-laboratory comparisons and EQA in the Mediterranean area. eJIFCC 2018; 29 (4): 253-258. http://www.ifcc.org/media/477614/ejifcc2018vol29no4pp253-258.pdfa • Value Proposition for Laboratory Medicine (C-VPLM), Chair: Andrew St. John (AU) 1. There are 4 separate planned papers in various stages of preparation. In their order of progress: a) A description of the value proposition for the effective application of point-of-care testing. The authors are Chris Price and Andrew St John b) A description of the value proposition for the application of advanced molecular diagnostics in cancer and transplantation. Michael Oellerich is leading this initiative. c) A general review of the technique of economic modelling and its application to laboratory medicine. Paul Julicher is leading this initiative. d) A comparison of how tests are evaluated and adopted in different countries, the barriers that exist which prevent effective adoption and whether these are addressed by the Value Proposition framework. Andrew St John is leading this initiative. 2. Two workshops are in the planning stages: a) In the UK, the committee is working with two organisations - KTN (Knowledge Transfer Network) and Innovate UK - to organise a workshop involving a range of stakeholders that would examine (i) process change and (ii) investment/disinvestment decisions in relation to the introduction of new tests. Chris Price is leading this initiative and it will involve Maurice O’Kane. b) A workshop is being planned by the committee that will review the clinical pathway for a specific test or tests. The participants will include all the stakeholders that contribute to the pathway including clinicians and other healthcare professionals. The workshop will highlight the key elements that contribute to and hinder the demonstration of value for that specific test. Likely tests to be considered include HbA1c and CRP by POCT. Discussions have commenced with funding agencies in the Federal Government. Andrew St John and Tony Badrick are leading this initiative. WORKING GROUPS activities: • Laboratory Errors and Patient Safety (WG-LEPS) Chair: Laura Sciacovelli (IT) 1. Laboratories’ quality indicator results are collected monthly through the dedicated website (www.ifcc-mqi.com) and their evaluation is in progress. 2. Identification of Performance Specifications for each Quality Indicator and publication of a scientific paper reporting the data. WG-LEPS is writing a scientific paper that reports the updating of Performance Specifications based on the results of Quality Indicators data collected in the last year. 3. Definition of specific plan by National Leaders of each country to promote the active use of Quality Indicators in the national laboratories. The planning foresees that the National Leader should (i) encourage the use of MQI; (ii) “personalise” the use of QIs in daily practice according to national practices, requirements and regulations; (iii) co-operate with the members of the WG-LEPS by providing valuable suggestions to improve the project The WG-LEPS is collaborating with the: a) Beijing Center for Clinical Laboratory (Prof. Wang Qingtao, BCCL Director, and Dr. Zhou Rui, CCL manager). Their involvement in the management and dissemination of quality indicators for the monitoring of activities concerning some specific molecular diagnostics of the intraanalytical phase that will be proposed to laboratories all over the world has been finalised;

IFCC

b) Quebec Society of Clinical Biology (Société Québécoise de Biologie Clinique) has already launched a programme for quality indicators comparison in Québec province with up to 60 laboratories participating. The Society will launch its programme for the rest of Canada at the annual meeting of the Canadian Society of Clinical Chemistry in order to promote quality in their laboratories and is completely free of charge. The collaboration is based on the sharing of the Model of Quality Indicators proposed by WG-LEPS and a common management of the quality indicator results. Moreover, joint initiatives will be realised in order to promote the use of quality indicators in all laboratories all over the world. 4. Involving national scientific societies, accreditation bodies and EQA/PT providers in different countries as a means of disseminating the MQI project and promoting participation of laboratories is continuing. The Chair participated in the Annual Meeting of the Quebec Society of Clinical Biology on 25th October 2018 by delivering a talk in order to promote the collaboration on the Quality Indicator project. • Harmonization of Interpretive Comments External Quality Assurance (WG-ICQA) - Chair: Samuel Vasikaran 1. The working group is supporting the development of locally led patient report comment EQA programme in Africa: 2. Submission for the inclusion of EQA for interpretative commenting in the revised ISO 15189 is concluded. The outcome is still awaited. 3. Collaboration with EFLM Working Group on Post-analytical Phase (WGPOST) is being discussed. • Personal Support (WG-PS), Chair: Graham Beastall (UK) 1. Positive publicity material for WG-PS explaining the roles of Expert and Mentor and how to reach them has been prepared. 2. The databases for Expert and Mentor have been rationalised so that they are accessible through a common portal. 3. All those listed on the Register of Experts have been contacted and asked if they wish to continue to be listed as an Expert and/or as a potential Mentor. 4. All IFCC Members have been contacted in order to increase awareness of WG-PS and to seek new nominations as Experts and Mentors. 5. An active campaign is being launched to promote the opportunities afforded by WG-PS. The campaign is being launched through IFCC Members, TF-YS and ‘Lab-Surfing’ and via social networking. The aim is to identify individuals who would benefit from being connected to Expert or Mentor. 6. Discussion with the IFCC Office regarding modifications to IFCC website to deliver Common Portal. 7. Publications: Articles are being prepared for IFCC e-News and Diagnóstico In Vitro for publication in early 2019. An interview with El Microscopio was recorded and broadcasted in December 2018. SPECIAL PROJECTS activities: • IFCC Visiting Lecturer Programme (IFCC-VLP) - Chair: Nader Rifai (US) In 2018, VLP applications from 12 member societies, involving 25 Visiting Lecturers, were approved. The Visiting Lecturer Programme is generously supported by Abbott Laboratories. • Working Group on Flow Cytometry (WG-FC) - Chair: Ulrich Sack (DE) 1. A winter school was held in St-Etienne, France from 5 – 9 March 2018. 2. A course was conducted in Istanbul, Turkey from 20 – 22 June 2018, sponsored by Beckman. 3. A course was conducted in Sao Paulo, Brazil from 28 – 30 August 2018, sponsored by Beckman. 4. A course was conducted in Astana, Kazakhstan from 19 – 21 September 2018, sponsored by Beckman and supported by the local university and scientific community. 5. A course on Flow Cytometry was conducted in Munich, Germany from 24 – 28 September 2018. 6. For each course, 30 to 36 participants attended the practical exercises. Lectures were also open to interested scientists and technicians. Local support was always excellent. Beckman Coulter supported the organisation, financing, and provided technical equipment and consumables. Local specialists were essential for practical work. 7. Publication: A manuscript on validation in cytometry has been submitted to Clinical Chemistry and Laboratory Medicine and is under revision. • Developing Quality Competence in Medical Laboratories (DQCML), Chair: Egon Amann (DE) 1. An Open DQCML Session (“Drop in session”) with National Representatives who may wish to seek support was offered during the IFCC General Conference on 9 November 2018. 2. Workshops conducted: a) Two workshops on IQC and EQA were conducted in Malawi (in the cities of Blantyre and Lilongwe) on 26 February and 1 March 2018. Lecturers were Graham Beastall, Annette Thomas and Egon Amann. These workshops supported the ambitions of Malawi to develop a programme of Quality Competence. b) A workshop on IQC and EQA was conducted in Nepal from 28 – 30 May 2018. The two national societies, NACC and NAMLS, jointly applied for this programme. Lecturers were Renze Bais, Annette Thomas and Egon Amann. The visit was also a able to asked to way to initiate an RCPAsponsored transfer of EQA materials to Nepal’s clinical laboratories. 20 labs have enrolled initially. 3. Reports on the Malawi and Nepal workshops were published in the IFCC eNews. All presentation materials from these workshops are available

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from the Chair and could be shared under the eAcademy web site. 4. The experience gained in the EQA Zambia Project that was led by Dr. Renze Bais in the provision of control and standard materials, logistics and support is being utilised for the workshop and ongoing material supply in Nepal. Leslie Lai, Chair EMD

COMMUNICATIONS AND PUBLICATIONS DIVISION (CPD) In 2018, the following members served on the CPD Executive Committee: Khosrow Adeli (CA, Chair), Edgard Delvin (CA, Vice Chair/Public Relations Coordinator), Eduardo Freggiaro (AR, Publications/Distance Learning Coordinator), Tahir Pillay (ZA, News Editor), J. Kappelmayer (HU, Editor eJIFCC), and Tricia Ravalico (US, Corporate Representative). Janine Grant (AU, Website Editor), Maria del Carmen Pasquel (EQ, WG- IANT Chair), Anthony Newman (NL, Publications consultant) were invited to attend the CPD meeting in Budapest, on occasion of the IFCC General Conference 2018. The following is a summary list of the key CPD activities in 2018: • Three face-to-face committee meetings were held in 2018: Buenos Aires, (AR) in March, Mannheim (DE) in June, and Budapest (HU) in November, on occasion of the IFCC General Conference; • Informal CPD meeting in Chicago (US) on occasion of AACC Lab Expo 2018; • CPD Chair, Prof. Khosrow Adeli (CA), completed his second term; • C-Pr Chair, Prof Edgard Delvin (CA) and WG eNews Chair, Prof Tahir Pillay (CA), completed their second term this year; • WG eJIFCC Chair, and eJIFCC editor, Prof János Kappelmayer (HU), began his first term in January 2018; • Calls for nominations were sent out for EC Corporate Representative for term 2018-2020, WG eNews Chair and C-PR Chair for term 2019-2021. Other calls for nominations were also sent for CPD functional unit member vacancies; • CPD Corporate member, Mrs Tricia Ravalico (US), began her first term in June 2018; • Actions to implement the IFCC Strategic plan in support of our IFCC Membership a) Maintaining support materials and web-based tools to demonstrate the benefits of IFCC membership to all countries with: • focus on improvement of internal communications within IFCC and its Member Societies; • major improvements for both the IFCC eNewsletter and the eJournal. Publication formats as well as news/scientific content have been enhanced considerably over the past year; b) Use and evaluate effectiveness of new support materials: • successful increase in eNews frequency from bimonthly (6 issues/year) to monthly (ten issues/year) in 2018; • eJIFCC began exploration of professional submission tools; • DiV (RIA Spanish Magazine) continues to ensure communication with Spanish-speaking professionals; • IFCC social presence (FB, LinkedIn, Twitter) is lively and well managed; an IFCC Instagram account was open in 2018 and plans for YouTube presence are progressing; • instant polling system selected and recommended for use at IFCC General Conference; c) Delivering the e-academy as the platform to support IFCC educational materials: • increased communication with the Spanish speaking countries with AMARA collaboration initiative; • Phase 2 preparation for release in 2019; • 4 eAcademy Coordinators nominated to coordinate the activities and further development; d) Develop and present a series of webinars to meet the needs of Members: Promotion of Distance Learning Opportunities for Member Societies & their Membership via eAcademy; e) Survey the membership to better understand needs, requests and proposals. • Enhancement of IFCC Public Relations/Visibility; • IFCC App continues to be updated with IFCC initiatives and activities. There are plans to release an improved and more interactive version in 2019/2020; • New initiatives to promote the image of the IFCC to its individual members, to the biomedical industry and to the worldwide health care community at large; • Contribution to IFCC congresses with organization of CPD Sessions & Symposia in 2018; • Completion of Electronic Journal of IFCC (eJIFCC) renumbering and ordering of all archived issues for indexing by MEDLINE/PUBMED; • Completion of indexing of all eJIFCC archived issues in PMC; • Acceptance by Scopus to select the eJIFCC for coverage by Elsevier in November 2018; • Communications to list eJIFCC into Google Scholar, Thomson Reuters, and Web of Sciences, continue. The following symposia were organised by the CPD in 2018: • “SPECIAL CPD SYMPOSIUM IN CLINICAL CHEMISTRY”, held on 2 March 2018 at the Facultad de Farmacia y Bioquímica – UBA, Buenos Aires, Argentina: • Welcome and Introductory Remarks – E. Freggiaro, AR; Global Initiatives in Pediatric Reference Intervals for Laboratory Biomarkers of Health and Disease – K. Adeli, CA; Developing New Diagnostic Probes for Immunoassays Based on Nanobodies and Next Generation Technology – T. Pillay, ZA; Management of bulk test results and special lab reports in a core laboratory – J. Kappelmayer, HU • Round table – All • Closing remarks: Khosrow Adeli, CA and Eduardo Freggiaro, AR • CALILAB congress (24-27 October – Buenos Aires, Argentina) • IFCC eCommunication Tools and Strategy: Mobile App, eAcademy,

eNews, and eJournal" – K. Adeli, CA • The IFCC Ibero-American Corner: strategies for the professional training and the laboratory quality (El rincón iberoamericano de la IFCC: estrategias para la capacitación profesional y la calidad del laboratorio)María del Carmen Pasquel, EC • Real continuous biochemical education in a virtual environment (Educación bioquímica continua real en un entorno virtual ) – E. Freggiaro, AR • IFCC General Conference, 9-11 November 2019 Budapest, Hungary • Future Communication Strategy for IFCC – Khosrow Adeli, Chair; IFCC eApp and ePublications – Tahir Pillay; Communication Strategy in Education and Dissemination – János Kappelmayer; A new award programme to inspire Healthcare Excellence – Patricia Ravalico Committee on Public Relations (C-PR), Chair: Edgard Delvin (CA) A Committee Meeting was held in Budapest which was attended by most members. ACTIONS: The C-PR held a conference call on 26 April 2018 during which the development of promotional material targeting the lay public and means of promoting IFCC educational material (e-Academy and others) were discussed. These will further be discussed during the C-PR meeting in Budapest. The Spring 2018 survey directed toward the individual members of the National Societies and Regional Federations resulted in a poor response rate. Hence it was proposed to have a second round and send the survey either through the IFCC mailing list or the National Representatives. However before proceeding some editing was suggested. Tricia Ravalico, Corporate representative, offered to review the questions and provide suggestions in terms of “marketing”; the questions concerning the IFCC website, eNewsletter, the e-NewsFlash, the e-JIFCC, the IFCC e-Academy and the IFCC App remaining central. The revision has been completed and the survey was sent to the National Representatives on 15 October 2018. We have started developing a presentation inspired by the brochure and PowerPoint presentation “Understanding Laboratory Medicine” in the form of a series of slides targeting the lay audience. Each is planned as a selfcontained story that can be broken down into a series of steps with different clinical subjects. They will be adapted to the local needs/policies, printed by National Societies or displayed on TV screens as revolving stills/ video at strategic points (hospital hallways, administrators’ meetings, clinics) and used during different events such as the laboratory week. An invitation has been sent to the IFCC SD & EMD Chairpersons to explore with the respective Chairs of their different Committees and working groups the possibility of writing timely articles on the value of laboratory medicine (promoting the role and value of laboratories in improving healthcare and patient safety targeting lay audiences) to be published in local newspapers, magazines & electronic media. A new set of display posters were developed and shown during the GC in Budapest. They received excellent feedback and will be updated for future events. The C-PR is developing new BROCHURES, in order to reflect the new IFCC pay-off. The C-PR re-wrote its TERMS OF REFERENCE in order to broaden its reach. Committee on Internet and e-Learning (C-IeL) Chair: Eduardo Freggiaro (AR) A Committee Meeting was held in Athens, along with a C-IeL and C-DL joint meeting. This committee started to work effectively in February 2018 when the two members from EMD were appointed. During the General Conference in Budapest the committee had its first face-to-face meeting and this meeting improved the team performance and cohesiveness. These are the main activities done during the last 10 months: • Corresponding members from the two previous committees were invited to continue their participation in the new C-IDL. IFCC office sent emails to confirm their membership under the new committee. Most of the members confirmed their participation. Our aim is to increase the linkage with corresponding members; • C-IDL agreed to use as official communication platform the Project Management Software (PMS) provided by InSoft. However, during the past period this tool has become less useful and most of the communication were conducted by email; • Both co-Chairs rewrote the terms of reference for the new committee and they are published on the website. • The IFCC Curriculum final version was published in the eAcademy. The link point to the official document was published in the eJIFCC (April 2018). This document is one of the most downloaded files from the IFCC website; • An invitation to prepare educational materials for eAcademy was sent to all the National Societies and was well received. Four NS replied and we are working on their proposals. IFCC eAcademy: Number of new items published. In 2018 the eAcademy reached the number of 117 resources published, 67 webinars and 51 external links; 24 webinars are completed with LO and MCQs ready to be uploaded and comply with eAcademy phase 2 features. 21 further webinars taken during conferences were reviewed in 2018 to fix synchronization errors. Funding: Siemens will continue providing funds for the project in general. Content production tool: A new tool for video presentations recordings was selected: Knovio. We opened a Gold account and in 2018 this tool was successfully used by Speakers. Platform update: the plan is to move the eAcademy website under the

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same installation as IFCC website. Phase 2 deployment: C-IDL provided feedback to the questions asked by InSoft regarding some relevant issues. At the moment, all the features are ready to be deployed (user’s profile, quizzes and certificates). The new features will be launched before the end of year 2019. eAcademy Coordinators: after the position was advertised, 4 coordinators were selected: Rojeet Shrestha, Paul Hamilton, David Armbruster and Frank Quinn. C-IDL wrote a standard operating procedure for module creation and encouraged coordinator to identify new potential Speakers scanning congresses programs and the IFCC database of experts.

Ariadna Arbiol-Roca, Claudia Elizabeth Imperiali, Magdalena Macià Montserrat, Ana Sancho Cerro, Anna Cortés Bosch de Basea, Lourdes Sánchez Navarro, Dolors Dot-Bach, José Valero Politi 7. The IFCC Curriculum - phase 1 IFCC Committee for Distance Learning – Ronda F. Greaves, Janet M. Smith, Graham Beastall, Chris Florkowski, Loralie Langman, Joanna Sheldon, Elvar Theodorsson 8. Letter: Serum ferritin as a biomarker of polycythemia vera? Stephen E. Langabeer 9. Book review: “Neonatology and Laboratory Medicine” Joseph B. Lopez

Website: Key website development and maintenance activities over the past 12 months have been as follows: Publication of 2018 News items, respectively Month and Number of items published: Jan: 2; Feb: 5; Mar: 5; Apr: 1; May: 6; June: 3; July: 5; Aug: 2; Sep: 4; Nov: 5; Dec:6. The following website developments completed in 2018: • Currency of web platform. The IFCC website was migrated from the Umbraco v4 platform to the current v7. Future updates will occur automatically as part of the support and service agreement with InSoft, during the monthly service window; • Update of interactive membership map.; • Addition of a new IFCC Division requiring an update to Blue link banner and slight widening of pages. This required an update to the Website Policy and Procedures; • On-going updates to various media files, links and pages as required; • New method for tracking downloads introduced from Feb 2018; • Updates relating to GDPR compliance: addition of cookies notification for first visit and homepage link to privacy and policies page; • eAcademy: Ongoing publication of content as approved by C-DL. Total items published to date: Phase 2 developments pending.

eJIFCC Volume 29 no 2 was published in July 2018. The issue contains 8 manuscripts, 5 of them guest-edited by Dr Harjit Pal Bhattoa (HU), on: “Laboratory investigation of vitamin D and bone metabolism markers”. 1. Laboratory investigation of vitamin D metabolites and bone metabolism markers Guest Editor: Harjit Pal Bhattoa 2. Vitamin D and its metabolites: from now and beyond Etienne Cavalier, Jean-Claude Souberbielle 3. Vitamin D and endocrine disorders: routine laboratory diagnostic implications Giovanna Muscogiuri, Harjit Pal Bhattoa 4. Laboratory aspects and clinical utility of bone turnover markers Harjit Pal Bhattoa 5. Practical guide for identifying unmet clinical needs for biomarkers Phillip J. Monaghan, Sarah Robinson, Daniel Rajdl, Patrick M.M. Bossuyt, Sverre Sandberg, Andrew St John, Maurice O’Kane, Lieselotte Lennartz, Ralf Röddiger, Sarah J. Lord, Christa M. Cobbaert, Andrea R. Horvath 6. Prevalence of anemia and its associated factors among children in Ethiopia: a protocol for systematic review and meta-analysis Zegeye Abebe, Wubet Worku Takele, Degefaye Zelalem Anlay, Daniale Tekelia Ekubagewargies, Zegeye Getaneh, Molla Abebe, Mulugeta Melku 7. Acute myeloid leukemia with severe coagulation disorder and central nervous system bleeding - a clinical diagnostic case report S. Hatzl, B. Uhl, M. Hinterramskogler, S. Leber, F. Eisner, M. Haring, P. Jud 8. Vitamin B12 immunoassay interference in a patient with Multiple Myeloma - troubleshooting in a two step reagent kit based on enhanced chemiluminescence testing V. Pant, A. Tumbapo, B. Kumar Yadav

Social Media: Facebook IFCC official page is the most influential compared to other social sites with 23,369 followers at October 2018. In terms of number of followers, IFCC Facebook page is at second position in the similar page with 1st being Clinical Chemistry. Amongst the professional societies of clinical chemistry, IFCC Facebook page can be considered as number 1. Up to October 2018, IFCC posts have been displayed in 197, 387 screens. IFCC Twitter has 1226 followers and 301 tweets as of October 2018. LinkedIn group has 3556 members and is being used to discuss various issues. Our LinkedIn page contains approximately 5000 followers but it seems like the page has been auto generated with unknown admin status. In 2018 a new page has been created and plans are to use it as official page. All the post are also being regularly posted in this page. Instagram: starting in Feb 2018, we have extended our social media presence to Instagram. It has 81 followers. Databases. The NPU, Register of Experts, and Publications databases are the only active databases currently on the website. An eAcademy database will be developed with the eAcademy phase 2 implementation. Working Group on Electronic Journal of the IFCC (WG-ejIFCC) Chair: János Kappelmayer (HU) Major accomplishment: All archived issues of eJIFCC, published online by PubMed since October 2016, have been fully reorganized and converted in accepted format for indexing in PMC. Full eJIFCC archive is now published in PMC. Scopus accepted eJIFCC for listing; next step will be application to WoS. The eJIFCC collection is available at: http://www.ifcc.org/ifcc-communications-publications-division-cpd/ifcc-publications/ejifcc-journal/e-journal-volumes/: eJIFCC Volume 29 no 1-2-3-4. eJIFCC Volume 29 no 1, the first edited by Prof. János Kappelmayer, director of a large clinical laboratory at the University of Debrecen, Hungary, was published in April 2018. The issue contains 5 manuscripts (+foreword), 1 letter, the IFCC curriculum and a book review 1. Foreword from the new editor-in-chief János Kappelmayer 2. Next-generation sequencing approach for the diagnosis of human diseases: open challenges and new opportunities Chiara Di Resta, Silvia Galbiati, Paola Carrera, Maurizio Ferrari 3. Integration of multigene panels for the diagnosis of hereditary retinal disorders using Next Generation Sequencing and bioinformatics approaches Chiara Di Resta, Ivana Spiga, Silvia Presi, Stefania Merella, Giovanni Battista Pipitone, Maria Pia Manitto, Giuseppe Querques, Maurizio Battaglia Parodi, Maurizio Ferrari, Paola Carrera 4. Influence of serum leptin levels and Q223R leptin receptor polymorphism on clinical characteristic of patients with rheumatoid arthritis from Western Mexico Luis I. Angel-Chávez, Elizabeth Ruelas-Cinco, Jorge Hernández-Bello, Elena Castro, Mirna Vázquez-Villamar, Isela Parra-Rojas, L. Michele Brennan-Bourdon, Salvador Muñoz-Barrios, Celia Guerrero-Velázquez, José Francisco Muñoz-Valle 5. Anemia and thrombocytopenia in the cohort of HIV-infected adults in northwest Ethiopia: a facility-based cross-sectional study Tekalign Deressa, Debasu Damtie, Meseret Workineh, Meaza Genetu, Mulugeta Melku 6. Reference intervals for a complete blood count on an automated haematology analyser Sysmex XN in healthy adults from the southern metropolitan area of Barcelona

eJIFCC Volume 29 no 3 was published in November 2018. The issue contains 12 manuscripts (+ 1 foreword), guest-edited by Prof. Sergio Bernardini (IT), on “Laboratory medicine – meeting the needs of Mediterranean nations (Part 1)”, along with 3 letters 1. Foreword of the editor-in-chief. János Kappelmayer 2. Laboratory medicine: meeting the needs of Mediterranean nations Guest Editors: Sergio Bernardini, Bernard Gouget Transmissible diseases in the Mediterranean area 3. Communicable diseases in the Mediterranean region Ghassan Shannan 4. Are medical laboratories ready for the diagnosis of parasitic diseases? Ahmet Özbilgin 5. Travel, migration and emerging infectious diseases Nicolas Vignier, Olivier Bouchaud Training and education in laboratory medicine 6. Is the profession of laboratory medicine uniform across the North Mediterranean countries? Konstantinos Makris 7. EFLM project “Exchange of practical knowledge and skills in Laboratory Medicine” – EFLMLabX Evgenija Homšak Improving health with emerging technologies 8. Economic evaluation as a tool in emerging technology assessment Nataša Bogavac-Stanojević 9. Who or what is SHERLOCK? Ann M. Gronowski 10.Advancement in POCT molecular testing: the multiplex PCR POCT devices for infectious diseases Alpaslan Alp 11. New solutions for the sample transport and results delivery: a digital lab Damien Gruson 12.Next generation sequencing: from research area to clinical practice Chiara Di Resta, Maurizio Ferrari 13.miRNA and other non-coding RNAs as promising diagnostic markers Dorota Trzybulska, Eleni Vergadi, Christos Tsatsanis Letters 14.Letter: NGS for metabolic disease diagnosis Dèlia Yubero, Rafael Artuch 15.Letter: Reflections on the mentor-mentee relationship as a symbiosis Josep Miquel Bauça 16.Letter: Inter-laboratory exchange of knowledge and technology around our Sea Guilaine Boursier eJIFCC Volume 29 no 4 was published in December 2018. The issue contains 12 manuscripts (+ 1 foreword), guest-edited by Prof. Sergio Bernardini (IT), on “Laboratory medicine – meeting the needs of Mediterranean nations (Part 2)”

Special Supplement to Lab Medica International • 32

IFCC

2018 Annual Report

1. Foreword from the editor-in-chief János Kappelmayer Improving efficiency in laboratory medicine 2. Traceability in laboratory medicine: what is it and why is it important for patients? Graham H. Beastall 3. Laboratory medicine in Palestine Rania Abu Seir, Osama Najjar 4. Inter-laboratory comparisons and EQA in the Mediterranean area Alexander Haliassos 5. An evidence-based laboratory medicine approach to evaluate new laboratory tests Tommaso Trenti 6. Which skills are needed and how they should be gained by laboratory medicine professionals for successful ISO 15189 accreditation Diler Aslan Perinatal and pregnancy laboratory medicine 7. Prenatal screening for chromosomal abnormalities: where do we stand today in Mediterranean countries? Demetrios Rizos 8. The role of laboratory medicine for health during pregnancy Adnan Alkhatib Mediterranean diet and the area’s specific diseases 9. Alcohol abuse Tomáš Zima 10.Urinary proteomics in biomarker discovery of kidney-related disorders: diabetic nephropathy and drug-induced nephrotoxicity in chronic headache Elisa Bellei, Emanuela Monari, Stefania Bergamini, Luigi Alberto Pini, Aldo Tomasi, Tomris Ozben 11. Standardization of the HbA2 assay Renata Paleari, Andrea Mosca 12.Surrogate biomarkers for monitoring healthcare quality for chronic diseases such as diabetes care Diler Aslan 13.The role of laboratory medicine in addressing migrant health problems Adekunle Bashiru Okesina, Ademola Adelekan Working Group on IFCC NEWS (WG-e-NEWS), Chair: Tahir Pillay (ZA) The WG membership consists of representatives from Spain, Serbia, Morocco, Nigeria, South Africa, Greece, Brazil, Canada, Cyprus, Malaysia, Mexico, Morocco, Nepal, Poland, Slovenia, Tunisia, Uruguay & Vietnam. Additionally, there are National Society liaisons from Australasia, Chile, Serbia, UK, USA, Paraguay, Spain, Taiwan, Pakistan, Latvia & Vietnam. In 2018 the rate of publication has reached the monthly frequency as the IFCC board has requested a shorter and more frequent newsletter. Therefore we now publish 10 issues of the newsletter annually and these appear every month, with the exception of January and August. The eNewsflash is used to highlight important IFCC news items especially time‐sensitive and urgent items. Requests for articles are sent to all eNewsletter WG members, National Societies liaisons and National Representatives (through the IFCC Office) with a reminder of the deadlines. The reports of the IFCC Young Scientists task force and the PSEP reports from awardees tend to feature prominently. This helps to highlight the contribution of the IFCC to international clinical chemistry across the world and also ensures that contributions from members continue to come to the newsletter. The eNews continue to coordinate with Social Media editor to post most popular articles on IFCC Social accounts. The eNews collection is available at: http://www.ifcc.org/ifcc-communications-publications-division-cpd/ifcc-publications/enewsletter/enews-volumes/ The eNews Flash collection is available at: http://www.ifcc.org/ifcc-communications-publications-division-cpd/ifcc-publications/enewsletter/enewsflash-archive/ Relationship with LabMedica International: LMI prints a selection of the articles. The eNews editor is on the editorial board of LabMedica. Working Group – Spanish (Ibero-American) Nomenclature and Transaltions (WG-IANT), Chair: Maria Del Carmen Pasquel (EC) Membership: new members representing all Ibero American IFCC countries are participating in the WG activities. The RIA section of IFCC website is continuously updated. There are new programs and initiatives planned and these are mainly focused on updating the RIA section of the website. DiV, Diagnóstico in Vitro, continues to be a major product of the WG-IANT activity. Three issues have been published in 2018. DiV main sections are: Editorial, News and Updates, Scientific Articles, Letters to the Editor, Young Scientists corner, Radio Interview El Microscopio. The DiV collection is available at: http://www.ifcc.org/div/. El Microscopio: Programmes are regularly broadcasted and some of them are in English, for a broader circulation. This successful initiative is in search of additional funding and tools for promotional purposes. Corporate Member Activities - Tricia Ravalico (US) Tricia Ravalico (Abbott) was appointed in June 2018 in replacement of Peter Bialk (Roche Diagnostics) who resigned. Tricia has provided great support for IFCC public relations. Her recent activities included supporting the C-PR for the IFCC brochures revision, supporting the IFCC, along with other partners, for the launch of the UNIVANTS of HCE (Healthcare Excellence Programme). Khosrow Adeli, CPD Chair, Tahir Pillay Incoming Chair

EMERGING TECHNOLOGIES DIVISION (ETD) The Emerging Technologies Division (ETD) has been approved by the Executive Board (EB), as new IFCC functional Unit, in Athens, June 9th 2017. The ETD Executive Committee has been approved by the EB in Durban, October 20th, 2017: Members: Ronda Graves, Damien Gruson, Paolo Fortina; Corporate Members: Peng Yin (Abbott), Markus Roessler (Roche); Consultants: Maurizio Ferrari, Larry Kricka, Jason Park. The ETD is an IFCC functional unit responsible for identifying and assessing emerging technologies and for translating the emerging and disruptive diagnostic and data analysis procedures from academic laboratories to clinical laboratories and from clinical laboratories to market. The ETD Responsibilities are: defining for each ET the clinical needs and criteria for education of specialists in Laboratory Medicine and caregivers; defining for ET the appropriate infrastructure and laboratory organization; defining for each ET pre-analytical, analytical and post-analytical processes necessary for clinical laboratory applications; defining for each ET quality programs and certifications required to meet criteria for accreditation up to ISO151811 standard; assess the clinical value of each test with regard to addressing unmet clinical need. The ETD Executive Committee met three times during 2018: March 11th in Rome; August 1st in Chicago and November 9th in Budapest. Three Committees have been approved to date by the EB in Budapest in November 2018: Committee Emerging Technologies in Pediatrics, Chair Tim Lang (UK); Committee Omics Translation, Chair Gregory J Tsongalis (US); Mobile Health and Bioengineering in Laboratory Medicine, Chair Bernard Gouget (FR). Five WGs are still under EB evaluation: WG-Volatolomics, Chair Larry Kricka (US); WG- Guidance for the implementation of custom-made genomic panels, Chair Jennifer Morrisette (US); WG on Open Innovation, Chair Damien Gruson (BE); WG Functional Genomics in Laboratory Medicine, Chair Ronda Graves (AU); Neonatal Laboratory Medicine, Chair Vijay L. Grey (CA). The ETD Officers, titular members and corresponding members, to date are 50 from 20 Countries. During 2018, ETD organized Symposia at the following Congresses: AFCB Ramallah, Palestine-April; STBC Tunis, Tunisia-May; ESC e-Cardiology Conference, Moscow-October; 15th Symposium for Balkan Region, April-Belgrade. Sergio Bernardini – ETD Chair

IFCC TASK FORCES • TASK FORCE ON ETHICS (TF-E) • A survey was e-mailed to all IFCC member societies regarding their current ethics documents and future needs regarding ethics documents on COI, code of ethics & relationship with industry. • Development of Ethics Toolkit for Member Societies. At present under development • Updated TF-Ethics website. • TF-Ethics held a committee meeting in Budapest during the General Conference 2018. Plans for 2019: • Complete and update the Ethics "toolkit" for Member Societies. • Create an E-learning course on professional ethics for IFCC volunteers. • Update of TF-Ethics website and include a section on “Highlights of recent events in Bioethics” • Create a table of documents collected so far stratified by organization. Committee members will approach organizations in their region to solicit more documents. • Compare Code of ethics documents creating a document that outlines similar sections. Nilda Fink, Chair • TASK FORCE FOR YOUNG SCIENTISTS (TF-YS) Education and Training TF-YS educational sessions conducted: • YS session at the 1st IFCC, EFLM, AFCB Conference “Laboratory Medicine: Meeting the needs of Mediterranean Nations” 2-4 July, 2018 – session theme ‘Laboratory Medicine Sustainability around Mediterranean Sea”: YS speakers Guilaine, Miljan, Josep and Pradeep; supported by Organising Committee • Functional Meeting and Talk TFYS at IFCC General Conference, 10-11 Nov 2018: participated by all core members • IFCC-TFYS and SYCL Networking at AACC 2018, July 29-Aug 2; participated by Santiago, Damien • TFYS session and YS Quiz at ACBICON 2018, Goa, India; participated by Pradeep, Damien, Danni • Round table of IFCC-TFYS and online Skype participation of Pradeep at “16th Panhellenic Congress of Clinical Chemistry”, 11-13 October, Alexandroupolis, Greece: another TFYS speaker Anna Velts supported by Congress Organizing Committee • Online Skype participation of Pradeep at “Congress of the Italian Society Clinical Chemistry (SIBioC)”, Naples, Italy, 16-18 Oct 2018 • Online Skype participation of Pradeep, Santiago at “2nd Conference of the Italian Society of Clinical Chemistry and Laboratory Medicine (SIBioC)” - Young Scientists Working Group (YS-WG); “2º Congresso Nazionale SIBioC GdS Young Scientists”, 3rd Dec 2018 • “CALILAB - X Congreso Argentino de Calidad en el Laboratorio Clínico y VIII Jornadas Latinoamericanas de la Calidad en el Laboratorio Clínico”. "IFCC YS-TF projects and activities" Santiago Fares Taie. Buenos Aires 24-27 de octubre 2018.

Special Supplement to Lab Medica International • 33

2018 Annual Report

Planned 2019 TF-YS educational sessions and networking at: 1. Session and functional meet TFYS at APFCB 2019, Nov 17-20, Jaipur, India and ACBICON 2019: joint Leadership workshop with IFCC-CCLM is also being planned; Young Scientists volunteer programme, travel grants by IFCC-TFYS 2. Symposium at Euromedlab 2019, May 19-23, Barcelona, Madrid: networking with Spanish YS 3. Tunisian Society of Clinical Biology organizes its 33th National Days, 2527 April 2019, Hammamet-Tunisia: proposed to schedule an IFCC TF-YS session on Thursday 27 April 2019: proposed by Chaabane Manel, TFYS corresponding member 4. Pakistan Society of Chemical Pathologists (PSCP) organising online YS session under theme of «Research Methodology», 13th March 2019 5. TFYS session at NACCON (Nepalese Association for Clinical Chemistry) 2019 and Annual Meeting on March 2-3, 2019 at Pokhara, Nepal 6. TFYS is planning to extend the network via regional programmes and social media further. 7. Dr Phillippe suggested TFYS to propose symposium for IFCC-WorldLab2020. 8. Prof Rajiv Erasmus assured of all help within African Federation AFCC and regions to spread TFYS activities. Webinar Series We have completed 6 webinars by now and finalising for next series to conduct with L3 Healthcare. Suggested Topics: "structuring a paper, selecting the best journal, dealing with peer-review, publishing ethics problem" for next 3 webinars to continue in 2019. Last webinar conducted at 13th Dec 2018: Title "Essential skills to structure a paper" Speaker: Anthony Newman, Clinical Chemistry programme, Life Sciences Dept., Elsevier, Amsterdam, The Netherlands Member YS Support. YS colleagues support to meet participation. Young Scientists volunteer programme, travel grants by IFCC-TFYS to join APFCB 2019. Seeking support from corporate members and APFCB committee. IFCC-EB announced travel support for EuromedLab2019, APFCB2019, ColaBioCli 2019. Mentorship Programme. To continue interviews; latest support from Maria Eugenia Shroeder, Uruguaya, Corresponding member TFYS to work with Danni; Danni has also proposed to support TFYS programme after 2018. Lab-Surfing. To continue operations on Lab surfing, we need support to meet maintenance and additions. 1. Lab surfing visibility need to enhance and register more and more YS. Also needing to attach more YS before it go for such other tools. 2. Santiago may write short news and updates, that we can share through different social and official channels to join YS. 3. Personal presence of YS through discussion, need based activities can be enhanced. 4. Newsletter - even 1 page is enough to connect. 5. YS Experts directory- can be added to access for various field of experts as shown during Guilaine ppt. 6. Updation of Labsurfing 7. Funding can be proposed for same as discussed. TFYS Survey. Now the members have been added approx. 2000 globally to all social media channels. Guilaine has started new extended Survey: "YS training & career". By the IFCC Task Force Young Scientists, this survey aims to acquire preliminary information of young colleague’s education, training, career path, research interest, field of work and association with TFYS. This will enable us to share and focus our energies to find support for base programmes that are needed. h t t p s : / / d o c s . g o o g l e . c o m / f o r m s / d / e / 1 FA I p Q L S d C Z 6 d m B f VYzuL0fHRMc73r-JABkdoJsW2YuHnqOEeUWIM-g/viewform Guilaine has already shared details during programme and slides as well. Social Media. We are continuing meeting needs and networking YS through all media Facebook, Google group, Linked In, Twitter, Online meetings of members. Outgoing Core-Members. Miljan, Danni, Lara are outgoing core members, completing 2nd term with TFYS. Committed and great team leaders. Call for nomination of TFYS core members process is completed through IFCC office and new members will be joining as core office bearers as a part of practice, for TFYS office 2019-21. Further information will be shared and updated with all members soon. Young Scientists Positions in IFCC task forces and sub-committees. Through years of efforts of TFYS team, we are able to convince IFCC-EB to bring YS positions into committees starting with scientific division. Formal announcements will be coming in time. Leadership & Management. Dr Pradeep was invited for closed meet of IFCC-CCLM where Dr Sedef, Chair CCLM invited to collaborate and extend the leadership and management programme with TFYS. Details will be shared by CCLM further. IFCC-CCLM and TFYS will be holding joint Leadership workshop under the banner of APFCB2019 at India. Pradeep Kumar Dabla (Chair)

FOUNDATION FOR EMERGING NATIONS - FEN Introduction: The FEN is established under Swiss law as a non-profit making charitable trust, which is devoted to fund raising and to supporting programmes that help to improve the quality and delivery of laboratory medicine

IFCC

services, particularly in emerging nations. Board of Directors: There are five members of the FEN Board of Directors. Dr Graham H Beastall (UK) Chair; Dr Michelle Rossier (CH); Prof Thomas Brinkmann (DE); Ms Lucia Monaco (IT); Prof Tomris Ozben (TR). Biographies of the Board of Directors are available from www.ifccfoundation.org Board Meetings: During 2018 the Board met (by Skype) on four occasions (April, July, October and December). There was a high level of participation by Directors. Confirmed and signed Minutes of those meetings are available on request. Achievements: During 2018 the FEN achieved the following: • Compliance with the Handelsregister des Kantons Schwyz and the Swiss Foundation Supervisory Authority • Publication of the annual report for 2017 • Approval of audited accounts for 2017 • Operation of the FEN website www.ifccfoundation.org • Publication of two newsletters • Promotion of the FEN through various IFCC media outlets • Fundraising initiatives • Support for and monitoring of one funded project Completed Projects: • ‘Africa LabMed Radio’ The FEN supported the purchase of specialist equipment to enable an internet radio station to be established for all countries in Africa. Young scientists have been recruited as reporters and the equipment has been used in several interviews, which were made available through YouTube and Facebook. Support from the African Federation of Clinical Chemistry and other partners is required to deliver the final component of the project – regular radio broadcasts across Africa. Ongoing Projects: • Proficiency of malaria microscopists in Ethiopia: The Ethiopian Public Health Institute has an ambitious programme to eliminate malaria from areas of the country. The proficiency of the microscopists who make the diagnosis requires improvement if this is to be achieved. The FEN provided an award for partnership working with EPHI to develop training support for microscopists. A survey of the competence, training status and further requirements of microscopists has been completed and is being prepared for publication. Fundraising and Finances: The greatest challenge faced by the FEN during 2018 was raising funds to support the ongoing work of the Foundation. During the year it was thought that the FEN may have to close because of a lack of funds. The FEN Board agreed that it should focus on its ‘Support a Professional’ programme. Funds to support this programme were obtained from SNIBE Diagnostics and the scholarship has been advertised in Pakistan in collaboration with the Pakistan Society of Chemical Pathologists. Audited accounts for the year to 31st December 2018 are in preparation and will be available on request. In summary: Income: Starting balance at 1 January 2018 10.488 CHF Funds added during year 8.884 CHF Total 19.372 CHF Expenditure: Operating costs 5.122 CHF Project support 2.415 CHF Total 7.537 CHF Closing balance at 31 December 2018 11.835 CHF Acknowledgement: The FEN acknowledges expert administrative support from Ms Paola Bramati of IFCC. Graham Beastall (Chair)

ORGANIZATIONS (REGIONAL) AFFILIATED WITH IFCC There are six main Regional Professional Laboratory medicine organizations which can be considered IFCC regional partners: • AFCB - Arab Federation of Clinical Biochemistry • AFCC - African Federation of Clinical Chemistry • APFCB - Asia-Pacific federation of Clinical Biochemistry • COLABIOCLI - Latin-American Confederation of Clinical Biochemistry • EFLM - European Federation Clinical Chemistry and Laboratory Medicine • NAFCC – North American Federation of Clinical Chemistry and Laboratory Medicine More information about these affiliate organizations and their activities can be found on our website (www.ifcc.org) and are included in the IFCC Annual report 2018, web edition.

FOR MORE INFORMATION ON THE IFCC CONTACT: IFCC Office • Via Carlo Farini 81, 20159 Milan, ITALY Tel: (39) 02-6680-9912 • E-mail: ifcc@ifcc.org Web: www.ifcc.org

Special Supplement to Lab Medica International • 34

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Nanopore Method Detects Influenza Virus at Particle Level team of Japanese researchers has introduced a novel sensor concept capable of discriminating various types of influenza virus in a label-free fashion by their distinct particle properties. Rapid diagnosis of influenza infection before onset of symptoms would improve health care by reducing risk for serious complications as well as by preventing infectious disease outbreaks. Sensor sensitivity and selectivity are critical to accomplishing this goal, as the number of virus particles is quite small at the early stage of infection. To overcome the low particle number problem, investigators at Osaka University (Japan; www.osaka-u.ac.jp) developed a nanopore device with electroosmotic flow (liquid motion induced by an electric current across the nanopore) properties that ensured that the pore channel would block the passage of non-virus particles. The nanopores were designed to have low thickness-to-diameter aspectratio structure so as to render additional sensitivity to the particle shape and surface charges. This provided resistive pulses holding a complex set of information concerning not only the nanoparticle volume but multiple physical properties of the intact viral particles. To evaluate the information set, the investigators employed machine-learning-driven pattern-analysis of the electrical signatures. This allowed for rapid detection and simultaneous subtype differentiation of virus particles with an ultimate sensitivity of single-particle discriminations. Results demonstrated the ability to identify allotypes with 68% accuracy at the single-virus level. “We used machine-learning analysis of the electrical signatures of the virions,” said contributing author Dr. Makusu Tsutsui, associate professor of scientific and industrial research at Osaka University. “Using this artificial intelligence approach to signal analysis, our method can recognize a slight current waveform difference, which cannot be discerned by human eyes. This enables high-precision identification of viruses.” “Our testing revealed that this new sensor may be suitable for use in a viral test kit that is both quick and simple,” said first author Akihide Arima, a researcher in the chemistry department at Osaka University. “Importantly, use of this sensor does not require specialized human expertise, so it can readily be applied as a point-of-care screening approach by a wide variety of healthcare personnel.” The nanopore technique for detecting influenza virus was described in the November 2, 2018, online edition of the journal Scientific Reports.

Image: An illustration showing detection of a single influenza virion using a solid-state nanopore (Photo courtesy of Osaka University).

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Liquid Biopsy Detects Cancer Across Multiple Biomarkers lthough biomarker-directed therapy is in its infancy in prostate cancer compared to some other tumor types, there is a great need for predictive biomarker testing, and great interest in noninvasive methods. However, comprehensive analysis of patients’ cellfree DNA has been limited to date. Prostate cancer is the most commonly detected male cancer in Europe and the third major cause of cancer-related death among men. Although the majority of metastatic hormone-naïve prostate cancers (mHNPCs) demonstrate a reliable response to initial androgen deprivation therapy, which targets androgen receptor (AR) signaling, progression to a castration-resistant state is inevitable. A large international team of scientists led by those at the Karolinska Institute (Stockholm, Sweden; https://ki.se) sequenced cell-free DNA from 364 blood samples taken from 217 prostate cancer patients with metastatic, castration-resistant disease, using a combination of targeted and lowpass whole-genome sequencing. Germline DNA was extracted from leftover EDTA blood. In addition, for 340 out of 364 circulating DNA (ctDNA)-analyzed blood samples, an additional blood sample was collected in a CellSave tube and shipped to the GZA Sint-Augustinus (Antwerp, Belgium; www.gza.be) for circulating tumor cells (CTC) enumeration within 72 hours on the FDA-cleared CellSearch platform (Menarini Silicon Biosystems, Castel Maggiore, Italy; www.siliconbiosystems.com). The team detected circulating tumor DNA in 86% of samples. They were also able to measure differences in the levels of circulating tumor DNA that corresponded to how many treatments a patient had had. Looking at specific biomarkers, such as the androgen receptor, that have

emerged as potential clinical predictors for prostate tumors, the group found for example that the fraction of patients with intra-AR structural variation increased from about 15% during first-line therapy to over 45% in fourth-line treatment. The authors concluded that ctDNA profiles appear to mirror the genomic landscape of metastatic prostate cancer tissue and may cost-efficiently provide somatic information in clinical trials designed to identify predictive biomarkers. However, intronic sequencing of the interrogated tumor suppressors challenges the ubiquitous focus on coding regions and is vital, together with profiling of synchronous white blood cells, to minimize erroneous assignments which in turn may confound results and impede true associations in clinical trials. The study was published on November 21, 2018, in the journal Genome Medicine. Image: The CellSearch Platform for identification, isolation, and enumeration of circulating tumor cells (Photo courtesy of Menarini Silicon Biosystems).

MALDI-TOF MS Identifies Oomycete Causing Pythiosis ythiosis is an invasive, difficult-to-treat, life-threatening infectious disease caused by Pythium insidiosum, a member of the unique group of fungus-like microorganisms called oomycetes. The disease has been increasingly reported worldwide. In the past decade, the matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) has emerged as a novel and powerful diagnostic tool for facilitating the clinical identification of many pathogenic microorganisms, including bacteria and fungi. Scientists at the Mahidol University (Bangkok, Thailand; https:// mahidol.ac.th) isolated a total of 13 strains of P. insidiosum, isolated from eight humans and five animals with pythiosis, from different geographic locations. All organisms were maintained on Sabouraud dextrose agar at 25 °C. Several small portions of a colony of each organism were transferred to a 50-mL flask containing 10 mL Sabouraud dextrose

broth, and incubated at 37 °C for one week, before harvesting fungal material for protein extraction. Protein was extracted from harvested organisms and was spotted onto a clean ground steel target plate (Bruker Daltonics, Bremen, Germany; www.bruker.com) in 40 replicates (for generating a MALDI-TOF MS database of P. insidiosum) or five replicates (for assessing the MALDI-TOF MS for identification of P. insidiosum), air dried at room temperature before being processed. After the matrix solution was air dried at room temperature, the sample was promptly analyzed, using a Bruker ultrafleXtreme mass spectrometer. Genomic DNA (gDNA) templates were extracted from the organisms and subjected to single nucleotide polymorphism-based multiplex polymerase chain reaction (PCR). The study was published in the December 2018 issue of the International Journal of Infectious Diseases. LabMedica International May/2019

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Automated Microscopy Compared For Routine Malaria Diagnosis icroscopic examination of Giemsa-stained blood films remains a major form of diagnosis in malaria case management. However, as with other visualizationbased diagnoses, accuracy depends on individual technician performance, making standardization difficult and reliability poor. Automated image recognition based on machine-learning, utilizing convolutional neural networks, offers potential to overcome these drawbacks. The application of digital image recognition to malaria microscopy, using artificial intelligence algorithms to replace or supplement the human factor in blood film interpretation, have been attempted, usually on thin films. A team of scientists collaborating with Intellectual Ventures (Bellevue, WA, USA; www.intellectualventures.com) conducted a cross-sectional, observational trial was conducted at two peripheral primary health facilities in Peru. They enrolled 700 participants whose age was between 5 and 75 years, and had a history of fever in the last three days or elevated temperature on admission. A finger prick blood sample was taken to create blood films for microscopy diagnosis, and additional drops of blood were spotted onto filter paper for subsequent quantitative polymerase chain reaction (qPCR) analysis. A prototype digital microscope device employing an algorithm based on machine-learning, the Autoscope, was assessed for its potential in malaria microscopy. The investigators reported that at one clinic, sensitivity of Autoscope for diagnosing malaria was 72% and specificity was 85%. Microscopy performance was similar to Autoscope, with sensitivity 68% and specificity 100%. At one clinic, 85% of prepared slides had a minimum of 600 white blood cells (WBCs) imaged, thus meeting Autoscope’s design assumptions. At the second clinic, the sensitivity of Autoscope was 52% and specificity was 70%. Microscopy performance at this second clinic was 42% and specificity was 97%. Only 39% of slides from this clinic met Autoscope’s design assumptions regarding WBCs imaged. The authors concluded that Autoscope’s diagnostic performance was on par with routine microscopy when slides had adequate blood volume to meet its design assumptions, as represented by results from one clinic. Autoscope’s diagnostic performance was poorer than routine microscopy on slides from the other clinic, which generated slides with lower blood volumes. The study was published on September 25, 2018, in the Malaria Journal.

Image: The Autoscope uses deeplearning software to quantify the malaria parasites in a sample (Photo courtesy of Intellectual Ventures). V

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PRODUCT NEWS SWEAT ANALYSIS SYSTEM

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The Sweat-Chek Analyzer is for total electrolyte analysis of sweat samples using the Wescor method. It is a practical system for small hospitals, local clinics, private practitioners, larger clinics and hospitals.

The Simplexa Group B Strep Direct assay enables the direct in vitro detection of Group B Streptococcus. The assay is more specific than traditional testing methods and features a fast workflow.

The qUAntify Advance Control monitors the precision of urinalysis test procedures and contains human urine solution. It offers 31 days of open vial stability for all analytes, including ketones, at room temperature.

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Diabetic Retinopathy Linked to Glycemic Variability In Type 2 Diabetes atent autoimmune diabetes in adults (LADA) refers to adult diabetes patients who are initially non insulin requiring, but have type 1 diabetes mellitus associated autoantibodies and who often progress to insulin dependency. LADA manifests as a wide spectrum of heterogeneous clinical and metabolic phenotypes that are midway between those of classic type 1 diabetes mellitus and type 2 diabetes mellitus. It is estimated that LADA accounts for 4% to14% of patients with a diagnosis of type 2 diabetes mellitus. Scientists affiliated with the Shanghai Jiao Tong University (Shanghai Shi, China; www.sjtu.edu.cn) conducted a cross-sectional analysis of 192 adults (mean age, 56.4 years; 47.9% women; mean BMI, 23.2 kg/m2) with LADA and 2,927 adults with type 2 diabetes (mean age, 57.7 years, 57.3% women, mean BMI, 25.1 kg/m2). The participants were consecutively enrolled in the first group and randomly chosen for the second. All participants were recruited from July 2005 to December 2015. All participants were continuously monitored for 72 hours with a retrospective CGM system (Medtronic Inc, Northridge, CA, USA; www.medtronic.com). Fundus photography was then used to confirm diabetic retinopathy (DR). The investigators found that found that diabetic retinopathy was more common among those with type 2 diabetes than in those with LADA (26.4% versus 20.3%). Diabetic retinopathy was significantly linked to age, diabetes duration, systolic blood pressure, HbA1c and measurements of glycemic variability in participants with type 2 diabetes based on univariate logistic regression. In participants with LADA, diabetes duration, systolic BP and diastolic BP were the lone risk factors for diabetic retinopa-

thy. They also noted that, overall, participants with LADA weighed less, had better BP and lipid profiles as well as higher glycemic variability and lower fasting C-peptide than those with type 2 diabetes. The authors concluded that their study provided evidence that intraday glycemic variability (GV), as assessed by continuous glucose monitoring (CGM), was associated with the presence of DR in type 2 diabetes mellitus patients, but not in LADA patients, suggesting that GV should be minimized to decrease the risk of DR in type 2 diabetes mellitus, whereas achieving an optimal HbA1c without increasing the risk of hypoglycemia might be the primary goal in the treatment of LADA. The study was first published on October 10, 2018, in the Journal of Diabetes Investigation. Image: The continuous glucose monitoring (CGM) system (Photo courtesy of Medtronic).

Vitamin D Measured in Patients with Diabetic Foot eripheral artery disease (PAD) is the underlying predisposing factor in the etiology of the majority of diabetic feet. Vitamin D plays a role in calcium and bone metabolism and it is known to be an important immune modulator agent. Osteoprotegerin (OPG) is a glycoprotein, which is a member of the tumor necrosis factor (TNF) family. Osteoprotegerin was first found in the bones and it acts as a strong anti-resorptive factor. The effect of osteoprotegerins is demonstrated by binding or neutralizing the receptor activator nuclear factor kappa B ligand (RANKL). Medical scientists at the Bağcılar Training and Research Hospital (Istanbul, Turkey; http://bagcilareah.saglik.gov.tr) conducted a prospective study on 105 patients including 58 patients with diabetic foot (42

males, 16 females; mean age 63.6 years; range, 31 to 90 years), who applied to the hospital between June 2014 and May 2015, and 47 newly diagnosed type 2 diabetes mellitus (DM) patients (27 males, 20 females; mean age 51.4 years; range, 29 to 85 years) (control group). Serum concentration of 25-hydroxyvitamin D (25(OH)D) was determined by using electrochemiluminescence immunoassay utilized in fasting patients’ morning blood samples. Serum concentration of OPG was determined by enzyme-linked immunosorbent assay (ELISA) (eBioscience kit, Bender Medsystems GmbH, Vienna, Austria; www.bionity.com) using the same blood samples. For OPG ELISA eBioscience kit, reference values for normal serum samples were 5-100 pg/mL. The study was published in the December 2018 in the journal Joint Diseases and Related Surgery.

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Individual Human Papilloma Virus Types Linked to HIV Infection lthough it is known that individuals living with human immunodeficiency virus (HIV) have a higher human papilloma virus (HPV) prevalence, the impact of individual HPV types on HIV acquisition is less clear. Human papillomavirus (HPV) is the most prevalent sexually transmitted disease (STI) worldwide among all sexually active adults and affects approximately 50% of HIV-negative men who have sex with men (MSM), which may include transgender women (TW) because the groups are often erroneously combined. An international team of scientists led by those at University of California, Riverside (Riverside, CA, USA; www.ucr.edu) recruited for a cohort study 600 participants, both MSM and TW in Peru, to examine MSM and TW, not only for HPV prevention but also possibly for HIV the relationship between anogenital warts and HIV acquisition. Incluprevention. The study was published on October 2, 2018, in the joursion criteria were: born anatomically male, aged 18 to 40 years, HIVnal PLOS ONE. negative, had anal intercourse with a male in the past 12 months, resident of metropolitan Lima, and willing to provide blood samples and Image: The LINEAR ARRAY HPV Genotyping Test is used for the detection of 37 high- and low-risk human papillomavirus genotypes (Phoanal swabs. to courtesy of Roche Diagnostics). The team collected anogenital specimens at the baseline visit using pre-wetted Dacron swabs from the coronal sulcus or glans penis, penile shaft, anus, and scrotum, combined NE DES W into one sample per participant, and IGN stored at -80 °C. DNA was extracted using the QIAamp Media MDx Kit (Qiagen, Hilden, Germany; www. qiagen.com) followed by polymerase chain reaction and HPV genotyping. WORLD’S MEDICAL PRODUCT MARKETPLACE Samples positive for -globin or at least one HPV genotype were considered adequate and included in the analysis (overall -globin positivity = SIGN UP 98%). The Roche Linear Array assay FOR FREE! (Roche Diagnostics, Basel, Switzerland; http://molecular.roche.com) was used to detect 37 HPV genotypes. The scientists reported that at baseline, 530 participants had HPV DNA present (61.1% with high-risk HPV, 84.9% with low-risk HPV). Among 571 participants who returned for any study visit, 73 (12.8%) became infected with HIV during the 2-year follow-up (6% HIV incidence). Compared to those without HIV, statistically significantly more participants with HIV had any HPV type present (97.3% versus 87.6%, respectively), more than one HPV type (79.5% versus 58.2%), or high-risk HPV (72.6% versus 51.4%). Some participants lost to follow-up could have been HIV-positive, which would have affected the relationship of HPV Connecting Buyers with and HIV infection. Suppliers Worldwide The authors concluded that their prospective study showed that particReach new sources of supply ipants with any HPV type, more than Identify latest products and technologies one HPV type, or high-risk HPV were Send inquiries directly to suppliers more likely to test positive for HIV. Receive latest product alerts Although most studies have shown Chat live with suppliers HPV–HIV coinfection, their findings illustrate the strong relationship beTradeMed provides a sophisticated yet easy-to-use global B2B platform for sourcing medical tween individual HPV types and HIV equipment. TradeMed connects buyers and sellers worldwide through a safe, secure and dyinfection. This further illustrates the namic network. Solely dedicated to medical products, TradeMed is the premier choice for medpotential utility of HPV vaccine for ical suppliers, hospital decisionmakers and buyers worldwide, regardless of size or budget.

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PRODUCT NEWS BLOOD CULTURE SYSTEM

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Genrui Biotech

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The BC120 uses an optical detection system to realize full automation of blood culture testing. Its temperature control system and vibrating model shorten the time of results and helps reduces the false positive rate.

The WP21E features a long-life halogen lamp, 5-inch touch screen and keypad, and easy-to-use software. It offers RT display of reaction curve, flowcell and cuvette modes, making it suitable for small labs/clinics.

The HbA1c net FS for the diagnosis and monitoring of diabetes delivers results equivalent to HPLC. The test is standardized against the IFCC reference method and traceable to DCCT/NGSP.

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Test Detects Protein Associated With Alzheimer’s and Chronic Traumatic Encephalopathy n ultrasensitive test has been developed that detects a corrupted protein associated with Alzheimer’s disease and chronic traumatic encephalopathy (CTE). This advance could lead to early diagnosis of these conditions and how they originate. Alzheimer disease (AD) afflicts 5.7 million people in the USA alone and their care is estimated to cost USD 232 billion annually. Like other proteins involved in neurological diseases, tau protein clusters can seed themselves and contribute substantially to the disease processes of Alzheimer’s and CTE. The diagnostic test originally developed for prion diseases to detect abnormal clusters of tau protein. A team of scientists collaborating with the Rocky Mountain Laboratories (NIAID, Hamilton, MT, USA: www.niaid.nih.gov) analyzed brain samples from 16 Alzheimer’s patients, two boxers with CTE, and numerous control cases involving other brain diseases. Tissue samples for neuropathological studies were obtained from representative brain regions. The following methods were used: Weigert’s hematoxylin–eosin, Woelcke–Heidenhain, Bodian, Gallyas, and thioflavin S. For immunohistochemistry, antibodies against tau, Aβ, glial fibrillary acidic protein (GFAP), prion protein, ubiquitin, and TAR DNA-binding protein-43 (TDP-43) were used. To probe the molecular basis for AD’s tau filament propagation and to improve detection of tau aggregates as potential biomarkers, the team exploited the seeded polymerization growth mechanism of tau filaments to develop a highly selective and ultrasensitive cell-free tau seed amplification assay optimized for AD (AD real-time quaking-induced conver-

sion or AD RT-QuIC). The reaction is based on the ability of AD tau aggregates to seed the formation of amyloid fibrils made of certain recombinant tau fragments and read on a BMG FLUOstar plate reader (BMG LabTech, Oretenberg, Germany; www.bmglabtech.com). The authors concluded that the distinctive seeding activity exhibited by AD and CTE tau filaments compared to other types of tauopathies in these seeded polymerization reactions provides a mechanistic basis for their consistent propagation as specific conformers in patients with 3R/4R tau diseases. Importantly, AD RT-QuIC also provides rapid ultrasensitive quantitation of 3R/4R tau-seeding activity as a biomarker. The study was published on December 20, 2018, in the journal Acta Neuropathologica. Image: The FLUOstar Omega is a multi-mode microplate reader and has six detection modes (Photo courtesy of BMG LabTech).

Rapid Malaria Test Detects Placental Infection alaria remains one of the most important parasitic infections in humans. It is endemic throughout the tropical and subtropical regions of the world and is responsible for more than 200 million clinical cases and more than 400,000 deaths each year. Plasmodium falciparum infected erythrocytes sequestering in placental tissue release Plasmodium lactate dehydrogenase (pLDH) and histidine-rich protein-II (HRP-II). These proteins can be detected in peripheral blood using monoclonal antibody-based rapid diagnostic tests (RDTs). Scientists affiliated with the University of Yaoundé 1 (www.uy1. uninet.cm) prepared Giemsa-stained blood smears for peripheral blood smear (Pbs), placental intervillous space (IVS) blood smear and placental tissue impression smear (PTIS) from HIV-negative women during de-

livery. If parasites were not detected after examining 200 microscopic fields of thick smears, the sample was considered malaria negative; however, when parasites were detected, parasitaemia was estimated per microliter of blood. Both thin film and impression smear were used to determine parasite species. Hemoglobin (Hb) levels in maternal blood were determined using the URIT-3300, Coulter Counter (Urit Medical Electronics Group, Guilin China; www.urit.com) and a woman was diagnosed as anemic if her Hb was less than 11 g/dL. The One Step HRP-II and pLDH RDT SD Bioline malaria antigen P.f/pan, (Standard Diagnostics Inc, Yongin-si, Korea; www.alere.com) was used to diagnose malaria infection in the peripheral blood samples. The study was published on December 4, 2018, in the Malaria Journal. LabMedica International May/2019

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LabMedica International

Resistance of Tumor Cells To Cancer Drugs Detected cquired resistance is developing during treatment of cancer patients who were initially responding to the therapy. Drug resistance is mediated by mutations acquired during therapy, in addition to other adaptive responses. Currently used in vitro assays to monitor the drug efficacy and acquired resistance are often performed using fluorescently labeled drug molecules, Western blot, and cytotoxicity assays. However, proteins are highly coupled within networks and signal transduction networks are complex. Scientists at the Ruhr-University Bochum (Bochum, Germany; www. ruhr-uni-bochum.de) used tyrosine kinase receptor inhibitors that have been approved for lung cancer therapy. They inhibit cell growth by binding to specific proteins on the cell surface. However, patients develop resistance to the drugs in the course of therapy, because of protein changes in cancer cells. A WITec alpha 300AR confocal Raman microscope (Ulm, Germany; www.witec.de) was used to acquire Raman micro-spectroscopic imaging of cancer cells. Raman micro-spectroscopic measurements were performed by raster-scanning the laser light over cancer cells to acquire a Raman spectrum at a speed of 0.5 seconds per pixel with a pixel resolution was 500 nm. The in vitro Raman results indicated that NSCLC cells with T790M and T790M/C797S EGFR mutations are resistant to erlotinib- and osimertinib, respectively, consistent with the observed responses of patients. The authors concluded that their study shows the potential of Raman micro-spectroscopy to monitor drug resistance and opens a new door to in vitro companion diagnostics for screening personalized therapies. The study was published on October 15, 2018, in the journal Scientific Reports.

Image: The WITec alpha 300AR confocal Raman microscope (Photo courtesy of WITec)

Molecular Influenza and Streptococcus Tests Get FDA Clearance ach year, a combination of influenza A and B virus strains circulate within the USA. The burden of influenza in the USA is currently estimated to be 9 to 36 million cases per year. The disease and its complications cause as many as 140,000 to 710,000 hospitalizations and 12,000 to 56,000 deaths annually. Influenza also poses a significant economic burden including medical care expenses and loss of productivity. Pharyngitis, or inflammation of the pharynx causing sore throat, is diagnosed in 11 million patients in USA emergency departments and ambulatory settings annually. Group A Streptococcus (GAS) is the most common bacterial cause of acute pharyngitis, accounting for 15% to 30% of cases in children and 5% to 20% of cases in adults. GAS is easily and frequently spread among families and other close contacts via respiratory secretions, and infection peaks in the late winter and early spring. The US Food and Drug Administration (Silver Springs, MS, USA; www.fda.gov) have cleared next-generation Influenza A & B 2 and Strep A 2 molecular assays for point-of-care testing. The new assays enable fast time-to-results for molecular influenza A & B and Strep A testing at the point of care. Both assays have also been granted CLIA waivers and are available for use with the Abbott ID Now platform (Abbott Diagnostics, Abbott Park, IL, USA; www.molecular.abbott), formerly the Alere I, a rapid, instrument-based, isothermal nucleic acid amplification system for the qualitative detection of infectious diseases. The Influenza A & B 2 assay provides point-of-care molecular detection and differentiation of influenza A and B virus in 13 minutes or less, and it calls out positive results in five minutes. The assay enables room temperature storage of all test components, which simplifies and streamlines test ordering and storage. The Strep A 2 test provides molecular detection of group A Streptococcus bacterial nucleic acid, the primary cause of bacterial pharyngitis, or sore throat, in six minutes or less, and it calls out positive results in two minutes. Culture confirmation is not required for negative results. Gregory Berry, PhD, D(ABMM), director of molecular diagnostics at Northwell Health Laboratories (Lake Success, NY, USA; www.northwell.edu ), said, “Rapid testing may also help reduce improper antibiotic usage, which can occur when treatment is based exclusively on a patient’s symptoms, and contributes to antibiotic resistance.”

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PRODUCT NEWS SPECIMEN SWAB

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CRP TEST

Puritan Medical Products

Agappe Diagnostics

Medix Biochemica

The Fecal Opti-Swab is intended for the collection/ transport/preservation of fecal/rectal swabs containing enteric pathogenic bacteria. The swab is packaged with a sterile standard tip HydraFlock swab.

The MISPA i4 automated analyzer offers high precision and quick turnaround results. Designed to increase workflow efficiency, it offers simple operation and a wide protein and chemistry panel.

The Actim CRP for C-reactive protein (CRP) detection estimates if an infection is viral or bacterial. The test delivers reliable results in five minutes, and helps determine the need for antibiotics or additional tests.

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Herpes Simplex Virus Assay, Sample-to-Answer Instrument Get FDA Clearance erpes simplex virus 2 (HSV2) is a widespread herpes virus, usually sexually transmitted and responsible for genital herpes. Herpes simplex virus 1 (HSV1) is a common virus life-long established in the peripheral nervous system. A sample-to-results diagnostic instrument and an assay to detect and differentiate herpes simplex viruses 1 and 2 have received 510(k) clearance. The instrument and assay are now commercially available in the USA. The instrument integrates extraction, amplification, and results interpretation, and is also an open platform compatible with commonly used fluorescent probes. It contains 12 independent thermal cyclers that can run different polymerase chain reaction (PCR) profiles in each run, with six detection channels for multiplex detection. It can also run multiple different assays from a single sample tube. The ELITe MGB HSV 1&2 Assay (EliTech Group, South Logan, UT, USA; www.elitechgroup.com) is cleared for use by the US Food and Drug Administration (FDA, Silver Springs, MD, USA; www.fda.gov) on swab specimens from cutaneous or mucocutaneous lesions in symptomatic patients with cold sores or genital herpes. The diagnostic instrument, called the Elite InGenius, is a fully automated benchtop instrument that performs real-time PCR-based testing on 12 tests in a run, requiring two minutes of hands-on time per sample. The Elite InGenius instrument can be used in various operational

modes, including extraction-only, amplification-only, or full-processing extraction, amplification, and result analysis with melt curve analysis capability. It was introduced as a CE-IVD marked instrument in 2015 with a core menu of transplant monitoring assays. The firm also currently markets a menu of CE-marked molecular diagnostics kits for detecting hospital-acquired infections, sexually transmitted diseases, respiratory infections, bacterial and viral meningitis. In addition, the EliTech Group manufactures and distributes diagnostic products for clinical chemistry, microbiology, and molecular biology. Image: The HSV2 ELITe MGB Kit is a real-time PCR assay designed for the detection and quantification of type 2 herpes simplex virus DNA (Photo courtesy of EliTech Group).

Generic Test Developed for Early Detection of Cancer ancer is one of the leading causes of death worldwide. Early detection of cancer significantly raises the chances for an effective treatment. Cancer identification methods are mainly based on imaging, biopsies and a few nonspecific biomarkers. There were about 18 million cancer cases diagnosed around the world in 2018. The number of new cancer cases per year is expected to reach more than 23 million by 2030. The most common cancers globally are lung cancer, breast cancer, and colorectal cancer. Scientists at the University of Bradford (Bradford, UK; www.bradford. ac.uk) and their collaborators adapted the Lymphocyte Genome Sensitivity (LGS) technique, modified by a slightly different method and examined 700 more blood samples from 598 patients with cancer or suspected cancer and 102 healthy individuals. To help increase the sensitivity of the test and detect cancer at the level of each individual, they joined with the IMSTAR team (Paris, France; www.imstarsa. com) who analyzed the cells with their fully automated Pathfinder

cell reader-analyzer system. The new test, which is called TumorScan, is a highly sensitive test to detect any cancer at an early stage through the response of the white blood cells to UV treatment. These patient blood samples have also been collected at the stage before confirming diagnosis and treatment. There were four of these individuals with cancer who had received anti-cancer treatment. The results from these patients showed a reverse pattern compared to non-treated cancer patients and followed the pattern seen in healthy individuals. The authors concluded that their study confirms that the modified method, TumorScan, which combines the adapted Comet assay with different UV treatments, designed and fully automated cell reader-analyzer, the IMSTAR Pathfinder, successfully improves the sensitivity of the original test (LGS test) for the detection of samples at the level of the individual. The study was published on October 12, 2018, in the journal FASEB BioAdvances. LabMedica International May/2019

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

NEWS

Leadership Basics For Clinical Laboratory Professionals: C-CLM Brings In A New Manual to Prepare Laboratory Leaders by Prof. Dr. Sedef Yenice, C-CLM Chair ost of us think we have a well-run laboratory because we have lots of resources such as guidelines, organizational policies, standard operating procedures, quality indicators, quality controls and all types of measurable data that help us manage and navigate through challenges we face on a daily basis. We also attempt to perfect our laboratory practice by means of in-services and inspections of all types, having continuing education, seminars, professional gatherings and meetings for all sorts of laboratory-related issues. Furthermore, we feel confident using mobile phones and tablets, computers and the internet or other contemporary technologies. We also make good use of software, websites, and other electronic tools to help form our opinions or facilitate our work. But, do we pay close enough attention to the day-to-day routine? For instance, do we achieve co-operation through teamwork, do we emphasize common goals, establish self-confidence in others through talents promotion, do we encourage initiatives, lead towards the best utilization of manpower – through motivation, do we develop good human relations, improve morale and overcome resistance to change? Or more importantly, do we analyze our effectiveness, or do we ensure that what we are doing is really working? As laboratory directors, we must make sure we devote enough quality time with the people who make our laboratories tick. They are the laboratory office clerks, phlebotomists, medical laboratory assistants and medical laboratory technologists at various stations throughout our laboratory, and they help make it sure that it runs smoothly and safely around the clock. They are the people that we cannot do without. As we all know, if it were not for these hard-working, dedicated professionals, our laboratories would be a chaotic place. However, do these individuals work hard but not smartly enough? And how can we find that out? Such barriers become so much a part of our daily routine that we stop noticing them. The success of organizational strategies is essentially dependent on an effective leadership strategy. Compiling the best players for a team is no guarantee for success without a great coach. Good leadership strategy ensures effective work teams. Recognizing that these are the challenges most of us face, the Committee on Clinical Laboratory Management (C-CLM) aims to support Clinical Laboratory professionals to discover their leadership strengths .and to help them reach the highest summits in work success. The Manual on “Leadership

LabMedica International May/2019

Basics For Clinical Laboratory Professionals” is one installment towards achieving these goals. This manual also complements the C-CLM Clinical Laboratory Leadership Certificate Program and it is part of the reading list for this program. We promote six leadership pillars towards business and personal success including demonstrating social intelligence; adopting a flexible leadership style; empowering others; developing trust; managing risks in an environment of uncertainty, and seeing the big picture. These strengths provide a valuable model in the Clinical Laboratory workplace, whether one is already in a leadership position or aspiring to get there. Cont’d on page 44

NEWS

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

Editorial by Katherina Psarra MSc, PhD ear colleagues, I was thinking about this editorial and I have been editing some of the files, you are so kind to send to the eNews. I admire how much is done all over the world to improve laboratory work in terms of effectiveness, of accuracy, of new tests discovery for the benefit of the patients.

I admire all the laboratorians and I would like to thank them on the part of IFFC, because despite their high work burden, they offer some of their precious time to IFCC by sending this valuable information. Go ahead and have a look at all this valuable information. You will be inspired and you will definitely look at your everyday routine with a different perspective. Your contributions to the eNews, your remarks about a better presentation, or anything are always very welcome.

Leadership Basics For Clinical Laboratory Professionals: C-CLM Brings In A New Manual to Prepare Laboratory Leaders Cont’d from page 43

According to James Nichols from Vanderbilt University Medical Center, “Management training is as much art as science. We all struggle with how to teach management. There is no one book you can go to and say, 'This is the Bible of management, and if you read this, you have good management skills.'’’ In accordance with this statement we have worked on the chapters of this manual in order to cast light on the major points, with a focus on the significance of leadership in medical laboratory management. This manual is simple, to the point and it offers direct information. The concepts discussed are beneficial to all laboratory management levels with sound advice about working with teammates. The leadership basics presented in this manual will make you reevaluate how you work towards a change. It’s an easy read we would recommend to anyone in the laboratory medicine world. Each chapter presents the most important facts and concepts related to the subject area. The chapters address topics such

as defining laboratory medicine leaders, effective leadership styles, skills/qualities of a good leader, the leader as a visionary and a motivator, work culture, and ethics in leadership. In addition, the assessment tools provided in the appendices are designed to provide readers with insight for the selection of the best leadership model, when starting to manage new people, selecting which leadership style to use and providing insight on the motivation level of persons under one’s authority. All contributing authors have reflected on their own professional excellence in their chapters, being educators and outstanding professionals in the laboratory medicine field. According to Keith Davis, “Leadership is the ability to persuade others to seek defined objectives enthusiastically. It is the human factor which binds a group together and motivates it towards goals”. For many laboratory professionals, leadership skills and style develop out of mentoring by senior scientists, managers, and directors within the workplace. While there are clear benefits from sound mentoring, bad habits and ineffective behavior and strategies can also be adopted. Good mentoring alone is insufficient to offer good leadership skills, calling thus on the need for structured training, and guidance. This manual addresses this gap by providing instructional material to help the leaders in laboratory medicine toward more effective leadership strategies and practices. We wish to thank the authors for their willingness to contribute to this publication and we hope that it is both educational and of practical use for chairs and managers.. "The greatest leader is not necessarily the one who does the greatest things. He is the one that gets the people to do the greatest things." – Ronald Reagan

New Leaderships Elected: Federation of Laboratory Medicine (FLM) On October 5, 2018, after elections during the IV Russian Congress of laboratory medicine there were changes in the presidium and the Bureau of the presidium Russian Federation of Laboratory Medicine (FLM). Mikhail Godkov is the new President of Russian FLM, Andrey Ivanov is the Vice-President, Arkadiy Goldberg the Executive Director and Sergey Shcherbo is the Chief Scientific Secretary. Congratulations to the newly elected board!

Pakistan Society of Chemical Pathology (PSCP) The Pakistan Society of Chemical Pathology (PSCP) elected a new President. Dr Aysha Habib Khan, Head Subcommittee on International relation, PSCP, Associate Professor and Section Head Chemical Pathology in the Department of Pathology and Laboratory Medicine, at the Aga Khan University, Karachi, Pakistan. Best wishes to Dr Aysha Habib Khan so that she will contribute with fresh energy and new ideas on the path of her predecessors!

Ecuadorian Society of Clinical Biochemists (SEBIOCLI) The Sociedad Ecuatoriana de Bioquímica Clínica (SEBIOCLI) is pleased to inform hat on March 16st 2019, the new Executive Board of the Society was elected. The new President for term 2019-2021 is Dr Francisco Vallejos. Best wishes to him and the Ecuadorean Board! LabMedica International May/2019

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Indonesian Association for Clinical Chemistry

Work Conference and Seminar: Driving Impacts In Laboratory Medicine Sanur Denpasar Bali, July 19-21, 2018 After the completion of the Human Genome Project, the diagnosis and treatment of various diseases began to enter a new stage, namely Next Generation Medicine based on Precision Medicine. All medical aspects, including the Clinical Laboratory are required to follow these developments. These changes include exploration and development of various new biomarkers based on genomics, transcriptomics or proteomics as well as refinement of the inspection methodology for the implementation of improved Quality Assurance qualifications as good laboratory standards. The Indonesian Association for Clinical Chemistry, as a forum for experts who have Clinical Chemistry competency in developing laboratory aspects, has the responsibility to initiate and participate in this change in Indonesia. For this reason, it has been necessary to organize a work conference with symposia and workshops in order to mediate, initiate and synchronize the renewal of knowledge by various experts in Indonesia. In the work conference, we held symposia and workshops where the development of reproductive issues, infections, geriatrics and oncology and various other disciplines were discussed in line with the renewal of diagnosis and treatment based on Next Generation Medicine.

Seminar and Workshop: Molecular Diagnostics Jakarta, Nov 30, 2018 IACC in cooperation with Indonesian Association of Clinical Pathologist and Laboratory Medicine (IACP) held a Seminar and Workshop on Molecular diagnostics with Applications of PCR to Infection and Cancer. The Seminar participants were around 100 people, Clinical Pathologist Doctors, Lab Scientists and Medical Technologists. The Workshop participants were 26 people.

Workshop: Total Value Ownership (TVO) IACC held a Workshop on Laboratory Management with the topic “Total Value Ownership”. The speaker was Patrick Gontard Group CEO,

New IFCC Committee on Bone Metabolism (C-BM) is Now on its Wheels! by Etienne Cavalier, PharmD, EuSpLM, PhD; Professor of Clinical Chemistry, University of Liège, CHU de Liège, Belgium he new IFCC Committee on Bone Metabolism (C-BM) results from the merger of 3 different IFCC working groups, namely on PTH (Chairwoman: Dr Catharine Sturgeon), vitamin D (Chairman: Dr Christopher Sempos) and bone marker standardization (Chairman: Dr Etienne Cavalier). The Chairmanship of this new Committee has been given by the IFCC Scientific Division Executive Committee to Etienne Cavalier (Belgium) for 2 years. The members of this committee’s board have just been elected and are Drs Annemieke Heijboer (The Netherlands), Candice Ulmer (USA), Samuel Vasikaran (Australia) and Harjit Pal Bhattoa (Hungary). They will be helped in their new tasks by Drs Sturgeon, Sempos and Vesper (consultants), Dr Konstantinos Makris (IFCC SD liaison), National and IVD representatives. The terms of reference for the new committee include the standardization/harmonization of PTH, vitamin D metabolites and bone markers assays. Indeed, the lack of standardization amongst these assays results in important issues potentially leading to different clinical decisions. The details of the projects of the C-BM can be found on the IFCC website www.ifcc.org/ifcc-scientific-division/sd-committees/c-bm/. In short, we aim to promote the use of commutable international standards, reference measurement procedures, accuracy-based external quality assessment schemes and performance guidelines for standardized methods. The C-BM will also try to find partnerships with clinical societies to involve clinicians in the process. We are already proud to announce that this committee will be a joined committee with the IOF (International Osteoporosis Foundation). The C-BM will have its first official meeting during the Euromedlab 2019 event in Barcelona on May 20th. From a personal perspective, I am really proud to lead such a talented team and I would like to thank Prof. Morris, Prof. Gillery and the IFCC office for their confidence, as well as our corporate partners for their support.

LabMedica International May/2019

Photo: Participants and facilitator after workshop basic molecular session

Labexa Group, France; CEO and Founder, Gontard and Cie, Switzerland. The Workshop was held in cooperation with Abbott Diagnostics in Jakarta. We invited some Clinical Laboratory CEOs, COOs and Managers to discuss about business aspects of Clinical Laboratory. In today’s healthcare environment, leaders are increasingly asked to demonstrate value in terms of operational and clinical care excellence across their healthcare institutions. The Clinical Laboratory is viewed as an important contributor to key performance indicators, and as a result, laboratory managers want to maximize the value that the laboratory brings to their institutions. The concept of Total Value of Ownership (TVO) considers all aspects of a laboratory’s processes and equipment and identifies areas where improvements can be made to maximize value. When the laboratory delivers services to its full potential, it can help improve outcomes system-wide, enabling the institution to make a positive impact on patient outcomes.

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Technology Award of Japan Society of Clinical Chemistry 2018 by Hideo Sakamoto, PhD and Shu-Ping Hui, PhD, International Exchange Committee of Japan Society of Clinical Chemistry he Technology Award of Japan Society of Clinical Chemistry (JSCC) is given annually to companies who have made progress in Clinical Chemistry. Four winners received the JSCC Technology Award in 2018. The award presentation ceremony was held at the 58th Annual Meeting of JSCC in Nagoya, Japan, on August 24-26, 2018. During the presentation, the award recipients were congratulated by Dr. Masato Maekawa, president of JSCC for their contribution to the advancement of Clinical Chemistry. Kaori Morota PhD works in Scientific Affairs, Abbott Japan Co., Ltd. The title of her awarded work is “Development and clinical application of AKI biomarker urinary NGAL”. Acute kidney injury (AKI) is a syndrome which has a broad range of etiologic factors depending on different clinical settings. Because AKI has significant impacts on prognosis in any clinical setting, early detection and intervention is necessary to improve the outcome of AKI patients. Urinary neutrophil gelatinase-associated lipocalin Photo: JSCC Technology Award presentation ceremony at 58th Annual Meeting of JSCC in (NGAL) is a useful biomarker for early diagnosis of AKI, Nagoya, Japan: Award recipients along with Dr. Masato Maekawa, President of JSCC differentiation of pre-renal AKI from renal AKI, and prediction of the AKI severity and mortality. In the clinical performance evaluation with Japanese patients admitted to the intensive type II deficiency has proven difficult by conventional methods. Recentcare unit (ICU), urinary NGAL values of the AKI patients on admission ly, Tsuda et al. developed assay systems for total protein S activity and were significantly higher than those of non-AKI patients. Since urinary total protein S mass. These assays reveal the specific activity of protein NGAL test was covered by public insurance in February 2017, its clini- S, enabling detection of type II protein S deficiency. The specific activical application has been started mainly at emergency department, ICU, ty of protein S is determined as the ratio of total protein S activity to toand division of nephrology and metabolism. By deciding treatment ap- tal protein S mass, and type II deficiency is known to show a low speproach for AKI patients based on urinary NGAL value in conjunction with cific activity. Using their novel method, 57 patients with various clinical other data such as symptoms and results of other tests, it would be ex- backgrounds were analyzed for their specific activities and the cut-off pected in the future to reduce length(s) of hospital stay and ICU stay, value, calculated from the receiver operating characteristic (ROC) curve, was 0.78. When healthy volunteers were screened, 6 of 238 inand to improve renal outcome and mortality. Naofumi Yoda, MS works in the Scientific Marketing Department, LSI dividuals showed specific activities below the cut-off value. After obtainMedience Corporation. The title of his awarded work is "Development of ing consent, 2 of these individuals were subjected to further genetic the rapid assay system of presepsin, a sepsis biomarker using CLEIA analysis, which revealed the protein S-Tokushima variant. Furthermore, technology". Sepsis is organ dysfunctions caused by infectious diseases when 19 individuals with a confirmed Tokushima variant gene were testand early detection and prompt treatment are encouraged by the guide- ed, the specific activities of all subjects were less than 0.78. Analysis of lines. Because blood culture test, which is thought as a gold standard of protein S specific activity can be used to detect protein S-Tokushima infections, is of low sensitivity and time-consuming, a new biomarker for with high sensitivity and specificity. Because VTE is life-threatening, unearly diagnosis of sepsis had been long awaited. Presepsin is a novel derstanding the risks of individuals, especially borderline populations sepsis biomarker, found in Japan, whose concentration in blood is in- such as pregnant women and perioperative patients, and taking precreased specifically in sepsis patients. In vitro experiments showed that ventive measures for them are important. It is also important to ensure phagocytosis without any gene expression is one of the production rapid diagnosis and treatment for VTE patients. New diagnostic kits for mechanisms of presepsin, which explained the prompt elevation of pre- evaluating the specific activity of protein S specific can be used to sepsin after the onset of infection. The reagent of presepsin for the screen easily and quickly not only for abnormalities in protein S activity PATHFAST, a compact automated instrument has been developed. This and mass, but also for mutations such as protein S Tokushima in the reagent makes it possible to measure presepsin i) with high sensitivity, routine setting of clinical testing. This system can be clinically applied ii) easily, iii) at bed side, iv) in a very short time (within 17 min). PATH- for the prevention, diagnosis, and intervention of VTE. Satoshi Kojima PhD works in the CL New Product Develop DepartFAST Presepsin was approved in Japan with a reimbursement in 2014, and it is recommended to be measured for severe stage patients as an ment, FUJIREBIO INC. The title of his awarded work is “Development of aid of diagnosis of sepsis in the latest version of Japanese guidelines for Lumipulse 25-OH Vitamin D.” 25-OH vitamin D (25-OHD) assay is widely sepsis (Strength of recommendation: 2B). PATHFAST Presepsin is now used for the monitoring of the status for vitamin D in human blood. Imused in countries all over the world, including some Asian countries. This munoassays are routinely used for the quantification of 25-OHD in each rapid assay system of presepsin is expected to contribute for decreas- hospital or Clinical Laboratory today. FUJIREBIO INC. developed a fully automated 25-OHD immunoassay, “Lumipulse G 25-OH Vitamin D” based ing mortality caused by sepsis. Tomohide Tsuda PhD and Xiuri Jin PhD work in the Immunology and on novel non-competitive immunoassay. Sandwich assay has theoreticalMDx Unit, R&D Center, Shino-Test Corporation. The title of their award- ly advantages of specificity and/or sensitivity against conventional competed work is “Development of novel methodology and assay systems for itive format. However, a competitive assay on the detection of hapten molprotein S.” Protein S deficiency is classified into three types, all of which ecules is generally chosen because of the circumvention of steric hinare risk factors for venous thromboembolism (VTE) in Japanese peo- drance of two antibodies. They established a quite unique anti-metatype ple. Among the three types of protein S abnormalities, type II deficien- antibody, which recognizes the immunocomplex between 25-OHD and its cy is characterized by a normal level of protein S and reduced levels of monoclonal antibody. The use of this antibody permitted to construct the protein S activity. Approximately 2% of the ethnic Japanese population non-competitive assay for the detection of 25-OHD. The assay showed carries a genetic mutation known as protein S-Tokushima, a variant good performance regarding sensitivity and reproducibility in wide range. showing decreased activity as a cofactor of activated protein C. This Moreover, the measurement value was well correlated with ID-LC-MS/MS, mutation is a major cause of type II deficiency. Because these carriers recognized as a reference measurement procedure by the JCTLM. The are more likely to develop VTE than non-carriers, according to their conventional assay for hapten molecule sometimes limits the dynamic odds ratios of 3.7–8.6, measurement of protein S may be a useful diag- range, accuracy or reproducibility. The use of an anti-metatype antibody nostic tool for VTE risk assessment. However, accurate diagnosis of might achieve sustainable performance improvement.

LabMedica International May/2019

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NEWS

Bioethics and Clinical Cases in the Pediatric Laboratory: Conference Highlights by Nilda E. Fink he 10th CALILAB Congress organized by Fundación Bioquímica Argentina (FBA) is a Congress on Quality in the Clinical Laboratory and was held in the Convention Center of the city of Buenos Aires from 24 to 27 October 2018. The Congress covered a variety of subjects such as Biosafety, Quality in Clinical Biochemistry, Histocompatibility and Genetics, genomics and other relevant topics in the Clinical Laboratory. Taking into consideration the IFCC recommendation to include activities on Ethics in every Congress, a symposium on “Bioethics and clinical cases related to pediatric laboratory” was included. The presentation was given by Dr. Graciela Queiruga, member of the Board of Faculty of Chemistry at the University of the Oriental Republic of Uruguay, former President of COLABIOCLI and SLEIMPN. Dr Queiruga introduced the basics on Bioethics defined as the systematic study of human behavior in the field of life sciences and health care, examined in the light of values and moral principles (Encyclopedia of Bioethics, 4th Ed. Macmillan Reference USA, 2014). She pointed out that the word Bioethics has been used since the early 1970s, and is considered as the ethical concepts of medicine which seeks to offer to the patient justice and equal access to care. She remarked that the beneficence and autonomy of the patient must always be in mind of those dedicated to the task of alleviating suffering and illness. She also emphasized that the natural limits of technical actions done by the human being are more and more imprecise, therefore, moral limits are needed more than ever. It is necessary to harmonize the amount of scientific information that presents ethical dilemmas and the need to be raised to the level of the international scientific community, in order to ensure respect for human life in the field of scientific research. Dr Queiruga pointed out that Pediatric Laboratory Medicine is an excellent field to apply the four principles of Ethics (Autonomy, Justice, Beneficence and Non-maleficence). For instance, an excellent example of the application of the principles of Bioethics is a national, free and mandatory program of Neonatal Screening that could detect a disease in time to treat and avoid mental retardation, neurological sequelae or death itself. In a program that reaches all babies born in her country, Uruguay, without distinction of the place of birth, the principle of justice is applied

The resolution of the Health authority that makes the early detection of certain diseases obligatory enables them to take samples without need for consent or autonomy and the procedure harmlessness is an example of non-maleficence. Dr Queiruga mentioned that Medicine’s goals have moved from an approach aimed at disease diagnosis and treatment to disease prediction and prevention, Millions of newborns are screened per year in the world; as an example 4,000,000 children are screened in USA for more than 50 diseases (29 central and 25 secondary diseases). The MsMs spectrometry has allowed these investigations in a single run with a single drop of blood. WHO states that the screening should be mandatory and free of charge if early diagnosis and treatment benefit the newborn (Kerruish NJ, Robertson SP. 2005 www.ncbi.nlm.nih.gov/pmc/articles/ PMC1734185). During her presentation Dr. Queiruga reviewed the most relevant international documents in the field such as the Universal declaration of bioethics and human rights UNESCO, 2005 https://unesdoc.unesco.org/ ark:/48223/pf0000142825.page=80 She accepted that not everything is beneficial and there are still controversies and difficulties. The possibility of false negatives, as well as cut-off points definition and performance of external and internal quality controls should be a concern of laboratorians. On the other hand, false positives cause stress to the parents when a new sample is requested. The program must control that they are within reasonable margins, treating to not increase costs with many useless examinations. During her presentation four cases of her own experience were discussed based in the concept that deliberation is the best methodology to manage and resolve ethical quandaries. She also pointed out that while residual samples are potentially a huge data bank for research purposes, the laboratory must be very careful to protect the identity of patients and the samples should only be used for charitable purposes. Finally, she stressed that a Neonatal Screening governed by the principles of Bioethics can be an immense contribution to the quality of life.

Labquality Days 2019 Held in Helsinki by Jonna Pelanti, Secretary, the Finnish Society of Clinical Chemistry he Finnish Society of Clinical Chemistry is the largest single owner of Labquality, the Finnish, independent service company focused on quality assurance of medical laboratories and point of care testing. Labquality organizes annually a large international congress on quality in laboratory medicine in Helsinki in February and the Finnish Society of Clinical Chemistry has a role in planning the program. The congress brings medical laboratory and quality management professionals together to enjoy the high-quality lectures and to meet colleagues from around the world as well. The themes of 2019 were “Quality Control reinvented?” and “Digital Health”. On the first day, Labquality Days presented speakers from all over the world to discuss quality control in the future. Sten Westgard (Westgard Quality Control, USA) pondered whether there are Westgard rules in the future or not. Following this, Tony Badrick (RCPAQAP, Australia) presented his ideas on the future of performing IQC and EQA with the help of mathematical parameters. Vincent Delatour (LNE, France) discussed the need for commutable certified reference materials to be used in EQA schemes and Marc Thelen (SKML, Netherlands) showed their multi-sample approach. Anja Kessler (Referenzinstitut for Bioanalytik, Germany) analysed the present and future of EQA and Hassan Bayat (Shahid Beheshti University of Medical Sciences, Iran) instructed the participants on the Max E(Nuf) quality control model and the need of understanding the required frequency in the laboratories QC planning. New acquaintances were made during the breaks and especially at the

LabMedica International May/2019

get together cocktail party after the first day. It was nice to see busy mingling taking place and to hear the vivid discussions between the lecturers and the participants painting mental pictures of the quality control procedures of the future. On the second day, the topics and the discussion moved towards future and new solutions around Digital Health. Anu Jalanko (Institute for Molecular Medicine, Finland) showed how genomic information is utilized now and how it should be used in the future and Markus Perola (National institute for Health and Welfare, Finland) gave examples of scientific discoveries encouraged by the Finnish biobank. Also new information and experiences regarding fast fluid exchange technology was shared with the audience by Saska Brajkovic, representing Lunaphore Technologies SA. Sten Westgard took the floor for the second time to describe the quite unbelievable case of the rise and fall of a 9-billion-dollar diagnostic disrupter company. Vilmundur Gudnasson (University of Iceland) showed information on the new risk assessment tools to identify individuals with atherosclerotic disease and the last session was presented by Sami Blom (Fimmic, Finland) about the empowering tool, deep learning AI offers to the pathologists. To summarize the two successful days, the lectures were of excellent scientific quality and the audience also had the privilege to hear the presenters in a panel discussion about quality control held on the first day. The speakers calibre was impressive, they gave their insights in great detail into upcoming changes in laboratory segments quality in the near and further future.

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NEWS VIEWPOINT

Pushing the Boundaries with Digital Technologies and AI by Dr. Bernard Gouget Chair, Committee on Mobile Health and Bioengineering in Laboratory Medicine (C-MHBLM), Past-Chair, IFCC Nominations Committee (NC), SFBC-International Committee; General Secretary of the International Francophone Federation of Clinical Biology and Laboratory Medicine (FIFBCML); President Healthcare Division Committee - Comité Français d’accréditation (Cofrac)

igitalization and AI continue to be a desirable topic to discuss when new technology trends come up in the conversation. AI is moving fast and is getting increasingly sophisticated at doing what humans do, but more efficiently, more quickly. AI isn’t just a new set of tools, it’s the new world from automation to augmentation and beyond. AI is already starting to change everything on a digital future. Improved diagnosis, more targeted treatments, a growing emphasis on preventive care and

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more involvement in patient care are the major influences driving healthcare digitalization today. But there are notable shifts in the understanding of which solutions to a raft of goals - clinical and economical - can be found in the staggering volume of data generated by the health sector at every touchpoint, from the rise of patient apps and devices to the rapidly evolving use of artificial intelligence in treatment and predictive modeling. Digitalization is not just a technical distinction but a trend transforming healthcare and laboratory processes and business models, that, while enabling healthcare providers to expand precision medicine, it can transform care delivery and improve patient experience. Digitalization, integration of AI and the use of data will compete for unveiling additional benefits inside the data value chain, delivering high value care, better diagnoses and treatment, because relevant data are available exactly where is needed at every level of delivery. The challenge is to translate the flood of data into meaningful information. Eric Topol, Director, Scripps research Translational Institute, in an independent and relevant report on behalf of the NHS Secretary of State for health and Social Care, published on February 2019, wrote that we are at a unique junction in the history of medicine with the convergence of genomics, biosensors, the electronic patient record and smartphone apps, all superimposed on a digital infrastructure, with artificial intelligence making sense of the overwhelming amount of data created,. The author proposes principles to support the deployment of digital healthcare technologies: The patient must be considered to be at the centre when assessing and implementing any new technology; There is remarkable potential for digital healthcare technologies to improve accuracy of diagnoses and treatments, the efficiency of care, and workflow for healthcare professionals, but implementation must only be carried out when there has been robust clinical validation; Patients who are willing to take greater charge of their care using digital tools and algorithms will be empowered, but this should always be an opt-in choice for them; A marked improvement in the patient-clinician relationship is possible, owing to the gift of time delivered by the introduction of these technologies; And the new medicine as envisioned will require extensive education and training of the medical workforce and the public, with cultivation of a cross-disciplinary approach that includes data-IT scientists, bioengineers, economists, ethicists in addition to the traditional mix of nurses and doctors, biologists and pharmacists.   Digitalization is rapidly evolving: to keep pace with its promising innovation, the shift from a disease- oriented to a health-oriented concept has to be considered. In the future, along IFCC-ETD we have to consider how technological developments, as genomics, AI, robotics will change the role and functions of the specialist in lab medicine and the implications for the skills required by health care professionals as well as the consequences for the curricula, education, training, development and lifelong training. Close collaboration with different and new IT, Med Tech, Pharma industry partners are essential to appropriate digital transformation, to encompass more personalized approaches as well as to develop new business models to make innovation possible to deliver the best digital future. As stated by E. Topol: The greatest challenge is the culture shift in learning and innovation with a willingness to embrace technology for health – wide improvement.

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

LabMedica International May/2019

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Industry News

Global Urinalysis Market Valued at USD 2 Billion by 2022

Global POC Diagnostics/ Testing Market To Reach USD 23 Billion by 2025

he global urinalysis market is expected to grow at a CAGR of 7.5% from 2018 to 2022 to reach a value of USD 2.14 billion by 2022, driven by a large base of the target population and increasing demand for urinalysis due to unmet clinical needs in the underdeveloped regions globally. Additionally, the introduction of highly advanced diagnostic tools and rising demand for cost-effective solutions will further fuel the robust growth of the global urinalysis market. These are the latest findings of Grand View Research, Inc. (San Francisco, CA, USA; www.grandviewresearch.com), a market research and consulting company. Urinalysis acts as a vital diagnostic tool for the analysis and management of target diseases such as urinary tract infection (UTI) disorders, kidney diseases, and diabetes. The growing prevalence of these target diseases is expected to drive the market demand for urinalysis in the coming years, providing significant opportunities for market players to invest in research and development. Moreover, changing lifestyles and varying food are expected to fuel the demand for urinalysis across the world over the coming years. Also, the increasing adoption of wireless technology for communication purposes, coupled with the development of miniaturized PoC urinalysis instruments, are further expected to advance the market growth in the coming years. However, the complete absence of adequate healthcare infrastructure in the underdeveloped economies worldwide is likely to limit the market growth to some extent. Additionally, the non-availability of the latest diagnostic tools in the developing economies globally is also significantly hampering market growth. Nevertheless, the development of advanced and cost-effective techniques for performing fast and highly precise diagnosis, coupled with easy-to-use solutions for catering to the unmet clinical needs in the developing as well as underdeveloped economies, are expected to drive the growth of the global urinalysis market over the coming years. Based on product type, the instruments segment is expected to record a significant growth during the forecast period due to the development of novel products such as automated urine sediment analyzers, microscopic urine analyzers and fully automated urine strip readers.

he global point of care (POC) diagnostics/testing market size is expected to grow at a CAGR of 3.3% over the forecast period 2019-2025 to reach USD 22.8 billion by 2025, driven by the ability of POC tests to render rapid and accurate results at bedside settings and in remote areas. The market growth is being further aided by the adoption of automated laboratory systems and highly integrated solutions that facilitate the diagnostic workflow. These are the latest findings of Research and Markets, (Dublin, Ireland; www.researchandmarkets. com), a global market research company. Increasing R&D activities by the key players for introducing novel POC tests and devices for the rapid detection and monitoring of diseases is expected to further boost the growth of the POC testing market. Additionally, the lack of skilled professionals or medical personnel with limited training, especially in diagnostics, who can also easily use these devices is also fueling the growth of the POC diagnostics/testing market. Moreover, the high prevalence of chronic disorders and cancer is resulting in a large customer base adopting cost-effective and immediate diagnostic tests, thereby propelling the growth of the POC diagnostics/testing market. This is further supplemented by a number of favorable initiatives to promote the employment of POC tests in diagnosis and screening procedures. Based on product, the glucose testing segment dominated the POC diagnostics/testing market in 2018 in terms of revenue due to the high prevalence of diabetes and introduction of a wide variety of glucose meters by companies. The Hb1Ac testing segment is also expected to show a similar trend due to stiff competition for delivering low-cost Hb1Ac tests among the key players in the market. The detection and analysis of circulating tumor cells during cancer progression is expected to help the cancer marker segment achieve the fastest penetration rate over the coming years.

Global Automated Immunoassay Analyzer Market Driven by Increase in Applications he global automated immunoassay analyzer market is expected to achieve significant growth over the coming years, driven by innovations in the existing products and increased clinical applications of these systems. These are the latest findings of Radiant Insights (San Francisco, CA, USA; www.radiantinsights.com), a market research and consulting company. Other factors such as the growing inclination towards lab automation, increase in the number of infectious diseases, rise in the use of these systems due to their extensive test menu at affordable prices, and increased use of immunoassay tests for cancer will further contribute to the growth of the global automated immunoassay analyzer market. However, the lack of skilled specialists due to increasing healthcare needs globally and unavailability of healthcare professionals in the developing economies is hampering the growth of the automated immunoassay analyzer market. The major players in the automated immunoassay analyzer market are increasingly focusing on new product launches along with technical enhancements and expansion of their product portfolio in order to meet the requirements for assay menus, test volumes, budgets, and automation levels among various laboratories. Moreover, the increasing number of biomedical tests for measuring proteins and growing awareness about analyzers in the developing countries are also fueling the growth of the automated immunoassay analyzer market.

LabMedica International May/2019

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JUNE 2019 EAACI Congress 2019 – European Academy of Allergy & Clinical Immunology. Jun 1-5; Lisbon, Portugal; Web: www.eaaci.org BIO International Convention 2019. Jun 3-6; Philadelphia, PA, USA; Web: convention.bio.org ESGH 2019 – European Human Genetics Conference. Jun 15-18; Gothenburg, Sweden; Web: www.eshg.org

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