LabMedica International April 2017

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

Vol. 34 No. 2 • 4 / 2017

DAILY CLINICAL LAB NEWS

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Molecular Flu/RSV Test Offers Results in 30 Minutes he new assay rapidly tests for influenza and respiratory syncytial virus (RSV) infections on the GeneXpert System and is now available in the EU and all countries recognizing the CE-Mark. Early symptoms for a wide variety of viral and bacterial respiratory infections are often clinically indistinguishable, yet treatment is

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Inflammatory Markers Predict Risk of Morbidity and Mortality nflammatory markers are known to be associated with cancer, chronic heart disease and other serious health conditions; however, the marker that is most useful in predicting these diseases continues to be debated.

A new study looking at deaths from cancer, cardiovascular disease and all causes suggests that an inflam-

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matory marker detected in blood tests in middle-aged adults can better predict the risk of death compared with another similar biomarker.

Scientists at the Institut National De La Santé Et De La Recherche Médicale (Paris, France; www.inserm.fr) and their colleagues analyzed data for 6,545 men and women aged 45 to

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Image: Courtesy of Stanford University Medical Center

Prenatal Genetic Test Accurate 5 Weeks into Pregnancy

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New Blood Test Diagnoses Concussion iagnosis of a clinically significant concussion, or a mild traumatic brain injury, can be difficult as it currently relies on a combination of patient symptom assessment and clinician judgment.

Equally problematic are the decisions to stop play or activities, or when patients who have suffered a concussion can safely return to normal activities without risking further injury. A blood test has been developed that can

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Cytosponge Test to Replace Uncomfortable Endoscopies ‘sponge on a string’ pill or Cytosponge test can identify which people with a condition called Barrett’s esophagus who have a low risk of developing esophageal cancer, sparing them uncomfortable endoscopies.

Barrett’s esophagus predisposes to adenocarcinoma, however, most patients with Barrett’s esophagus will not progress and endoscopic surveillance is invasive, expensive, and fraught by issues of sampling bias and

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new non-invasive testing method known as Trophoblast Retrieval and Isolation from the Cervix (TRIC), offers the accuracy of more invasive assays, but can diagnose genetic disorders a little more than one month into the pregnancy.

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Circulating Cell-Free DNA Predicts Gastric Cancer Prognosis astric cancer is the second most common cancer and the fourth leading cause of cancer death and the most significant prognostic indicator is TNM Classification of Malignant Tumors (TNM) staging.

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Software Platform Enables Somatic Variation Analysis

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n upgraded information-processing platform enables clinical genetics and molecular pathology laboratories to achieve higher performance and efficiency in somatic variation analysis of tumor-tissue sequencing data and in reporting of tissue-typing results, among other features.

Agilent Technologies (Santa Clara,

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INSIDE Clinical News . . . . . . . . . 4-42 IFCC Annual Report . . . . . 27 IFCC News . . . . . . . . . . . . . 43 Product News . . . . . . . 14-42 Industry News . . . . . . . . . .49 International Calendar . . . 50 PUBLISHED IN COOPERATION WITH

CA, USA; www.agilent.com) has released its Cartagenia Bench Lab 5.0, a major new version that addresses inherent challenges of interpreting and reporting on genomic variants data.

Cartagenia Bench Lab, registered as an exempt Class I Medical Device in the US, helps high-throughput diagnostic Cont’d on page 4

International Federation of Clinical Chemistry and Laboratory Medicine

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Software Platform Enables Somatic Variation Analysis cont’d from cover

labs to validate and automate their variant assessment and reporting pipelines. The software enables clinical geneticists and molecular pathologists to combine single nucleotide polymorphisms (SNPs); small insertions and deletions (INDELs); and copy number variations into one seamless analysis. Variant curation tools allow users to review variants, collaboratively build evidence, and securely share it with peers and data-sharing communities. With a range of new features for somatic variant classification, review, and curation, the 5.0 release represents a significant leap forward.

Cartagenia Bench provides direct access to over 100 curated and publicly available databases with information on actionable variants, trials, drugs, and therapy options such as CIViC, COSMIC, N-of-One, OncoMD, and CollabRx. The software’s variant curation tools enable labs to build an internal knowledge base of predictive, prognostic, diagnostic, and functional evidence of previously curated variants. By accessing tumor typeontology and variant information from the curated and public databases, labs can efficiently implement their variant assessment standard operating procedure to more effectively filter variants and access knowledge based on the tumor’s tissue type.

“Translating genomic data into actionable information is challenging,” said Herman Verrelst, Agilent vice president and general manager of the company’s Genomics Solutions Division and Clinical Applications Division, “The 5.0 release offers molecular pathology labs access to clinical-grade analysis tools and knowledge – one of the key pain points for the implementation of next-generation sequencing (NGS) in routine oncology testing – to help them efficiently interpret sequencing data of tumor samples and provide actionable information by accessing publicly and curated databases containing peer reviewed evidence on diagnostic, prognostic, and therapeutic variants.”

“Since we implemented our routine diagnostic pipeline on Agilent’s bench platform, we’ve appreciated the close collaboration with the team and how they

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

translate our needs into new software versions,” said Petra Nederlof, head of Molecular Diagnostics, Netherlands Cancer Institute (Amsterdam).

“We are truly excited by our partnership with Agilent as it extends our reach into the global molecular pathology community,” said Dr. Malachi Griffith from McDonnell Genome Institute, Washington University School of Medicine (St. Louis, MO, USA), “With the incorporation of the CIViC knowledge base in Agilent’s bench platform, all users will now have direct access to the predictive, prognostic, and diagnostic evidence curated by CIViC domain experts.”

Agilent will be showcasing Cartagenia Bench Lab 5.0 and other solutions at the NGS in Molecular Pathology Symposium, November 30-December 2, 2016, at the Netherlands Cancer Institute. “We’re excited about co-organizing this event with Agilent,” said Dr. Nederlof, “We have a strong agenda of international experts who will share expertise from their clinical diagnostic practices.” The symposium will include tracks on clinical variant assessment and lab reporting, automation, somatic variant classification, NGS panel composition, and data-sharing initiatives.

Image: The upgraded Cartagenia Bench Lab 5.0 addresses inherent challenges of interpreting and reporting on genomic variants data (Photo courtesy of Agilent Technologies).

Prenatal Genetic Test Accurate 5 Weeks into Pregnancy he latest developments in prenatal technology make it possible to test for genetic disorders a little more than one month into pregnancy using a non-invasive technique.

Single-gene mutations are responsible for a large number of diseases and contribute to a sizeable fraction of pediatric hospitalizations and deaths. Current methods for prenatal diagnosis of such mutations are limited because they are invasive, except for detection of circulating fetal DNA, which is safe but can be difficult to perform accurately, and most cannot be performed early in pregnancy.

Scientists at the Wayne State University (Detroit, MI, USA; www.wayne.edu) isolated intact trophoblast cells from Papanicolaou (Pap) smears collected noninvasively at 5 to 19 weeks of gestation for next-generation sequencing of fetal DNA. Consecutive matched maternal, placental, and 20 fetal samples were profiled by multiplex-targeted DNA sequencing of 59 short tandem repeat and 94 single-nucleotide variant sites across all 24 chromosomes.

The non-invasive testing method known as Trophoblast Retrieval and Isolation from the Cervix (TRIC),

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offers the accuracy of more invasive tests, such as the needle-directed amniocentesis, and can also be utilized five to 10 weeks earlier than current testing modalities.

The method isolates several hundred fetal cells that migrate from the placenta into the uterus using a retrieval technique akin to the common Pap smear, and can be done as early as five weeks into pregnancy. The data revealed fetal DNA fractions of 85% to 99.9%, with 100% correct fetal haplotyping. This noninvasive platform has the potential to provide comprehensive fetal genomic profiling as early as five weeks of gestation.

D. Randall Armant, PhD, the principal investigator and Professor of Obstetrics and Gynecology, said, “Because the cells we purify by TRIC are placental cells that have a critical function early in pregnancy, their protein profile has been examined to determine if it becomes different in pregnancies that have serious complications like a miscarriage, undersized fetus or preeclampsia. Since TRIC provides the cells of interest, we can probe their RNA and protein profiles using nextgeneration proteomics and transcriptomics approaches.

The study was published on November 2, 2016, in the journal Science Translational Medicine.

Published in cooperation with the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).

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ISSN 1068-1760 Vol.34 No.2. Published, under license, by Globetech Media LLC; Copyright © 2017. All rights reserved. Reproduction in any form is forbidden without express permission. Opinions expressed are solely those of the authors, and do not represent an endorsement, or lack thereof, by the Publisher of any products or services.

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Cytosponge Test to Replace Uncomfortable Endoscopies cont’d from cover

the subjective assessment of dysplasia. A large team of scientists led by those at University of Cambridge (Cambridge, UK; www.cam.ac.uk) conducted a multicenter cohort study; patients with Barrett’s esophagus underwent the Cytosponge test before their surveillance endoscopy. They collected clinical and demographic data and tested Cytosponge samples for a molecular biomarker panel including three protein biomarkers (P53, c-Myc, and Aurora kinase A), two methylation markers Myogenic Differentiation 1(MYOD1) and Runt-related transcription factor 3 (RUNX3), glandular atypia, and tumor protein 53(TP53) mutation status.

The discovery cohort consisted of 468 patients with Barrett’s esophagus and intestinal metaplasia.

Of these, 376 had no dysplasia and 22 had highgrade dysplasia or intramucosal adenocarcinoma. In

the discovery cohort, a model with high classification accuracy consisted of glandular atypia, P53 abnormality, and Aurora kinase A positivity, and the interaction of age, waist-to-hip ratio, and length of the Barrett’s esophagus segment.

In the validation cohort of 65 patients, 51 were non-dysplastic and 14 had high-grade dysplasia. In this cohort, 25 (38%) of 65 patients were classified as being low-risk, and the probability of being nondysplastic was 96.0%. The moderate-risk group comprised 27 non-dysplastic and eight high-grade dysplasia cases, whereas the high-risk group, which was 8% of the cohort had no non-dysplastic cases and five patients with high-grade dysplasia.

The authors concluded that a combination of biomarker assays from a single Cytosponge sample can be used to determine a group of patients at low risk of progression, for whom endoscopy could be

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avoided. This strategy could help to avoid over diagnosis and overtreatment in patients with Barrett’s esophagus. Rebecca Fitzgerald MD, a professor and lead investigator, said, “Most people who have Barrett’s esophagus will not go on to develop esophageal cancer, but at the moment there is no way of identifying who will and who won’t. Our study is the first step in using the Cytosponge to answer this question.” The study was published on November 10, 2016, in the journal The Lancet Gastroenterology & Hepatology.

Image: The Cytosponge, a well-tolerated and effective means to sample the lining of the esophagus (Photo courtesy of the University of Cambridge).

New Blood Test Diagnoses Concussion cont’d from cover

now accurately diagnose a concussion using a form of blood profiling known as metabolomics. A multidisciplinary team of scientists at Western University (London, Canada; www.lawsonresearch.ca) obtained plasma from male hockey players, 12 who were concussed and 17 non-concussed athletes, and assayed for 174 metabolites with proton nuclear magnetic resonance and direct injection liquid chromatography tandem mass spectrometry. Data were analyzed with multivariate statistical analysis and machine learning. For the relatively inexpensive test, blood is drawn from an individual that may have suffered a concussion as the result of a sudden blow to the head (or from transmitted forces from a sudden blow to the body) within 72 hours of the incident.

The scientists reported that the estimated time from concussion occurrence to blood draw at the first clinic visit was 2.3 ± 0.7 days. Using principal component analysis, the leading 10 components, each containing nine metabolites, were shown to account for 82 % of the variance between cohorts, and relied heavily on changes in glycerophospholipids. The number of metabolites required to achieve the 92 % diagnostic accuracy was minimized from 174 to as few as 17 metabolites. Receiver operating characteristic analyses generated an area under the curve of 0.91, indicating excellent concussion diagnostic potential.

Mark Daley, PhD, a professor and co-investigator of the study, said, “We looked at all of these metabolites in concussed male adolescent patients and in non-concussed male adolescent patients and it turns out that the spectrum is really different.

There is no one metabolite that we can put a finger on but when we looked at all of them, those profiles are different enough that we could easily distinguish concussed patients from non-concussed. In fact, with fine tuning we can now look at sets of as few as 20 to 40 specific metabolites and maintain the diagnostic accuracy level of the test over 90%.”

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Inflammatory Markers Predict Risk of Morbidity and Mortality cont’d from cover

69 (mean 55.7) years from the Whitehall II cohort study. They assayed the inflammatory biomarkers 1-acid glycoprotein (AGP), interleukin-6 (IL-6) and C-reactive protein (CRP) levels from fasting serum samples collected in 1997–1999 and mortality follow- up was until June 2015.

For CRP measurement, a high-sensitivity immunonephelometric assay was used in a BN ProSpec nephelometer (Dade Behring, Deerfield, IL, USA; www.healthcare.siemens.com); IL-6 levels were measured with a high-sensitivity enzyme-linked immunosorbent assay (R&D Systems, Minneapolis, MN, USA; www.rndsystems.com); and AGP levels were measured with nuclear magnetic resonance spectroscopy as part of more complete biomarker profiling.

Over the mean follow-up of 16.7 years, 736 deaths occurred, of which 181 were from cardiovascular disease and 347 from cancer. AGP did not predict mortality beyond the first five years of follow-up while over this period; IL-6 and CRP had stronger associations with mortality. Only IL-6 predicted all-cause mortality (adjusted Hazard Ratio [HR] 1.22) and cancer-related mortality (adjusted HR 1.13), over the entire follow-up period, whereas CRP predicted only cardiovascular mortality (adjusted HR 1.30).

Archana Singh-Manoux, PhD, a professor and lead author of the study, said, “When a recent metabolomics study highlighted the importance of AGP, our question was how relevant is this marker when compared to other known inflammatory markers. The novelty of our approach lies in being able to assess risk of mortality in the short- and long-term. Our findings show IL-6, which is already known to be important to heart disease, to do better than AGP. Biomarker studies are progressing fast, and it is important to undertake checks like in the one in our study, to shape future research on biomarkers.” The study was published on November 28, 2016, in the Canadian Medical Association Journal.

Image: The BN ProSpec system and nephelometer (Photo courtesy of Siemens Healthineers).

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Molecular Flu/RSV Test Offers Results in 30 Minutes cont’d from cover

different depending on cause of infection, highlighting the importance of accurate diagnostic tests. With Xpert Xpress Flu/RSV from Cepheid (Sunnyvale, CA, USA; www.cepheid.com), healthcare providers can now use a single test to provide fast referencequality results for patients suspected of influenza or RSV infection. It provides reliable diagnosis of influenza and RSV infection within 30 minutes, twice as fast as its predecessor, Xpert Flu/RSV XC, but with comparable performance characteristics (when run in Flu-only or RSV-only reporting mode, positive results can be reported in soon as 20 minutes).

The new assay features a novel design that employs multiple targets for each virus. The built-in redundancy provides very high test sensitivity, avoiding the impact of seasonal drift that has historically been a problem with molecular tests, while maintaining high specificity.

“For too long, clinicians have been asked to treat

suspected cases of influenza empirically, since goldstandard RT-PCR based tests took too long to process in the critical first 24 hours of symptom onset,” said David H. Persing, MD, PhD, chief medical & technology officer, Cepheid, “With the arrival of fast molecular tests like Xpert Xpress Flu/RSV, patients and their healthcare providers can now expect an accurate diagnosis and access to targeted therapies substantially more quickly. Unnecessary treatment with antimicrobial agents can also be avoided. This supports clinical efforts to improve the patient experience, and further streamlines workflow in the laboratory, which can be particularly challenging in the midst of a busy respiratory virus season.”

The GeneXpert System uses proprietary Xpert test cartridges. It provides the ability to perform from 1 to 80 Xpert tests simultaneously, and so can meet the throughput requirements from lower volume point-ofcare settings to higher volume reference laboratories.

Image: The Xpert Xpress Flu/RSV test provides results within 30 minutes, twice as fast as its predecessor Xpert Flu/RSV XC (Photo courtesy of Cepheid).

Circulating Cell-Free DNA Predicts Gastric Cancer Prognosis cont’d from cover

However, there is no clinically established blood test, which has the predictive ability to determine gastric cancer for their clinical stages and therefore, the development of a preoperative blood test for assessment of clinical stage of gastric cancer is desirable.

Scientists at the Soochow University (Suzhou, China; www.suda.edu.cn) respectively assessed plasma samples from 40 healthy controls and 73 patients with gastric cancers: two stage 0, 17 stage I, 11 stage II, 33 stage III, and 10 stage IV. Blood samples were draw before antitumor therapy, within one to three weeks after surgery, and during the follow-up period. DNA was purified from 2 mL of plasma using QIAamp circulating nucleic acid kit (Qiagen, Hilden, Germany; www.qiagen.com).

Quantitative polymerase chain reaction (qPCR) targeting the Alu repeats was performed using two different sets of primers amplifying the long and short segments. DNA integrity was calculated as a ratio of the long to the short fragments of Alu repeats. Realtime PCR amplification was performed using a using a Bio-Rad CFX96 Real-Time PCR Detection System (Bio-Rad, Hercules, CA, USA; www.bio-rad.com).

Circulating cell-free DNA (ccf-DNA) in plasma may contain both specific and non-specific of tumor markers. The concentration and integrity of ccf-DNA may be clinical useful for detecting and predicting cancer progression. The team found that plasma DNA concentration was significantly higher in patients with stage III and IV gastric cancers than in healthy controls. Plasma DNA

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concentration was independent of age. In 73 patients with gastric cancer, median plasma DNA concentration was not correlated with depth of tumor invasion, lymphovascular invasion, and lymph node metastasis.

The authors concluded that that ccf-DNA was higher in plasma from patients with advanced gastric cancer than those from healthy controls. CcfDNA levels dropped after operation and elevated again at tumor progression. Ccf-DNA may be valuable in monitoring progression and prognosis of gastric cancer. In addition, they also tested a new pair of Alu219 primers that have high efficiency and may be applicable for measurement of DNA integrity. The study was published on December 9, 2016, in the journal BMC Cancer.

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AI May Improve Diagnostic Interpretation of Lung Function Tests first study in the field of lung testing suggests that diagnosis of long-term lung diseases could be improved using artificial intelligence (AI) algorithms developed to interpret results compiled from currently used tests.

The study, presented September 4 at the European Respiratory Society’s International Congress (London, UK, September 3-7, 2016; http:// erscongress.org/about-ers.html), is the first to explore the potential use of AI for improving accuracy of diagnosis of lung diseases. Current testing requires a series of assays including a spirometry test (measures the volume amount and the flow speed of air during breathing), followed by a body plethysmography test (measures static lung volumes and airways resistance), then finally a diffusion test (measures amount of oxygen and other gases that cross the lungs’ air sacs). Analysis of the results of these tests is largely based on expert opinion and international guidelines, attempting to detect patterns.

The new study included data from 968 people who were undergoing complete lung function testing for the first time. All participants received a first clinical diagnosis based on lung function tests and additional tests (e.g. CT scans, electrocardiogram, etc.). Final diagnosis was validated by a consensus of the large group of expert clinicians.

The researchers subsequently investigated whether “machine learning” (utilizing algorithms that can learn from data analysis and perform predictions) could be used to effectively analyze a complete set of lung function tests. They developed an algorithm process in addition to the routine lung function parameters and clinical variables of smoking history, body mass index, and age. Based on the pattern of both the clinical and lung function data, the algorithm provided a suggestion for the most likely diagnosis.

Wim Janssens from University of Leuven (Leuven, Belgium; www.kuleuven. be/english), study senior author, said: “We have demonstrated that AI can provide us with a more accurate diagnosis in this new study. The beauty of our development is that the algorithm can simulate the complex reasoning that a clinician uses to give their diagnosis, but in a more standardized and objective way.”

Clinicians currently rely on analyzing the results using population-based parameters. With AI, the machine can observe a combination of patterns simultaneously to help produce a more accurate diagnosis.

This has been done in other healthcare fields, such as with an automated interpretation of results from an electrocardiogram being routinely used in clinical practice as a decision support system.

Marko Topalovic, University of Leuven,

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study first author, said: “The benefit of this method is a more accurate and automated interpretation of pulmonary function tests, and thus better disease detection. Not only can this help non-experienced clinicians, but it also has many benefits for healthcare overall as it is time saving in achieving a final diagnosis as it could decrease the number of redundant additional tests clinicians are taking to confirm the diagnosis.”

The next step will be to test the algorithm in different populations and increase the system’s decision power using continuous updates on lung function data with validated clinical diagnoses.

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Image: Artificial Intelligence (AI) can be used to help improve the accuracy of the diagnosis in lung diseases (Photo courtesy of the IANS).

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PCR Better at Identifying Breast Tumor Subtypes Than Immunohistochemistry recently published study suggested that a RT-qPCR (reverse transcription quantitative real-time polymerase chain reaction) assay was superior to classical immunohistochemistry for subtyping breast tumors.

The biological subtype of breast cancer influences the selection of systemic therapy. Distinction between luminal A and B cancers depends on consistent assessment of the marker protein Ki-67 (encoded by the MKI67 gene), but substantial intra-observer and inter-observer variability exists when immunohistochemistry (IHC) is used.

A study compared the BioNTech Diagnostics GmbH (Mainz, Germany; www.biontech.de) MammaTyper RTqPCR-based diagnostic kit with IHC in the assessment of Ki-67 and other standard factors used in breast cancer subtyping.

MammaTyper is based on quantitative one step RT-qPCR technology, combining reverse transcription of

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mRNA and subsequent quantitative PCR of the resulting cDNA. Signal detection is performed in real time by fluorescently labeled hydrolysis probes. Expression results are normalized against two reference genes.

Additionally a calibrator corrects for inter-run and inter-instrument variations. Besides quantitative and highly reproducible performance data the test kit delivers fast and reliable results by ready-to-use assay mixes.

Results of MKI67 mRNA expression measurements with MammaTyper showed that patients who expressed a low level of MKI67 had a significantly better prognosis with regard to disease-free survival and overall survival than patients with a high MKI67 expression. In contrast, measurement of Ki-67 protein expression

by IHC showed no significant difference between these two groups for the prognosis of the two parameters.

The MammaTyper kit is CE / IVD marked for use in breast cancer subtyping. In addition to detection

of MKI67, MammaTyper demonstrated precise quantitative detection of the biomarkers ERBB2 (HER2 – Human epidermal growth factor receptor 2), ESR1 (ER – Estrogen receptor alpha), and PGR (PR – Progesterone receptor).

“The positive study data for MammaTyper underline our commitment to making personalized medicine broadly available for treating cancer,”

said Dr. Sierk Poetting, managing director of BioNTech Diagnostics.

The study was published in the May 24, 2016, online edition of the journal Breast Cancer Research and Treatment.

Image: The MammaTyper in vitro diagnostic test kit for breast cancer subtyping (Photo courtesy of BioNTech Diagnostics).

Novel Test Differentiates Malignant Prostate Cancer Grades promising new test has been introduced that detects prostate cancer more precisely than current tests, by identifying molecular changes in the prostate specific antigen (PSA) protein and can also differentiate between high-risk and low-risk disease, as well as benign conditions.

Although widely used, the current PSA test relies on detection strategies that have poor specificity for cancer, 25% of men who have a prostate biopsy due to an elevated PSA level actually have prostate cancer, and an inability to determine the aggressiveness of the disease.

Urologists at the Cleveland Clinic (OH, USA; http://my.clevelandclinic. org) carried out a clinical trial, which involved six healthcare institutions and 132 patients, to date. It examined the ability of novel test to distinguish patients with and without biopsy-confirmed evidence of cancer. It also evaluated the test’s precision in differentiating patients with high-grade (Gleason = 7) cancer from those with lowgrade (Gleason = 6) disease and benign findings after standard ultrasound-guided biopsy of the prostate.

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The scientists obtained 99 plasma samples from multiple clinical sites, collected within 30 days prior to prostate biopsy from patients with blood PSA between 2 and 26 ng/mL. The new test was evaluated against 12 core transrectal ultrasonography guided biopsy results as gold standard.

The new test is called the IsoPSA test (Cleveland Diagnostics, Inc, Cleveland, OH, USA) identifies the molecular structural changes in protein biomarkers. It is able to detect cancer by identifying these structural changes, as opposed to current tests that simply measure the protein’s concentration in a patient’s blood.

Eric Klein, MD, chair of Cleveland Clinic’s Glickman Urological & Kidney Institute, said, “While the PSA test has undoubtedly been one of the most successful biomarkers in history, its limitations are well known. Even currently available prostate cancer diagnostic tests rely on biomarkers that can be affected by physiological factors unrelated to cancer.”

The study was presented at the American Urological Association annual meeting held May 6-10, 2016, in San Diego, CA, USA. LabMedica International April/2017

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Electrophotonic Silicon Biosensor Speeds Up Blood Test Analyses new sensor has been developed that is capable of detecting multiple proteins and enzymes in a small volume of blood, which could significantly speed up diagnostic healthcare processes.

The complexity and heterogeneity of many diseases, and their dependence on lifestyle and genetics, demand new in vitro diagnostic technology that can provide quantitative measurement of multiple disease biomarkers in real time and at low cost.

Scientists at the University of York (Heslington, UK; www.york.ac.uk) have developed a biosensor that combines light and electricity, to detect multiple disease biomarkers in one smaller sample of blood. The technology could make blood tests more comfortable for patients and enable results to be processed quicker. The team is using the new technology in urine samples for urinary tract infections (UTIs), which has a high resistance to antibiotic treatment. If the biosensor can identify biomarkers of the infection and of resistance, it is more likely that the correct course of antibiotic treatment will be prescribed the first time around, rather than on repeat visits, which is often the case with UTIs. The investigators created a device capable of

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multiplexed detection that consists of a pair of photonic electrode ring resonators in the same microfluidic chamber. To explore the dual sensing capabilities of the device, they used the electrophotonic technology to monitor and quantify electrochemical reactions occurring at the silicon surface. The combination of electrochemical and photonic sensing not only provides access to complementary information, but also the ability to regulate the local surface chemistry via electrochemical processes in situ.

Thomas F Krauss, PhD, a professor and co-author of the study, said, “These sensors can give fast, real time results and at low cost. The length of time and money that it takes laboratory technicians to identify just one protein in a patient sample is a real challenge for the UK National Health Service (NHS) and can result in emotional distress for patients. Not only can this new technology speed the

process up, but it can test for a number of proteins and enzymes together in just one sample, increasing the chances of a successful and timely diagnosis.” The study was published on September 14, 2016, in the journal Nature Communications.

Image: A single electro-optical device: ohmic contacts fabricated on the doped silicon substrate allow electrochemical control over the sensor surface (Photo courtesy of the University of York).

Circulating Immune Cells Act As Idiopathic Pulmonary Fibrosis Biomarkers atients with fibrotic lung diseases, such as idiopathic pulmonary fibrosis (IPF), show progressive worsening of lung function with increased shortness of breath and dry cough.

To-date, this process is irreversible, which is why scientists are searching for novel biomarkers or indicators, which enable earlier diagnosis of this disease, with the aim to better interfere with disease progression.

Scientists at the Helmholtz Zentrum München (Munich, Germany; www.helmholtz-muenchen.de) prospectively included 170 patients in the analysis,

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divided into 69 IPF, 56 non-IPF interstitial lung disease (ILD), 17 with hypersensitivity pneumonitis, 27 with nonspecific interstitial pneumonia, 12 with connective tissue disease- (ILD), and 23 chronic obstructive pulmonary disease (COPD) patients, as well as 22 healthy controls.

For immunophenotyping, the team collected fresh venous blood in EDTA-coated vacutainer tubes. Briefly, whole blood or peripheral blood mononuclear cell (PBMC) buffy coats were used for flow cytometry detection of myeloid-derived suppressor cells (MDSC) and lymphocyte subtypes.

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Erythrocytes were lysed with a Coulter Q-Prep working station (Beckman Coulter, Brea, CA, USA; www.beckmancoulter.com). Data acquisition was performed in a BD LSRII flow cytometer or a BD fluorescence-activated cell sorter (FACS) ARIA II (Becton Dickinson, Heidelberg, Germany; www. bd.com) if cells were sorted. The T-cell suppression assay and MDSC co-cultures were also performed.

Peripheral blood mononuclear cell (PBMC) Messenger ribonucleic acid (mRNA) levels were analyzed by real time polymerase chain reaction (qRTPCR). The investigators detected increased MDSC in IPF and non-IPF ILD compared with controls (30.99 ± 15.61% versus 18.96 ± 8.17%). Circulating MDSC inversely correlated with maximum vital capacity in IPF, but not in COPD or non-IPF ILD. MDSC suppressed autologous T-cells. The mRNA levels of co-stimulatory T-cell signals were significantly downregulated in IPF PBMC. Importantly, CD33+CD11b+ cells, suggestive of MDSC, were detected in fibrotic niches of IPF lungs.

Oliver Eickelberg, MD, a professor and lead investigator said, “We were able to show that MDSC are primarily found in fibrotic niches of IPF lungs characterized by increased interstitial tissue and scarring, that is, in regions where the disease is very pronounced, and as a next step, we seek to investigate whether the presence of MDSC can serve as a biomarker to detect IPF and to determine how pronounced it is. Controlling accumulation or expansion of MDSC or blocking their suppressive functions may represent a promising treatment options for patients with IPF. ” The study was published on September 1, 2016, in the European Respiratory Journal.

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PRODUCT NEWS HEMATOLOGY ANALYZERS

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CLINICAL CHEMISTRY ANALYZER

BLOOD GAS ANALYZER

Horiba ABX

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Radiometer

The Yumizen H500 OT comes with flexible sampling to accommodate all sample types, particularly for rapid screening in critical care, emergency care and pediatric clinics. The Yumizen H500 CT provides enclosed, cap-piercing sample handling to meet the health and safety demands of the lab.

The Selectra Pro S offers a throughput of 140 tests per hour and provides a test menu of ready-touse, liquid-stable reagents with automated reagent management capability. The system is ideal for primary, STAT or back-up testing needs for smaller or satellite laboratory locations.

The ABL90 FLEX PLUS offers an uptime of more than 22 hours a day and a throughput of 44 samples per hour. Its dedicated Micromode measurement produces 17 critical parameters from a blood sample as small as 45 µL, making it suitable for ICUs, hospital delivery rooms, and NICUs.

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PCR-Based Blood Test Accurately Diagnoses Active Tuberculosis panel of three genes has been established that accurately distinguishes individuals with active tuberculosis (TB) from healthy individuals or from patients with chronic TB or AIDS. Active pulmonary tuberculosis is difficult to diagnose and treatment response is difficult to monitor effectively. In response to a World Health Organization (WHO) call for new non-sputum diagnostics, investigators at Stanford University (Palo Alto, CA, USA; www.stanford.edu) developed a simple, PCR-based assay to test for active TB in samples of patients’ blood.

The investigators screened a total of 14 datasets containing 2,572 samples from 10 countries from both adult and pediatric patients. Of these, three datasets comprising 1,023 samples were used to discover a set of three genes (GBP5, DUSP3, and KLF2) that were highly diagnostic for active tuberculosis.

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The diagnostic power of the three gene set to separate active tuberculosis from healthy controls, latent tuberculosis, and other diseases was validated in eight independent datasets composed of both children and adults from ten countries.

The assay was shown to be 86% sensitive and 99% in children.

Expression of the three-gene set was not masked by HIV infection status, bacterial drug resistance, or BCG vaccination. Furthermore, in four additional cohorts, the investigators showed that the tuberculosis score declined during treatment of patients with active tuberculosis.

“One-third of the world’s population is currently infected with TB. Even if only 10% of them get active TB, that is still 3% of the world’s population – 240 million people,” said senior author Dr. Purvesh Khatri, assistant professor of medicine at Stanford

University. The study was published in the February 19, 2016, online edition of the journal Lancet Respiratory Medicine.

Image: A high magnification scanning electron micrograph (SEM) showing a number of Gram-positive Mycobacterium tuberculosis bacteria (Photo courtesy of the CDC).

Vascular Disease Plasma Marker Confirmed in Diabetes Patients re-kallikrein (PK) has previously been suggested as a marker for diabetic vascular disease of the kidneys, but a new study supports the idea that increased plasma PK levels are an independent risk factor for whole-body diabetic vascular disease, similar to the risks of high triglycerides or high blood pressure in heart disease.

The types of blood vessel malfunction seen in patients with diabetes causes the cells of the intimamedia to spread to the surface, allowing PK to contact them directly and this contact closes the circuit of an alternative pathway of chronic inflammation.

Scientists who study the kallikrein-kinin system suspect that this chronic inflammation is responsible for the blood vessel thickening observed in diabetic kidney disease, retinopathy, and atherosclerosis.

Scientists at the Medical University of South Carolina (Charleston, SC, USA; www.musc.edu) and their colleagues enrolled participants in Epidemiolo-

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gy of Diabetes Interventions and Complications (EDIC), a multicenter longitudinal observational study of the development of macrovascular complications and further progression of microvascular complications. The study was conducted on a subset of 636 subjects from the Diabetes Control and Complications Trial DCCT/EDIC cohort.

Plasma PK was activated with 0.4 nmol/L Hageman factor fragment (betaFXIIa), and the formed plasma kallikrein was detected by hydrolysis of the chromogenic substrate H-D-Pro-Phe-Argparanitroanilide (DiaPharma; Franklin, OH, USA; www.diapharma.com) according to the published procedure, and was expressed as units per milliliter (U/mL). Factor XII:coagulant and high molecular weight kininogen (HK):coagulant, plasma concentrations of fibrinogen and plasminogen activator inhibitor (PAI-1) activity levels were also determined.

Carotid intima-media thickness was measured by B-

mode ultrasonography.

The circulating levels of plasma PK were measured in 636 type 1 diabetic subjects from plasma collected in years 1997–1999. The PK levels were symmetrically distributed and ranged from 0.2-3.0 U/mL, with a mean value of 1.29 U/mL. A positive and significant association was found between PK levels and body mass index (BMI), and with HbA1c, a marker of metabolic control. They also found that patients with higher levels of PK in their blood have thicker layers of intima-media in the vasculature of their carotids.

Ayad A. Jaffa, PhD, the senior author of the study said, “These preclinical studies not only will give us insights into the involvement of plasma PK in vascular disease, but will also contribute to development of novel treatment strategies for diabetic vascular disease.” The study was published ahead of print on November 24, 2015, in the journal Diabetes.

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PRODUCT NEWS PCR DETECTION KIT

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Certest Biotec

Helmer

DiaSys Diagnostic Systems

The VIASURE kit is designed for specific detection and differentiation of Zika, Dengue and/or Chikungunya viruses in samples from patients with signs/symptoms of infection. The test is intended for use as a diagnostic aid, in combination with clinical and epidemiological risk factors.

The i.Series line offers the i.C3 Information Center door-mounted, touch screen interface with constant temp monitoring and control. The line allows the customization of drawer, shelf, and basket combinations and locations, enabling improved inventory control and operational efficiency.

The InnovaStar is an automatic, compact POCT analyzer for daily use that delivers results comparable to lab analyzers for HbA1c, CRP, glucose and hemoglobin from whole blood samples. The ease of use of InnovaStar is further improved by the integration of a colored touch screen.

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Rapid Diagnostic Test Performance Assessed for Placental Malaria omen experiencing pregnancy-associated malaria may exhibit normal symptoms of malaria, but may also be asymptomatic or present with more mild symptoms, including a lack of the characteristic fever. This may prevent a woman from seeking treatment despite the danger to herself and her unborn child.

During pregnancy, a woman faces a much higher risk of contracting malaria and of associated complications. Prevention and treatment of malaria are essential components of prenatal care in areas where the parasite is endemic. The diagnosis of placental malaria is important for program evaluation and clinical care, but is compromised by the suboptimal

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performance of current diagnostics.

Scientists at the University of North Carolina (Chapel Hill, NC, USA; www.unc.edu) and their colleagues used placental and peripheral blood specimens collected from delivering women in Malawi, and compared estimation of the operating characteristics of microscopy, rapid diagnostic test (RDT), polymerase chain reaction, and histopathology using both a traditional contingency table and a latent class analysis (LCA) approach.

The team found that the prevalence of placental malaria by histopathology was 13.8%, but concordance between tests was generally poor. Relative to histopathology, RDT sensitivity was 79.5% in peripheral and 66.2% in placental blood; using LCA, RDT sensitivi-

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ties increased to 93.7% and 80.2%, respectively. The scientists concluded that their results, if replicated in other cohorts, indicate that RDT testing of peripheral or placental blood may be suitable approaches to detect placental

malaria for surveillance programs, including areas where intermittent preventive therapy in pregnancy is not used. The study was published on August 15, 2016, in the American Journal of Tropical Medicine and Hygiene.

Biomarker of Aggressive Prostate Cancer Discovered he level of a specific molecule present in prostate tumors is an indicator of whether the cancer is aggressive and likely to spread and this will aid future clinical tests to help doctors decide how best to treat prostate tumors.

Many men with prostate cancer have slow-growing tumors that do not require surgery, radiation or other treatments that can leave patients impotent, incontinent or both, but doctors often have difficulty telling the difference between these indolent tumors and those that will prove to be more aggressive. Scientists at the Washington University School of Medicine (St. Louis, MO, USA; https:// medicine.wustl.edu) and their colleagues obtained radical prostatectomy microarray and clinical data from 910 patients in three published institutional cohorts. The scientists measured levels of Prostate Cancer Associated Transcript 14 (PCAT-14) from prostate tumors after their surgical removal. The scientists found that levels of PCAT-14, a ribonucleic acid (RNA) molecule, were elevated across 180 prostate cancer patients treated at three different institutions.

Analyzing another 910 tumor samples from patients with known treatment outcomes, the investigators also

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showed that the patients with more aggressive tumors, perhaps surprisingly, had lower levels of PCAT-14. Patients with slow-growing tumors had higher levels of the molecule. That may seem counterintuitive, but according to the team, the data suggest that high levels of this RNA molecule suppress tumor spreading. So when levels decrease, that suppression is lost and the cancer cells are free to metastasize.

The team also showed that low levels of PCAT-14 were associated with poor response to androgen deprivation therapy, a hormone-based treatment for prostate cancer that is less toxic than chemotherapy and radiation therapy.

Christopher A. Maher, PhD, an assistant professor of medicine and senior author of the study said, “We looked at all similar RNA molecules in these prostate tumors and only PCAT-14 was consistently altered in all prostate cancer patients and able to distinguish indolent and aggressive disease. Our study suggests that levels of the molecule called PCAT-14 may be a marker of whether the tumor is likely to be aggressive, helping doctors decide whether to intensify a patient’s treatment.” The study was published on July 23, 2016, in the journal European Urology.

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HDL High and Low Levels May Cause Premature Death igh and low levels of high-density lipoprotein (HDL) cholesterol may increase a person’s risk of premature death although commonly touted as “good cholesterol” that helps to reduce risk of both stroke and heart attacks.

Cholesterol is a fatty substance found in blood that can narrow and block heart vessels, causing cardiovascular disease and stroke and for years, HDL cholesterol has been credited with helping to remove plaque-building “bad cholesterol” from arteries.

Scientists at the Washington University School of Medicine (St. Louis, MO, USA; https://medicine.wustl.edu) studied kidney function and HDL cholesterol levels in a cohort of more than 1.7 million male veterans from October 2003 through September 2004 and then followed participants until September 2013 or until death. They sought to characterize the relationship of HDL cholesterol and risk of death and examine the association by estimated glomerular filtration rate (eGFR) levels.

The team found that patients with low HDL cholesterol and low eGFR had a higher burden of comorbid illnesses. In adjusted survival models, compared with the referent group of patients with low HDL cholesterol (≤25 mg/dL), intermediate HDL cholesterol levels (>25 to <34, ≥34 to ≤42, and >42 to <50 mg/dL) were associated with lower risk of death across all levels of eGFR. The lower risk was partially abrogated in those with high HDL cholesterol (≥50 mg/dL), and the risk of death was similar to the referent category among those with eGFR<30 or ≥90 mL/min per 1.73 m2.

There was a significant interaction between eGFR and HDL cholesterol in that lower eGFR attenuated the salutary association of HDL cholesterol and risk of death.

Presence of coronary artery disease attenuated the lower risk of high HDL cholesterol and all-cause mortality in those with eGFR ≥60 mL/min per 1.73 m2.

Ziyad Al-Aly, MD, an assistant professor of medicine and the study’s senior author, said, “The findings surprised us. Previously it was thought that raised levels of the good cholesterol were beneficial. The relationship between increased levels of HDL cholesterol and early death is unexpected and not fully clear yet. This will require further study.” The study was published in the August 2016 issue of the Clinical Journal of the American Society of Nephrology.

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form the arterial plaque that is generally associated with cholesterol (Photo courtesy of Shutterstock).

Image: Low-density lipoproteins can V

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PRODUCT NEWS DIGITAL IMMUNOASSAY SYSTEM

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DATA MANAGER

RAPID IMMUNOASSAY TEST

BD Diagnostic Systems

Instrumentation Lab

Luminex

The BD Veritor Plus is designed for the detection of influenza A&B, RSV and group A strep, with enhanced documentation functionality. It provides accurate test results within minutes and is suitable for healthcare providers and clinical lab professionals.

The HemoHub allows users to view critical results and analyzer status in RT, set up automatic reruns and reflexes, and minimize interruptions. It standardizes testing across systems/networks by allowing users to monitor QC and provide better patient care from a single workstation.

The ARIES Flu A/B & RSV assay is for the detection/differentiation of influenza A&B, and RSV from nasopharyngeal swabs. It features integrated sample processing control to ensure the assay run is successful from extraction through amplification with results delivered in less than two hours.

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Rapid New Test Detects Chlamydia Infection novel system DNA probes with bespoke electrochemical tags attached to accurately detect for infectious diseases and this system has significant benefits over existing diagnostic tests, allowing for faster results. The World Health Organization (WHO; Geneva, Switzerland; www. who.int) has estimated that 499 million new sexually transmitted infections (STIs) occur each year and this novel diagnostic tool could soon be helping to win the fight against the spread of these diseases.

Atlas Genetics Ltd. (Bath, UK; www.atlas genetics.com), the ultra-rapid Point-of-Care (POC) molecular diagnostics company, has announced that it has received approval to CE marking its Chlamydia trachomatis (CT) test to be launched on the Company’s io platform. By meeting the requirements of the in vitro Diagnostics (IVD) Directive (98/79/EC), the CT test is now cleared for sale within the European Union.

The evaluations conducted on the io CT test

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demonstrated that performance is equivalent to the gold standard laboratory test and will not be compromised by the transition of testing away from the central laboratory to the point-of-care (POC) setting, or by the level of experience of the operator performing the test. This is the first molecular POC test for a Sexually Transmitted Infection (STI) to enter the market, capable of delivering test results in just 30 minutes. With the speed and accuracy of the io CT product, the testing and treatment of patients within a single, brief visit to the clinic now becomes a reality. The Chlamydia test is the first in a pipeline of tests to be launched on the io platform.

Further menu development will include tests for Gonorrhea, Trichomonas vaginalis and other STIs, for both the European and US markets. While Atlas’ commercialization strategy is initially focused on the area of sexual health, the io platform technology can be applied in a wide range of infectious disease and oncology diagnostic test areas.

Image: The io system is a highly novel molecular diagnostic system for the ultra-rapid diagnosis of a broad range of infectious diseases including sexually transmitted infections (Photo courtesy of Atlas Genetics).

Aberrant Gene Expression Predicts Metastatic Endometrial and Lung Cancers he spread of cancer cells from the initial site of occurrence, the primary site, to other secondary tissues is called metastasis, and contributes to poor or limited response of cancer cells to treatments, which results in death. For example, cancer cells initially in the lungs can begin to spread to other organs, including the brain and liver.

Gynecologic cancer typically originates from the female reproductive organs, and includes endometrial and ovarian cancer, among others. Survival rates are typically very poor for these cancer-types, with limited response to existing therapies and a major reason for poor survival rates is late diagnoses, by which time the cancer cells have spread to secondary sites.

Scientists from Georgia State University (Atlanta, GA, USA; www.gsu.edu) and the University of Oklahoma College of Medicine (Oklahoma City, OK, USA; www.ouhsc.edu) obtained more than a hundred clinical endometrial cancer specimens and matching serum. Using multiplex arrays and a variety of exper-

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imental approaches, they analyzed the specimens for gene targets that positively or negatively correlated with metastatic potential of the tumors. Data were translated to reflect the patient’s age at diagnosis, disease stage, grade and histology.

Serum specimens were evaluated for levels of cpeptide, interleukin-6 (IL-6,) insulin, leptin, monocyte chemoattractant protein-1 (MCP-1 or CCL2) and tumor necrosis factor alpha (TNFα) using a custommade multiplex kit subset of the MILLIPLEX MAP Human Metabolic Hormone Magnetic Bead Panel (EMD Millipore; Billerica, MA, USA; www.emd millipore.com), for levels of adipsin and adiponectin, using the Bio-Plex Pro Human Diabetes Adipsin and Adiponectin Assay (BIO-RAD Laboratories Inc., Hercules, CA, USA; www.bio-rad.com) and for levels of angiopoietin-2, follistatin, G-CSF, HGF, IL-8, leptin, PDGF-BB, PECAM-1 and VEGF, they used the BioRad Bio-Plex Pro diabetes kit.

The scientists found that enhanced neuropilin-1 (NRP-1) expression significantly correlated with in-

creased tumoral expression of vascular endothelial growth factor 2 (VEGFR2) and serum levels of hepatocyte growth factor (HGF) and cell growth-stimulating factor (C-GSF). Tumoral NRP-1 also was positively associated with expression of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD9), a pro-metastatic protein.

In the highly metastatic lung cancer cell line (H1792), stable LKB1 depletion caused increased migration in vitro and accentuated NRP-1 and NEDD9 expression in vivo.

Imoh S. Okon, PhD, a professor and lead author of the study said, “In this study, we found that enhanced neuropilin-1 (NRP-1) and NEDD9 levels in endometrial and lung cancer positively correlated with metastasis, while liver kinase B1 (LKB1) inhibited the migration of cancer cells. Our study provides strong translational potential with respect to biomarkers that play critical roles in the development of endometrial/ lung tumors.” The study was published on December 20, 2015, in the journal Oncotarget.

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Tumor Analysis Method Identifies High-Risk Prostate Cancer new way to identify which prostate cancer patients are likely to develop aggressive types of the disease, even if their tumors at first appear to be lower risk, has been created.

Prostate cancer is a biologically heterogeneous disease with variable molecular alterations underlying cancer initiation and progression. Despite recent advances in understanding prostate cancer heterogeneity, better methods for classification of prostate cancer are still needed to improve prognostic accuracy and therapeutic outcomes.

A team of scientists led by those at Cedars-Sinai Medical Center (Los Angeles, CA, USA; www. cedars-sinai.edu) computationally assembled a large virtual cohort of human prostate cancer transcriptome profiles from 38 distinct cohorts and, using pathway activation signatures of known relevance to prostate cancer, developed a novel classification system consisting of three distinct subtypes (named PCS1–3). They validated this subtyping scheme in 10 independent patient cohorts and 19 laboratory models of prostate cancer, including cell lines and genetically engineered mouse models.

The team found showed that one of the three subtypes of prostate cancer they identified, which they called PCS1, was generally aggressive. In the patients they studied, this subtype showed a high likelihood of spreading and progressing to poor clinical outcomes, including fatalities. Patients experienced poor outcomes even when the tumors had been assigned low Gleason grades. The two other subtypes, PCS2 and PCS3, progressed more slowly. Currently, patients with low-grade tumors often receive no treatment and instead are closely monitored, under a strategy known as active surveillance. The new study indicates active surveillance may not be enough for some of these patients.

An additional advantage to the new subtyping is that it can be performed on tumor cells circulating in the blood. This finding has the potential to improve realtime monitoring of tumor evolution during treatment. Michael Freeman, PhD, the study’s principal investigator said, “About 60% of prostate cancer patients we treat won’t progress to aggressive cancer. The problem was that we didn’t have a way of knowing which patients fall into that 60%. We hope our findings help physicians provide more patients with optimal treatments, resulting in healthier outcomes.” The study was published on September 1, 2016, in the journal Cancer Research.

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Image: A colorized scanning electron micrograph (SEM) of human prostate cancer cells (Photo courtesy of Dr. Gopal Murti).

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PRODUCT NEWS BLOOD GAS ANALYZER

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AUTOMATED ID/AST SYSTEM

BIOMARKER TEST

Siemens Healthineers

BD Diagnostic Systems

EKF Diagnostics

The RAPIDLab 348EX delivers accurate results in about 60 seconds from a small sample of whole blood and dialysate fluid. It features a color touch screen, barcode scanner, and front panel access to sensors, reagents, and waste, making it ideal for performing tests in smaller laboratories.

The BD Phoenix M50 ID/AST can simultaneously perform from 1 to 100 ID/AST determinations. It features a one-panel design and pour-and-cap procedure, and offers the flexibility of random entry on-demand loading, custom antibiotic panels, and single or batch inoculation.

The Glycated Serum Protein (GSP) LiquiColor test is designed for use on the Siemens Vista analyzer. The GSP assay enhances the versatility of the Vista system for the specialized glycemic monitoring of diabetics with hemoglobinopathies, or conditions that affect red blood cell lifespan.

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Handheld Blood Test Device Detects Heart Attacks new handheld blood test device is able to rapidly diagnosis heart attacks at the point of care, and has been specifically designed for use in emergency departments to dramatically reduce the time physicians take to diagnose heart attacks.

For patients presenting at emergency departments with chest pains, the device can be used to administer an immediate test, with results delivered while the patient is being assessed and a medical history taken and this reduces the time for the physician to decide on treatment.

The new system works by measuring the level of cardiac troponin I (cTnI), a protein that is excreted by the heart muscle into the blood following a heart attack. Current guidelines for the diagnosis of myocardial infarction require blood test results of the biomarker cardiac troponin for the 90% of patients who present at the emergency department (ED) with chest pain but are not diagnosed by an electrocardiogram (ECG). Physicians often have to wait up

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to six hours before it can be decided if they can safely discharge the patients or if they need to admit them into the hospital for further tests.

The use of device, called the Minicare I-20 cTnI (Philips, Amsterdam. The Netherlands; www.philips.com) supports a reduction of the diagnostic protocol by up to three hours.

Each blood test has dedicated software and a single use, disposable cartridge containing the application-specific test. The technology has been designed to detect multiple target molecules at low concentrations within the same blood sample and to show the results on the device’s display within minutes.

Paul O Collinson MA MB BChir FRCPath MD FACB FRCP, the Consultant Chemical Pathologist and Professor of. Cardiovascular Biomarkers, at St George’s University Hospitals (London, UK,; www.stgeorges.nhs.uk), said, “Blood samples are

usually analyzed in the hospital laboratory, which can easily take more than an hour to get the result back to the ED physician. Point-of-care testing can significantly help to reduce the turnaround time.”

Image: The new Minicare I-20 handheld device detects proteins in the blood stream following a heart attack, providing results in just 10 minutes (Photo courtesy of Philips Healthcare).

Blood Analyses Predict Delirium Risk in Older Surgical Patients elirium, or sudden severe confusion due to rapid changes in brain function that can occur with physical or mental illness, affects 15% to 53% of older surgical patients and has been linked with longer hospital stays, greater postoperative complications, and higher rates of discharge to nursing homes.

In the USA health care costs attributable to delirium are upwards of USD164 billion annually, yet there are no established biological markers to guide the diagnosis or management of the condition. Recent studies may now help clinicians assess an individual patient’s risk of developing post-operative delirium, enabling preventive measures to safeguard their health.

Scientists at the Beth Israel Deaconess Medical Center (Boston, MA, USA; www.bidmc.org) and their colleagues screened plasma from adults without dementia aged 70 and older undergoing major non-cardiac surgery using data from the Successful Aging after Elective Surgery Study. Of the 566 pa-

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tients enrolled, 24% experienced delirium. Plasma was collected at four time points: preoperatively (PREOP), in the post anesthesia care unit (PACU), on postoperative day two (POD2) and at the onemonth follow-up appointment (PO1MO).

Cases and controls were matched on six variables that may influence the relationship between C-reactive protein (CRP) and postoperative delirium: age within five years; baseline general cognitive performance (GCP) within five points; and an exact match for sex, surgery type, presence of vascular comorbidity, and apolipoprotein E (APOE) 4 carrier status. For APOE genotyping, DNA was extracted from cellular material collected at PREOP and analyzed.

The initial proteomics phase used isobaric tags for relative and absolute quantitation (iTRAQ) mass spectrometry assay to examine five sets of matched case-control plasma samples across the four time points in the discovery cohort. Mass spectrometry data was obtained using the AB Sciex 4800 MALDI-

TOF/TOF instrument (AB Sciex, Framingham, MA, USA; www.sciex.com). After analyzing five matched pairs using the iTRAQ system, they selected one protein that met two criteria for enzyme-linked immunosorbent assay (ELISA) validation. ELISA plates were read using a Synergy plate reader (BioTek Instruments Inc, Winooski, VT, USA; www.biotek. com) at Optical Density (OD =450nm).

C-reactive protein emerged from the proteomics analysis as the strongest delirium-related protein.

Validation by ELISA confirmed that compared with controls, cases had significantly higher C-reactive protein levels in the discovery, replication, and pooled cohorts at the PREOP median paired difference [MPD] was 1.97 mg/L, 0.29 mg/L, 1.56 mg/L, the PACU MPD was 2.83 mg/L, 2.22 mg/L, 2.53 mg/L) and the POD2 MPD was 71.97 mg/L, 35.18 mg/L,63.76 mg/L time points, but not at one month postoperative. The study was published on March 25, 2016, in the journal Biological Psychiatry.

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HEMATOLOGY ANALYZER

URINE ANALYZER

Siemens Healthineers

Diatron

77 Elektronika

The CLINITEK Status+ automatically checks each test strip for humidity exposure, common sample interferences, and strip identification for Siemens test strips. It automatically times and reads every specimen, and provides in-office test results in about one minute.

The Aquila offers a throughput of 60 tests per hour, requires a sample size of only 10 µl, and consumes less than 10 ml of reagent per test. It is equipped with an onboard reagent pack sufficient for approximately 200 measurements and includes a touch screen and intuitive user interface.

The UriSed mini offers a throughput of up to 60 tests / hour and a total measurement cycle of less than one minute. Its cost-effective operation makes it ideal for a wide range of medical and clinical settings such as hospitals, clinics, emergency departments, and outpatient laboratories.

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Microbiologists Display Prototype Of Rapid Bacteriological Test Device prototype rapid diagnostic device was shown in a proofof-concept study to identify pathogenic microorganisms with accuracy comparable to that of bacterial culture but with much shorter turnaround time.

Investigators at Massachusetts General Hospital (Boston, USA; www. mgh.harvard.edu) based their device on the principle of fluorescence anisotropy, the phenomenon where the light emitted by a fluorophore has unequal intensities along different axes of polarization. Their “Polarization Anisotropy Diagnostics” (PAD) device uses changes of fluorescence anisotropy when detection probes recognize target bacterial nucleic acids.

The compact PAD device included a disposable cartridge for sample preparation and multi-well detection. To per-

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form the test bacterial RNA was extracted from a sample in the disposable plastic cartridge. Following polymerase chain reaction amplification of the RNA, the material was loaded into a two-centimeter plastic cube containing optical components that detected target RNAs based on the response to a light signal of sequence-specific detection probes.

These optical cubes were placed on an electronic base station that transmitted data to a smartphone or computer where the results were displayed.

The assay was fast (two hours) compared to two to three days for classical culture. When applied to clinical samples obtained from interventional procedures, the PAD determined the overall bacterial burden, differentiated bacterial species, and identified drug resistance and virulence status. “This prototype still

needs several improvements, including building a self-contained system housing all functions, further reducing the current assay time to less than one hour and expanding the panel of probes to even more pathogens and resistance factors,” said senior author Dr. Hakho Lee, associate professor of radiology at Massachusetts General Hospital. “But we can see three immediate applications for a system that can provide such rapid and accurate results – quickly diagnosing a patient’s infection, determining whether antibiotic-resistant bacteria are present in a group of patients, and detecting bacterial contamination of medical devices or patient environments.”

The PAD device was described in the May 5, 2016, online edition of the journal Science Advances.

Image: A smartphone readout from the Polarization Anisotropy Diagnostics (PAD) system reveals the pathogens responsible for an infection and factors such as antibiotic resistance (Photo courtesy of Dr. ChenHan Huang and Dr. Ki Soo Park, Massachusetts General Hospital).

Field-Applicable Molecular Test Diagnoses Tegumentary Leishmaniasis utaneous and mucosal leishmaniases are widely distributed in Central and South America. Leishmania of the Viannia subgenus are the most frequent species infecting humans. L. (V.) braziliensis, L. (V.) panamensis are also responsible for metastatic mucosal leishmaniasis.

Conventional or real time polymerase chain reaction (PCR) are more sensitive diagnostic tests than microscopy, but the cost and requirement for infrastructure and trained personnel makes it impractical in most endemic regions. Primary health systems need a sensitive and specific point of care (POC) diagnostic tool.

Scientists at the University of Texas Medical Branch (UTMB, Galveston, TX, USA; www.utmb. edu) and their colleagues in South America, evaluated DNA purified from lesion biopsies of nine pa-

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tients from Peru who were infected with L. braziliensis and four with L. guyanensis, as well as five non-leishmanial (PCR-negative) skin lesions.

They also evaluated many different banked strains from diverse species.

The investigators developed a novel POC molecular diagnostic test for cutaneous leishmaniasis caused by Leishmania (Viannia) spp. Parasite DNA was amplified using isothermal Recombinase Polymerase Amplification (RPA) with primers and probes that targeted the kinetoplast DNA. The amplification product was detected by naked eye with a lateral flow (LF) immunochromatographic strip.

In the clinical samples they found 100% agreement between PCR and RPA-LF. The RPA-LF had an analytical sensitivity equivalent to 0.1 parasites per reaction. The test amplified the principal L. Viannia

species from multiple countries: 33 L. (V.) braziliensis, 17 L. (V.) guyanensis, and nine L. (V.) panamensis. The less common L. (V.) lainsoni, L. (V.) shawi, and L. (V.) naiffi were also amplified.

The specificity was confirmed by the lack of amplification of L. donovani, L. chagasi, L. mexicana, L. amazonensis, L. major, Trypanosoma cruzi and human DNA. The authors concluded that the high analytical sensitivity and clinical validation indicated the test could improve the efficiency of diagnosis, especially in chronic lesions with submicroscopic parasite burdens. Field implementation of the RPA-LF test could contribute to management and control of cutaneous and mucosal leishmaniasis. The study was published on April 16, 2016, in the journal Public Library of Science Neglected tropical Diseases.

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International Federation of Clinical Chemistry and Laboratory Medicine

2016 ANNUAL REPORT HIGHLIGHTS OF THE YEAR 12th IFCC General Conference, Madrid, Spain (19-21 March) 14th Asia Pacific Federation for Clinical Biochemistry and Laboratory Medicine (APFCB) Congress, Taipei, Taiwan (26-29 November) 15th IFCC-Roche Bergmeyer Conference, Eibsee, Germany (7-9 March) “Biomarkers in the Diagnosis and Monitoring of Cancer” IFCC-Roche Specialized Conference, “Biomarkers in Alzheimer’s Disease”, Mexico City, Mexico (20 May) IFCC VLP programme (www.ifcc.org/ifcc-education-division/emd-special-projects)

PRESIDENT’S MESSAGE his is my report after the second year as IFCC President and I am very proud to summarize what has been done during 2016.

During the year IFCC again increased its membership as welcomed two new Affiliate Member Societies: “Society for Medical Technology & Laboratories-Jordan” and the “Nepalese Association for Clinical Chemistry”. Collectively, there are 89 Full Members, 12 Affiliate members and 47 Corporates Members and IFCC represents >45,000 senior laboratory medicine specialists.

The important work of IFCC takes place in its Divisions, Committees, Task Forces and Working Groups. During 2016 >320 experts volunteered to work on 47 IFCC projects, which cover a wide range of clinical, scientific, educational and communication related topics.

Full details may be found in the IFCC website (www.ifcc.org) and reports may be found in this Annual Report. IFCC also contributes expert input to a number of global organizations.

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The IFCC Strategic Plan. The Executive Board for 2015-2017 has identified and agreed below strategic objectives for its term of office. They follow the overall IFCC strategic plan and its principal objectives. They are intended to be in addition to the ongoing work of Division Executives. There are 33 strategic actions which have been classified into the following four broad areas: 1. Supporting our membership.

2. Broadening our horizons.

3. Improving the quality of laboratory medicine.

4. Improving the effectiveness of IFCC. The Executive Board worked effectively during 2016 and completed 28 actions. Five actions are still in progress and should be completed next year. The Executive Board worked effectively during 2016 and completed 28 actions.

Five actions are still in progress and should be completed next year. I would like to outline some of the achievements in addition to those already reached in 2015: • Evaluate the performance and the financial balance of Divisions through their mandatory report; • Deeply promote the Foundation for Emerging Nations-FEN as a new income stream for IFCC; • Increase multi-languages educational material; • Perform a wide-ranging of SWOT analysis of IFCC, evaluate the findings and publish a report with recommenda-

EXECUTIVE BOARD (EB) The Executive Board held three meeting during 2016. The first one was held in Madrid on March 18 on occasion of the IFCC General Conference, successfully attended by 273 Participants, 71 National Societies, 14 Corporate Members, 33 Closed meetings and 13 Interactive sessions were organized. A survey has been performed with 138 answers/273 participants; 41,3 % experienced the first time at the GC, the overall satisfaction was good and more than 95% of the attendants considered the GC an important event for the IFCC. The second EB meeting was held in Philadelphia in connection with the AACC Annual Meeting, on July 30-31; the third EB meeting was held in Taiwan in connection with the APFCB Congress on November 24-25.

In January 15-16 a strategic SWOT Meeting was held in Milan and EB agreed on the IFCC Vision: "We advance excellence in laboratory medicine for better healthcare worldwide, establishing a prioritization of targets, reviewing the Strategic Plan.

Besides two new members societies joined IFCC in 2016: Society for Medical Technology & Laboratories-Jordan and the Nepalese Association for Clinical Chemistry as Affiliate Members).

In 2016 we were glad to welcome KHB Shanghai Kehua Bioengineering as a new Corporate Member.

A letter was sent to National Societies of the Full and Affiliate members requesting for their annual report. More than fifty reports were received to be included in the IFCC Annual report 2016 which is available on the IFCC Website (www.ifcc.org).

Thanks to the members of the EB for their support and friendship, thanks to all IFCC officers and to the staff of Emmezeta-MZ Congressi in Milan (Paola Bramati, Silvia Cardinale and Silvia Colli Lanzi).

Sergio Bernardini, Executive Board Secretary

TREASURER’S REPORT During my second year of term as the IFCC treasurer, with the valuable help and assistance of the IFCC office, the annual dues of Full, Affiliate and Corporate Members have been received, the adherence of IFCC operating units to their allocated budgeted have been monitored and detailed records of all transactions have been kept, reimbursements have been processed as quick as possible after the receipt of the claims. Close collaboration has been achieved with the IFCC investment bank, (LGT) to optimise the financial return on IFCC investments. The current and historical performances of the portfolio mandate at the LGT Bank and the investment charges for different investment models (basic fee with brokerage fees and all-in-fee models) were presented to the IFCC Executive Board (EB). The performance of investments has not been good over the past couple of years due to the reflection of global stock markets. The investment charges paid were too high especially in the periods when the returns on investment low. The high investment charge fees tempted to look at alternative ways to manage investments with the result that a more competitive fee structure has been identified. It is this reduced fee structure from another reputable investment bank (Credit Swiss) that has prompted IFCC EB to move IFCC’s investment portfolio from the LGT Bank to CS. The annual accounts and financial actions have been reviewed by an external independent auditor in order to finalize the actual income and expenses at 31st December 2016.

Comparison of 2016 Proposed Budget with Actuals at December 31, 2016: IFCC Net Income. The 2016 budget was expected to be closed with a deficit of CHF -1.297.341. Instead, it was closed with a less negative balance of CHF -436.459 (Fig. 1).

Total Operational Revenues and Financial Income. The actual total operational revenues and financial income in 2016 were CHF 1.006.430 (Fig. 2)

IFCC Speakers Bureau (www.ifcc.org/ifcc-education-division/speaker-s-bureau) Roche/IFCC Travel Scholarship Webinars and Distance Learning Modules (www.ifcc.org/ifcc-education-division/webinars/ifcc-webinars) e-Academy open educational resources (http://eacademy.ifcc.org) Experts Database (www.ifcc.org/ifcc-education-division/experts) IFCC FEN - Foundation for Emerging Nations (www.ifccfoundation.org) Implement cooperation and agreements with IFCC Regional Federations

by Maurizio Ferrari, IFCC President tions of planned actions; • Further develop and promote “Shaping the Future of Laboratory Medicine”; • Introduce and support the “Med Tech Ethical Code”; • Devise and introduce a strategy to increase the attractiveness of IFCC to Corporate members; • Establish a new high level project with WASPaLM that aims to promote the quality of laboratory medicine through the support of the value of Laboratory Medicine; • Increase the number of young scientists participating in the IFCC Functional Units; • Consolidate the mentoring programme as a Special Project and promote its gradual expansion; • Open the call for nominations for the EB Treasurer and Secretary positions (2018-2020); • Open the call for nominations for the “IFCC Medal for outstanding services”; • General Conference, Madrid, March 19-21, 2016; • IFCC Speakers Bureau (http://www.ifcc.org/ifcc-education-division/speaker-s-bureau/); • Webinars and Distance Learning Modules (http://www.ifcc.org/ifcc-education-division/webinars/); • e-Academy, open educational resources (http://eacademy.ifcc.org/); • Experts Database (http://www.ifcc.org/ifcc-education-division/experts/).

Over the last year we increased the activities focused to outline the clinical effectiveness of laboratory medicine.

For IFCC this has been exemplified by the work of many Task Forces and by the increasing collaboration with international clinical organizations. This trend will surely gain further momentum in the years ahead for laboratory medicine is truly central to clinical decision making in healthcare.

Finances. The annual accounts for 2016 were audited in March 2017 and copies are available upon request from the IFCC Office. IFCC had a financially difficult year but our finances are still sound as we prepare for the future.

We prepared a clear budget for 2017, trying to contain the increasing expenses but with the goal to improve as much as possible the activities of IFCC in favor of our Members.

Finally, I wish to thank, after my second year as President, the Executive Board and the Chairs of Divisions for their skill, wisdom, commitment and inspiration. Our excellent team in the IFCC Office in Milan (Paola Bramati, Silvia Cardinale and Silvia Colli Lanzi) has again demonstrated their dedication and professionalism in supporting our Members. Above all, however, IFCC owes a great debt to many scientists and medical doctors who work on a voluntary basis giving freely their time and expertise in the interest of improving the quality, delivery and relevance of clinical chemistry and laboratory medicine worldwide. It is gratifying that we are seeing an increase in the number of experts who want to work for IFCC. These people are the true strength of IFCC as we move forward.

The main revenue sources were in decreasing order in CHF: Corporate members’ contributions (CHF 290.081); SD Sponsorships (CHF 244.352); Full & Affiliate Members’ contributions (CHF 184.879); bank profits/interests (CHF 67.643); Royalties (CHF 68.616 ); EMD funds (CHF 46.314); Conferences support (CHF 47.347); awards (CHF 31.971); scholarships (CHF 25.227).

Dues (CHF) Full members: 181.314; Corporate members: 290.081; Affiliate members: 3.565; Total: 474.960 Figure 3. IFCC membership dues collected in 2016.

2016 OUTSTANDING DUES: FULL MEMBERS: CHF 15.785; CORPORATE MEMBERS: CHF 34 800 IFCC MEETINGS INCOME PARTITION IFCC meetings’ revenues are not part of regular yearly income. The average yearly income of IFCC arising from the meetings can be calculated dividing the revenue by the frequency of the event. The yearly income of IFCC from EuroMedLab 2015 Paris and WorldLab 2014 Istanbul) subdivided per year is shown in Fig.4.

The income of IFCC from the membership dues and annual meetings income (excluding sponsorships and other revenues) in 2016: CHF 474.960 (dues) + CHF 451.820 (annual meeting income) = CHF 926.780 SPONSORSHIP Divisions and some Functional Units raise some sponsorships funds that give them certain flexibility in conducting projects. These sponsorships are used for the specific projects in due time. The total amount of sponsorships available for specific projects in 2017 is CHF 504.500. The total amount of sponsorship funds including awards, scholarships, VLP and TF-PLM surplus available in 2017 are CHF 638.915 (Fig 5).

TOTAL OPERATIONAL COSTS AND FINANCIAL CHARGES The actual total operational costs and financial charges in 2016 were CHF 1.442.889. (Fig 1 and Fig. 6). This figure includes the sponsorship expenses of CHF 268.362. The total amount of expenses except sponsorship in 2016 was CHF 1.174.527. CHF 10.000 was given to each of the four regional federations upon receipt of their annual activity reports. The total amount of the contribution of IFCC to International/Regional Organisations in 2016 was CHF 67.575. The amount paid for BIPM-JCTLM Participation was CHF 67.147. Efforts of the Chairs of Divisions, Committees/Working Groups and Task Forces to remain within their allocated budgets, even below in 2016 have been appreciated.

IFCC INVESTMENT AT LGT IN 2016 The adopted strategy of IFCC for its portfolio management, the actual value of the portfolio; the historical performances (Figure 7) and risk tolerances of different portfolios were discussed at the IFCC EB. IFCC had chosen the ”Growth” portfolio containing alternative investments among the five LGT Bank portfolios till the end of 2015. The financial outcome for 2015 was disappointing, mainly because of the loss of value of investments and the exchange rate between EUR and CHF. EUR has lost approximately 15% against CHF in January 2015. The EB at his meeting in Quito in September 2015, decided to move the portfolio from “growth” to “balanced”.

The performance net cumulative of the IFCC investments till November 2016 is shown in Fig. 8 as -0.29%.

The IFCC Executive Board (EB) at its last meeting on November 24, 2016 evaluated carefully the current and historical performances of its portfolio mandate at the LGT Bank and the investment charges for different investment models (basic fee with brokerage fees and all-in-fee models). IFCC EB understood that the performance of investments at the LGT Bank has not been good over the past couple of years due to the reflection of global stock markets. IFCC EB considered the investment charges too high especially in the periods when the returns on investment are low. The high investment

Special Supplement to Lab Medica International • 23

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2016 Annual Report

Figure 1. 2016 proposed budget versus to actual at 31st December 2016.

Figure 3. IFCC membership dues collected in 2016.

IFCC

Figure 4. IFCC annual meetings income from EML Paris and WL Istanbul.

Figure 5. The Sponsorship amount carried from 2016 to 2017.

Figure 7. Historic Performance of IFCC Portfolio (2010-2015)

Figure 2. INCOME at 31st December 2016: CHF 1.006.430.

Figure 8. Performance of investments indicated as monthly return in 2016.

Figure 6: 2016 functional units' expenses, compared to their allocated budget (CHF)

charge fees tempted IFCC EB to look at alternative ways to manage investments with the result that a more competitive fee structure has been identified. It is this reduced fee structure received by the treasurer from another reputable investment bank (Credit Swiss) that has prompted the IFCC EB to move its investment portfolio from the LGT Bank to Credit Swiss. Following the decision of the Executive Board, the portfolio mandate with LGT was cancelled on December 14, 2016, a safekeeping mandate was given to Credit Suisse, in the meantime the transfer of the securities from LGT to Credit Swiss was completed on January 12, 2017 (35 assets).

The important issues of the agreement with Credit Swiss 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, only 0.20% p.a. for the safekeeping fee when invested in CS Portfolios). Plus brokerage fees.

EXPECTED CONSEQUENCES: • The risk profile of the portfolio at Credit Swiss (Moderate) is lower that the risk profile at the LGT Bank (Balanced in 2016 and Growth in 2015).

• Less risk means that there will be fewer transactions and less brokerage fees.

• The number of transactions will be less leading to the less time and work spent by the IFCC Auditor to follow and control the transactions of the previous year.

• The total amount of the investment fees to be paid to the Credit Swiss is expected to be less than paid to the LGT. FUTURE FORECASTS: • Financial difficulties are anticipated in 2017 due to shortage of income since the sole income of IFCC will be confined to the dues to be collected.

• The meeting incomes from Athens and Durban will be available 6 months after these meetings (earliest end of 2017, most probably in 2018).

• In 2017, IFCC activities and meetings can be kept as planned spending all the cash available at Credit Swiss.

• There might be a need to transfer the missing amount from the capital invested at Credit Swiss.

Tomris Ozben, Treasurer

CORPORATE MEMBERS Rolf Hinzmann, MD, PhD (Roche), Corporate Representative at IFCC Executive Board (1st term 2015-2017) Let me start with a big thank you to the Corporate Members for their significant contributions to IFCC activities. By the end of 2016 the total number of IFCC's Corporate Members was 47, providing the IFCC with annual fees of CHF 290.000 which was around 24% of IFCC's total annual income. In addition, Corporate Members continued sponsoring of IFCC conferences, workgroups, scientific awards, e-learning programs and travel scholarships. In 2016 we were glad to welcome KHB Shanghai Kehua Bioengineering as a new Corporate Member while regrettably three companies left IFCC: Wiener Lab, Biocrates Life Sciences, and Millipore.

In January 2016 I encouraged IFCC to conduct an analysis of its strengths, weaknesses, of opportunities and threats (SWOT). The results of the SWOT analysis were presented at the General Conference in Madrid in April 2016 where we had - for the first time at a General Conference - a session fully organized by the IVD industry. During this session I invited all delegates to submit proposals how IFCC could become more attractive for corporate members. We received around a hundred proposals which were later classified, consolidated, discussed by the IFCC Executive Board, and incorporated into IFCC's Strategic Action Plan: • Extend the role of Corporate Members within IFCC and improve communication.

• Increase public awareness for the medical value provided by diagnostic lab tests.

• Together with clinical societies, support medical claims leading to reimbursement.

• Emphasize the importance of quality and provide expertise in standardization.

• Align more with others (CLSI, FDA, clinical societies, etc.) to avoid inconsistency and duplication of guidelines and recommendations.

• Continue to provide opportunities for exhibitions, industry symposia and networking with lab professionals during high-level academic conferences, thereby following the rules defined by the IVD industry in the MedTech Europe Code of Ethical Business Practice.

• Pursue the opportunities of data analytics in laboratory diagnostics.

The EuroMedLab in Barcelona will be he first conference where the transition period of the MedTech Europe Code has ended and IVD industry can no longer sponsor delegates or speakers to attend conferences. For more information please check out the MedTech Europe website.

Rolf Hinzmann, Corporate Members Representative

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IFCC

2016 Annual Report COMMITTEE ON CONGRESSES AND CONFERENCES (C-CC)

The 33rd meeting of the IFCC Executive Committee on Congresses and Conferences (C-CC) was held on occasion of the AACC Annual Meeting in Philadelphia, PA, USA. International Congresses of Clinical Chemistry & Laboratory Medicine (ICCCLM) WorldLab Congresses: 23rd IFCC WorldLab 2017 Durban, South Africa (22-25 October 2017 - http://www.durban2017.org), Congress Chair: Prof RT Erasmus; Scientific Chair: Prof TS Pillay; 24th IFCC WorldLab 2020 Seoul, South Korea (24-28 May 2020 - http://www.ifcc2020.org), Congress President: Prof. WonKi Min; Chair of the Organizing Committee: Prof. Junghan Song T IFCC Regional Congresses of Clinical Biochemistry and Laboratory Medicine APFCB 2016 Congress - Taipei, Taiwan (November 26-29, 2016 - http://www.apfcbcongress2016.org). The 14th APFCB Congress was held at Taipei International Convention Center (TICC), Taipei, Taiwan. Chairman is Woei-horng Fang; Executive Secretary - Jui-Ching Wu; Scientific Chair - Shu-Chu Shiesh.

APFCB 2019 Congress – Jaipur, India (November 17-20, 2019 - http://www.apfcbcongress2019.org), Congress Chair: Prof.

Praveen Sharma EuroMedLab Congress 2017 – Athens, Greece (11-15 June, 2017 - http://www.athens2017.org/). 22nd IFCC-EFLM EuroMedLab Congress of Clinical Chemistry and Laboratory Medicine - 25th Balkan Clinical Laboratory Federation Meeting and 15th National Congress of GSCC-CB, Congress Chair: Prof. Alexander Haliassos President of the Congress is Dr. Alexander Haliassos.

T23rd EuroMedLab Congress 2019 – Barcelona, Spain (19-23 May, 2019), Congress Chair: Dra. Imma Caballé COLABIOCLI 2017 Congress – XXIII Congreso Latinoamericano de Bioquímica Clinica – Punta del Este, Uruguay (17-20 September, 2017). Organization on going, Congress Chairs: Dra. Queiruga and Dra. Stella Raymondo AFCC Congress, Congress Chair: Prof. Vanessa Steenkamp. The 5th Congress of the AFCC will be a joint Congress with WorldLab 2017 in Durban, South Africa.

IFCC Specialized Conferences 15th Roche Bergmeyer Conference – Eibsee, Germany (7-9 March 2016). Theme of the 15th Bergmeyer Conference was: “Biomarkers in the Diagnosis and Monitoring of Cancer”. The Proceedings of the Conference were published in Scand J Clin Lab Invest. (http://www/tandfonline.com/toc/iclb20/76/sup245).

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accredited for compliance against ISO 15195 and IEC/ISO 17025 as Calibration laboratories, and by two National Metrology Institutes (NMIs).

Dr. Graham Jones and Mr. Craig Jackson published the following review on JCTLM. Jones GRD and Jackson C. The Joint Committee for Traceability in Laboratory Medicine (JCTLM) – its history and operation. Clinica Chimica Acta 2016;453:86-94.

• Joint Committee for Guide in Metrology (JCGM) Working Group 1 (GUM): WG1 held a meeting at the Bureau of International Weights and Measures (BIPM), Sèvres, May 30 – June 3, 2016. Since the previous meeting, the BIPM Director wrote to the NMIs and MOs that responded to the request for feedback on the draft revision of the GUM (JCGM 100) advising that each of the thousand plus comments they had submitted will receive a response from the working group. Until this task is complete, further development of options for overhauling the style and technical content of the revised GUM will be deferred.

Working Group 2 (VIM): WG2 has focused on developing a Draft Outline of the fourth edition of the VIM (VIM4) with completion of the Draft Outline expected by the end of 2016. The scope of the VIM4 is being expanded from the VIM3 to encompass nominal properties in a significantly more comprehensive manner. At the moment, 58 new entries for inclusion into the VIM4, which are related to nominal properties, are being evaluated by WG2. A key principle for the VIM4 is to try to incorporate simplified language, similar to that used in the ‘VIM Definitions with Informative Annotations’. WG2 is considering changing the name of the VIM4, to the ‘International Vocabulary of Metrology 4th Edition (VIM)’, from the VIM3 ‘International vocabulary of metrology – Basic and general concepts and associated terms (VIM) 3rd edition’. The motivation was to remove ‘concepts’ from the title, which was a cause of some confusion. A draft document will be available by the end of 2018 to circulate to the member organizations for comment.

• Institute for Reference Materials and Measurements (IRMM) Close collaboration with IRMM continues through a number of joint ventures involving SD Committees and Working Groups.

The organization “IRMM” is now referred to as the Joint Research Center (JRC). Within the JRC there are five Directorates.

Directorate F is focused on Reference Materials.

• 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

• 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.

• National Institute of Biological Standards and Control (NIBSC)

IFCC Specialized Conference “Biomarkers in Alzheimer Disease”, Mexico City, Mexico (May 20th, 2016), supported

by ROCHE. The conference was held at the “Camino Real Hotel Polanco”, with the support of ROCHE. Chairs of the Organizing Committee were Prof. Sergio Bernardini and Dr. Rosa Sierra-Amor.

NIBSC, previously part of the Health Protection Agency (HPA), is now a new Centre of the Medicines and Healthcare Products Regulatory Agency (MHRA) alongside the Clinical Practice Research Datalink (CPRD). The MHRA is an executive agency of the Department of Health, UK. C. Burns serves as an Observer to the SD.

IFCC General Conference The event was held in Madrid, Spain at the Auditorium Marriott Hotel, from March 19th – 21st, 2016. Closed meetings of IFCC functional units were planned before the conference on March 17th-18.

The primary goal of the Conference was to bring together IFCC Functional Units, as well as friends and partners from all around the world in an open dialogue under one roof to discuss the issues Lab Medicine is facing, and to develop possible strategies to become more effective in the on-going development of our profession.mThere were 273 participants and 59 accompanying persons from 71 national societies plus 14 representatives from industry. In addition of the board session, the event featured 18 plenary conferences, 12 training seminars, 3 round tables, numerous breakout discussions and networking opportunities covering various aspects of the IFCC strategic plan, and the progress and outcomes achieved by the IFCC functional units led by the divisions and the executive board. A survey was conducted to better understand the scientific and educational needs and aspirations of the full members and partners and to provide feedback on accumulated experience.

There were 138 responses and the overall satisfaction rate was over 95%.

The EFLM Science Committee and SD leadership agreed there should be close liaison and communication between the two groups. The purpose is to share information on activities and look for areas of mutual interest. It was agreed the leadership of the SD and the EFLM Science Committee should meet formally once per year, preferably at a major conference. 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 are that these activities do not overlap with the IFCC SD. The EFLM SC has more of a focus to promote and improve science through education within the field of clinical chemistry and laboratory medicine. Results of the Committee’s work are actively disseminated at conferences and workshops, published in scientific journals (e.g. CCLM) and available on the EFLM web site.

• European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Congresses with IFCC Auspices: 70 events A significant achievement of the C-CC in 2016 has been the development of several new guideline documents and the revision of several existing guidelines. These are the guideline documents posted in the C-CC section of the IFCC website.

Guideline for Compliance with Applicable Codes of Ethical Business Practice One of the most significant activities of the C-CC in 2016 has been the development of a document entitled IFCC Guidelines for Compliance with Applicable Codes of Ethical Business Practice. The requirement for these Guidelines is based on the introduction of the MedTech Europe Code of Ethical Business Practice. This code is applicable to the in vitro diagnostics industry and third party educational event organizers such as the IFCC and national societies. Although not specifically listed, the Guidelines also indicate the IFCC requirement for compliance with similar site-specific applicable codes of ethical business practice. Posting of this document to the C-CC section of the IFCC website is pending approval of the IFCC Executive.

Following documents have been revised to reflect the requirement for compliance with applicable code of ethical business practice; documents have been posted in the C-CC section of the IFCC website.

1. Guidelines and Application Form for IFCC Auspices 2. Congress Guidelines and Application Forms for WorldLab (ICCCLM) and EuroMedLab 3. Guidelines for Development of the Scientific Program for WorldLab (ICCCLM) and EuroMedLab 4. Guidelines for a Satellite Meeting of an IFCC Sponsored Congress or Conference Both document 3 and 4 are officially new documents, developed in collaboration with MZ Congressi, based on a document that were initially developed by the COC for EuroMedLab Milano 2013 and subsequently used for EuroMedLab 2015 and 2017.

James Wesenberg, C-CC Chair

SCIENTIFIC DIVISION (SD) During 2016, the following members served on the SD Executive Committee: Ian Young (UK) (Chair), Philippe Gillery (FR) (Vice-Chair), Joseph Passarelli (US) (Secretary), Giampaolo Merlini (IT), Christa Cobbaert (NL), Tsutomu Nobori (JP) (Members) and James Pierson-Perry (US) (Corporate Representative). Four representatives of International Organizations are invited to attend the SD meetings as consultants: Gary Myers (JCTLM), Heinz Schimmel (IRMM) David Bunk (NIST) and Chris Burns (NIBSC). Two meetings were held during 2016: March 18 (full day), 20 & 21 (partial) (Madrid, ES, in conjunction with the General Conference) and November 25-26 (Taipei, TW).

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.

JCTLM Governance: The revised text of the Declaration of Cooperation (DoC) between the BIPM, IFCC and ILAC was signed in April 2016 by the three Sponsoring Organizations, and is published on the JCTLM website.

The JCTLM Executive approved the re-appointment of Dr. Myers as Chairperson for a second two-year term, and the BIPM’s continued role as Secretariat for the JCTLM..

JCTLM Membership: The JCTLM Executive Committee is investigating establishing liaison with other international organizations in different laboratory medicine disciplines as potential future members of the JCTLM Executive Committee. As a first step JCTLM has reached out to the International Council for Standardization in Haematology (ICSH).

JCTLM WG on Traceability Education and Promotion: the WG has eight (8) different work stream projects underway. In addition, WG-TEP website has been launched at www.jctlm.org. This website is aimed at non-specialists in traceability and is intended to deliver news and educational resources. In that context it is complementary to the existing BIPM/JCTLM website and the JCTLM database.

JCTLM Database: The current status of the database as of December 2016 is as follows • 293 certified reference materials (CRMs) amongst which 33 are in List II (i.e. Reference Materials value assigned using an internationally agreed protocol), and 3 are in List III (i.e. Reference Materials for nominal properties), • 180 reference measurement methods covering 80 analytes, and • 146 reference measurement services covering 39 analytes. These services were delivered by 15 reference laboratories

World Health Organization (WHO) WHO meetings occur each Fall. Philippe Gillery participated in the World Health Organization Expert Committee on Biological Standardization (ECBS) meeting as IFCC-SD representative in Geneva (CH) from October 16th to 18th, 2016. There were relatively few topics relevant to the SD. The SD decided that there were no new projects or collaborations to consider.

Congresses (WorldLab, Regional and other congresses) IFCC General Conference, Madrid, Spain, March 18 -21, 2016: 1. SD Executive Summary – I. Young; 2. Standardization of laboratory tests - why it is needed – G. Beastall; 3. Standardization of laboratory tests - how to do it – G. Miller; 4. Standardization - the example of thyroid function tests – L. Thienpont; 5. Discussion 14th Asia-Pacific Federation for Clinical Biochemistry and Laboratory Medicine Congress, Taipei, Taiwan, November 2629, 2016: Standardization as a Global Activity: 1. International co-ordination of standardization activities – I. Young, Belfast, UK (also acted as chair); 2. Standardization of Thyroid Function Tests - changes are coming – L. Thienpont, Ghent, BE was originally invited but presentation made by G. Beastall, UK; 3. Measurement and clinical utility of CSF proteins – K. Blennow, Gothenburg, SE.

• Congresses with IFCC Auspices ROCHE BERGMEYER CONFERENCE. The Roche Bergmeyer Conference was held on March 7-9, 2016. The conference topic was Biomarkers in the Diagnosis and Monitoring of Cancer.

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) by Robert Flatman, Chair During 2016 ongoing progress towards C-NPU terms of reference included: Term of Reference 1. To continuously provide advice for the management, updating and publishing of the NPU terminology.

Accomplishments include: 1. Applications for formal National Release Centre status from both Norway and Sweden received, accepted and formalized. These formal agreements are an important accomplishment from the conception and implementation of the NPU Steering Committee, and help clarify the governance relationships between IFCC, IUPAC and major international NPU users; 2. Following on from 2015 planning work, the NPU Steering Committee website was finalized (http://www.npu-terminology.org). The website is searchable for NPU terms, explains the functions of the Steering Committee, and has lists news and publications relevant to the NPU terminology.

Term of Reference 2. To make recommendations on NPU for reporting clinical laboratory data that conform to or adapt current standards of authoritative organizations and that will improve their utilization for health care. Accomplishments include: 1. Project on Molecular Biology terms for the NPU terminology continues; 2. On-going project for better definition of poorly identified NPU terms - Project for establishing definitions for non-referenced terms in the NPU terminology ongoing.

Term of Reference 3. To provide a connection with other organizations concerned with NPU, such as the Bureau International des Poids et Mesures (BIPM), the European Committee for Standardization (CEN) and the International Organization for Standardization (ISO), and, by extension, clinical laboratory sciences societies, such as the International Union of Pure and Applied Chemistry (IUPAC), and the in vitro diagnostics industry, to ensure that problems encountered by health care professionals in the area of NPU are considered by those organizations. Accomplishments include: 1. IUPAC representation continues with Helle Johannessen, Urban Forsum continuing as elected representatives; 2. Danial Karlsson and Colin Humphries (IUPAC) attended IHTSDO meeting late 2016. IHTSDO does not see NPU as a priority currently. Alternative proposal that the NPU terminology could exist within SNOMED-CT discussed briefly, but there would need to be substantial further investigation on benefits or risks for any work on this to proceed.

Term of Reference 4. To act as a consultant group on NPU in clinical chemistry and, by extension, in the rest of clinical laboratory sciences to international scientific panels, regional and national clinical laboratory sciences organizations, editors of scientific journals, manufacturers of clinical laboratory instrumentation and products, and to individual clinical laboratory professionals and other health care professionals. Accomplishments include: 1. Individual NPU members continue to be active with their societies, particularly in the informatics and terminology arenas; 2. Completion of the IUPAC project “Vocabu-

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lary on nominal property, nominal examination, and related concepts for clinical laboratory sciences (see publications below for final recommendations paper details); 3. Chair (RF) part of the Australian informatics harmonization project sponsored by Australian Government - RCPA Pathology Information, Terminology and Units Standardization Project (PITUS) on both Steering Committee and Working Group 2; 4. Revision of the IUPAC book “The Silver Book” completed.

• C-Molecular Diagnostics (C-MD) by Deborah Payne, Chair During 2016 ongoing progress towards C-MD’s terms of reference included: Term of Reference 1. Foster dynamic exchanges between IFCC and molecular diagnostic laboratories and industry. Accomplishments Include: 1. Helen Parkes provided presentation on standardization of reference materials; 2. Updated website on EQA programs with input from various EQA suppliers.

Term of Reference 2. Produce guidelines on clinical validation of tests, conduct and report on molecular diagnostic tests. Accomplishments Include: One manuscript published (see Publications) Term of Reference 3. Provide reference materials; and create a network of locus-specific IFCC Molecular Diagnostics Centers.

Accomplishments Include: 1. Expanded Network to a total of 17 laboratories including the pre-existing expert laboratories.

Seven laboratories are outside Europe, Canada, and the USA; 2. Identified candidate Expert Laboratories and reviewing applications of 10 laboratories. Addition Information: The C-MD aims to gain experience with utilizing survey tools to engage the molecular diagnostic community. The C-MD expects that surveys will be a powerful tool to generate discussions on standardization and quality assurance in molecular diagnostics. Expanding the number of expert laboratories is a top priority. A goal of the C-MD committee is to capture topics of interest for network and expert laboratories. The C-MD envisions that the use of the survey tool such as survey monkey will help identify quality needs and other needs of the molecular diagnostic community.

• C-Reference Systems for Enzymes (C-RSE), by Ferruccio Ceriotti, Chair During 2016 ongoing progress towards C-RSE terms of reference included: Term of Reference 1. IFCC Enzyme Reference Measurement Procedures: New 37°C IFCC enzyme reference procedures are being developed on the basis of the existing 30oC IFCC. Accomplishments include: Development of a reference measurement procedure for Pancreatic Lipase: a series of experiments were performed to ameliorate the method transferability, unfortunately with limited success. Some important weak points were identified and the Japanese group did further work to try overcoming them. A new formulation of the reagent has been proposed and tested with promising results in Germany, experiments in Italy are in place.

Terms of Reference 2. Network of Enzyme Reference Laboratories: Coordination of a group of reference laboratories from hospitals, academy and industry, which are able to perform adequate measurements according to a list of stated requirements. Accomplishments Include: Not accomplished.

Terms of Reference 3. Enzyme Reference Materials: Evaluate reference materials provided by IRMM within the network of reference laboratories prior to certification. The materials are available as primary reference materials for calibration and/or validation of lower order procedures for the measurement of the catalytic concentration of enzymes. Accomplishments include: A recertification campaign for a primary reference material for LD, CK and ALT by the network in cooperation with IRMM was completed last year. The results were elaborated by JRC-ERM and the new materials are now available. A commutability evaluation of candidate Reference materials for amylase has been organized and will be concluded within the end of 2016. C-RSE concludes its course at the end of 2016. It will continue as WG “Development of reference methods for pancreatic enzymes”.

• C-Traceability in Laboratory Medicine (C-TLM) by Lothar Siekmann, Chair During 2016 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 C-TLM supports the JCTLM which has been established approximately 13 years ago by the IFCC, the BIPM, and the ILAC. All details are available on the JCTLM website: www.bipm.org/jctlm/. Based on the proposals of the review teams and the working group chairs, the JCTLM Executive decided in its meeting on December 6 - 5, 2016 on the listing of reference materials, methods and services. JCTLM Working Group 2 conducted its first meeting in December 2015. The working group deals with the project of "Education and Promotion".

Term of Reference 2. Establish an External Quality Assessment Scheme (EQAS) for reference laboratories and act as an advisory committee. Accomplishments include: IFCC External Quality Assessment for Reference Laboratories (Anja Kessler): RELA ring trials are currently provided for 38 measurands. The results of RELA 2014 were published on the website (www.dgkl-rfb.de:81). 59 laboratories participated in RELA2014 and the organizer received 351 results from these laboratories. Every year in each group of measurands a "key measurand" is announced in order to encourage laboratories to select this measurand in case that they are not able to provide results for all measurands in that group. The key measurands for RELA 2015 are total cholesterol, magnesium, ALT, HbA1c, total protein, testosterone, digoxin, total triiodothyronine, and 25-OH-Vitamin D3. The results of the RELA 2015 were already published on the website (www.dgkl-rfb.de:81) in July 2016 and will be reported to the C-TLM at its next meeting in Athens in June 2017.

Term of Reference 3. Promote the establishment and maintenance of IFCC reference laboratory networks for clinically relevant measurands. Accomplishments include: HbA1c Network (Cas Weykamp): like in previous years the Network organized 2 intercomparison studies with participation of all approved and candidate network laboratories as well as all laboratories of the designated comparison method networks in the US, Japan and Sweden. All IFCC network laboratories met the quality criteria and kept their status of approval. The BCCL (Beijing Center Clinical Laboratory) gained the status of approved network laboratory.

Term of Reference 4. Traceability of total protein measurement results (Gerhard Schumann). Accomplishments include: A reference measurement procedure for TP is not yet listed in the BIPM/JCTLM data base. The reference material SRM927e from NIST for calibration fulfils the required high level of analytical and metrological quality, provided the certified value based on amino acid analysis is used. A reference system for TP should consider the existing performance criteria for TP measurements in medical service laboratories. Biuret methods for TP are used in medical service laboratories on various analytical platforms. The activities of the Committee focus on: Consensus on the Doumas et al. publications from 1981 as a template for a RMP for TP; Re-investigation of the biuret procedure with reference to the publications of Doumas et al.; Consensus on the use of SRM-927e as the primary reference material for calibration; Comparisons of SRM-927 versus a highly purified HSA preparation to investigate the effect of the biuret procedure on albumins with different chemical structures (amino acid sequences) of BSA and HAS; Investigations of the relevant measurement uncertainty components, provision of a statement for combined expanded MU and declaration of the calibration and measurement capability (CMC); A concept to bring the IFCC reference system into practice despite a possible shift of the values and of reference intervals when using the certified BSA concentration (related to amino acid analysis) for calibration.

• C-Reference Intervals and Decision Limits (C-RIDL)

by Kiyoshi Ichiara, Chair (new Chair as 2016: Yesim Ozarda) During 2016 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: The results of the global reference interval (RI) study were finished and reported in papers in 2016 by Clin Chim Acta (CCA) (see Publications). The studies in Turkey for RI of haematological parameters and in USA including Mayo and ARUP data were finished and presented in Madrid at the General Conference (March 2016).

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: Country-specific RIs for 12 countries (China, Japan, Turkey, Russia, UK, USA, Saudi Arabia, Argentina, India, Philippines, South Africa, and Pakistan) were derived and related analyses on RVs were carried out. The traceability of test results was confirmed by common measurement of the serum panel. When found to be biased, the test results were recalibrated according to the traceable values assigned to the panel. Comparison of the RVs across 12 countries after alignment based on the panel test results was fully described in Part One of the key note paper (see Publications).

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 list of analytes in the global RI study published by CCA is the most commonly used tests in the clinical laboratory. A relevant issue for this Term of Reference is also the exploration of biological sources of variation (SV) of measurands. By merging RVs from 12 countries, SVs were harmoniously analysed using multiple regression analysis and ANOVAs. The most intriguing finding in 2014 was the differential effect by ethnicity of body mass index (BMI) on test results. The finding was reinforced by inclusion of 12 countries in this year’s analysis.

Gender and age-related changes in RVs were nearly consistent across the countries. The analyses of SVs across the countries were fully described in Part Two of the key note paper.

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 primary ac-

IFCC

tion was taken on this TR. 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 Data Management System was built, which enables alignment of all the results from the global study through flexible conversion of test results from one laboratory to another based on common test results for the serum panel. The new lot of serum panel (80 sets altogether) each consisting of 100 specimens of multiracial origins, which were value assigned with the help of C-TLM, were measured by four countries for the purpose of ensuring traceability. It was also measured by the Hamilton General Hospital in Canada (HGH) for the purpose of comparing RVs between the adult and pediatric populations.

Term of Reference 6. Collaborate with other organizations and/or to undertake establishment of reference intervals or decision limits for measurands (analytes) identified as a priority. Accomplishments include: No action was taken on this so far.

Term of Reference 7. Work in close collaboration with other Cs and WGs of SD and other IFCC Divisions for the development and appropriate clinical utilization of reference intervals and decision limits. Accomplishments include: The specimens in the new lot of the serum panel were value assigned for 12 biochemical analytes (creatinine, urea, uric acid, triglyceride, total cholesterol, AST, ALT, LDH, ALP, GGT, CK, and AMY) with the support of the Committee on Traceability in Laboratory Medicine.

The panel was actively used in the ongoing global multicentre study.

Additional Information: A website will be made available to provide the reference intervals obtained from the global study for practice of Evidence Based Laboratory Medicine. It will allow interactive viewing of RIs for EBLM by specifying sources of variation (gender, age, country, BMI, ABO blood groups, level of alcohol drinking, smoking, and exercise) or by specifying any two laboratory tests for analysis of correlation.

• C-Standardization of Thyroid Function Tests (C-STFT) by Linda Thienpont, Chair During 2016 ongoing progress towards C-STFT terms of reference included: Term of Reference 1. To develop reference measurement systems for free thyroid hormones and TSH. Accomplishments include: 1. Both free T4 and TSH reference measurement systems were implemented in 2015-16 by performing the Phase IV studies, i.e., the final method comparisons with panels of clinically relevant samples (called the free T4 standardization and TSH harmonization panel) intended to technically recalibrate the FT4 and TSH assays and supply the proof-of-concept; 2.

The first follow-up panel for TSH was also assigned by all-procedure trimmed mean (APTM) targets in parallel with the harmonization panel. It is stored at NIBSC; 3. Two manuscripts currently have been prepared describing the results of the final method comparisons, the outcome of the recalibration exercises and proof-of-concept studies (= reference interval studies), one for TSH, one for free T4. The TSH-manuscript was submitted to Clin Chem. The free T4 manuscript has been circulated for review and will be submitted to Clin Chem early in 2017.

Term of Reference 2. To establish a network of laboratories competent to offer reference measurement services for thyroid hormones. Accomplishments include: 1. To establish a network, UGent has assembled a panel of 20 frozen sera from presumably healthy subjects, and assigned it with free T4 concentrations by the IFCC RMP. The samples are stored at -70°C. These samples have and/or will be made available to the potential new partners within the network for validation of their performance; 2. The above mentioned samples were recently used in a first method comparison with the laboratory of the Radboud University Medical Center of Nijmegen. The outcome looks promising; however, the day to day variation at the lab of the candidate network member is too high. The laboratory agreed to further optimize the implementation of the IFCC RMP; 3. Also at the CDC the implementation of the FT4 IFCC RMP has been initiated. The first method comparison data will be available soon.

Term of Reference 3 and 4. Term of ref 3: To provide an infrastructure for procurement of serum panels and Term of ref 4: Demonstrate that the traceable assays can use a common reference interval; use this as a basis for further elaboration of the reference intervals by the IVD manufacturers; consult with clinicians about the need for ethnic, age- or sub-population-specific reference intervals in co-operation with C-RIDL. Accomplishments include: Term of ref. 3: In order to source samples for the final method comparisons (Phase IV) and the samples for the reference interval studies, the committee established a relationship with 2 commercial vendors but also with several clinicians. The committee aims at sustaining the excellent relationship with the clinicians; Term of ref. 4: The pilot reference interval study is completed and the results are incorporated in the above mentioned manuscripts. The key takeaway in the manuscript is that these studies provided the proof-of-concept that common reference intervals are feasible for assays with calibration traceability to the free T4 and TSH reference measurement systems. Particularly, the TSH proof-of-concept was convincing, while the free T4 might need some improvement.

Term of Reference 5 and 6. Term of ref. 5: Liaise with key stakeholders to implement the use of the traceable assays in routine clinical practice. Term of ref. 6: Through collaboration with IFCC EMD, provide educational materials for manufacturers, clinicians and patients which will support the implementation of traceable assays. Accomplishments include: Term of ref. 5: two members of C-STFT, supported by the IFCC past-president, published in several journals a call for benefit-risk analysis by involved stakeholders (general practitioners, endocrinologists, patients). Unfortunately, few answers came in, but the balance clearly was in favour of benefit. Clinicians seemed not afraid of risks when reference intervals change, because they rely on the guidance from the clinical community. Patient organizations are more concerned. The C-STFT started a discussion forum with members of the Society Members of IFCC to learn how the laboratory community prepares the implementation of newly calibrated assays and changed reference intervals. Two new tools were developed to monitor the stability of the poststandardization/harmonization calibration basis of the assays. They are intended to prevent risks due to non-sustainability of the new calibration basis. The tools and their utility to the purpose meanwhile are published. The chair is trying to recruit more laboratories to have reliable peer groups of all systems involved in the C-STFT activities. The hope is to receive the support from manufacturers. In addition, C-STFT and IVD industry are in close contact with the FDA to comply with the regulatory requirements upon implementation of the recalibrated immunoassays. No date for final implementation has been fixed.

Working Groups • WG - Standardization of Hemoglobin A2 (WG-HbA2) by Renata Paleari, Chair During 2016 ongoing progress towards WG-HbA2 terms of reference included: Term of Reference 1. To promote the standardization of hemoglobin A2 measurement through the definition of an international reference system, including a reference measurement procedure and primary and secondary reference materials. Accomplishments include: The ID-MS candidate reference measurement procedure based on peptide mapping and calibration with recombinant hemoglobins (HbA0 and HbA2) has been finalized and implemented in two different reference laboratories of the WG. During 2016, the measurement conditions have been completely optimized and the experimental work for the validation of the candidate reference measurement procedure has been completed.

Term of Reference 2. Development of a secondary certified reference material for hemoglobin A2 (in cooperation with the IRMM). Accomplishments include: The stability study on the first pilot batch of candidate reference material (lyophilized hemolysate) has been continued. The material is quite stable with respect to HbA2 content for more than seven years when stored at -20°C. Moreover, no degradation products were detectable. MetHb content was also very low, essentially identical to the one measured on blood before the processing. In the framework of the IFCC-ICSH joint group, a multicenter study has been defined with the aim to evaluate the alignment of current high performing HbA2 methods and to test the commutability of various control materials including the WHO-NIBSC International Reference Material for HbA2. Three laboratories are involved in the study and 8 analytical methods (7 HPLC and 1 CE) will be tested. All the necessary materials have been prepared and shipped to the laboratories. The experimental work is in progress.

• WG - Standardization of Carbohydrate-Deficient Transferrin (WG-CDT)

by Jos Wielders, Chair During 2016 ongoing progress towards WG-CDT terms of reference included: Term of Reference 1. Maintaining a network of CDT reference laboratories that perform the HPLC candidate reference method. Accomplishments include: While waiting for the IFCC-SD review of the manuscript for (c)RMP for CDT, no further action was taken in 2016. Last round with blinded samples was in 2015.

Term of Reference 2. Development of a reference material for CDT (suitable for harmonization of present methods) Accomplishments include: The reference material was developed in 2014. No further actions in 2016.

Term of Reference 3. To appoint the HPLC reference method, the reference interval and measurement uncertainty in a formal publication. To develop a formal IFCC RMP. Accomplishments include: The final manuscript describing validation of the cRMP according to ISO15193 and its use was sent to the IFCC-SD chair. After approval by the IFCC-SD, board and national societies it was accepted and declared to be a RMP. The Epub in ClinChimActa appeared in the last days of December.

Term of Reference 4. Guidance of diagnostic firms in standardization towards the (c)RMP. Accomplishments include: Little progress could be made while waiting for the IFCC response towards the cRMP validation manuscript.

• 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) by Lorin Bachmann, Chair During 2016 ongoing progress towards WG-SAU terms of reference included: Terms of Reference 1. Physiologic variability of UA in stable mild kidney disease (funded by NKDEP). Accomplishments

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include: No activity due to funding limitation and lack of identification of investigators willing to perform the studies.

Terms of Reference 2. Status of harmonization among commercial immunoassays for UA (funded by NKDEP). Accomplishments include: The objectives of this project are to: 1.) Assess current status of harmonization of routine measurement procedures versus ID-LCMS candidate reference measurement procedure using native patient samples; 2.) Evaluate analytical performance characteristics of urine albumin measurement procedures; 3.) Evaluate commutability characteristics of the Japan Society for Clinical Chemistry (JSCC) and diluted IRMM ERM-DA470k/IFCC reference materials; and 4.) Assess utility of candidate reference materials for use in standardization of routine measurement procedures. Findings included: a) Bias was greater than ± 10 percent for 14 of 16 quantitative methods vs. ID-LCMS indicating that standardization is needed; b) Several methods had non-constant bias with concentration suggesting that calibration technique needs investigation; c) Dilution caused changes in bias for some methods. d) CV total was greater than 10 percent for five methods showing that improvement in precision is needed for those assays; e) In general, sample specific effects were not clinically significant.

Recommendations for manufacturers include: 1) method imprecision should be reduced, especially at low urine albumin concentrations that may influence CKD risk assessment, 2) methods that showed a non-constant calibration bias over the method measuring interval should be investigated and corrected and 3) methods with poor dilution protocols should improve their user information to include specified dilution buffers and validate their protocols for matrix bias. To facilitate standardization of routine methods, NIST SRM 3666 is currently being prepared based on the specifications developed by the WGSAU and the LWG of the NKDEP. The next step is to perform a freeze-thaw study to assess the ability to use frozen patient samples for the commutability study for NIST SRM 3666. 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 urine albumin results.

Samples spanning the concentration range of 15 – 1,000 mg/L were included in the study. The non-frozen and frozen aliquots were shipped to 10 manufacturers for albumin measurement. Median bias for frozen vs. non-frozen 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%. The preliminary data was presented at the joint NKDEP/IFCC WG-SAU meeting on August 3rd, 2016 held in conjunction with the AACC annual meeting in Philadelphia, PA. Term of Reference 3. Establish a reference procedure and reference materials for the measurement of albumin in urine. Reference measurement procedure for UA (funded by NKDEP and NIST). Accomplishments include: The Mayo Clinic (John Lieske) ID-LC-MS/MS candidate reference measurement procedure was included in a manuscript (see Publications). This procedure was also used in the status of harmonization among commercial immunoassays project. The Mayo reference method was used to assign albumin values for CAP and CEQAL urine samples. NIST has developed and performed an inhouse validation of an ID-LC-MS/MS reference measurement procedure for urine albumin. It is anticipated the NIST procedure will enable assessment of the molecular forms of albumin in urine that may be of importance in the specificity requirements for routine measurement procedures. NIST and Mayo continued to perform comparison studies for their respective IDMS candidate reference measurement procedures. However, both parties continued to observe unexplained differences among results for the two methods. It was discussed during the NKDEP/IFCC WG-SAU meeting that standardizing pre-analytical protocols between the two methods may improve agreement.

Terms of Reference 4. Reference materials for UA and urine creatinine (funded by JSCC and NIST). Accomplishments include: SRM 2925 Human Serum Albumin is a primary certified reference material for use with higher order reference measurement procedures for albumin. It is solid recombinant human serum albumin (~1 g/L). Value assignment is by amino acid analysis using ID-LC-MS/MS. The material is available. SRM 3666 is currently being prepared based on the specifications developed by the WG-SAU and the LWG of the NKDEP. A contract to a commercial vendor for the production of SRM 3666 was awarded in September 2014. However, the vendor has not satisfied the contract requirements. In order to obtain urine samples for SRM 3666, Virginia Commonwealth University has agreed to serve as a residual urine sample collection site. A preliminary protocol was drafted and needs to be finalized.

• WG - Standardization of Pregnacy-Associated Plasma Protein A (WG-PAPPA)

by Saara Wittfooth, Chair During 2016 ongoing progress towards WG-PAPPA terms of reference included: Term of Reference: Develop a reference system for standardization of PAPPA measurement employed as marker for prenatal screening. Accomplishments include: Due to the maternity leave of the Chair, there have been limited activities in 2016. The chair submitted a revised project plan to the SD including schedule and cost estimates. The WG previously used purified material to assess ability to standardize assays, but this did not work for all assays. The group will assess the potential of harmonization and the goal of making assay results more comparable.

• WG - Standardization of Insulin Assays (WG-SIA)

by Amy Saenger, Chair; Mike Steffes, Co-Chair During 2016 the WG-SIA continued ongoing progress towards its terms of reference.This is a joint project between ADA and IFCC. Establishment of a reference measurement procedure for serum insulin is on-going. Several labs are currently testing samples with the candidate reference method. At the same time the WHO is vetting a reference material via C. Burns at NIBSC. This material will be used as calibrator for the mass spec procedure to assign values. The plan is to use the mass spec method, reference material, samples or pools or some combination of these to bring the immunoassays closer together. The next meeting is planned for in October in conjunction with the 2017 WorldLab in Durban.

• WG - Standardization of Troponin I (WG-TNI) by David Bunk, Chair During 2016 the WG-TNI continued ongoing progress towards its terms of reference. The WG continued developing a CRM for Troponin I in serum (NIST SRM 2922). The plan is to mix pools from a normal population and one from cardiac patients.

The normal pool will be evaluated in an interference study prior to being used in the production of SRM 2922. If okay, a limit of blank study will be performed with a few different methods being considered. Once complete, value assignment will be performed. Plans for this work were outlined and discussed with a focus on how best to ensure and validate measurement quality during the value-assignment process. It was suggested that participating manufacturers be queried about their measurement batch times for the anticipated sample analyses for both the value-assignment and commutability studies. Assay manufacturers present at the WG-TNI meetings expressed concerns that performing a re-calibration of their cTnI platforms in the middle of their lifespans would be a significant financial and bureaucratic burden. The WG plans for a next face-to-face meeting in August 2017 in conjunction with the AACC in San Diego.

• WG - Harmonization of Autoantibody Test (WG-HAT) by Joanna Sheldon, Chair During 2016 ongoing progress towards WG-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 certification process for IgG anti proteinase 3 antibodies is showing significant differences between methods and comparable to the results for the IgG anti myeloperoxidase antibodies. Some of the issues are likely to relate to the specificity of different methods with different epitopes of the antigens and this makes further investigation into the causes of variation between methods vital. It may also lead to better definitions of the antigens or epitopes that are important and the clinical utility of these tests.

Term of Reference 2. To identify autoantibodies where a common calibrator could reduce the inter-assay variability. Accomplishments include: Diagnostic companies are becoming more receptive to the concept of proper standardization for autoantibodies although there remains some reluctance. The WG has been asked to consider production of reference materials for more autoantibodies but believe that it should continue with the plan to generate a robust process and concentrate on IgG anti MPO (complete) PR3 (final stages of certification), GBM (raw material sourced), B2GP1 (issues with value assignment so a further commutability study is necessary) and CCP. Term of Reference 3. To identify or produce commutable materials that could be used as interim calibration material for autoantibody assays Accomplishments include: IgG anti PR3 antibodies: The value assignment process is complete and the certification report is in the IRMM validation process. The WG delayed wide publicity of the ERMDa 476 until the reference preparation for IgG anti proteinase 3 is also ready. This will be a more logical release of reference material for the two ANCA related antibody specificities. The WG continue to try to find a way of working with the FDA. Liaison with manufacturers and EQA providers is ongoing but will become more formal once both reference materials are certified. The change from “units” to mg/L is likely to alter cut off values and clinical interpretation in many assay. It is likely that an additional FDA approval phase in needed for kits using ERM-DA476/IFCC – the WG is currently in discussion with the FDA. Education: The WG is preparing information to guide companies on how to transfer values from ERM-DA476/IFCC to their local or kit calibrators. Goal is a consistent message about ERM-DA476/IFCC and informing users of how it is best implemented. The WG is currently in discussion with the UKNEQAS and CAP and actively seeking contact with other EQA providers. The incorporation of ERM-DA476/IFCC into pack information will be a major task for companies and will take many months. IgG anti cardiolipin and IgG anti beta-2 glycoprotein I antibodies: Some of the validation testing has shown a possible issue with the commutability of the material; therefore a further commutability study in needed in order to select an appropriate material.

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: ERM Da 476 is now a certified refer-

5

ence material. IgG anti proteinase 3 is in the final stages of certification by the IRMM. Additional Information: The WG-HAT has been working on this valuable project for 6 years with considerable effort from a small group of clinicians and scientists. It has been a challenge to develop the reference materials and prove, in principle, that it was possible. It has been appropriate to have been a working group but now that there are two materials for IGG anti MPO and IgG anti PR3, the WG will need to increase visibility and have a much greater impact on the laboratory clinical chemistry and immunology community and on the rheumatology and nephrology communities. The WG needs to raise its profile and participate in much broader activities while continuing to develop more reference materials and identify the sources of variation in autoantibody testing.

• WG - Quantitative Mass Spectrometry Proteomics (WG-cMSP)

by Sylvain Lehmann, Chair During 2016 the WG-cMSP continued ongoing progress towards its terms of reference. It was recognized that different laboratories participating in the WG have different operating procedures to perform quantitative mass spectrometry analyses for peptides and proteins. The WG has an ongoing QA/QC program on hepcidin to exchange standards to be able to compare and adjust values obtained in the different laboratories. The WG is also collaborating with the LNE to evaluate the possibility to generate a CRM for hepcidin. Samples and purified materials have been sent to 5 labs (2 within the WG and 3 in France).

A few of their procedures might be able to develop into reference method. However, realization in developing a reference method for hepcidin has proven difficult and remains uncertain. The SD decided that this WG will close at the end of 2016 and thank the chair and members for their service.

• WG - Parathyroid Hormone (WG-PTH) by Cathie Sturgeon, Chair During 2016 the WG-PTH continued ongoing progress towards its terms of reference. The WG continues to work on developing a reference system for PTH. Currently, activities are focused in three areas: 1. Assessment of commutability; 2. Development of a reference measurement procedure: Several groups are involved including Mayo, CDC, and NIST; 3. To gain a better understanding of what is the actual measurand being measured as many manufacturers have gone to third generation assays. Manufacturers are highly supportive and engaged.

• WG-CSF Proteins (WG-CSF) by Kaj Blennow, Chair During 2016 ongoing progress towards WG-CSF terms of reference included: Term of Reference 1. Develop an international reference material for cerebrospinal fluid (CSF). Accomplishments include: Collection of CSF material and preparation of the Certified Reference Material (CRM): University of Gothenburg, Sweden has collected a large (5 litre) pool of CSF to be the basis for the reference material. A study has been performed to test that no individual high-volume sample shows interference in the mixing to obtain the pool. Results show acceptable agreement between expected (calculated) and measured values, meaning that these samples will be suitable for the CRM. A first commutability study has been done, comparing the candidate CRM as well as spiked variants and pools containing detergents.

In this study, the SRM mass spec method for Aβ1-42 was compared with several immunoassays (ELISA, Luminex, and MesoScale). A large series of individual patient samples was analyzed together with aliquots of the CSF candidate CRM. The analysis showed high correlations between the SRM method and the immunoassays, and also very good commutability of the candidate CRM, but not for different variants of artificial CSF, or for samples containing detergents. Based on these results, a second commutability study has been performed, in which a common calibrator (Aβ1-42 peptide) was used, and the candidate CRM included (neat and spiked at 3 levels). In this study, the SRM mass spec method for Aβ1-42 was compared with eight different immunoassays (Innotest ELISA, Luminex, and MesoScale, and also IBL, Roche, Vitros/Saladax, ADx, Simoa). A large series of individual patient samples was analyzed together with aliquots of the CSF candidate CRM, spiked at three levels. The analysis showed high correlations between the SRM method and the immunoassays, and also very good commutability of the candidate CRM, but less commutability for spiked variants. For these reasons, it was decided that the high-volume samples for the CRM will be pooled based on the original Aβ1-42 levels, so that three different CRMs will be produced with high, medium and low levels. Three reference materials have now been produced for Aβ42, with high, middle and low Aβ42 concentration. Homogeneity and stability have been verified, long-term stability (1 year) is good. The value assignment is on-going, with four LC-MS datasets received. Establishment of reference methods for the key measurands for assignment of values to the reference material: This part of the project is focused on developing a SRM mass-spec method for Aβ 1-42 in CSF, to qualify as a reference measurement procedure (RMP). There are five laboratories that are working on this in a collaborative effort. All labs have developed SRM mass spec assays for CSF Aβ1-42. The assays have been compared in a detailed Round Robin study in which both human CSF samples and the calibrators have been analyzed in all labs. The results show very good correlations and agreements between assays. The Round Robin study has been reported in a paper (Pannee J, et al. Round robin test on quantification of amyloid-β 1-42 in cerebrospinal fluid by mass spectrometry. Alzheimers Dement 2016;12(1):55-59. A second Round Robin study has been performed in which the master calibrator is used, to test a common procedure for calibration in preparation of the value assignment of the CRM. Data from this study showed linear correlations and good agreement between the five methods with a variation <4%. Both Univ. of Gothenburg and Univ. of Pennsylvania have made a full validation, according to ICH guidelines, of their SRM mass spec assays for CSF Aβ1-42. Both the Roche/Gothenburg and the UPenn methods are now accepted and listed as a RMP by the Joint Committee for Traceability in Laboratory Medicine (JCTLM).

There is a growing use of Aβ40, and it had previously been discussed that a reference material would be useful. The consensus of the IFCC-WG CSF was that an indicative value for Aβ40 would not be useful, but the existing LS-MS method for Aβ42 could be adapted for Aβ40, and submitted as reference method to IFCC and JCTLM. In the meantime JRC has assessed homogeneity and stability (including one-year stability) for Aβ40 in the materials produced for Aβ42. Therefore the certification of Aβ40 in one of these materials would require only the value assignment measurements.

• WG-Standardization of Bone Marker Assays (WG-SBMA) by Howard Morris, Chair During 2016 ongoing progress towards WG-SBMA terms of reference included: This is a joint activity with the International Osteoporosis Foundation.

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: The protocol for an assay comparability study of the two major clinical assays for CTX has been prepared. The study is being conducted at four European centres collecting data on the effects of serum or plasma specimen, fasting or non-fasting subjects and males and females presenting to osteoporosis clinics on the comparability of the results of assays from two manufacturers used by clinical laboratories. The study is funded by the two IVD companies involved.

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: Same as for Term of Reference 1. The results from the WG will be reported at the IOF Business meeting being held in Florence, Italy 24 March 2017 in conjunction with the World Congress of Osteoporosis.

• WG-Commutability (WG-COMM) by Greg Miller, Chair During 2016 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: A draft recommendations document is fairly complete. The recommendations address: definition of commutability; individual clinical samples for inclusion in a commutability assessment; pools of clinical samples for use in a commutability assessment; reference material(s) to be included in a commutability assessment; qualification of measuring systems for inclusion in a commutability assessment; statistical designs to assess commutability (two approaches, one based on difference in bias between patient samples and a candidate RM and the other based on calibration effectiveness of a candidate reference material); criteria to make a determination that a RM is commutable (criteria are based on intended use for medical decisions); replacement of a RM with a new preparation; correction to the assigned value of a non-commutable certified reference material (CRM) used in a calibration traceability hierarchy; and information on commutability to be provided in the certificate for a RM. The plan is to publish five papers to divide the large amount of content into manageable papers: (1) general recommendations; (2) statistical evaluation approach based on difference in bias; (3) statistical evaluation approach based on calibration effectiveness of a RM; (4) validation of a replacement batch of a RM; (5) correction of an assigned value for a RM for non-commutability with one or more measurement procedures. It is not likely that all five papers will be completed in 2017.

Term of Reference 2: Establish how to define the degree of commutability which is required for a given reference material, taking into account its intended use and the intended use of the measurand. The degree of commutability becomes the criteria used in the assessment process. Accomplishments include: Described in term of reference #1.

Term of Reference 3: Propose standard terminology to describe the degree of commutability of a reference material, taking into account its intended use. Accomplishments include: Described in term of reference #1.

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2016 Annual Report

Term of Reference 4: Provide guidance to manufacturers and laboratories about what information should be provided by manufacturers in relation to the commutability of reference materials used to establish the calibration traceability of a measurement procedure. Accomplishments include: Not addressed.

Term of Reference 5: Develop educational materials regarding commutability for manufacturers, laboratories and users of laboratory results. Accomplishments include: Not addressed.

Additional Information: The chair has discussed publication approaches with Nader Rifai, Editor-in-Chief, Clinical Chemistry, for the quantity of material in the final recommendations. An approach of several papers with substantial use of supplemental data is likely to be acceptable.

Face to face meeting is scheduled on June 11, 2017 during the EuroMedLab meeting in Athens.

Ian Young, SD Chair and Gary Myers, SD Secretary

EDUCATION AND MANAGEMENT DIVISION (EMD) COMMITTEES activities: • IFCC Committee on Clinical Molecular Biology Curriculum (C-CMBC)

by Evi Lianidou, Chair 1. The C-CMBC website was updated where general Information about the Course can be found at http://www.ifcc.org/ifcceducation-division/emd-committees/c-cmbc/ 2. The 8th Course on “Molecular Diagnostics for Beginners” was conducted in Tirgu Mures, Romania, on December 5-10, 2016, in collaboration with the National Representative, Dr. Ioanna Brudasca, President of the Romanian Association of Laboratory Medicine (RALM).

3. Organization of a symposium in EuroMedlab 2017, entitled: “The Liquid Biopsy approach: Following the tumor in peripheral blood”. The symposium will take place in June 2017 during Athens EuroMedlab 2017.

• Analytical Quality (C-AQ) by Egon Amann, Chair 1. A survey on national EQA services was conducted in 2014/2015. Based on this survey, the “Directory of EQA Services” database was established and placed on the C-AQ website for consultation by interested parties. This database requires occasional updates and this was done in 2016, but the systematic update by contacting IFCC Full Member National Societies and affiliated members and asking them for possible changes, feedback and experiences is still pending. It is planned to replace the Directory of EQA Services by the Proficiency Testing – External Quality Assurance Programs in Laboratory Medicine database (PTDB; see ptdb.ifcc.org) in 2017. PTDB was initiated by Alexander Haliassos and was released as a prototype version for review by C-AQ committee members in its first version on November 9, 2016. The present version is not final and needs further refinement. C-AQ members find this database helpful when searching for analytes. PTDB will replace the existing Directory of EQA Services on the C-AQ website. PTDB will be maintained jointly by the IFCC Task Force on Proficiency Testing (TF-PT) and C-AQ. 2. A minimum requirement EQA Setup Checklist has been prepared to assist countries to plan and design an EQA scheme.

The EQA Setup Checklist is available on the C-AQ web site. It is planned to expand the presently available information with additional, more detailed procedures for the planning of a new EAQ scheme (for example, to achieve ISO 15189 accreditation).

3. A “Resource table for EQA” was established and placed in the C-AQ website at the end of 2015. This database is a compilation of relevant documents on pre- and post-analytical steps and other topics related to analytical quality. This database was reviewed in 2016 and found to be current and adequate. It should be re-reviewed in 2017.

4. Development of eLearning presentations on “Principles of EQA” and “Principles of IQC”. Presentations on the above topics already exist on the C-AQ website. It is planned, however, to expand such topics to offer suitable materials to the IFCC eAcademy. The two “voice-over” presentations on IQC and EQA are still pending. David Ducroq of WEQAS has useful presentations on Traceability and Uncertainty for inclusion into C-AQ Resources web site section and for eAcademy.

5. A joint C-AQ / C-CLM workshop entitled “What is the best strategy to achieve compliance with QMS- and QC-requirements in the clinical laboratory?” was conducted at the IFCC General Conference in Madrid in 2016. Feedback from participants of this workshop was very positive. A report has been written for future reference and an article has been published in the IFCC eNews, July-August 2016 issue for broader distribution of the relevant learnings to National Societies and other interested parties.

6. Egon Amann participated in the Biennial Scientific International Conference of the Association of Clinical Chemists of Nigeria (ACCN) in Lagos from October 12-14, 2016, a DQCML sponsored activity. Other IFCC officers in attendance were Maurizio Ferrari, Graham Beastall, Mike Thomas and Catherine Sturgeon. EA moderated a workshop entitled: What is the best strategy to achieve compliance with QMS- and QC-requirements in the clinical laboratory? and delivered a lecture entitled: Standardization of laboratory tests: Why is it needed and how is it done? The output of this workshop provided input for the interactive workshop Quality challenges going forward: understanding the needs of Nigeria moderated

by Cathie Sturgeon, Graham Beastall and Mabel Charles-Davies. The conference was considered successful and a national QMS/QC-improvement program was initiated by the ACCN. 7. PUBLICATION: Achieving compliance with QMS- and QC-requirements in the Clinical laboratory: What is the best strategy? E. Amann, S. Yenice (joint C-AQ / C-CLM publication) in the IFCC eNews/ LabMedica International August-September, 2016.

• Evidence-Based Laboratory Medicine (C-EBLM) by Chris Florkowski, Chair 1. The EBLM Curriculum has been completed. This is intended to be used as a template for allocation of topics for inclusion as units in the IFCC eAcademy. This was achieved through collaboration of all members of the EBLM and discussed at the General Meeting in Madrid, where some refinements were suggested.

2. Submission of units to the IFCC eAcademy. At the time of writing, at least TWO units have been uploaded to the IFCC eAcademy, together with key words and questions. The Curriculum has been used to define relevant topics, which have been assigned to individual EBLM members to work on using the Present.Me tool. It is anticipated to enlarge this in 2017.

3. Guideline appraisals (initiated by J Wils) – with a focus on endocrine areas is being conducted. To date, EBLM members have participated in guideline appraisals, including several on adrenal insufficiency, using the AGREE II instrument. Other guidelines, including diagnosis of primary hyperaldosteronism and adrenal incidentaloma, have been circulated to the EBLM committee for review. Dr J Wils is collating the data, with a view to an eventual EBLM group publication.

4. A Questionnaire on EBLM resources and requirements for training has been formulated. This has been developed by Dr K Capote and Dr N Gimenez and is undergoing pilot testing before global circulation. IFCC CPD has agreed to support C-EBLM with the distribution and eventual collation of the data. The goal is to present the data at the IFCC Worldlab in Durban, 2017 and to achieve a full publication.

5. C-EBLM website pages were updated in 2016.

6. Dr Hernan Taie (Argentina) continues to contribute his excellent Iberian Laboratory Medicine Radio Station that is broadcasted in Spanish. C-EBLM members have contributed to the programming of this effort and have provided several lectures. These activities were presented at the Madrid meeting.

7. Dr C Florkowski presented at a symposium at the EFLM-UEMS conference in Warszawa, Poland: POCT and clinical outcomes – quality of evidence.

8. Symposium on EBLM has been accepted at COLABIOCLI, 2017, Uruguay. Contributors: K Capote; N Gimenez; H FaresTaie.

9. Symposium on EBLM has been accepted at IFCC Worldlab, Durban 2017. Contributors: all EBLM members.

10. PUBLICATIONS: Dr C Florkowski has been invited to submit a review to Critical reviews in Laboratory Medicine on: POCT and clinical outcomes – quality of evidence. Other full members of the C-EBLM will be recruited as co-authors.

• Clinical Laboratory Management (C-CLM) by Sedef Yenice, Chair 1. C-CLM teamed up with C-AQ to produce a joint publication on “Developing Quality Systems in the Clinical Laboratory” (Refs. Minutes of Face-to-Face Meeting/June 21, 2015, EuroMedLab Paris 2015, by C-CLM and Minutes in Paris, 22 June 2015, by C-AQ). Target audiences of this monograph are developing countries. Sedef Yenice provided a detailed report with a gap analysis on the contents of previous published two monographs and proposed a list of contents/themes along with prospective authors from C-CLM on September the 13th, 2015. A chapter on Ethics has been contributed by the Task Force on Ethics. It is planned to upload this document to the C-CLM website in January 2017.

2. An interactive workshop on “What is the best strategy to achieve compliance with QMS- and QC-requirements in the clinical laboratory?” was jointly conducted with C-AQ at the IFCC General Conference on 20 March 2016, Hotel Auditorium, Madrid, Spain. A post-implementation report was submitted to EMD-EC on April 14, 2016, and the related article was published in the July-August 2016 issue of IFCC’s eNews. (Ref. What is the best strategy to achieve compliance with QMSand QC-requirements in the clinical laboratory? July-August 2016 issue of IFCC eNews, pages 9-13).

3. “Terms of Reference” of C-CLM were updated on the website on June 29, 2016.

IFCC

4. Development of a training module on Leadership is in progress.

5. In order to complement the training module, a guide entitled "A TRAINING MANUAL ON LEADERSHIP BASICS FOR CLINICAL LABORATORY PROFESSIONALS" is being prepared. C-CLM is currently working on the 2nd draft.

6. Sedef Yenice delivered a lecture on "Evolving clinical laboratory management through implementation of a risk assessment plan" on May 12, 2016, at the session on "Laboratory Management", analytical conference 2016 in Munich (10.05.2016-12.05.2016) www.gdch.de/analyticaconf2016 and https://www.gdch.de/fileadmin/downloads/Veranstaltungen/Tagungen/2016_Tagungen/Analytica_2016/analytica_conference_2016_web.pdf. MO chaired the session "Laboratory Management" and gave a talk on "QMS Standards in the medical laboratory (EN 15189, EN 17020, EN 17025, Rilibäk or SLIPTA)".

7. Michael Orth delivered a lecture on "Direct-to-Consumer Testing: The Business with Lifestyle Tests" on September 22, 2016, at the AACC Conference (https://www.aacc.org/publications/cln/cln-stat/2016/september/1/the-consumer-angle-inpoint-of-care-testing).

8. A symposium on “Improvement in Clinical Laboratory Services: Approaches to Adding Value” has been accepted for the IFCC WorldLab, on October 25, 2017. C-CLM will, in addition, conduct a satellite educational workshop entitled "Intelligent Clinical Laboratory Management: Impacts on Quality System Improvement" at the IFCC WorldLab, on October 22, 2017, Durban, South Africa. Application for partial funding through the FSASP has been approved.

9. Sedef Yenice delivered a talk on “Patient-centric and value-based management at the clinical laboratory” during the National Biochemistry Congress of Turkish Biochemical Society that was held on November 2-5, 2016, at Sivas Cumhuriyet University, Sivas – Turkey. The abstract was published in the Turkish.

• Distance Learning (C-DL) by Janet Smith, Chair 1. On-going approval of educational material for the website as it becomes available.

2. Development of the IFCC curriculum is ongoing.

3. Continuing development of the eAcademy in collaboration with the Committee on the Internet and e-Learning (C-IeL). The eAcademy development is going well. The second phase was launched in March 2016 at the IFCC General Conference in Madrid. The third phase, which will permit the issue of a certificate of completion of modules to those using the eAcademy is currently under development by Insoft.

4. The mass spectrometry module continues to be developed by Dr Ronda Greaves and material is gradually being added to the eAcademy on this topic.

5. A joint C-DL / C-IeL workshop on using the eAcademy to aid National Societies and individual laboratory professionals in training and CPD programmes was conducted during the IFCC General Conference in Madrid. We were pleased with the reception the workshop received and for the support expressed by IFCC Officers for the work the two committees are undertaking.

6. Janet Smith has undertaken IFCC-VLP visits to Estonia and Romania in 2016 to speak about the eAcademy. At both congresses, there was great support and enthusiasm for the initiative.

7. The proposal for a joint EMD/CPD symposium on the eAcademy at the COLABIOCLI Congress in Uruguay in September 2017 has been accepted.

8. To continue to collaborate with other EMD committees in the development of e-learning modules. Most progress has been made by the C-EBLM. The first modules of a series on EBLM have been published on the website.

9. Identification of relevant presentations from IFCC and National Society conferences for recording to populate the eAcademy is on-going. It was decided at meetings in Madrid that we should concentrate on the preparation of short modules, on priority topics, prepared by recognised experts, using the present.me software. We are grateful to those experts who have prepared modules which have already been uploaded to the eAcademy as well as to those currently preparing material for us.

10. We have also provided links to high quality webinars produced by other organisations. Most recently, we have approved links to webinars on aspects of gastrointestinal disorders, prepared by Petr Kocna, a member of C-IeL 11. Liaison with the IFCC Office continues over communication with and permissions from authors whose work is to be published on or linked from the IFCC website, as well as on website and IT issues.

• Education in the Use of Biomarkers in Diabetes (C-EUBD) by Garry John, Chair 1.

2.

3.

4.

Annual Inter-study Laboratory Network has been accomplished with good outcome.

Data gathering of Questionnaire has been completed and the data is being refined for publication.

EurA1c project: bloods have been circulated around Europe.

A grant from the UK Economic and Social Research Council has been awarded to organise a training meeting for developing countries.

5. WHO/IFCC Handbook has been completed and is awaiting WHO approval.

6. Helped develop and organise a Satellite Meeting of IFCC EuroMedLab Athens, June 2017.

7. Developing a Satellite Meeting for Durban WorldLab. The outline programme is in place.

WORKING GROUPS activities: • Laboratory Errors and Patient Safety (WG-LEPS) by Laura Sciacovelli, Chair 1. A Consensus Conference on “Harmonization of quality indicators in laboratory medicine: two years later” that aimed to approve the Model of Quality Indicators (MQI) to be used in clinical laboratories over the world, and to define the criteria to evaluate the quality indicator data (quality specifications) was held on 26th October 2016 in Padova, Italy. A scientific paper will be published with all findings of the meeting.

2. Quality indicator results of participating laboratories collected through dedicated website (www.ifcc-mqi.com) has been written up and a scientific paper has been sent to the Journal Clinical Chemistry and Laboratory Medicine for publication.

3. Collaboration with other international Working Groups/Task forces in order to define quality specifications for quality indicators.The EFLM WG-PRE and WG-POST have been involved and attended the Consensus Conference.

• Cancer Genomics (WG-CG) by Jason Park, Chair; Paolo Fortina, Co-Chair 1. The membership of the working group has been expanded to increase non-US members.

2. The outline of the first document has been completed and is currently in preparation for publication. A presentation at the IFCC General Conference was made by Jason Park and Paolo Fortina on “Cancer Genomics: Revolution in Medical Practice”.

3. A symposium on Clinical Cancer Genomics was held at the APFCB Congress in Taipei, November 2016. The speakers were as follows: Paolo Fortina (Thomas Jefferson University, USA); David Wang (UT Southwestern Medical Center, USA); Jason Park (UT Southwestern Medical Center, USA) 4. Financial support for the working group has been received from Softgenetics and Affymetrix. Additional support is being solicited for future activities.

• Harmonisation of Interpretive Comments External Quality Assurance (WG-ICQA)

by Samuel Vasikaran, Chair 1.

2.

3.

4.

Harmonised goals for EQA of IC have been developed.

Standard methods of assessment, nomenclature and marking scales for EQA of IC have been devised.

Input from similar schemes in Histopathology has been obtained.

A position paper has been published: Assuring the quality of interpretative comments in clinical chemistry. Vasikaran S, Sikaris K, Kilpatrick E, French J, Badrick T, Osypiw J, Plebani M; IFCC WG Harmonization of Quality Assessment of Interpretative Comments. Clin Chem Lab Med 2016; 54(12): 1901-1911.5.

5. Proposal for a Workshop on Interpretative Commenting at IFCC WorldLab 2017, Durban has been accepted by the Congress Scientific Committee.

SPECIAL PROJECTS activities: • IFCC Visiting Lecturer Programme (IFCC-VLP) by Elizabeth Frank, Chair There has been an overwhelming response to this programme. However, due to paucity of funds we had to decline a few countries. Now with Abbott sponsoring the programme in 2017 we will be able to reach many more nations. In 2016, 13 VLPs were approved. Details of VLPs approved in 2016 are attached in a separate file.

• Working Group on Flow Cytometry (WG-FC) by Ulrich Sack, Chair 1. The annual flow cytometry workshop took place from October 26 to 28 in St Petersburg, Russia. The established principle was continued: intense interaction between participants and trainers; 3 topics a day with short introduction and extensive practical exercises; duration of 3 days; and emerging and relevant scientific topics with clinical impact for daily practice.

2. The first Latin American Course was offered in Cordoba/Argentina, March 9 to 11 in 2016.

3. The webpage has been updated, and new members entered the working group. The homepage is updated bi-monthly.

4. Publication. A report of the activities of the working group was published in the IFCC eNews, Sept/Oct 2016.

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2016 Annual Report

• Developing Quality Competence in Medical Laboratories (DQCML)

by Michael Thomas, Chair 1. A brief synopsis of the aims and objectives, resources, successes and future work of the DQCML Project was presented

by Michael Thomas within the EMD Session at the IFCC General Conference, March 2016.

2. On-going engagement and collaboration with Chairs of EMD Committees and the VLP Programme by seeking their support in the delivery of Quality Systems initiatives and utilising when appropriate their expertise and resource in the delivery of programmes under the DQCML Project.

3. To seek to engage and assist IFCC Members in the development of Quality Systems in their countries through the delivery of educational lectures, seminars and workshops, specifically: a. To follow-up contact with the President of the Association of Clinical Biochemistry of Sri Lanka and to identify the needs of laboratories in Sri Lanka for accreditation (ISO 15189) and support the organisation and delivery of a 2-day accreditation workshop in 2016. b. To follow-up contact the President of the Ukrainian Society of Clinical Laboratory Diagnostics to identify the needs of laboratories in Ukraine and formulate a programme plan for delivery in 2016.This matter remains outstanding due to changes in National officers locally and will be carried forward to the work plan for 2017.

4. To ensure that any presentations delivered under the auspices of the DQCML Project can subsequently be made available through appropriate electronic means via the IFCC web site and eAcademy. Hilary Lumano has been approached to record a presentation of his experiences of the RQA Zambia project for publication on the IFCC web site under the eAcademy 5. Continued support is being offered for the EQA Zambia Project being led by Dr Renze Bais, for example in the provision of logistics and support for an educational seminar in 2016/2017. DQCML continues to update Renze Bais on the project’s progress. It is hoped that Hilary Lumano will record a presentation of his experiences of the project for publication on the IFCC web site under the eAcademy.

6. To determine those activities that may be appropriate in supporting the ambitions of Malawi to develop a programme of Quality Competence following an exploratory visit and report by the IFCC Past President, Graham Beastall in January 2016. Graham Beastall undertook a scoping visit to Malawi to better understand the needs of this new national Member.

It is likely that they will submit an application for a DQCML project in the future and this should be encouraged and included in the work plan for 2017.

7. By invitation, a one-day symposium was delivered as part of the 6th Scientific Conference of the Association of Clinical Chemists of Nigeria on 13th October 2016 on Sustaining Quality Practice and Process in Developing Countries. The presentation is likely to encourage a further application from the Nigerian Association in 2017.

8. Michael Thomas was interviewed for the El Microscopio radio programme.

9. Publications: A short article on the DQCML Project was published in the September-October issue of IFCC eNews and an abridged version appeared in LabMedica International in November 2016.

IFCC Mentoring Programme, Chair: Donald Young. The number of Mentors has been expanded to 24 and that of Associates to 36. Attempts to work with CLSI to recruit Associates have been deferred by CLSI several times.

The pool of Spanish-speaking mentors has been enlarged with Rosa Sierra Amor’s endorsement of using the Spanishspeaking experts as potential mentors although most have not yet been invited to participate and are not included in the number above. Then Associates from Latin America must be identified. In 2017 the Spanish-speaking experts will be asked if that would also wish to become mentors.

A major difficulty for the programme has been to get Associates to respond to requests from either the Director or their selected mentors. The number of Mentors needs to be increased to expand number of interests of associates that can be addressed. As a routine practice individuals who have participated in the IFCC PSEP/PMEP programmes are now invited to become Associates. The IFCC Secretary has agreed to make available the e-mail addresses of IFCC’s Register of Experts so they can be consulted directly without the need to go through the IFCC Office. Agreement of the individual experts will be sought.

Leslie Lai, EMD Chair

COMMUNICATIONS AND PUBLICATIONS DIVISION (CPD) In 2016, the following members served on the CPD Executive Committee: Khosrow Adeli (CA, Chair), Edgard Delvin (CA, Vice Chair/Public Relations Coordinator), Peter Vervaart (AU, Publications/Distance Learning Coordinator), Tahir Pillay (ZA, News Editor), G. L. Kovács (HU, Editor eJIFCC), and Bruce Jordan (CH Corporate Representative). Janine Grant (AU, Website Editor), Maria del Carmen Pasquel (EQ, WG- IANT Chair), Ellis Jacobs (US, IFCC Labs are Vital representative) and Anthony Newman (NL, Publications consultant) were invited to attend the CPD meeting in Madrid, on occasion of the IFCC General Conference 2016. A Call for nominations was issued to replace Dr Peter Vervaart as Secretary/Publications Distance Learning Coordinator and Dr Bruce Jordan Member / Corporate Representative, who completed their second term in office.

The following is a summary list of the key CPD activities in 2016: Two face-to-face committee meetings were held in 2016: Madrid, (ES) in March, and Budapest-Pécs (HU) in September.

• Informal CPD meeting in Philadelphia on occasion of AACC. • Major improvements have been implemented for both the IFCC eNewsletter and the eJournal. Publication formats as well as news/scientific content have been enhanced considerably over the past year.

• A new contract with Insoft has been signed for IFCC publications – eJIFCC and eNews, allowing to publish up to a total of 600 pages/year.

• The release of a new IFCC eNews Flash, a completely new editorial product, designed and launched.

• The release of a new innovative IFCC App fully designed and launched.

• IFCC social presence (FB, LinkedIn, Twitter) is lively and well managed, with a slow but constant increase in contacts.

• Promotion of Distance Learning Opportunities for Member Societies & their Membership via eAcademy continues.

• Increased communication with the Spanish speaking countries with pilot project participation into AMARA collaboration initiative.

• Enhancement of IFCC Organization’s Public Relations/Visibility.

• 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.

• Focus on improvement of internal communications within IFCC and its Member Societies.

• Contribution to IFCC congresses with organization of CPD Sessions & Symposia in 2016 (and in 2017).

• The Electronic Journal of IFCC (eJIFCC) has been accepted for indexing by MEDLINE/PUBMED. Most recent issues of the journal are now available online on PubMed central.

• First communications to list eJIFCC into Google Scholar, Thomson Reuters, Scopus, and Web of Sciences, have been sent.

C-Public Relations (C-PR) by Edgard Delvin, Chair Committee Meeting: A C-PR meeting was held in Madrid, to which most members attended.

2016 Survey: A survey directed towards the individual members of the National Societies and Regional Federations proposed by the C-PR members was conducted and results presented at the GC. Use of IFCC documents by National Society Members: Improvement of the traceability (downloads, dwell time, frequency) on the use of the documents produced by the different IFCC functional units by the members of the National Societies and Regional Federations has been identified as a must by the C-PR since this would allow increasing the visibility of IFCC. Participation in the 1st International Congress on Personalized Health Care: This event was held in Montreal in June 2016. Prof. Delvin made a presentation on the added-value of laboratory medicine. This participation is part of the endeavour to promote the image of the IFCC to its individual members, to the biomedical industry and to the world-wide health care community at large.

Poster: In addition to the new posters created with Bruce Jordan’s support, Magdalena Krintus developed a new standing poster for the promotion of IFCC. It was presented at EFLM meeting in Warsaw with an excellent feedback from public.

Labs Are Vital Consortium: The Board, chaired by Michael Oellerich, has held 2 regular conference calls for the Board Meeting, to which Prof. Delvin participated as Clinical Editor on behalf of the IFCC. The LRV program has been revitalized and has posted 30 or more Podcasts or videos since February 2016 at http://www.labsarevital.com/. El Microscopio provided a number of them.

C-Internet and e-learning (C-IEL) by Peter Vervaart, Chair Committee Meeting: A C-IeL meeting was held in Madrid, followed by one joint with C-DL. C-IeL continues to work closely with the C-DL and Insoft in developing electronic/distance learning materials and access for IFCC members utilising the ‘e-Academy’.

A call for nominations has been issued to replace Dr Freggiaro.

7

Publications: Documents of Committees and Working Groups: the database (available on the website) continues to be updated as publications are forthcoming; Silver Book has been published in print (and as an eBook); Conference proceedings.

Bergmeyer conference proceedings published in Scandinavian Journal of Clinical and Laboratory Investigation and on IFCC website; IFCC GC proceeding are available on IFCC website.

Website: The website continues to develop in ‘real time’ therefore there is no plan at this stage for a Phase II launch (other than the eAcademy). It continues to be a major communication tool, a repository of resources, a window for IFCC members and Functional Units and a hosting platform for IFCC initiatives and projects Several major and minor updates have been done in 2016. Policy and Procedure for IFCC functional unit web pages have been prepared and final version will be ready for circulation in short.

Databases: The NPU, Register of Experts, and Publications databases are the active databases currently on the website. An eAcademy membership database is being developed with the eAcademy.

Distance Learning Programs and eAcademy: The second phase of the eAcademy was launched in Madrid. Siemens has agreed sponsorship of live webinars. There is ongoing publication of content as approved by C-DL. The distance learning pages of the website continue to develop and we are now able to offer access to a significant amount of content, which has been reviewed by the C-DL. Jointly the C-IeL. C-DL will continue to work on the development of the eAcademy. Total items published between June 2015 (launch) and Sept 2016: 46 webinars; 50 external links. Webinars in preparation include the following topics: A series on immunoassay; Uncertainty and traceability; BNP/NTProBNP, GH/IGF1; The R-A-A system; The first three of a comprehensive set of modules on serum proteins and immunology.

WG-Electronic Journal of the IFCC (WG-ejIFCC) by Gabor Kovacs, Chair Major accomplishment: Officially published online by PubMed in October 2016 Next steps: Indexing in Google Scholar, Scopus, Web of Sciences-Thomson Reuters followed by IF attribution. The ejIFCC collection is available at: http://www.ifcc.org/IFCC-COMMUNICATIONS-PUBLICATIONS-DIVISION-(CPD)/IFCC-PUBLICATIONS/EJIFCC-(JOURNAL)/E-JOURNAL-VOLUMES Membership: Dr. Rajiv Erasmus (ZA) discontinued his membership in the editorial board. New editorial board members: Gary Myers (US), Jillian R. Tate (AU), Ronda Greaves (AU), János Kappelmayer (HU), Allan Jaffe (US).

VOLUME 27 no 1/2016: The issue was dedicated to Harmonization of Clinical Laboratory Results. Guest Editors: Jillian R. Tate (AU), Gary L. Myers (US): http://www.ifcc.org/ifcc-news/archive-2016/2016-02-09-ejifcc-vol-27-n%C2%B0-1/ VOLUME 2/2016: The issue was dedicated to Celebrate the 70th anniversary of the Hungarian Society of Laboratory Medicine. Guest editor: Janos Kappelmayer (HU), president-elect of the Hungarian Society: http://www.ifcc.org/ifcc-news/archive2016/2016-04-20-ejifcc-vol-27-n%C2%B0-2/ VOLUME 3/2016: The issue was focused around new markers of cardiac diseases. Guest editor: Allan S. Jaffe (US): http://www.ifcc.org/ifcc-news/archive-2016/2016-08-01-ejifcc-vol-27-n%C2%B03/ VOLUME 4/2016: The issue was dedicated to Recent Developments in the Clinical Application of Mass Spectrometry. Guest editor: Ronda Greaves (AU): http://www.ifcc.org/ifcc-news/archive-2016/2016-12-22-ejifcc-vol-27-n%C2%B04/

WG-IFCC News (WG- eNews) by Tahir Pillay, Chair 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.

A working group meeting was last held in Paris on 22 June 2015. The next one is likely to take place during EuroMedLab 2017 in Athens.

The newsletter provides regular updates of the structure and strategy of the IFCC, Working groups, and Divisions and several of these have now appeared. In recent months, we have taken a decision to insert more hyperlinks to documents to limit the number of pages in each edition. Occasional articles have also been published in Spanish and French. The schedule of 6 issues per year has been maintained with good content.

The eNews collection is available at: http://www.ifcc.org/ifcc-communications-publications-division-(cpd)/ifcc-publications/enewsletter/enewsletter-volumes/ New IFCC e-News FLASH was Launched in May • Provides quick updates on IFCC activities to keep open the communication channel • In 2016: 5 issues + a Special one - on occasion of President elect election • From 2017: 6 issues/year + special issues for breaking news!

• 15.000 professional readers all over the word • Bi monthly email distribution • The eNews Flash collection is available at: http://www.ifcc.org/ifcc-communications-publications-division-(cpd)/ifcc-publications/enewsletter/enews-flash-archive/ .

Relationship with LabMedica International. LMI prints a selection of the articles. The eNews editor is on the editorial board of LabMedica.

WG-Spanish (Ibero-American) Nomencalture and Translations

by Maria del Carmen Pasquel, Chair Membership: new members are participating into the WG activities representing all Ibero American IFCC countries. The RIA section of IFCC website is continuously updated and a selection of presentations given at the IFCC GC in Madrid were translated into Spanish, and published on the website. New programs and initiatives are planned, mainly focused on updating the RIA section of the website and on the next congress to be held in Punta del Este, UY, in 2017. DiV, Diagnostico in Vitro has been renewed, restyling it in accordance with eNews. Three issues have been published in 2016. 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 – by Bruce Jordan Bruce Jordan (Roche Diagnostics) has been a very active participant in the CPD EC and has provided great support for IFCC public relations. His recent activities have included: • New IFCC posters that were displayed on occasion of the Madrid GC • Supporting IFCC CPD meeting logistics at IFCC GC in Madrid • Supporting the IFCC Specialized Conference on Biomarkers in Alzheimer Disease (Mexico City, 20th May 2016) Khosrow Adeli, CPD Chair

IFCC TASK FORCES • TASK FORCE ON ETHICS (TF-E) Achievements during 2016: Produced a chapter on Ethics for the IFCC Handbook, in final editing stages now. Was submitted to Leslie Lai January 2016 for online IFCC training/teaching handbook entitled “Essentials of Clinical Laboratory Management in Developing Regions"; Gronowski presented lecture entitled "Ethics in Laboratory Medicine: Using “Pearls” as an innovative teaching method" which was presented at the General Conference meeting Madrid 2016; Created 3 ethics teaching modules "Pearls" for Clinical Chemistry Trainee Council website.

Plans for 2017: Updating white paper on publications ethics on the IFCC website with more links to regional and local resources links still in process; Create Ethics "toolbox" for Member Societies (starting with example COI and code of ethics from member societies);Create Pearl on Ethical considerations of biobanking; Create Pearl on Ethical cases in laboratory medicine; Draft an IFCC newsletter article on TF accomplishments and future plans.

Ann Gronowski, Chair

• TASK FORCE ON PEDIATRIC LABORATORY MEDICINE (TF-PLM) Planning for XIV ICPLM in Durban ZA: venue, Symposia topics, chairs and co-chairs determined. Financial support still difficult to find, mainly because there is little paediatric expertise in Africa with very few children’s hospitals. Industry support in Africa is sorely lacking. Attempts to generate financial support from aid organisations and the UN/WHO have not met with good response. The most common response is no response; Circulation of Survey Monkey regarding laboratory management of paediatric critical risk results. Report presented in Madrid 2016; Further discussion regarding Alkaline Phosphatase replacement therapy and ALP reference intervals; Discussion with Prof. Ichihara of Reference Intervals and Decision Limits (CRIDL) regarding collaboration in regard to reference interval development held in Paris 2015; Discussion with Communications and Publications Division (CPD) regarding p(a)ediatric focused issue of eJIFCC; Four webinars regarding reference in-

Special Supplement to Lab Medica International • 29

8

2016 Annual Report

tervals in childhood are being prepared for eAcademy of the IFCC. Also, a curriculum for paediatric clinical chemistry is being prepared for the e-Academy with a September finish date.

Michael Metz, Chair

• TASK FORCE ON PHARMACOGENETICS (TF-PG) Achievements in 2016: Organisational: Organizing Eu-PIC/IFCC/ESPT network meeting (Rotterdam (May 26-27); Further collaboration with the IFCC C-MD (chair: Debs Payne) on Expertcenters Pharmacogenetics and dissemination of knowledge; Investigating organization of a PGx seminar in Washington, involving/ accessible for US Congress members (with AACC PM Division); Extend the TF-PG with one young scientist; TF-PG meeting in Madrid during General Conference (March). Education: Organize a PGx Workshop at the IFCC 2016 Madrid meeting; Organizing speakers and topics for Athens 2017 EuroMedlab and Durban 2017 Worldlab for updating IFCC members on latest PGx developments Research; Investigate 2016 grant opportunities with IFCC as partner (Eu-PIC May 26). Guideline development: Publish guideline paper on CYP2D6/psychiatry in collaboration with EPA; Publish a guideline paper on standards for PGx testing; Investigate the feasibility of a guideline paper of CYP2D6/tamoxifen and with the European Society for Oncology; Reevaluate and update TPMT guideline for publication; Investigate the feasibility of a guideline paper as follow up to the ESC guidelines on clopidogrel/CYP2C19 testing recommendations; Investigating further collaborations with IUPHAR, Genomic medicine Alliance and IATDMCT (guidelines). Expected publications 2016: Comment EHJ on ESC guidelines involving CYP2C19 testing/ clopidogrel; Guideline for Capecitabine/DPYD testing with the European Soc Oncology; Guideline for TPMT/azathioprine testing; Guideline on PGx testing procedures Points for attention of IFCC Executive Board: Approval to extend the TF-PG with one additional member, being a young scientist, currently missing from this committee. Publications : Pharmacogenetic Allele Nomenclature: International Workgroup Recommendations for Test Result Reporting. Various, Clin Pharmacol Ther. 2015 Oct 19. doi: 10.1002/cpt.280; European Society Cardiology (ECS) Guidelines for management of ACS on clopidogrel: a conflict with FDA and EMA recommendations? Various.

Ron van Schaik, Chair

• TASK FORCE ON CHRONIC KIDNEY DISEASE (TF-CKD) (JOINT WITH WASPALM) Achievements in 2016: Organisational: Meeting between Chair and EB liaison in Philadelphia, August 2016; TF meeting held in Philadelphia, August 2016 (Minutes available); Future programme of activities being discussed with Members; Need to update membership recognized; Two publications on national CKD guidelines arising from TF encouragement; Lecture in Lagos, Nigeria, October given based on TF past achievements; Symposium In APFCB Taipei, November 2016 organised by previous Chair. Plans for 2017: TF meeting at EuroMedLab, Athens in June; Open meeting on CKD at EuroMedLab, Athens in June; Symposium on kidney diseases at EuroMedLab, Athens in June. Comment: TF-CKD has had a quiet year following the change of Chair; Since August there has been activity and plans are in place for 2017; This is a joint TF with WASPaLM, although there is little or no contribution from WASPaLM; There are several Corresponding Members who are doing useful projects in their own countries and TF-CKD is the ‘glue’ that holds these together; TF-CKD is one of the longest established TF. 2017 will be an important year for it to see if it can regain momentum Flavio F Alcantara, Chair

• TASK FORCE FOR YOUNG SCIENTISTS (TF-YS) Achievements during 2016: Update to membership of core group; Now 35 Corresponding Members and growing; Regular meetings and discussions by social media; Publication of Research Guide in both text and webinar (e-Academy) format; TF meeting held during General Conference in Madrid in March 2016; Session on scientific writing in Harare, Zimbabwe in June 2016; Session in Lagos, Nigeria in October 2016; Open workshop on the YS workforce planned for Taipei in November 2016; Symposium planned at ACBICON in Mangaluru, India in December; Complimentary Educational Webinar: ISO Accreditation: New Trends and Global Differences – September 2016; Project Award from FEN to establish ‘Lab Surfing’ – see www.lab-surfing.com; Regular updates to the TF-YS pages on the IFCC website. Plans for 2017: TF meeting and open session at EuroMedLab Athens, June 2017; Symposium at WorldLab Durban, October 2017; Collaboration with WASPaLM to support YS session at WASPaLM congress in Japan, November 2017, Further webinars (TBA); Promotion of ‘Lab Surfing’, Research Guide Pradeep Kumar Dabla, Chair

• TASK FORCE ON CLINICAL APPLICATIONS OF CARDIAC BIOMARKERS - (TF-CB) Prof. Jordi Ordoñez-LLanos, MD, PhD is completing his second term at the end of 2016. He proposed Dr Fred Apple as the new Chair among the TF-CB members and expressed his willingness to continue his service in the TF-CB as a consultant, to aid to the new Chair in his first service period. Dr Apple accepted to serve and IFCC EB approved him as the new chair of the TF-CB. A call for nominations has been issued to appoint four TF-CB members positions.

The Chair suggested to be given freedom to nominate as Consultants, clinicians and laboratorians, provided wide geographic distribution is respected. The TF-CB has several on-going projects that require both of the full work and complicity of the members. The complicity will be readily reached if the members to be appointed are well-experienced in the TF-CB topics.

The main aim of the TF-CB in the evaluated period (2011-2016) was to educate on cardiac biomarkers; during this period high sensitive cardiac troponin assays were introduced in the clinical practice. Given the characteristics of these assays, the TF-CB decided to devoid its efforts to educate on these assays. The results were the mentioned manuscripts as well as specific educational materials available at the IFCC website.

Jordi Ordoñez-Llanos, Chair

• TASK FORCE ON POINT OF CARE TESTING (TF-POCT) Achievements in 2016: TF met in March on occasion of the IFCC General Conference and discussed a variety of issues, especially the potential to have a PoCT meeting in Durban attached to WorldLab and development/update of documents. Several teleconferences were held to develop an appropriate program and identify appropriate speakers.

The cost of satellite meetings was raised at discussion time with some countries reporting costs associated with going to a conference make it prohibitive; efforts have been considerable in order to raise sponsorship money to make the satellite PoCT Meeting possible in Durban; the program was developed in order to rest both local people and international participants.

Talks will be predominantly given by TF members to reduce meeting overheads and make this possible.

Participants who register for the main meeting will receive free registration to the PoCT satellite meeting. TF acknowledge contribution of corporate members to make the satellite possibile.

A meeting was held at AACC meeting in Philadelphia involving any members who were attending AACC. This group was particularly interested in developing a document on blood gases, template should be available on IFCC website at the end of 2017.

The group chaired by Cynthia Bowman on “How Glucose Meters be evaluated for critical care” has been very active as well.

Rosy Tirimacco, Chair

IFCC

InSoft, the IT provider of the IFCC, appointed in November 2014, using the preliminary workflow and schematic of the database - web application that was finalized during the meeting of the TF at the EuroMedLab 2015 in Paris, started the implementation of this project.

Achievements in 2016: During the first months of 2016 InSoft continued the development of the Database project and a functional prototype has been presented at the Madrid General Conference of IFCC. During this meeting the Chair of the TF-PT presented an interactive workshop entitled “Meeting the clients with the producers on Proficiency Testing of rare analytes” describing the aims, the projects, and the prototype of the online database - web application. The presentation can be found at: http://www.ifcc.org/media/412855/S6.12.Haliassos_WS_GC2016.pdf. Moreover, at the Madrid General Conference, the members of the TF-PT had their third annual meeting. Following this meeting the TF-PT chair in cooperation with Amann Egon, chair of the Analytical Quality (C-AQ) committee, prepared two mails, approved afterwards by the President of IFCC, to be sent automatically by the database - web application when this project will be rolled out, to the scientific community. These mails will invite the PT-EQA providers to cooperate for this project and register or update the data of their organizations in the database. Moreover, will request the cooperation of the National Representatives of the IFCC in order to spread the word about the functionalities of the database - web application project to the PT-EQA providers of their countries.

During the fall of 2016 the chair of TF-PT participated at the EQALM EB meeting (Barcelona, October 13th & 14th, 2016) where was finalized the participation and the help of the EQALM members for the implementation, updating and maintenance of the TF-PT database, especially the “P”roviders section. The final details of the scientific program for the co-organized symposium on “EQA-PT issues” at the next EuroMedLab Athens 2017 had been discussed during this meeting.

The roll out of the “P”roviders database by InSoft was accomplished at the end of 2016, and the database can be found at the URL: http://ptdb.ifcc.org.

During the last quarter of the year another four (4) corresponding members, nominated either by National Societies (3) or

by Corporate Members (1), had been added to the TF-PT. Plans for 2017: After the implementation of the “P”roviders database by InSoft the development of the “A”nalytes section will be started adding all the common analytes from the already registered EQA-PT providers.

Also during the winter of 2017 the next meeting of the TF-PT members is planned by teleconference. The fourth face to face annual meeting of the TF-PT members will be organized during the EuroMedLab Athens 2017, as well as the symposium on EQA-PT issues co-organized with the EQALM and entitled: “External quality assurance - just a necessary evil or a valuable tool in laboratory management?”.

Alexander Haliassos, Chair

FOUNDATION FOR EMERGING NATIONS - FEN The Foundation for Emerging Nations (FEN) was established under Swiss law as a non-profit making charitable trust, registered on 15th February 2016. The FEN is devoted to fund raising and to supporting programmes that help to improve the quality and delivery of laboratory medicine services, particularly in emerging nations.

The FEN Board of Directors are: Dr GH Beastall (UK) Chair, Dr M Rossier (CH), Prof T Brinkmann (DE), Ms L Monaco (IT) and Prof T Ozben (TR). The current five Directors have a good geographical distribution and varying backgrounds in laboratory medicine, education and fundraising.

During 2016 the Board met (by Skype) on four occasions; achievements were reached on following topics: - entry on to the Handelsregister des Kantons Schwyz; - Approval of the Swiss Foundation Supervisory Authority granting of tax-free status; - Appointment of the Seedamm Business Center AG in Pfaffikon, Switzerland as the formal address for the FEN; - Appointment of Ametis Revision Sàrl, Geneva as formal auditor for the FEN; - Establishment of a bank account with Credit Suisse, Geneva using start-up funding provided by IFCC; - Approval of the FEN business plan and fundraising strategy; - Creation of the FEN website www.ifccfoundation.org; - Launch of the FEN at the IFCC General Conference in Madrid; Promotion of the FEN through various IFCC media outlets and through Labmedica International (English and Spanish versions); - Publication and distribution of first FEN newsletter; - Two calls for project proposals followed by assessment of the received proposals; - Fundraising initiatives; - Funding approval for three projects, as follows: Laboratory based surveillance for communicable disease in Malawi: The FEN approved an application from the Malawi Association of Medical Laboratory Scientists (MAMLS) to support two laboratory scientists to receive laboratory-based disease surveillance training at the ‘amref health Africa’ headquarters in Nairobi, Kenya. The training course aims to build capacity of laboratory staff in the implementation of laboratory-based surveillance and public health actions, based on the evidence from laboratory data. On completion of their training the two scientists will develop training materials, which will be promoted and made available to clinical laboratories throughout Malawi. This project is supported by the Ministry of Health in Malawi and is a good example of collaboration in the interests of improving public health.

‘Lab Surfing’: A resource to facilitate global exchange between young scientists: ‘Lab Surfing’ is a project designed by the IFCC Task Force for Young Scientists (TF-YS) and proposed by YS from Argentina, India and Nigeria. It will support the construction and launch of a website to connect YS from around the world, and especially from emerging nations. The specific aim of the Lab Surfing project is to facilitate self-organised exchange programmes between YS who are trainees in laboratory medicine. The outcome of ‘Lab Surfing’ will be measured in terms of the number of YS using the site, their countries of origin and the exchanges that derive from those contacts.

‘Adopt a Professional’ : Collaboration to support the training of laboratory medicine specialists: The ‘Adopt a Professional’ project is a collaboration between the FEN and the Societá Italiana di Biochimica Clinica e Biologia Molecolare Clinica (SIBioC). The FEN and SIBioC have signed a memorandum of understanding to collaborate in providing training in laboratory medicine to scientists from designated emerging nations. Trainees will be selected on merit to spend time training in an Italian centre of excellence. Trainees will be supported after their visit through a mentorship scheme. Fundraising for the first trainees has been achieved and recruitment has commenced. The first trainees will enter the ‘Adopt a Professional’ project in 2017.

Finances: Audited accounts for the year to 31st December 2016 are available on request. In summary: Income: Expenditure: Start-up donation from IFCC 50 000 CHF Cost of establishing FEN 11 719 CHF Fundraising 15 013 CHF Project funded 9 054 CHF Operating costs 1 308 CHF Total 65 013 CHF Total 22 081 CHF Balance at 31/12/16: 42 932 CHF Conclusion: In presenting this first annual report the Board Of Directors confirms that the governance of the FEN is sound.

The Board believes that the FEN has had a positive year of achievement, which it intends to develop further during 2017.

• TASK FORCE ON PROFICIENCY TESTING (TF-PT) Organization, history and previous achievements: The TF-PT is “a multidisciplinary effort in the analysis and the exploration of the Proficiency Testing issues. This could lead to the establishment of specialized schemes under the hospices and recommendations of the IFCC and could greatly enhance and help to the prevalence of the methods derived from the work of the federation and to the harmonization of laboratory results.”

The main project of the TF-PT is the creation of an online database - web application accessible via web browsers but also via specific applications for the major mobile platforms with much more functionalities and ease of use. The roots of this database will be the analytes (tests, measurands) that will be filed with all possible synonyms (one of them will be the "official" as proposed from the Nomenclature, Properties and Units (C-NPU) committee of the IFCC C-SD) as also as the methods (assays, instruments, reagents etc) also with all possible synonyms. Another part of the DB, maintained with the cooperation of the IFCC committee for Analytical Quality (C-AQ) and of EQALM, will be the PT providers section containing all their contact information, their programs with the analytes, frequencies, type of statistics, commutability of control materials, their accreditation or certification status etc.

During 2014 the TF-PT had his kick-off meeting at the WorldLab 2014 in Istanbul, afterward the chair of the TF had a meeting with the board of EQALM in Toulouse at the end of October 2014 in order to request a close cooperation and the participation of EQALM to the TF-PT. Early October 2015, TF-PT and EQALM agreed to co-organize a symposium on EQA issues at the next EuroMedLab Athens 2017.

Moreover at the EuroMedLab 2015 congress in Paris the members of the TF-PT had their second annual meeting. The result of this meeting was the production of two draft documents: one entitled “Exploration and Clarification of Specifications for the TF-PT Project” containing analytically the terminology of the project, and one entitled “Webpage IFCC Market Place Forum Supply and Demand EQA” describing the basic workflow diagram of the proposed application-database with various examples in a table form.

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 2015, web edition.

FOR MORE INFORMATION ON THE IFCC CONTACT: 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

Special Supplement to Lab Medica International • 30

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

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Singulex, Inc. (Alameda, CA, USA; www.singulex.com) is developing its SMC technology for clinical immunodiagnostics and scientific discovery, to enable physicians and researchers to detect disease biomarkers that were previously undetectable. Singulex Clinical Lab Testing Services currently provide a comprehensive menu of advanced cardiovascular disease testing utilizing SMC technology.

“Receiving ISO 13485 certification validates the quality processes we have put in place to build Singulex into the Next Generation Immunodiagnostics Company, and are very pleased that NSAI recognizes Singulex as meeting the highest quality of standards,” said Guido Baechler, Singulex president and CEO. The certification from this independent organization ensures quality, safety, and efficiency, and prepares Singulex for market entry of its Sgx Clarity System, an automated in vitro diagnostics platform currently under development for hospital and reference labs worldwide.

The system is currently undergoing evaluation in Europe and may achieve the CE-Mark by the end of Q1 2017. Singulex is planning to submit the Sgx Clarity System to the FDA in early 2017.

“Achieving ISO certification ensures that laboratorians, physicians, and patients will receive the highest quality diagnostic information as we commercialize the Sgx Clarity System, the most sensitive fully-automated immunoassay analyzer,” said Baechler.

Singulex’s SMC technology, which will power next-generation immunodiagnostics delivered through the Sgx Clarity System, provides immunodiagnostic assays that are 100 times more sensitive than those on other testing platforms, enabling unprecedented security to medical decisions. The sensitivity of SMC technology allows physicians to measure what they could not see before, allowing to better understand all stages of disease and help determine a patient’s health status, including disease risk. SMC technology has been scientifically established through clinical studies involving greater than 100,000 patients, resulting in greater than 110 peer reviewed publications.

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mage: The Sgx Clarity system, being developed for highly sensitive next-generation immunodiagnostic detection, provides simple and intuitive operation (Photo courtesy of Singulex).

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IMMUNOASSAY SYSTEM

HBA1C ANALYZER

BMG Labtech

Beckman Coulter

Trinity Biotech

The SPECTROstar Nano performs assays in microplates or via a built-in cuvette port, and captures a full UV-visible spectrum in less than 1 second per well. Its speed, simple push-button operation, and capacity to store individual assay protocols make it ideal for absorbance measurements.

The UniCel DxI 800 processes up to 400 tests/hour using ready-to-use reagents, and has a load capacity of 120 samples. The reagents and consumables can be loaded without using the console computer or pausing the system, and it offers a broad menu for various disease states.

The Tri-stat POC device uses boronate affinity technology and a two-phase optical system to analyze three samples simultaneously and deliver accurate results in 10 minutes. It requires only a small sample of whole blood, and minimal operator intervention.

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Microfluidic Chip Developed for Ultrasensitive Glucose Detection ighly sensitive and rapid detection of blood glucose is a diagnostic necessity in medicine as, for instance, lack of insulin and too much blood sugar are two main causes of diabetes, both of which can be detected by measuring blood glucose.

Fiber optics and microfluidics have been used to develop a cheap, ultra-sensitive lab-on-a-chip device that can quickly measure glucose in just a drop of sweat. The technology behind it belongs to a new field called “optofluidics” that brings together photonic sensing (using the properties of light to detect chemicals) and microfluidics (precise control of tiny amounts of fluid along microchannels).

Scientists at the Hong Kong Polytechnic University (Kowloon, Hong Kong SAR, China; www.polyu.edu. hk) and their colleagues combined a

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new fiber optic biosensor with a microfluidic chip to create an interference-free optofluidic device for ultra-sensitive detection of glucose levels. The fiber optic sensor they created is very sensitive to changes in the refractive index of the material that surrounds it. To transform it into a glucose monitor, the team used a film of glucose oxidase as a sensing material as it reacts with glucose in solution.

To both support the sensing film and further enhance the signal, the team incorporated layers of two other materials – polyethylenimine (PEI) and polyacrylic acid (PAA), into the sensor. The result was several layers of PEI/PAA, with a top layer of glucose oxidase that was then embedded in the microchannel of the chip. After running several tests, the investigators found the fiber optic sensor was very sensitive on its own and can de-

tect glucose oxidase concentrations as low as 1 nM, but after they integrated it into the microfluidic chip, the sensor’s performance remarkably further improved. The sensor improved not only in detection range, but also in response time, which shortened from six minutes to 70 seconds.

A. Ping Zhang, PhD, an Assistant Professor and co-author of the study said, “Photonic approaches are seen as one of the most promising techniques for ultra-sensitive sensing, and when you integrate photonics with

the tiny platform that microfluidic chips offer, you can make a small labon-a-chip analysis system for fast and reliable results.” The study was published on April 28, 2016, in the journal Biomedical Optics Express.

Image: The lab-on-a-chip device integrates a fiber optic biosensor with a microfluidic chip and detects glucose levels from droplets of sweat. It is shown here next to a Hong Kong dollar, which is the same size as the USD coin (Photo courtesy of Dr. A. Ping Zhang).

Two New Types of Childhood Leukemia Discovered cute lymphoblastic leukemia is a rare disease, but the most common form of cancer in children and nowadays the treatment is very successful, but requires intense interventions at the risk of causing many side effects.

There is therefore a need to distinguish between different types of acute lymphoblastic leukemia, in order to adapt the treatment according to the severity of each case, and to detect possible relapse. Previous studies of childhood acute lymphoblastic leukemia have shown that there are six major groups of acute lymphoblastic leukemia in children.

A large team of international scientists led by those at Lund University (Sweden; www.lund university.lu.se) studied leukemia cells from more than 200 children using next-generation sequencing

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technology (NGS), and were able to study the genome of cancer cells, which is how they discovered the two new types of cancer. The discovered two new types, together representing about 10% of all childhood leukemia, can now be added to the other groups.

The investigators were able to delineate the fusion gene landscape in a consecutive series of 195 pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL). They used ribonucleic acid (RNA) sequencing, to find in-frame fusion genes in 127 (65%) cases, including 27 novel fusions.

They describe a subtype characterized by recurrent IGH-DUX4 or ERG-DUX4 fusions, representing 4% of cases, leading to overexpression of DUX4 and frequently co-occurring with intragenic ERG deletions. They identified a subtype

characterized by an ETV6-RUNX1-like gene-expression profile and coexisting ETV6 and IKZF1 alterations. The study provides a detailed overview of fusion genes in pediatric BCP ALL and added new pathogenetic insights, which may improve risk stratification and provide therapeutic options for this disease.

Thoas Fioretos, MD, PhD, a professor and principal investigator of the study said, “Like all types of cancer, childhood leukemia is caused by genetic mutations in normal cells, which are then transformed into cancer cells. Finding the critical mutations in the diseased cells are an important condition for understanding the mechanisms of the disease and ultimately discovering new therapies,” The study was published on June 6, 2016, in the journal Nature Communications.

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Performance of Hematology Analyzer and Peripherals Evaluated he complete blood count and leukocyte differential count are the basic, most common tests in hematology laboratories.

More tests can be performed at the same time; labor reduced, and results made more precise by an advanced automated hematology analyzer and slidemaker/stainer.

Reducing review of unnecessary blood film without missing true abnormal samples is the goal of automated hematology analyzers, because manual review increases laboratory cost, labor, and turnaround time.

For the same reason, automated slidemaker/strainers demand quick, high-quality blood films.

Hematologists at the Gachon University Gil Medical Center (Incheon, Korea; www.gilhospital.com) selected 408 samples to evaluate a new hematology analyzer. Samples were collected from patients who needed a peripheral blood smear test by physicians’ recommendation and from patients who had regular

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checkups. Two hundred of 408 samples showed flags, and 208 samples did not show any flags by the regular analyzer used in the laboratory.

The scientists compared the CAL 8000 (Mindray Bio-Medical Electronics Co, Ltd, Shenzhen, China; www.mindray.com) which is a cellular analysis line consisting of the Mindray BC-6800, an automated hematology analyzer, and the Mindray SC-120, an automated slidemaker/stainer and compared the analyzer results with the data from the XE-2100 automated hematology analyzer (Sysmex, Kobe, Japan; www.sysmex.com) and the slidemaker with a manual method.

The team reported that most parameters measured by the BC-6800 matched well with the XE2100 and manual differential. The flag efficiency of the BC-6800 for blasts (95.3%) and atypical lymphocytes (92.6%) were higher while immature granulocytes (89.7%) and nucleated red blood cells (94.1%)

were lower than that of the XE-2100. Additionally, the BC-6800 detected four of five samples infected with malaria parasites. The SC-120 showed no carryover and expected repeatability. There was good agreement on the five-part differential including abnormal cells between blood films by the SC-120 and manually prepared blood films. The shape of the red blood cells (RBC) was also comparable between blood films. The authors concluded that the performance of BC-6800 was comparable with the XE-2100, and has a further advantage of detecting infection of malaria parasite. The SC-120 agreed well with manual differential and morphology assessment although the SC-120 needed the adjustment for stain precipitate and steaks. Therefore, the CAL-8000 is effective for precise, fast hematology work, and has useful application for malaria endemic areas. The study was published on September 23, 2016, in the Journal of Clinical Laboratory Analysis.

New Technology Quickly Diagnoses Malaria he gold standard for malaria diagnosis is manual microscopic evaluation of Giemsa stained blood smears; however, the utility of this approach is limited by the skill of an expert microscopist. Further, both the staining process and microscopic examination can be time consuming. A computerized method has been developed that relies on computers and light-based holographic scans correctly identified malaria-infected cells in a blood sample and this technique does not require any human intervention and could form the basis for a rapid field test for malaria.

A multidisciplinary team of scientists from Duke University (Durham, NC, USA; www.duke.edu) collected whole blood samples from healthy donors and red blood cells (RBCs) were isolated and purified.

RBCs were infected with a Plasmodium falciparum, and synchronized. During the 48-hour life cycle, infected RBCs were isolated from the general RBC population by magnetic sorting via a magnetic cell separation system (MACS, Miltenyi Biotec, Bergisch Gladbach, Germany; www.miltenyibiotec.com) to separate uninfected RBCs from those containing parasites. The team used quantitative phase spectroscopy system (QPS) to image red blood cells. Refocused images are analyzed to extract 23 morphological descriptors based on the phase information.

Machine learning algorithms were used to distinguish uninfected RBCs from three different hemozoin containing stages of P. falciparum infected RBCs (early trophozoite–ET, late trophozoite–LT, and schizont–S).

The authors concluded that one of the main strengths of using machine learning algorithms to analyze the extracted parameters is that the identification of RBC infection will be based on quantified metrics and pre-built classifiers that requires minimal operator training. In order to enable automated imaging in the future, a microfluidic device with controlled flow rates can be combined with the analysis approach that would allow high throughput. The study was published on September 16, 2016, in the journal PLOS ONE.

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RAPID IMMUNOASSAY TEST

HEMATOLOGY ANALYZER

Alere

Trinity Biotech

Mindray

The Alere Reader detects and identifies completed lateral flow assays, analyzes the intensity of the test and control line, and displays results on the touch screen. It features barcode technology to maximize data entry accuracy and minimize human error, while ensuring QC controls are tested.

The Uni-Gold S. pneumoniae single-use rapid immunoassay is designed for the qualitative detection of Streptococcus pneumoniae antigen in patients with suspected pneumonia or meningitis.

The 15-minute test has a three-step procedure and does not need to be warmed up before use.

The CAL 8000 (NEW) is a new generation cellular analysis line, with higher level of automation, functionality and flexibility. The system consists of up to four units of BC-6800 analyzers, and two units of SC-120 auto slide makers and strainers, with a total throughput of up to 500 tests per hour.

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Simple Black Box Turns a Smartphone Into a Home Diagnostics Lab n innovative use of the smartphone camera may allow individuals to skip visits to the doctor or clinic by enabling the performance of sophisticated blood or urine tests at home.

Dipstick assays traditionally suffer from user error due to imprecise sample delivery, inaccurate readout timing, and uncontrolled lighting conditions. To prevent these types of errors innovators at Stanford University (Palo Alto, CA, USA; www. stanford.edu) have developed a novel system for in-home testing. The system for dipstick urinalysis comprises a reusable manifold and companion software.

The all-acrylic manifold is reusable, reliable, and low in cost. Clever engineering ensures that a uniform volume of urine is deposited on each of the dipstick’s ten pads at just the right time. A simple

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timing mechanism ensures results are read out at the appropriate interval. Results are obtained by capturing videos using a mobile phone’s camera and by analyzing them using custom-designed software.

Results obtained with the proposed device were found to be as accurate and consistent as a properly executed dip-and-wipe method, the industry gold-standard, suggesting the potential for this strategy to enable confident urinalysis testing in home environments.

“It is such a hassle to go into the doctor’s office for such a simple test,” said first author Gennifer T. Smith, a doctoral student in electrical engineering at Stanford University. “This device can remove the burden in developed countries and in facilities where they do not have the resources to do these tests.”

The device was described in detail in the May 11, 2016, online edition of the journal Lab on a Chip.

Image: The black box is part of an experimental urinalysis testing system meant to enable a smartphone camera to capture video that accurately analyzes color changes in a standard paper dipstick in order to detect conditions of medical interest (Photo courtesy of Stanford University).

Blood Transfusions in Malaria Zones Made Safer atients, especially children, who undergo blood transfusions in sub-Saharan Africa, are at high risk of transfusion-transmitted malaria. Every year, approximately 214 million people worldwide are infected with acute malaria, the majority of whom are in Africa and the disease is caused by the parasite Plasmodium.

A new trial suggests that treating donated blood with a new technology that combines ultra-violet (UV) radiation and vitamin B is safe and could minimize the risk of malaria infection following blood transfusions. Commonly used procedures for whole blood include nucleic acid testing, blood filtration or bacterial culture, but these are not done in most developing countries because of a lack of resources.

Scientists at the University of Cambridge (UK; www.cam.ac.uk) and their colleagues carried out a randomized, double-blind, parallel-group clinical trial of eligible adult patients, aged 18 years or more, with blood group O+, who required up to two whole blood unit transfusions within three

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days of randomization and were anticipated to remain in hospital for at least three consecutive days after initial transfusion. There were 223 adult patients who needed a blood transfusion because of severe anemia or hemorrhage took part in the study.

The team analyzed blood samples for all of the transfusion recipients on the day of the transfusion and 1, 3, 7 and 28 days later. By studying the sequences of Plasmodium genes present in the blood, they were able to tell whether the patients were likely to be carrying the donor parasite after the transfusion. A total of 65 patients were not previously carrying the parasite, half received parasite treated blood, and the other half received parasite untreated blood. There were 8/37 patients (22%) who received untreated blood later tested positive for malaria parasite, compared 1/28 (4%) of patients who received treated blood.

Treatment of whole blood was with the Mirasol Pathogen Reduction Technology (Terumo BCT,

Lakewood, CO, USA; www.terumobct.com). Coagulation parameters, platelet counts and hemostatic status of the patients was similar whether patients received treated or untreated blood. The technology did not appear to affect the coagulation properties of the blood, and patients who received the treated blood had slightly fewer allergic reactions to those who received the untreated blood (5% versus 8%).

Jean-Pierre Allain, MD, a professor and lead author of the study said, “Testing for parasites such as malaria is expensive and until now, there have been no technologies capable of treating whole blood, which is most commonly used in transfusions in sub-Saharan Africa. This is the first study to look at the potential of pathogen-reduction technology in a real-world treatment setting and finds that although the risk of malaria transmission is not completely eliminated, the risk is severely reduced.” The study was published on the April 21, 2016, in the journal the Lancet.

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Study Leads to Improved Diagnosis Of Inherited Heart Muscle Disease n a groundbreaking study of Mendelian gene pathogenicity, using comparative population genetics, researchers have developed more accurate diagnostics for inherited cardiomyopathy. The approach improves interpretation of the medical significance of gene mutations in patients being tested for a genetic condition.

In the study, experts from the University of Oxford (Oxford, England, UK; www.ox.ac.uk) and Royal Brompton Hospitale (London, UK; www. rbht.nhs.uk) compared genetic data from nearly 8,000 patients who have cardiomyopathy (CM) with over 60,000 reference samples from the general population. The aim was to reassess the role that variants in different genes play in causing the condition.

The large CM patient data set was from the Oxford Molecular Genetics Laboratory and the Laboratory of Molecular Medicine, Partners HealthCare (Boston, USA) and was compared with a large general population data set from ExAC, a new database compiled by an international consortium led by the MacArthur Lab (USA).

Rare variants in genes that are typically associated with dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), and arrhythmogenic right ventricular cardiomyopathy (ARVCM), were examined. The study found that rare variants in some of these genes were not more common among the CM patients than the general population. This shows they are unlikely to be valid disease-causing genes and that having rare gene variants is collectively more common than previously thought.

Only 8 of 48 genes previously implicated in DCM, and 2/3 of genes that are regularly screened for HCM, were found to be much more common among the CM patients, thus more likely to be disease-causing genes. As a result, a more targeted approach can be taken with increased confidence to provide a CM diagnosis if one of these gene variants is found. In the past, clinical labs may have taken a more conservative approach, meaning that patients might have received an inconclusive result.

CMs are the most common cause of sudden death in otherwise healthy young people. Since the condition can be genetic, relatives of CM patients often undergo heart tests. Those found to have no symptoms but have the same gene variant as their family member can be monitored and treated, often before the condition can be detected by currently used tests.

Also currently, if genetic testing was inconclusive for a patient, immediate relatives usually receive life-long follow-up care.

BHF Professor Hugh Watkins, head of Radcliffe Department of Medicine, Uni-

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versity of Oxford (UK), said: â&#x20AC;&#x153;These results will help diagnostic laboratories avoid testing genes that canâ&#x20AC;&#x2122;t be interpreted reliably, and be more confident in interpreting variants in the genes that we have shown to be valid.â&#x20AC;?

The study, by Walsh R et al, was published online August 17, 2016, in the journal Genetics in Medicine.

Image: A human heart and cardiogram overlay. Researchers have found that a new approach, using comparative population genetics, improves inter-

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pretation of the medical significance of gene mutations in patients being tested for a genetic condition, such as inherited cardiomyopathy (Photo courtesy of Shutterstock / University of Oxford).

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DIABETIC MARKER

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BioFire

DiaSys Diagnostic Systems

Dymind Biotechnology

The FilmArray System offers user-friendly multiplex PCR with incorporated sample preparation, amplification, detection and analysis all in one system. The five panels test for viruses, bacteria, parasites, yeast and antimicrobial resistance genes, with accurate results in about an hour.

The ß-Hydroxybutyrate is an important marker to detect and monitor diabetic ketoacidosis (DKA), a serious condition in diabetes mellitus. The ß-Hydroxybutyrate 21 FS can be used on common clinical analyzers, and shows improved performance and excellent stabilities.

The DF50 is a compact 5-Part hematology analyzer that provides 27 parameters, three histograms and four scattergrams. It also features a 10.4-inch TFT touch screen display, a throughput of up to 60 tests per hour, and supports capillary blood test mode.

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Newborn Screening Test Developed For Deadly Neurological Disorder newborn screening test has been introduced that identifies infants with Niemann-Pick disease type C, an often fatal condition in which cholesterol builds up and eventually destroys brain cells.

Although this disease was untreatable in the past, new therapeutics are now in clinical trials, but they are most likely to be effective if treatment is started as early as possible, before neurodegeneration has occurred. Niemann-Pick type C disease (NPC) typically is not diagnosed until at least age two, after neurological symptoms have begun to develop.

A team of collaborating scientists led by those at Washington University School of Medicine (St. Louis, MO, USA; www.medicine.wustl.edu) screened more than 5,000 dried blood spot specimens. Of these, 44 were known to be samples from NPC patients; 134 were samples from people who were known carriers; and the remaining 4,992 were control samples from people without the condition. A high-throughput mass spectrometry–based method was developed and validated to measure the glycine-conjugated bile acid in dried blood spots.

The teams used metabolomic profiling to identi-

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fy potential markers and discovered three unknown bile acids that were increased in plasma from NPC, but not control subjects. The bile acids most elevated in the NPC subjects were identified as 3β,5α,6β-trihydroxycholanic acid and its glycine conjugate, which were shown to be metabolites of cholestane3β,5α,6β-triol, an oxysterol elevated in NPCs. The NPC patients have about thirty fold higher amounts of this bile acid in the blood than healthy individuals. Importantly, levels of this bile acid also could distinguish between patients with NPC and carriers of the disease who show no symptoms. Analysis of dried blood spots from the controls, the NPC carriers, and the NPC subjects provided 100% sensitivity and specificity in the study samples.

Daniel S. Ory, MD, a Professor of Medicine and the senior author of the study said, “These types of tests can be quite automated. If you’re running 500 samples per day, you can test many specimens at once at robotic handling stations that many state laboratory facilities already have. The cost of materials and labor would be on par with current accept-

ed newborn screening tests. Once established, a reasonable estimate of the cost of running these tests would be less than USD 1 per sample.” The study was published on May 4, 2016, in the journal Science Translational Medicine.

Image: Dried blood spots are used to screen newborns for a number of rare inherited conditions. A new dried blood spot screening test has been developed for Niemann-Pick type C, a rare neurodegenerative condition that usually is not diagnosed until after damage to brain cells has begun (Photo courtesy of Washington University School of Medicine).

Palm-Sized Device Quickly Detects Ebola Virus he gold standard method for identifying the Ebola virus in a blood sample requires packaging samples in cooled containers and sending them to specialized laboratories, often far away from where patients live.

These laboratories use a method called reversetranscription polymerase chain reaction, or RT-PCR, to check for the virus. The prolonged testing process delays detection, treatment and real-time monitoring of viral loads in body fluids that can harbor the virus even after it is no longer detected in the blood.

Scientists at the Korea Institute of Science and Technology Europe (KIST, Saarbrücken, Germany; www.kist-europe.de) and their colleagues have de-

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signed and tested an instrument, which could simultaneously perform four RT-PCRs that included two controls and two patient blood samples. Conventional tests require several hours to more than a day for results to come in. The new process was completed in slightly over 30 minutes. The amount of blood required was 100 nL and could potentially come from just a finger prick.

The device was shown to concurrently perform four PCRs, one positive control with both Ebola and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) RNA and one negative control. The device successfully detected the Ebola ribonucleic acid (RNA). In addition to diagnosing the illness, the test also yielded information about how many

RNA copies each sample contained. In addition to diagnosing the illness, the experts say that the tool could also potentially help health care workers track patients’ viral loads in semen, breast milk and eye fluids after recovery.

A comparison of threshold cycles (CT) from the two samples provided relative quantification. The entire process, which consisted of reverse transcription, PCR amplification, and melting curve analysis (MCA), was conducted in less than 37 min. The next step will be integration with a sample preparation unit to form an integrated sample-to-answer system for point-of-care infectious disease diagnostics. The study was published on April 11, 2016, in the journal Analytical Chemistry.

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Protein Particle Parameters Help Differentiate Acute Kawasaki Disease awasaki disease (KD) is a self-limited vasculitis that typically presents in young children as an acute illness with fever and mucocutaneous changes. If KD is incorrectly diagnosed or left untreated, coronary artery aneurysms (CAA) may develop, predisposing KD patients to long-term cardiovascular complications including myocardial ischemia and infarction.

Glycosylation patterns of serum proteins, such as 1-acid glycoprotein, are modified during an acute phase reaction. The response of acute KD patients to intravenous immunoglobulin (IVIG) treatment has been linked to sialic acid levels on native IgG, suggesting that protein glycosylation patterns vary during the immune response in acute KD. Scientists at Rady Children’s Hospital (San Diego, CA, USA; www.rchsd.org) and their colleagues enrolled 75 children diagnosed with KD according to established criteria and treated at Rady Children’s Hospital between November 2005 and June 2011. Forty-eight age-similar, healthy children

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undergoing minor orthopedic surgical procedures and 48 febrile children with acute illnesses of viral or bacterial origin were also included in the study as healthy or febrile controls.

White blood cell count (WBC), absolute neutrophil count (ANC), percent polymorphonuclear cells (PMN), high sensitivity C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were measured as part of clinical care. Nuclear magnetic resonance (NMR) spectra were acquired from EDTA plasma for the NMR LipoProfile (lipoprotein particle) test at LipoScience (now LabCorp, Raleigh, NC, USA; www.labcorp.com). The NMR Profiler platform is comprised of a 9.4T (400 MHz 1H frequency) spectrometer (Bruker Biospin, Fremont, CA, USA; www.bruker.com ) with an integrated fluidics sample delivery system.

GlycA, a marker of protein glycosylation, was elevated in acute KD subjects compared to febrile controls with bacterial or viral infections, IVIGtreated subacute and convalescent KD subjects, and healthy children. Acute KD subjects had in-

creased total and small low-density lipoprotein particle numbers (LDL-P) (and decreased total high density lipoprotein particle number (HDL-P) compared to febrile controls. Consequently, the ratio of LDL-P to HDL-P was higher in acute KD subjects than all groups tested. While GlycA, CRP, ESR, LDL-P and LDL-P/HDL-P ratio were able to distinguish patients with KD from those with other febrile illnesses, the combinations of GlycA and LDL-P or GlycA and the LDL-P/HDL-P ratio were best at discerning KD in patients 6 to 10 days after illness onset.

The authors concluded that high levels of GlycA confirm enhanced protein glycosylation as part of the acute phase response in KD patients. When combined with common laboratory tests and clinical characteristics, GlycA and NMR-measured lipoprotein particle parameters may be useful for distinguishing acute KD from bacterial or viral illnesses in pediatric patients. The study was published on September 5, 2016, in the journal BMC Pediatrics.

Rapid Method Developed for Direct Antimicrobial Susceptibility Testing apid identification (ID) and antimicrobial susceptibility testing (AST) of the causative agent(s) of bloodstream infections (BSI) are essential for the timely selection of an appropriate antimicrobial therapy, which may result in a better outcome for patients and contribute to combat the emergence of antimicrobial resistance.

A method has been established able to provide rapid AST results, further referred to as direct AST. To this aim, an approved system, initially conceived for urine screening, and for AST of bacterial isolates from urine was used. In order to adapt the system to rapid AST from positive blood cultures, two different protocols, protocol 1 (PR1) and protocol 2 (PR2), were evaluated.

Scientists at the University of Pisa (Italy; www.unipi.it) and their collaborators inoculated blood specimens from patients admitted to the Pisa University Hospital in the period July-December 2014, into blood culture bottles and transferred to the Bactec FX instrument (Becton Dickinson, Franklin Lakes, NJ, USA; www.bd.com) for monitoring bacterial growth. From each patient, only the first positive blood culture (BC) apparently monomicrobial at the Gram staining was included in this study.

BC positive at the Bactec FX instrument were subjected to Gram staining and subcultured onto appropriate solid media. Isolated colonies were identified by MALDI-TOF (Bruker Daltonics, Bre-

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93.1% and 93.8 % of Gram-positive cocci, respectively. In particular, 100% categorical agreement was found with levofloxacin for Enterobacteriaceae by both PR1 and PR2, and 99.0% and 100 % categorical agreement was observed with linezolid for Gram-positive cocci by PR1 and PR2, respectively.

There was no significant difference in accuracy between PR1 and PR2 for Gram-negative bacteria and Gram-positive cocci.

The authors concluded that their newly described method seems promising for providing accurate AST results. Most importantly, these results would be available in a few hours from blood culture positivity, which would help clinicians to promptly confirm or streamline an effective antibiotic therapy in patients with bloodstream infections. The study was published on August 12, 2016, in the journal BMC Microbiology.

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men, Germany; www.bruker.com) and AST was performed by Vitek 2 (bioMérieux, Marcy l’Étoile, France; www.biomerieux.com). Direct AST of bacteria was performed by a Alfred 60AST automated bacterial culture device (Alifax SpA, Polverara, Italy; www.alifax.com) and carried out using two different protocols, PR1 and PR2. By PR1, bacteria were recovered from positive BC by serum separator tubes or by PR2 after a short-term subculture in liquid medium.

The direct MALDI-TOF method concordantly identified with the current method 97.5% of the Gram-negative bacteria and 96.1 % of the Grampositive cocci contained in monomicrobial blood cultures. The direct AST by PR1 and PR2 for all isolate/antimicrobial agent combinations was concordant/correct with the current method for 87.8% and 90.5 % of Gram-negative bacteria and for

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The ECL 760 random access system allows for a wide range of clotting and chromogenic tests and immunological assays to be performed. The system can accept 23 reagents at a time, trace samples to rack and position, and onboard cooling and stirring is available for 20 reagents.

The Biolumi 8000 is a modular IVD laboratory analytical system that combines immunology (280 tests/hr), biochemistry (1600 tests/hr), electrolyte (1000 tests/hr) and sample handling modules (280 samples/hr). The flexible combination is designed to satisfy different requirements in the lab.

The PA200 features 50 samples on board capacity, continuous sample loading, and STAT function.

A wide test menu is provided including HbA1c, CRP, hs-CRP, RF, D-Dimer, ASO, Cys-C, AntiCCP, mALB, IgM, IgG, IgA, C3, C4, etc., with a throughput of 180 tests per hour.

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Internet-Based Tool Simplifies Infectious Disease Diagnosis n Internet-based tool for diagnosis of infectious diseases through the rapid interpretation of DNA sequencing data is now available to the medical community.

The metagenomics analysis software that powers the “Taxonomer” program was developed at the University of Utah (Salt Lake City, USA; www.utah.edu). Metagenomics, the genomic analysis of a population of microorganisms, makes possible the profiling of microbial communities in the environment and the human body at unprecedented depth and breadth. Its rapidly expanding use is revolutionizing the understanding of microbial diversity in natural and man-made environments and is linking microbial community profiles with health and disease.

The Taxonomer program is an ultrafast, webtool for comprehensive metagenomics data analysis and interactive results visualization. The DNA sequence data for a clinical sample is uploaded via the Internet to Taxonomer. In less than one minute, the tool displays a thumbnail inventory of all pathogens

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in the sample, including viruses, bacteria, and fungi. Taxonomer is unique in providing integrated nucleotide and protein-based classification and simultaneous host messenger RNA (mRNA) transcript profiling.

Using real-world case studies, the developers showed that Taxonomer detected previously unrecognized infections and revealed antiviral host mRNA expression profiles.

“Our benchmark analyses show Taxonomer being ten to a hundred times faster than similar tools,” said senior author Dr. Robert Schlaberg, assistant professor of clinical pathology at the University of Utah. “Taxonomer provides a critical step forward, as it is extremely fast, accurate, and easy enough to use for implementation in diagnostic laboratories.”

To facilitate datasharing across geographic dis-

tances in outbreak settings, Taxonomer is publicly available through a web-based user interface at the address http://taxonomer.com.

Results of the Taxonomer study were published in the May 26, 2016, online edition of the journal Genome Biology.

Image: The metagenomics pathogen detection tool could change how infectious diseases are diagnosed (Photo courtesy of the University of Utah).

Alpha-Thalassemia Affects HbA1c Measurement major glycated hemoglobin, known as HbA1c, is characterized by non-enzymatic binding of glucose to the N-terminal valine residue of the hemoglobin b-chain, is a widely used biomarker in the management of diabetes. α-Thalassemia is a benign condition that is seen some in patients with diabetes mellitus and is due to impaired production of alpha chains from 1,2,3, or all 4 of the alpha globin genes, leading to a relative excess of beta globin chains. The degree of impairment is based on which clinical phenotype is present.

Clinical medical scientists at the Peking University Shenzhen Hospital (Guangdong, China; www. pkusz.edu.cn) tested a total of 189 EDTA whole blood samples from all patients for complete blood counts with red cell indices and HbA2 using an

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XN9000 analyzer (Sysmex Corporation, Kobe, Japan; www.sysmex.com) and hemoglobin capillary electrophoresis (Sebia Benelux, Vilvoorde, Belgium; www.sebia.com). Samples were separated into several aliquots and frozen at –80 °C before HbA1c analysis.

Plasma samples were tested for fasting glucose (FG), albumin, fructosamine, and ferritin immediately after centrifugation. The effects of the number of functionalα-genes on HbA1c measurement was investigated by boronate affinity high-performance liquid chromatography (HPLC; Ultra²; Trinity Biotech, Kansas City, MO, USA; www.trinitybiotech.com).

In patients with two or three functional α-genes, HbA1c values were not significantly different from those of controls; however, in individuals with α-

thalassemia with one functional α-gene (i.e., HbH disease), HbA1c levels were significantly different from those of controls. HbA1c values were significantly lower in individuals with HbH disease than in control individuals and patients in the other two α-thalassemia groups.

The authors concluded that HbA1c values in samples from individuals with two or three functional αgenes basically reflected the normal mean blood glucose level, while those in samples from individuals with one functional α-gene did not. Therefore for patients with HbH disease, HbA1c values cannot be used for the assessment of diabetes because HbA1c values do not reflect the mean blood glucose level.

The study was published on May 17, 2016, in the Journal of Clinical Laboratory Analysis.

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LabMedica International

Body Surface Area Helps Predict Response to Blood Transfusion he risks associated with unnecessary transfusion of blood products, including infections, transfusion reactions, and, in some clinical situations, alloimmunization, makes a judicious approach to transfusion is of the utmost importance.

However, despite several decades of experience with red blood cell (RBC) transfusion, the ability to predict transfusion requirements based on the expected rise in hemoglobin (Hgb) has been limited. As a result, decisions regarding RBC transfusion have been based on clinical experience and gestalt.

Medical scientists at the Eastern Virginia Medical School (Norfolk, VA, USA; www.evms.edu) determined the variability of response to red blood cell transfusion and to predict which patients will have an Hgb rise higher or lower than that predicted by the long-standing convention of “one and three”. The study was a retrospective chart review in a single hospital and data for 167 consecutive patient encounters were reviewed. The dataset was

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randomly divided into derivation and validation subsets with no significant differences in characteristics. Pre-transfusion Hgb was checked no earlier than 12 hours prior to transfusion, and post-transfusion Hgb checked between three and 24 hours after transfusion.

DeltaHgb was defined as post-transfusion Hgb minus pre-transfusion Hgb per red blood cell unit. They classified all the patients in both the subsets as “high responders” (DeltaHgb greater than 1 g/dL) or as “low responders” (DeltaHgb equal to or less than 1 g/dL). In univariate analysis, age, sex, body weight, estimated blood volume, and body surface area were significantly associated with response category. The mean DeltaHgb per RBC unit in the series was 1.23 g/dL. This lends support to the rule of thumb, which lacks large published datasets to support this rule. Then, multiple different prediction models were tested using a variety of variables.

The authors concluded that the best-performing model used body surface area (BSA) and correctly classified 69% of patients, with a sensitivity of 84.6% and a specificity of 43.8% when tested on an independent dataset without any overlap with the derivation dataset. The study was published on September 21, 2016, in the Journal of Blood Medicine.

Image: A bag of donor’s blood before cross matching and transfusion (Photo courtesy of the Nursing Times).

Blood Test for Colorectal Cancer Recurrence Proves Highly Sensitive hen diagnosed early, before cancer has spread, the relative five-year survival rate for colorectal cancer (CRC) is 90%, but only approximately four out of 10 CRC cases are detected early.

Regular blood testing for carcinoembryonic antigen (CEA), every three to six months is currently the only blood test recommended for routine monitoring of CRC, and while CEA measurement is the most sensitive simple test to aid in the monitoring of CRC, its sensitivity depends on what blood level, or changes in it, are chosen for positivity.

Scientists at the Flinders University of South Australia (Bedford Park, Australia; www.flinders.edu.au) collected blood samples from any adults 18 years of age or older who were recently diagnosed but without residual macroscopic disease after initial treatment for CRC (AJCC stages I–IV) or who were already undergoing surveillance monitoring for CRC recurrence at Flinders Medical Centre during the period of 24 months from November 2013.

The concentration of CEA was determined using the LIAISON CEA test (DiaSorin S.p.A., Saluggia, Italy; www.diasorin.com ). A sample with CEA levels of 5 ng/mL or above was deemed positive, as commonly applied. The presence of methylated branched-chain amino acid transaminase 1 (BCAT1) and ikaros family zinc finger protein 1 (IKZF1) DNA in 3.9 mL plasma was determined as previously reported. The goal of the study, which incorporated clinic visits, blood sampling, and diagnostic imaging, was to compare the sensitivity and specificity of the BCAT1/IKZF1 blood test (Clinical Genomics, Bridgewater, NJ, USA; www.clinical genomics.com) to CEA, when applied on a single occasion, for detection of recurrent CRC in patients undergoing surveillance. True- and false-positive rates for radiologically or histopathologically confirmed recurrence were compared and absolute

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sensitivity and specificity derived from these.

Of the 122 participants evaluated, 28 had recurrence and 94 had no clinically detectable disease. Among those with recurrent disease, 19/28 (67.9%) were positive for methylated BCAT1/ IKZF1 while only 9/28 (32.1%) were positive for CEA, of greater than 5 ng/mL, representing a significant two-fold detection improvement with the two-gene test. Among the 94 patients without clinically detectable recurrence there was no significant difference in the percentage positive for methylated BCAT1/IKZF1 compared to CEA. In this study population, sensitivity estimates of the methylated BCAT1/IKZF1 test were 75% and 66.7% for local and distant recurrence, respectively, compared with 50% and 29.2% for CEA. Nine

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patients were positive for both tests, while the two-gene test detected an additional 10 cases that CEA failed to detect in the blood sample collected closest to the time of radiologic assessment for recurrence.

Lawrence LaPointe, PhD, President and CEO of Clinical Genomics said, “These data demonstrate that a blood-based virculating tumor DNA (ctDNA) test for methylated BCAT1/IKZF1 routinely detects recurrence that CEA testing misses. We believe our two-gene test has the potential to fill an urgent and unmet clinical need, and are committed to advancing its clinical development as a new tool for improving patient outcomes.” The study was published on October 11, 2016, in the journal Cancer Medicine.

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HEMATOLOGY ANALYZER

CLIA PROCESSOR

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Erba Mannheim

Vircell

The KT6610 counts and differentiates WBC by triangle laser scattering without the use of PC, and processes 60 samples per hour. It is designed to fulfill and exceed the demands of small labs, clinics, and hospitals by providing accurate results in a more economic way.

The Elite 580 offers a throughput of 80 samples per hour, and can report on 29 parameters using only a small sample volume. The system features three counting modes for CBC or CBC plus differentials, and can store patient-related information for up to 100,000 samples.

The VirClia Plus chemiluminescent immunoassay (CLIA) processor offers fast results with the capacity to deliver 96 tests in less than three hours. Other features include an eight-channel pipetting arm, six heated incubator slots, washable stainless tips, and clot detection.

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Cell-Free DNA Sequencing Confirms Myelodysplastic Syndrome Diagnosis he use of next-generation sequencing (NGS) methods to analyze cell-free DNA (cf-DNA) in the blood of patients with myelodysplastic syndrome (MDS) yields more accurate results than the current standard approach of Sanger sequencing.

Myelodysplastic syndromes (MDSs) are a heterogeneous group of disorders, characterized by the presence of clonal neoplastic cells in bone marrow that lead to ineffective hematopoiesis and peripheral blood (PB) cytopenias. The major criteria for the diagnosis of MDS are the presence of peripheral cytopenia and dysplasia.

Scientists at the NeoGenomics Laboratories (Irvine, CA, USA; www.neogenomics.com) collected PB samples were collected from 16 patients confirmed to have MDS by bone marrow evaluation and from four age-matched normal controls. All patients had blasts of less than 5%. This included patients with refractory cytopenia with unilineage dysplasia, refractory cytopenia with multilineage dysplasia, and refractory anemia with ring sideroblasts (RARS). The team extracted cf-DNA from plasma and cellular DNA from PB cells.

Total nucleic acid was isolated from plasma us-

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ing NucliSENS EasyMAG automated platform (BioMérieux, Marcy-l’Étoile, France; www.biomerieux.com). DNA was then quantified using Qubit 2.0 Fluorometer (Thermo Fisher Scientific, Waltham, MA, USA; www.thermofisher.com). NGS and Sanger Sequencing were performed for several specific genes. Polymerase chain reaction products were purified and sequenced in both forward and reverse directions using an ABI PRISM 3730XL Genetic Analyzer (Applied Biosystems, Foster City, CA, USA; www.appliedbiosystems.com).

Upon deep sequencing of the plasma cfDNA, all 16 patients showed at least one mutated gene, confirming the presence of an abnormal clone consistent with MDS. No abnormality was detected in any of the four samples from normal control individuals. Eight patients (50%) showed mutation in one gene and the remaining eight patients (50%) showed mutations in two or more genes. Five of the 16 patients (31%) showed mutations detected

by NGS of cf-DNA, while Sanger sequencing of PB cellular DNA showed no evidence of mutation.

Garth D. Ehrlich, PhD, FAAAS, Editor-in-Chief

of the journal where the study was published, said, “This is a remarkable finding that cell-free DNA provides a more sensitive assay for detecting cancer than does the traditional approach of analyzing cellassociated DNA.” The study was published on July 14, 2016, in the journal Genetic Testing and Molecular Biomarkers.

Image: The NucliSENS EasyMAG automated platform for total DNA extraction (Photo courtesy of BioMérieux).

Microcantilever-Based Sensor Detects BRAF-Mutated Malignant Melanoma novel nanosenor comprising minute cantilevers labeled with malignant melanomaderived RNA enabled identification of patients with the BRAFV600E mutated form of the disease in less than 24 hours. In the United States there are more new cases of skin cancer than the combined incidence of cancers of the breast, prostate, lung, and colon each year, and malignant melanoma represents its deadliest form. About 50% of all cases of malignant melanoma are characterized by a particular mutation – BRAFV600E – in the BRAF (rapid acceleration of fibrosarcoma gene B) gene. Recently developed highly specific drugs are available to treat BRAFV600E mutated tumors

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but require diagnostic tools for fast and reliable mutation detection to promote successful treatment.

Investigators at the University of Basel (Switzerland; www.unibas.ch) and the University Hospital Basel (Switzerland; www.unispital-basel.ch) labeled nanomechanical microcantilevers with RNA from BRAFV600E mutated malignant melanoma cells.

They conducted a preliminary clinical trial in which they used RNA-labeled cantilever array sensors to demonstrate identification of a BRAFV600E single-point mutation by sampling total RNA obtained from biopsies of metastatic melanoma of diverse sources (surgical material either frozen or fixated with formalin and embedded in paraffin).

Results revealed that the method was faster than the standard Sanger or pyrosequencing methods and was comparably sensitive as next-generation sequencing. Processing time from biopsy to diagnosis took less than 24 hours and did not require PCR amplification, sequencing, and labels.

“It is essential that we are able to identify the mutations reliably in tissue samples. That is the only way of ensuring that patients get the right treatment and successful outcomes,” said contributing author, Dr. Katharina Glatz professor of pathology at University Hospital Basel. The nanosensor was described in the August 4, 2016, online edition of the journal Nano Letters.

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Field Performance for Rapid Detection of Influenza Virus Analyzed linical differentiation of influenza A virus from infections caused by influenza B virus and the other viruses is unreliable, however effective antiviral treatment is only available for influenza A virus infections and must be administered early in the course of disease to be effective.

Historically, rapid influenza virus antigen diagnostic tests (RIDTs) were simple to perform but were insensitive, particularly for recently introduced strains of influenza A virus and influenza B virus. In contrast, the more recently introduced digital immunoassays (DIAs) have improved analytical performance.

Microbiologist at Medical Faculty of Istanbul University (www.istanbul.edu.tr) conducted single-blinded cross sectional study nine different family medicine centers in Istanbul, Turkey between 01 November 2014 and 01 May 2015. Nasopharyngeal specimens were collected by the physicians at the time of the initial patient visit, typically within three days of the onset of symptoms. Two specimens were collected, from each patient: one for realtime polymerase chain reaction RT-PCR and one for the point-of-care (POC) test.

The POC test used was the BD Veritor System for Rapid Detection of Flu A + B (Becton, Dickinson and Company, Franklin Lakes, NJ, USA; www.bd.com).

It is a rapid digital chromatographic immunoassay for the direct, qualitative detection of influenza A and B viral nucleoprotein antigens from nasal and nasopharyngeal swabs of symptomatic patients and differentiates influenza A and B viral antigens from a processed sample using a single device. The RT-PCR results were reported with the analysis of amplification plot in the Light Cycler 480 II (Roche Diagnostics, Mannheim, Germany; www.roche.com).

A total of 122 patients out of 238 were positive for influenza by RT-PCR including 42 with influenza A H1N1, 11 with influenza A H3N2, two with influenza A undetermined strains, and 68 with influenza B. One patientâ&#x20AC;&#x2122;s PCR test was positive for both influenza A and B but the Veritor test was negative for both viruses. The clinical sensitivity and specificity of the Veritor test in all age groups was determined to be 80% and 94%, respectively. Positive predictive value was 93% and the negative one was 81%.

The authors concluded that the field performance of the rapid influenza test, the BD Veritor System for Rapid Detection of Flu A + B, was high and found to be useful with respect to rational antiviral use, avoiding unnecessary antibiotic usage and the management of cases by the family physicians. The study was published on September 9, 2016, in the journal BMC Infectious Diseases.

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Image: The BD Veritor system for rapid detection of Influenza A+B (Photo courtesy of Becton, Dickinson and Company).

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LabMedica International

PRODUCT NEWS DIAGNOSTIC SYSTEM

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The GeneXpert Omni POC system leverages existing cartridge technology to deliver accuracy, speed, and ease-of-use. Advanced microfluidics regulate all aspects of the testing process within the test cartridge, from sample preparation and NA extraction, to amplification and detection.

The Selectalyte measures serum concentrations of sodium, potassium and chloride, and takes just one minute to process and print results for all three. Users can choose to perform a two-point calibration or enable an automatic feature to maintain the instrument in a state of readiness.

The DocUReader 2 Pro desktop analyzer reads and evaluates the LabStrip U11 Plus urine test strips, and can carry out 120 tests/hour in fast mode or 50 tests/hour in normal mode. Its high accuracy, flexibility, connectivity as well as security and QC functions, make it ideal for POC testing.

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Electrical Immunosensor Detects Acute Myocardial Infarction eart disease and especially acute myocardial infarction (AMI) are the leading causes of death for both men and women and therefore, a fast and reliable diagnosis of heart attack or cardiac episode are urgently needed.

The most commonly used biomarkers are creatine kinase-MB, myoglobin, cardiac troponin T, and cardiac troponin I (cTnI), which is a subunit of the troponin complex found in cardiac muscle and is a highly specific and sensitive biomarker for the clinical diagnosis of AMI. Biomedical engineers at Ulsan National Institute of Science and Technology (South Korea; www. unist.ac.kr) developed a new sensor for early detection of heart attack in humans. The apparatus comprises of rapid, label-free, and highly sensitive singlewalled carbon nanotube (SWCNT) electrical immunosensor, featuring two pairs of electrodes. The system works by measuring the level of cardiac troponin I (cTnI), a protein that is excreted by the heart muscle into the blood following a heart attack.

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The two concentration electrodes were imbedded between upper and lower dielectric layers, facing each other, underneath the -COOH-functionalized SWCNT channels deposited between the detection electrodes. Therefore, the gap between these imbedded concentration electrodes can be reduced to maximize the electric field intensity for dielectrophoresis (DEP)mediated concentration of cTnI, thereby greatly reducing the detection time to one minute and enhancing the limit of detection (0.7–0.8 pg/mL). Fluorescence images were acquired using an Eclipse 80i epifluorescence microscope (Nikon, Tokyo, Japan; www.nikon.com).

The authors concluded that their immunosensor demonstrated high selectivity for cTnI over myoglobin, Tris-Borate-EDTA (TBE), and human serum.

Therefore, the novel immunosensor presented holds considerable potential for use as a platform for sensing distinct types of proteins, along with the

feasibility of miniaturization and integration for biomedical diagnosis. The study was published in the August 2016 issue of the journal Biosensors & Bioelectronics.

Image: The core material used for the new immunosensor that detects proteins in the blood stream following a heart attack, providing results in just one minute (Photo courtesy of Ulsan National Institute of Science and Technology).

Simplified Assay Quantifies Circulating Activated Protein C he protein C (PC) anticoagulant pathway plays a crucial role in the regulation of fibrin formation by inactivating the pro-coagulant cofactors factor Va and factor VIIIa. The physiological relevance of PC in the regulation of blood coagulation arises from the description of increased risk of venous thromboembolism (VTE) associated with both hereditary PC deficiency and low circulating activated protein C (APC) levels. Available assays for circulating levels of APC are either time-consuming or difficult to use in a routine laboratory, or have a detection limit above normal levels.

Scientists at the Instituto de Investigación Sanitaria La Fe (Valencia, Spain; www.iislafe.es) developed a simplified assay that measures both the in vivo free APC and the in vivo APC complexed to PC

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inhibitor (PCI). They measured APC levels, with both assays, in 339 plasma samples, 165 from patients with venous thromboembolism (VTE) and 174 from healthy individuals.

The PCI antigens were determined and PCI concentration was expressed in nM, assuming a molecular weight for PCI of 57,000 and a concentration of plasma PCI, in pooled normal plasma, of 87.7 nM. APC: PCI complexes were determined by a sandwich enzyme-linked immunosorbent assay (ELISA).

Microplates were coated with a monoclonal antibody to PC and complexes were detected with peroxidase-labeled polyclonal antibodies to PCI. APC concentration in the complex is expressed in nM, assuming a molecular weight of APC of 57,000.

The investigators found that the mean APC level in the 339 samples was 0.038 ± 0.010 nM, using a

previous assay that measures only the in vivo APC level, and 0.041 ± 0.010 nM with the present new assay. The mean APC level in VTE patients was 0.034 ± 0.009 nM (previous assay) and 0.037 ± 0.009 nM (new assay), significantly lower than those in controls. In both groups there was a significant correlation between the levels obtained by the two assays.

The authors concluded that their results show that both assays are equivalent, and confirm that the APC level is lower in VTE patients than in healthy individuals. Therefore, the new simplified assay, which measures the sum of circulating free APC and APC complexed to PCI, may be used to estimate the level of circulating APC, and will allow its use in routine laboratories. The study was published on August 1, 2016, in the journal Clinica Chimica Acta.

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Edited by Tahir Pillay MBChB, PhD, FRCPath(Lon), FCPath(SA)

NEWS

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

6th International Francophone Federation Congress in Beirut Draws Representatives from 20 Countries Lab Medicine at the Heart of Cultural Dialogue and the Universal Sharing of Languages

by Dr. Bernard Gouget Counselor for Public Health FHF; Chair-Human Health Care Committee-COFRAC; IFCC Chair-Nominations Committee; General Secretary of the International Francophone Federation Of Clinical Biology and Laboratory Medicine (FIFBCML)

n Arabic proverb says: “al lougha fârisson yah’milouka ila biladen baïda” (language is a messenger carried to distant countries).

The 6th Journées of the International Francophone Federation (FIFBCML) and the 7th Congress of the Syndicate of Biologists of Lebanon, held from March 2 to 5, brought together more than 600 biologists from twenty countries in Beirut to share ideas at the heart of Lebanon, a country whose beauty has been celebrated by many French poets and novelists. A successful gamble for Dr. Christian Haddad, SDBL President; Dr. Marc-Antoine Zablith, Chair Organizing Committee; Dr. Salam El-Samad, Chair Scientific Committee, who committed themselves to pooling energies and resources between Mediterranean, Arab, African, Francophone and European countries in order to promote quality laboratory medicine, and to reinforce the strong bonds between Lebanon, FIFBCML, the Arab Federation (AFCB) and the IFCC. The official language of Lebanon is Arabic. However, half of Lebanese speak French and English is also widely used. Therefore, the opening ceremony was in Arabic while French and English were mixed in throughout the three days of science revolving around new diagnostics, innovation and clinical strategies.

A WHO representative recalled that antimicrobial resistance creates one of the greatest challenges to global public health today. It is causing worldwide loss of ability to effectively treat and cure many infections, it poses extraordinary long-term danger to health with major implications and consequences for modern medicine, health systems, development, economics, agriculture... There is evidence of misuse and abuse of antibiotics worldwide both by providers and by users. It is today a critical issue in Syria because since the beginning of the crisis 6 years ago the control of communicable diseases as Tuberculosis, AIDS are sometimes beyond control.

The new biomarkers were also a hot topic: biomarkers in the diagno-

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sis of dementia with a clear evidence on the utility of the cerebrospinal biomarkers; cardiac biomarkers on prognosis and management of heart failure and new tools for colorectal cancer screening to prepare the Lebanon national campaign.

In addition, the congress held many aspects on quality management, standardization of methods and harmonization of results. Automation and consolidation of the medical labs, emergency tests, blood transfusion clinical application of flow cytometry in acute leukemia drew large number of participants.

The opportunities and challenges of m-health were discussed as it is an evolving strategy that is changing the way the world operates today.

Communicating and working in a multi-network environment is an issue for the profession. The marriage of diagnostics and mobile connectivity means more than just a new stream of gadgets. It is the next big wave of where the diagnostics field will go. Mobile health provides an opportunity for lab medicine to be more efficient and to achieve important cost reductions by enhancing an individual patient’s stake in the management of their health, with wellbeing apps encouraging the adoption of healthier lifestyles, collectively improving public health. Mobile health devices furthermore allow the user to monitor vital signs, and providing valuable support to healthcare professionals.

A brilliant presentation on the evolution of hematology was a chance to revisit the history of Lebanon. It is one of the oldest countries in the world. It is named a hundred times in the Old Testament and the metaphor for it: “Country of Cedars” is widely cited in the Bible.

The Holy Book says that these majestic trees were planted by God Himself, hence their eternal longevity. Lebanon is small in area and population, but great in the values that it embodies: tolerance, dialog, openness to the world and ability to accomplish a miracle: bringing together Christians, Muslims and agnostics to live under the same government by

Photo: The International Francophone Federation (FIFBCML) and the Arab Federation of Clinical Biology (AFCB) delagatioons received by Michel Aoun President of the Republic of Lebanon (between Dr Ch Haddad (under the flag) and Dr Marc Antoine Zablith).

perpetuating the aspiration of nations that want to share culture, science and language. In Lebanon, French is cultural fact and a social choice, both based on deeply-rooted emotional ties with France. For both of these reasons, Lebanon has occupied a privileged place from the outset in organizations of the Frenchspeaking world.

In the fullest sense of the term, French is a language loved by the Lebanese. It is, for many folks, more than an idiom, a sum of values, a factor of East-West cultural osmosis, a symbol of openness to the world, a passport for a better future. Economic globalization is expressed in English and constrains all countries, including France. To be convinced, if need be, that English now prevails over French, it is enough to see and read the shop signs and advertising posters on the road from Beirut to

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Byblos, which are all the more aggressive in that they are often not even translated into Arabic. The capital of Lebanon is much more than the Paris of the Middle East: it is a city with multiple identities, a gem that must be defended in the heart of a tormented region.

It was a great honor for Frenchspeaking delegations and delegations of the Arab Federation to be received by General Michel Aoun, President of Lebanon (photo). He sent us a strong message: “Lebanon is a harbor of stability and freedom.

The general interests of peace should be prioritized, the dynamics of cooperation in the field of education and research should be strengthened, and the knowledge of how to live together should be valued". It is up to us to proudly carry these values beyond the Middle East, to everywhere in the world!

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

NEWS

The Joint Committee for Traceability in Laboratory Medicine (JCTLM): An Example of Global Leadership from IFCC

by Graham H Beastall, IFCC representative on the JCTLM Executive Committee aboratory medicine specialists will be aware of the growing importance of global harmonisation as a driver for reducing variability in clinical laboratory results. Today it is recognised that harmonisation should be considered across the total testing process [1] and IFCC and its Regional Federations are giving active leadership in this area as recent special editions of journals confirm [2,3]. Harmonisation is a key component of the IFCC ‘Shaping the Future’ programme, described in a series of articles in e-News during 2016.

One area of harmonisation where

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IFCC is a global leader is in helping to reduce the between method variability of important biomarkers. The IFCC Scientific Division, working in collaboration with the diagnostics industry, has a proud record of producing reference materials and reference measurement procedures (methods) that may be adopted as ‘global standards’ for the production of the methods used in every clinical laboratory. This initiative is conducted in partnership with JCTLM.

History of JCTLM A detailed history of JCTLM has been

published recently [4]. The JCTLM was established in 2002 through a declaration between IFCC, the International Bureau of Weights and Measures (BIPM), and the International Laboratory Accreditation Cooperation (ILAC) in response to the implementation of the European Community Directive 98.79/EC on in vitro medical devices. Today these three organisations are supported by almost 40 other organisations as National, Regional and Stakeholder Members of JCTLM. IFCC provides both Executive Board and Scientific Division input to the JCTLM Executive Committee.

What does JCTLM do?

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The aim of JCTLM is to support worldwide comparability, reliability and equivalence of measurement results in laboratory medicine, for the purpose of improving health care and facilitating national and international trade in in vitro diagnostic devices, by: Promoting the concept of traceability of measurement results to the Système International d'Unités (SI) or, where necessary, to other internationally agreed references; Evaluating reference materials, reference measurement procedures and reference measurement services for laboratory medicine with respect to conformity with appropriate international standards; Producing educational materials and activities promoting the value of traceability in laboratory medicine and raising awareness amongst stakeholders; Promoting close links between Reference Laboratories in Laboratory Medicine and National Metrology Institutes; Facilitating the identification and prioritisation of measurands requiring international traceability and comparability and thereby encouraging appropriate organisations to accept responsibility for the development of suitable reference methods and measurement procedures and certified reference materials; Encouraging the in vitro diagnostic (IVD) industry to apply the agreed reference measurement systems; Encouraging EQAS organizers to apply the agreed reference measurement systems.

Where can I find more information about JCTLM? There are two linked sources of information about JCTLM: www.jctlm.org. This new website has been designed to provide educational support and regular news updates on the importance of traceability in laboratory medicine and on reducing between method variability as a contributor to im-

proved patient safety and better clinical outcomes. The website provides freely available educational support in three main categories: relevant publications; presentations made at international conferences; and support materials including webinars and PowerPoint presentations. This website will be most useful to trainers and trainees in laboratory medicine and to laboratory medicine specialists. It is also a traceability portal to the wider healthcare community. www.bipm.org/jctlm. This website has been established for many years as the JCTLM database. From this website it is possible to access, at no charge, the large list of available reference materials, reference methods and reference laboratories. This website is used widely by diagnostics companies, National Metrology Institutes and those actively involved in method standardisation projects.

The 2017 JCTLM Newsletter was published in March and may be accessed from either of the two websites.

How can IFCC Members engage with JCTLM? IFCC Members can engage with JCTLM by: Becoming a National, Regional or Stakeholder Member of IFCC. This will extend the global reach and influence of JCTLM and facilitate twoway communication. There is no cost involved in achieving JCTLM membership. A leaflet on JCTLM membership may be downloaded from the JCTLM website; Including a symposium or workshop on traceability in laboratory medicine in a regional or national scientific meeting. JCTLM will be happy to suggest speakers; Ensuring that training in laboratory medicine includes content on traceability in laboratory medicine, as recommended by a recent editorial [5]. Suitable material for trainees is available from www.jctlm.org; Providing a link from your website to www.jctlm.org and/or www.bipm. org/jctlm.

References 1. Plebani M. Harmonization in laboratory medicine: the complete picture. Clin Chem Lab Med 2013; 51: 741-751 2. Several articles. Harmonization of laboratory medicine – a global activity. Clin Chim Acta 2014; 432: 1-166 3. Several articles. IFCC Scientific Division – An update of the ongoing activities. Clin Chem Lab Med 2013; 51: 915-1041 4. Jones GRD, Jackson C. The Joint Committee for Traceability in Laboratory Medicine – its history and operation. Clin Chim Acta 2016; 453: 86-94 5. Cobbaert C. Time for a holistic approach and standardization education in laboratory medicine. Clin Chem Lab Med 2017; 55: 311-313 LabMedica International April/2017

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

NEWS

IFCC Welcomes New Chair of the Scientific Division he IFCC is happy to welcome the new Chair of the Scientific Division, Prof Philippe Gillery (FR).

Prof. Gillery’s professional competence and this expertise will greatly benefit IFCC activities. IFCC wishes him all the best for this work within the Federation.

Prof. Philippe Gillery, MD, PhD, is Professor of Biochemistry and Molecular Biology at the Faculty of Medicine of Reims, University of Reims Champagne-Ardenne, France. He is the chair of the Laboratory of Paediatric Biology and Research and of the Biology and Pathology Department of the University Hospital of Reims, France.

He has been appointed as ViceChair of the IFCC Scientific before

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being nominated as Chair in January 2017. He is Associate Editor of the Clinical Chemistry and Laboratory Medicine Journal.

His research interests are related to the effects of nonenzymatic posttranslational modifications on protein structure and functions, and to their involvement in the pathophysiology of diabetes mellitus and other chronic diseases like atherosclerosis and chronic kidney diseases. He has published more than 180 articles in peer-reviewed journals.

His major strategic orientations for the IFCC Scientific Division are as follows : 1) Maintain and amplify the high level of involvement of IFCC-SD in the field of standardization / har-

IFCC Office Moves to New Premises in Milan

monization.

Continue and/or complete ongoing projects, with a robust performance management and adherence to agreed timelines Pick up priority measurands, in relation with the harmonization consortum Identify new areas, in collaboration with key partners (automimmune tests, drugs).

2) Maintain and amplify the visibility of IFCC scientific activities inside and outside IFCC. Participate actively in all IFCC and regional federation meetings, in scientific meetings of clinical societies in areas covered by SD and in IFCC publications Reinforce relations with partners (BIPM, NMIs, WHO), focussing on specific expertise areas of SD. Strenghten interactions with other IFCC divisions or task forces for identifying new markers suitable for standardization / harmonization, in cooperation with corporate members (importance of clinical relevance and interest for effective implementation of the tests in laboratories)

3) Prepare the future.

Focus SD activities on new areas of clinical chemistry and laboratory medicine Close co-operation with other IFCC divisions, including any new focus on in innovation.

Select and involve new members in SD Cs and WGs (key actors getting older or retiring, specific skills required in new areas of interest), especially young scientists (with EB support and the sustanability).

Ensure the maintenance of IFCC networks (cf C-TLM).

Photo: (From left to right) Paola Bramati,

Silvia Colli Lanzi, Silvia Cardinale e are excited to announce that IFCC has a new office in Milan.

The new IFCC premises are located in the MZ International Group offices in Milan. The new office is active since midJanuary and demonstrates IFCC commitment to growth and expansion, and commitment to deliver outstanding services to all IFCC members and partners.

The IFCC office is responsible for carrying out, under the direction of the EB and in conjunction with Division and Committee members, all the administrative and communication activities of the Federation. The IFCC Office reports to the EB through the Secretary.

The IFCC Office is responsible for the efficient administration of IFCC affairs and maintains the Archives of the organization. It also maintains contacts with Member societies and it assists the regional organizations with which the IFCC has agreements, as well.

Paola Bramati, in IFCC since 2005, is responsible for the contacts with the Executive Board. She is in charge for the activities related to the IFCC membership (Full Members, Affiliates and Corporate), as well as the Scientific Division, and Administrative duties linked to IFCC Finances.

Paola’s background is connected to communication, tourism and marketing. Before joining IFCC, she has been working for more than 15 years in the airline business dealing with day-today passengers’ operations, sales,

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marketing and pricing. Her education is related to foreign cultures and languages, as she had the chance to study abroad learning English, Spanish, French and German.

Silvia Cardinale, in IFCC since 2014, is in charge for the activities of the Congresses and Conferences Committee, as well as of the Education and Management Division.

Before joining IFCC, she has been working for 16 years in an American multinational publishing house as Marketing and Communication Assistant and lately as Assistant to the General Manager. She was responsible for the commercial agreements and for the contacts with other associated companies in Europe and worldwide. Her education is related to her Degree in Modern Foreign Languages and Literatures.

Silvia Colli Lanzi, in IFCC since 2011, is in charge for supporting the activities of the Communication and Publications Division, as well as those related to IFCC special projects, such as Professional Exchange Programmes, Scholarships and Awards, and IFCC Task Forces.

Silvia has been working in the communication industry for more than two decades and she is also responsible for the press desk and the communication activities for some Italian and international companies, managing the relations with the press and carrying on all the PR activities on their behalf.

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

In Memoriam: Prof. Victor Blaton

by Michel Langlois, AZ Sint-Jan Brugge-Oostende, Brugge, Belgium

ictor Blaton was born October 7, 1937 in Belgium. He was married to Dina Vandenbroeke and father of five children – Stefan, Sofie, Sylvie, Benedicte, Filip – and 10 grandchildren. He was basically trained in science and biochemistry at the KULeuven (Catholic University Leuven). As PhD he was a postdoctoral fellow at the same University. He followed the postgraduate training to become clinical biologist in 1973, recognized for laboratory medicine.

In 1970, he became director of the Simon Stevin Institute for Scientific Research in Bruges, Belgium.

He was working on fundamental and clinical research of lipoproteins in atherosclerosis and cardiovascular diseases, especially on the protective role of high density lipoproteins (HDL) in inflammatory processes of atherosclerosis. Lipidology was his passion, and cardiac prevention became his mission. His main interest was the comparative study of biochemistry in non-human species (primates) in order to find models for

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studying atherosclerosis development in humans. In 1977 he was installed as staff member – clinical biologist – in the department of Clinical Chemistry at the AZ St.-Jan Hospital in Bruges and became director of the same laboratory in 1997. His activities resulted in many publications in top scientific journals and in PhD theses of his co-workers. He was founder and President (19962000) of the Belgian Lipid Club, a prestigious club of scientists aiming to promote recommendations and treatments for the prevention of cardiovascular diseases.

He became Professor in Medical Biochemistry at the University of Leuven in 1982, and he was nominated as Lecturer and Visiting Professor at the Northwestern University Medical School in Chicago, Illinois (1989). He presented and organised many courses and International meetings, such as the European Atherosclerosis Society (EAS) Congress in Bruges in 1998. He was nominated in 1982 as NATO expert – scientific adviser for the prevention of myocardial infarctions in soldiers and in 1992 he obtained the NATO-

Award for Sciences. He obtained many other prestigious awards, most recently the EFLM-Roche Award in 2013.

Vic was a leader with a vision and strong pro-European mission. When he was President of the Belgian Society of Clinical Chemistry in 19881993, he initiated and participated in the creation of FESCC and EC4. He believed that the creation of a true operational structure is essential for the European harmonization in education and training of the professionals and the laboratory practice guidelines. He became president of FESCC (Forum European Societies in Clin Chem) in 2000 for a first term and in 2003 for a second term. He was able to merge together the two organisations FESCC and EC4 in one new European branch of IFCC, named EFCC – the European Federation of Clinical Chemistry and Laboratory Medicine – in 2007. As first President of EFCC (EFLM) in 20072009 and also thereafter, he stimulated the professional integration of countries of the Balkan region in Europe. Vic was a figurehead, a kind of father figure in times of major political and economic changes in Europe, and not only for our profession. In his career he took part in different activities and founded projects to support the developing countries in Africa and South-America. This illustrates his good heart and engagement for healthcare and socio-economic welfare, more than laboratory medicine.

Vic will be remember as a smiling man who always wanted the best for everyone. We will miss his friendship, his advice, his stimulating force, his enthusiasm. We keep the many beautiful moments with Vic alive and in our memory.

By Nada Majkic-Singh, Society of Medical Biochemists of Serbia

pon learning the sad news of the passing of Prof. Victor Blaton, the Society of Medical Biochemists of Serbia feels obliged to remember our many years of scientific and expert collaboration and personal friendship with him. Prof.

Victor Blaton first came to Belgrade as the president of FESCC in June 2005, to join the celebration of the 50th anniversary of the Society of Medical Biochemists of Serbia and Montenegro. On this occasion, the First Symposium for Balkan Region was held, entitled “Education, Management and Standards in Laboratory Medicine”, which, as the president of the FESCC, Prof. Blaton wholeheartedly supported and even asked for such symposia to be regu-

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larly organized. The tradition of holding this Symposium has lasted to this day. Prof. Blaton was a coordinator, teacher and participant of practically every Symposium held.

As the President of FESCC, he promoted the importance and goals of this European organization, bringing it closer to our medical biochemists.

Prof. Blaton was also a welcome guest and teacher at our national congresses, as well as the Congresses of the Balkan Federation, of which four were organized in Serbia with great success. For his contribution to the promotion of clinical chemistry and laboratory medicine in our country, the Balkan region and globally, the Society of Medical Biochemists of Serbia presented Prof.

Blaton with the highest reward of the Society, our Honorary Diploma.

Prof. Blaton last stayed in Belgrade in May 2015, on the occasion of the 60th anniversary of the Society of Medical Biochemists of Serbia and the 12th EFLM Symposium for Balkan region. Prof. Blaton truly wanted to get to know the way of life, the customs and the people of Serbia and the Balkan, and I will never forget his desire to learn about the wines that can be found in Serbia. I knew he was a wine connoisseur, but once he confused me with a question: how to obtain the wine called “Probus” from Fruska Gora? I had never heard about this brand of wine, however, upon my request, some colleagues soon brought two bottles of this rare wine that he took to Belgium. They are probably still in his collection. The last time we met was in October of last year in Tirana, at the Congress of the Balkan Federation of Laboratory Medicine. We were all very happy to see each other again and evoke memories of previous meetings and events.

All of us who loved and valued him had a hard time hearing about his sudden death, so in this way we would also like to pay our respect and express our condolences to his great family.

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

NEWS

THE WORLD OF IFCC

Spanish Society of Laboratory Medicine (SEQCML): An Update he Spanish Society of Laboratory Medicine collaborates with the nation’s Ministry of Health and 50 societies in the project "A Commitment to Quality by Scientific Societies in Spain".

The clinical laboratory reinforces its commitment to quality in the National Health System with 5 recommendations of things "not to do" Unnecessary tests are performed daily in clinical laboratories, despite having little or no efficacy and not being cost-effective.

Clinical laboratory professionals should be committed to reviewing and evaluating the analytical tests requested by clinicians and avoiding unnecessary testing.

The SEQCML has a Strategic Plan in advanced stages of development that includes an extensive test optimization policy, with the philosophy of "not to do" at the forefront.

The Spanish Society of Laboratory Medicine (SEQCML), a member of the "Not To Do" project of the Ministry of Health, has implemented 5 recommendations to reinforce its commitment to quality and efficiency in the National Health System.

These are guidelines aimed at reducing the number of unnecessary tests in daily use at clinical laboratories, that is, those that have not demonstrated efficacy, have little or dubious effectiveness, and are not cost-effective.

The creation of the recommendations and the inclusion of the SEQCML in this project respond to the need for "direct involvement of the clinical laboratory in this initiative for commitment to quality", explains Dr. Francisco A. Bernabeu, member of the Board of the SEQCML and the person responsible for the "Not To Do" project. In his view, "Clinical laboratory practitioners should collaborate with requesting clinicians in seeking to improve the quality and efficiency of patient care."

The "Not To Do" initiative was launched in 2013 by the Ministry of Health, Social Services, and Equality in response to an initiative of the Spanish Society of Internal Medicine (SEMI), which in turn was based on similar international experiences such as "Choosing Wisely" in the United States, or that developed by NICE in the United Kingdom.

The project is part of the activities of the Spanish Network of Health Technology Assessment Agencies. To date, 50 scientific societies have participated. The SEQCML joined in 2015, but it was in 2016 when the five agreements on things "not to do" in the clinical laboratory were presented. The recommendations are as follows: Do not request multiple tests on the initial assessment of a patient with suspected thyroid disease. First, request a test of thyroid stimulating hormone (TSH), and if it is abnormal, continue with additional evaluation or with treatment.

The determination of total CK or CK-MB, or AST, or LDH, or myoglobin for the diagnosis of myocardial damage (or myocardial infarction) is not recommended.

Do not test for allergen-specific IgE in a patient whose clinical history shows no symptoms of adverse reactions or without previous "in vivo" tests. In any case, do not perform systematic studies of various immunoglobulins against allergens without a thorough review of the patient's medical history.

Do not carry out population screening for vitamin D deficiency by measuring serum 25-hydroxy vitamin D (Calcidiol).

Do not request a sedimentation rate or erythrocyte sedimentation rate (ESR) to assess inflammation in patients with undefined diagnosis. To detect proinflammatory status in the acute

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phase, request C-reactive protein (CRP).

Dr Bernabeu points out that "these five measures were selected from a large number proposed by the SEQCML expert group, from which 10 were selected and of these the five priority recommendations (through the Delphi method)." These guidelines were presented, along with those of seven other scientific societies, in the "Commitment to Quality by Scientific Societies in Spain" Conference, held on May 31, 2016.

Dr. Silvia Izquierdo, member of the SEQCML and President of the Laboratory Accreditation Commission, explains: "Clinical laboratory professionals must make a commitment to review and evaluate the analytical tests requested by clinicians and to avoid unnecessary testing". In her opinion, "sometimes clinicians request tests from the laboratory for reasons that deviate from the true purpose: diagnosis, monitoring, confirmation of a clinical suspicion, and prognosis." It is here that "the responsibility of the clinical laboratory doctor plays a key role". Dr. Izquierdo believes that sometimes lists of services are not updated adequately, and these "should be revised and modified in accordance with recommendations established by the scientific societies related to clinical laboratories and with agreements established by clinicians".

This SEQCML project is part of its strategic approach to accreditation of clinical laboratories, in which new steps will be taken soon. Dr. Bernabeu explains: "The SEQCML has a Strategic Plan in advanced stages of development in which the philosophy 'not to do' is a central element. One of the main aims of the Plan is the promotion of excellence in scientific and technical activities, in which demand management and benchmarking play a prominent role. Laboratory professionals also have a lot to contribute in their role as consultants, as reflected in the Plan´s focus on enhancing Laboratory Medicine."

This is a necessity, as "variability in the use of the tests available in the clinical laboratory can have consequences for the patient, since it is possible to end up doing analytical determinations that are not effective", says Dr. Izquierdo. In this vein, the close relationship between the implementation of new regulations (ISO 15189: 2012) and the "not to do" tests stands out. This standard "makes available to the clinical laboratory professional an appropriate request form", which is important for improving quality and efficiency in daily clinical practice.

NEWS

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

Pakistan Society Holds Seminar On World Rare Disease Day

by Dr Lena Jafri, MBBS, FCPS, Assist. Prof. Clinical Chemistry, Department of Pathology and Laboratory Medicine, Aga Khan University, Pakistan he Department of Pathology and Laboratory Medicine, Aga Khan University Hospital (AKUH) and Pakistan Society of Chemical Pathology (PSCP) at AKUH Karachi Pakistan jointly organized ‘CME Seminar on World Rare Disease Day’. This CME seminar was arranged to mark the occasion of world rare disease day, which is observed worldwide on the last day of February each year. The objective was to create mass awareness about rare diseases and to ensure that patients with rare disease have access to treatment. We have been organizing this CME since the last 2 years. The theme for this year world rare disease day was research; with the slogan: 'with research, possibilities are limitless!'.

‘For most of the rare diseases, the reality is that the answers to most basic questions are missing. It is only through research that identification of previously unknown diseases and understanding of diseases evolve. Research leads to the development of new innovative treatments and in some cases a cure.’ said Dr Aysha Habib Khan, Associate

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Professor and Section Head, Chemical Pathology, AKUH while delivering the welcome address. She added that research is considered a key in bringing hope to the millions of people living with a rare disease across the world and their families. Dr Hafsa Majid Consultant Chemical Pathologist at AKUH gave an overview of rare diseases and highlighted the challenges faced in the diagnosis of these diseases in Pakistan.

She shared the local data of Inherited Metabolic Diseases (IMD) diagnosed with locally available expertise at AKUH for organic acidurias & aminoacidopathies in high-risk Pakistani pediatric population. During the past few years many rare diseases have been reported with further additions to this never-ending list, explained Dr Majid.

Dr Zeeshan Ansar, Assistant Professor at the section of Molecular Pathology AKUH, gave an enlightening talk on ‘Clinical Application of Multiplex Ligation-dependent Probe Amplification’. In comparison to PCR, MLPA amplifies multiple genes in one run. Additionally MLPA can detect car-

Photo: Panel of speakers in the question answer session at ‘CME Seminar World Rare Disease Day.

rier status of inherited disease. Dr Salman Kirmani, Associate Professor, Chair Department of Pediatrics and Child Health discussed the importance of chromosomal microarray for diagnosing rare disorders. He explained that with use of this latest technology, it is now possible for smaller and more complex chromosome defects to be identified. Dr Kirmani explained that this technology is able to identify numerical abnormality; however, it cannot detect structural defects or anomalies easily.

Dr Lena Jafri, Assistant Professor Consultant Chemical Pathologist at AKUH emphasized the importance of College of American Pathologists (CAP) proficiency testing surveys as an educational and learning tool in her talk ‘Competency Based Educational Challenges of Biochemical Genetics Laboratory’. She discussed few cases from CAP surveys and highlighted its importance in reliability and validity of patient reporting. ‘Inherited Metabolic Disorders In Pakistan-reaching the unreached’ was an interesting talk by Dr Bushra Afroze, Consultant Pediatrician & Clinical Geneticist at AKUH,

who specializes in treating IMD. She introduced the audience to her new venture of tele health clinic between two clinical locations in two different cities of the country. She explained with real life cases how she has been managing patients with rare diseases from a distance. She emphasized that a strong liaison between clinicians in a country like Pakistan with limited clinical expertise in IMD can be a pragmatic approach to provide services to more patients at their doorsteps.

Dr Farooq Ghani Associate Professor and Service Line Chief Department of Pathology and Laboratory Medicine in the closing remarks appreciated the teamwork of pathologists and pediatricians at AKUH in putting together this CME seminar and in helping the children and families with rare disease. We know that there is a dearth of awareness regarding these rare diseases and the need of the hour is to spread knowledge about them in order to prepare ourselves in such a way so that we can limit the dreadful effects of such diseases. This CME was an attempt in this regard with eminent speakers from Pathology & Pediatrics.

A New Resource for the eJIFCC he eJIFCC, that has now been officially indexed by MEDLINE/ PUBMED, is happy to present Dr Reinhard B. Raggam as a case-report editor. He will follow the editorial process for the section dedicated to case descriptions that will enrich each issue of the eJIFCC for the broad interest to the community of laboratorians. eJIFCC is a platinum open-access journal, i.e. there is no charge to read, or to submit to this journal. Our numerous high-quality articles, debates, reviews, case studies and editorials are addressed to clinical laboratorians. The journal also publishes general news articles, IFCC publicity/news, educational materials and has a letters section. Besides offering original scientific thought in our featured columns, we provide pointers to quality resources on the world wide web. We aim to assist the development of the field of clinical chemistry and laboratory medicine worldwide. Manuscripts are fully peer reviewed and immediately free to access and download from www.ifcc.org.

The eJIFCC is a member of the Com-

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mittee on Publications Ethics (COPE).

“The eJIFCC welcomes case reports that illustrate new approaches to established clinical – diagnostic problems or describing a new clinically associated diagnostic problem. To be of value appropriate for publication, a case report must provide a significant learning point for other laboratory physicians and clinical chemists. Case reports should be provided with a summary not longer than 150 words, followed by a structured main text (INTRODUCTION, CLINICAL-DIAGNOSTIC CASE, DISCUSSION, TAKE HOME MESSAGES/ LEARNING POINTS) not exceeding 1500 words. Case reports will also allow 2 tables and 2 figures, the maximum number of references is 15, 3-5 keywords are mandatory. Please provide disclosures & contribution of authors at the end of manuscript text.”

IFCC OFFICE Via Carlo Farini 81, 20159 Milan, ITALY Tel: (39) 02-6680-9912 • Fax: (39) 02-6078-1846 E-mail: ifcc@ifcc.org • Web: www.ifcc.org Office Hours: 8.30-13.00 and 13.30-17.30 Staff Members: Paola Bramati, Silvia Cardinale, Silvia Colli-Lanzi LabMedica International April/2017

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Industry News

Molecular Diagnostics Market Approaching USD 7 Billion per Year he size of the molecular diagnostic testing market has reached USD 6.7 billion and is being driven by the growing threat of infectious disease and cancer, as well as the development of new products. These are the latest findings of Kalorama Information, an independent medical market research firm.

The main technologies for clinical molecular diagnostics comprise nucleic acid amplification tests (NAATs) based on real-time PCR (qPCR) and other amplification-detection protocols; direct nucleic acid probe tests such as in situ hybridization (ISH) and its fluorescent ISH (FISH); nextgeneration sequencing (NGS); amplification followed by probe-based hybridization on arrays (or microarrays); and other related methods.

According to Kalorama, nucleic acid amplification tests and sequencing-based tests will be the future of the molecular diagnostics market.

Meanwhile, qPCR and next-generation sequencing will be the preferred choice for cancer testing and prenatal screening due to their superior sensitivity and non-invasive sampling.

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Competitive displacement is expected in cytogenetics, new cancer tests and blood culture tests, though in situ hybridization will retain application markets in cancer testing with a share of 47% of the total molecular diagnostics market for cancer in 2021.

Over the next five years, infectious disease is expected to account for 60% of the global molecular diagnostics. Time to results for real-time PCR and isothermal amplification remain vital for various infectious disease testing applications, such as respiratory testing, hospital-acquired infections, bloodstream infections, and molecular point-of-care tests.

The molecular infectious disease diagnostics segment is defined by test decentralization with the introduction of NAAT platforms, which can be operated in hospital laboratories, and near-patient points of care, such as physician office labs and outpatient clinics. Larger clinical laboratories find integrated design from sample preparation to results analysis and user friendly features equally appealing as it frees up personnel.

Siemens Healthineers to Provide Clinical Lab Services for Two New Hospitals in Turkey iemens Healthineers has entered into a five-year contract to take over the clinical laboratory service operations for two new hospitals in Turkey. The hospitals in Bilkent, Ankara, and in Mersin are being built and operated as Public Private Partnership (PPP) by DiA Construction, a subsidiary of DiA, for the Turkish Ministry of Health.

The new hospitals are expected to improve healthcare as part of a Turkish government program to restructure the country's healthcare system, which began in 2003. According to the Turkish government, the Bilkent health campus, which has nearly 3,800 beds and an affiliated hotel, congress center and commercial area, is the largest project in the healthcare sector to be ever constructed from scratch in the country.

From mid-2018, over 10,000 medical staff will manage almost 25,000 patients daily at the Bilkent health campus, while the hospital in Mersin, which became operational towards the end of January 2017, will hold about 1,300 beds.

Siemens Healthineers will operate the laboratories at both the hospitals

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in partnership with lab doctors from Turkey's Ministry of Health. The company will assume the laboratory services for biochemistry, microbiology, hematology, immunology, emergency, genetics, pathology and point of care testing within these hospitals.

It also will provide the design, medical and technical equipment, appliances, consumables, service and maintenance, apart from the laboratory technical staff. The contract is expected to grant minimum revenue of nearly Euro 30 million, based on guaranteed annual test volumes, and is likely to surpass Euro 100 million, based on anticipated test volumes.

"This project combines our expertise in equipping laboratories with our service portfolio. It is a milestone for us and, at the same time, also a proof point for how we enable our customers to meet their current challenges and to excel in their respective environments. The new business model is designed to support our customers in increasing efficiency and containing costs right from the beginning," said Bernd Montag, Chief Executive Officer, Siemens Healthineers.

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

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

APRIL 2017 ENDO 2017 – Endocrine Society Annual Meeting. Apr 1-4; Orlando, FL, USA; Web: www.endocrine.org MEDICAL FAIR INDIA. Apr 6-8; New Delhi, India; Web: http://medical fair-india.com ECCMID 2017. Apr 22-25; Vienna, Austria; Web: www.eccmid.org/ eccmid_2017

MAY 2017 Biomarkers & Diagnostics World Congress 2017. May 2-4; Philadelphia, PA, USA; www.biomarkerworldcongress.com ISLH 2017 – International Society of Laboratory Hematology. May 4-6; Honolulu, HI, USA; Web: www.islh.org LABVOLUTION 2017. May 16-18; Hanover, Germany; Web: www. biotechnica.de Diagnostica / Hospitalar 2017. May 16-19; Sao Paulo, Brazil; Web: www.hospitalar.com

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JULY 2017 FEMS 2017- 7th Cong. of European Microbiologists. July 9-13; Valencia, Spain; Web: www.fems-microbiology2017.kenes.com AACC 2017 – 68th Annual Meeting of American Association for Clinical Chemistry. July 30-Aug 1; San Diego, CA, USA; www.aacc.org

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AACC . . . . . . . . . . . . . . . . . . .41 Advanced Instruments . . . . . .17 Advanced Instruments . . . . . .35 Agro-Bio . . . . . . . . . . . . . . . . .12 Alcor . . . . . . . . . . . . . . . . . . . .45 Awareness Technology . . . . . .39 Brand . . . . . . . . . . . . . . . . . . .21 Cellavision . . . . . . . . . . . . . . .52 COLABIOCLI 2017 . . . . . . . . .50 EliTech Group . . . . . . . . . . . . . .2 FEBS 2017 . . . . . . . . . . . . . . .49 DiaSys . . . . . . . . . . . . . . . . . .31 Dymind . . . . . . . . . . . . . . . . . .16 EliTech Group . . . . . . . . . . . . . .2 Erba . . . . . . . . . . . . . . . . . . . . .7 Erba . . . . . . . . . . . . . . . . . . . . .9 EFLM Symp. Balkan Region .49

– EuroMedLab 2017 . . . . . . . . .47 133 GBC . . . . . . . . . . . . . . . . . . . .33 108 Hecht, Karl . . . . . . . . . . . . . . . .8 111 Instrumentation Laboratory . . .11 – IFCC WorldLab 2017 . . . . . . .46 – ISLH 2017 . . . . . . . . . . . . . . . .51 – LabMedica.com . . . . . . . . . . . .6 137 Lee Company, The . . . . . . . . .37 143 Mast Group . . . . . . . . . . . . . . .43 113 Nova Biomedical . . . . . . . . . . .13 110 ProteomeTech . . . . . . . . . . . .10 105 Randox . . . . . . . . . . . . . . . . . . .5 103 SNIBE . . . . . . . . . . . . . . . . . . . .3 119 SNIBE . . . . . . . . . . . . . . . . . . .19 144 Vicotex . . . . . . . . . . . . . . . . . .44 115 Zivak . . . . . . . . . . . . . . . . . . . .15

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