Ortho Clinical Diagnostics (Ortho) and EKF Diagnostics (EKF) recently announced an agreement that allows Ortho customers to access EKF’s Stanbio Chemistry Beta-Hydroxybutyrate (BHB) LiquiColor^® assay. This is an important marker used in conjunction with clinical findings and other lab tests for the diagnosis and management of ketoacidosis and its main causative factor, diabetic ketoacidosis (DKA). The high-quality, fully automated assay is now available for use on Ortho’s VITROS^® 4600 Chemistry System and the VITROS^® 5600 Integrated System.

Diabetic ketoacidosis is a serious complication that can lead to a disruption of chemical balance in the body, and can be fatal if left undiagnosed. EKF’s enzymatic Beta-Hydroxybutyrate (BHB) assay is used primarily for determining both the presence and degree of ketosis in suspected diabetic ketoacidosis cases. The BHB assay produces a quantitative value that is specific to the BHB ‘ketone body’. These qualities make the BHB assay the new clinical diagnostic standard of care for ketone testing.

“Ortho is committed to delivering a broad menu of assays to our customers in the clinical lab, whether through in-house development or collaborations like the one with EKF,” said Ortho’s chief Operating Officer Robert Yates.

Ortho and EKF are collaborating to provide the BHB assay as a validated MicroTip Partnership Assay (MPA) application in the U.S. and Canada. This MPA utilizes the User Defined Assay (UDA) feature, which provides the capability to program assay parameters as defined in the EKF Stanbio Assay Application Sheet. The Beta-Hydroxybutyrate LiquiColor^® assay has been CLIA classified by the U.S. Food and Drug Administration (FDA) as a MODERATE complexity assay on the VITROS^® 4600 Chemistry System and VITROS^® 5600 Integrated System.

“Diabetic ketoacidosis is a serious condition, and our collaboration with Ortho Clinical Diagnostics will help to deliver the important BHB assay to their existing customers” said EKF’s Diagnostics Head of Sales, Gilbert Mejia.

EKF Diagnostics’ Stanbio Chemistry portfolio is a broad range of liquid-stable reagents, calibrators, standards and controls. LiquiColor^® and Liqui-UV^® reagents are designed for maximum stability, ease-of-use and are optimized for today’s chemistry analyzers. In addition to its BHB test for ketosis, EKF continues to build on its successful range of esoteric reagents.

Rare variants combined with background genetic risk factors may account for many unexplained cases of familial breast cancer, and knowing the specific genes involved could inform choice of prevention and treatment strategies.
Researchers Na Li, MD, Ian Campbell, PhD, lead investigator; and their colleagues at the Peter MacCallum Cancer Centre in Melbourne, Australia, focused their study on patients at high risk of breast cancer: those with a personal or family history who were seeking an explanation.
“When you know which gene is conferring the risk of breast cancer, you can provide a more precise estimate of risk, know what to expect and watch out for, and tailor risk management strategies to the patient,” said Dr. Campbell. Unfortunately, in about half of these high-risk patients, no known genetic cause was found, suggesting a more complicated explanation. In such cases, cancer geneticists had long suspected that polygenic risk (risk conferred by a combination of genetic variants) was involved.
Genes do not work on their own, but rather as part of one’s overall genetic context, explained Dr. Li. “That ‘polygenic risk’ background is like a landscape full of hills and valleys, with each risky variant like a house on top of it,” she said. “If you inherit a high-risk variant – a tall house – but live in a valley, your overall risk of breast cancer may end up being average because your genetic landscape pulls it down.”
The concept of background genetic risk is not new, but for many years, scientists did not have the tools to collect and analyse the thousands of genomes needed to quantify it. Recent improvements in next-generation sequencing technology have addressed this challenge. As a result, Dr. Li and colleagues were able to sequence up to 1,400 candidate breast cancer genes in 6,000 familial breast cancer patients and 6,000 cancer-free controls. In this large sample, they searched for potential cancer-associated genes suggested by the literature, collaborators, and their own previous results, and identified at least 46 genes that were at least twice as likely to have mutations among participants with breast cancer than in those without.
They also used the data to calculate a polygenic risk score for each patient, and combined this score with data on their high and moderate-risk variants to estimate each patient’s overall risk of developing breast cancer. In the coming years, the researchers plan to expand the study internationally to further test and refine their findings across populations. They also hope to bring these more precise risk estimates into the clinic, to more accurately reassure women about their personal risk of cancer, or – if risk is high – advise preventive strategies such as screening at a younger age.

American Society of Human Genetics
www.ashg.org/press/201710-breast-cancer.shtml

Children who are considered to be at risk of developing eye cancer should receive genetic counselling and testing as soon as possible to clarify risk for the disease. This is the consensus of leading ophthalmologists, pathologists and geneticists, who worked for two years to develop the first U.S. guidelines on how to screen for the most common eye tumour affecting children. The goal is to ensure retinoblastoma is detected at the earliest possible stage so ophthalmologists can save the lives and vision of more children.
Retinoblastoma is a cancer that starts in the retina, the very back of the eye. It can also spread to other parts of the body, including the brain and bones. There are approximately 350 new cases diagnosed each year in the United States.
The disease primarily affects young children. It can be either hereditary or non-hereditary. Children with hereditary retinoblastoma often develop retinal tumours in both eyes within the first years of life. Early diagnosis, when tumours are small, improves the child’s chance of survival and their chance of keeping their vision and their eyes.
Development of these guidelines began when ophthalmologist Alison Skalet, M.D., Ph.D., of the Casey Eye Institute in Portland, Ore., searched for an optimal screening strategy for her own patients and found little published guidance.
For the next two years, Dr. Skalet and Patricia Chévez-Barrios, M.D., ophthalmologist, and pathologist from Houston Methodist Hospital, led members of the American Association of Ophthalmic Oncologists and Pathologists, and a team of experts to devise guidelines. The effort was also supported by the American Association for Pediatric Ophthalmology and Strabismus, the American Academy of Ophthalmology, and the American Academy of Pediatrics.
The guidelines address a knowledge gap among ophthalmologists and other health care professionals in the U.S. regarding risk for inherited retinoblastoma and best practices for screening examinations. It is anticipated that they will also influence care in other countries. Therefore, the guidelines were written to provide a general framework for care that can be modified based on local resources, and provider and parental preferences. The recommendations acknowledge paediatric anaesthesia and genetic testing may be limited in many developing countries, preventing strict adherence. So, the guidelines offer direction in cases when these resources are unavailable.
Dr. Chévez-Barrios said the new guidelines meet the team’s goal to focus care on children at the highest risk for disease while decreasing unnecessary examinations for children at lower or no risk of developing retinoblastoma.
“We wanted to make sure all the doctors who come in contact with these patients are aware of how to diagnose and treat them so we can save more eyes, more vision and of course more lives,” said Dr. Chévez-Barrios.
Ophthalmologists say there are signs to look for that may indicate retinoblastoma. They include a white colour in the pupil when a light is shone in the eye, such as when taking a flash photograph. Also, eyes that appear to be looking in different directions could be a sign of trouble. They encourage parents to make an appointment with their child’s paediatrician if they notice any changes to their child’s eyes.

American Academy of Ophthalmology
www.aao.org/newsroom/news-releases/detail/genetic-testing-for-children-at-risk-of-eye-cancer

Normally, the heart contracts and relaxes to a regular beat. In atrial fibrillation, the upper chambers of the heart beat irregularly, which affects blood flow into the two lower large chambers. This can lead to stroke, heart failure and other heart-related complications.
Atrial fibrillation triggers were first identified in the pulmonary veins. Hence, the isolation of these veins has become one of the standard treatments for atrial fibrillation. Subsequently, other sites in the heart have been found to trigger and/or drive atrial fibrillation, including the superior vena cava (SVC). Notably, patients with arrhythmogenic SVC have long myocardial sleeves (circularly and longitudinally oriented bundles of heart cells) around the SVC and high amplitude electrical potentials within them.
Although these anatomical features in arrhythmogenic SVC all point to the possibility of genetic factors being involved in atrial fibrillation, this topic has remained largely unstudied. Furthermore, findings of genetic studies previously conducted in people of European ancestry could not be generalized and transferred to those of Asian ancestry.
This critical knowledge gap drove a team of researchers from Tokyo Medical and Dental University(TMDU) in Japan to study the clinical and genetic factors associated with atrial fibrillation in an Asian population. The team discovered two variants of single-nucleotide polymorphism (SNP), a variation in a single nucleotide that occurs at a specific position in the genome, which were significantly associated with SVC arrhythmogenicity.
“We found that among six variants identified in a previous genome-wide association study in Japanese patients, SNPs rs2634073 and rs6584555 were associated with SVC arrhythmogenicity,” said Yusuke Ebana, first author of the study.
“We also determined that SVC arrhythmogenicity was conditionally dependent on age, body mass index, and left ventricular ejection fraction,” Ebana added.
To arrive at that conclusion, the research team conducted a meta-analysis of clinical and genetic factors of 2,170 atrial fibrillation patients with and without SVC arrhythmogenicity across three major hospitals in Japan. Surface electrocardiogram and bipolar intracardiac electrograms were continuously monitored. Additionally, a mapping catheter was placed in the SVC to map the circumferential SVC region using computed tomography (CT) or transesophageal echocardiography as a reference. All the patients were followed-up at least every three months.
“The genes closest to the two SVC variants we found were PITX2 and NEURL1, with the former reported as a left-right determinant in cardiac development,” said Tetsushi Furukawa, senior author of the study. “We speculate that the suppression of NEURL1 in SVC patients with the risk genotype could be the cause of arrhythmogenic SVC leading to atrial fibrillation,” Furukawa added.

Tokyo Medical and Dental University (TMDU)
www.tmd.ac.jp/english/press-release/20171018/index.html

Research by Genevan scientists on gene expression and the non-coding genome is a significant breakthrough for the future of personalized medicine.
Geneticists have taken an important step towards true predictive medicine by exploring the links between disease and genetic activity in different tissues. They thus constructed a model, the first step in identifying sequences in the non-coding genome indicating a disease-related pathogenic effect. In a second study, they went even further by associating the risk of developing a disease – in particular schizophrenia, cardiovascular diseases or diabetes – with the variability of the activity of the genome in different types of cells. And their results brought some surprises. Their findings may well revolutionize how each of us, according to his genome, will take care of his health in the future.
These studies are based on data from the international GTEx project, for "Genotype-Tissue Expression", launched in 2010 and co-directed by Professor Emmanouil Dermitzakis, geneticist at the Faculty of Medicine of the University of Geneva (UNIGE) and director of the Health 2030 Genomics Center. The objective of this project was to collect as many tissues as possible from a large number of individuals to understand the effects of genes and their variations. The data published over the last 7 years have allowed scientists worldwide to make considerable progress in analysing genomic variations specific to each of these tissues and predispositions to diseases.
Examining different types of human tissue from hundreds of people has led to a better understanding of how genomic variants – those changes in the spelling of DNA code inherited from our parents – could control how, when, and how many genes are activated and deactivated in different tissues, increasing the risk of developing a wide range of diseases. One of the main discoveries of the GTEx consortium is that the same variant present in multiple tissues may have a different effect depending on the tissue involved. A variant that affects the activity of two genes associated with blood pressure will, for example, have a greater impact on the expression of these genes in the tibial artery, even if the activity of the genes is higher in other tissues. .
To evaluate the influence of variants on gene activity, the researchers perform an analysis called "eQTL". An eQTL – or quantitative locus of expression of the characters – consists of an association between a variant at a specific location of the genome and the level of activity of a gene in a particular tissue. By comparing the eQTLs of different tissues to the genes associated with diseases one can therefore determine which tissues are most related to a disease. But if we can associate a region of the genome with a phenotype (a disease, for example), scientists were not yet able to determine exactly which nucleotide – the bricks of our DNA – when it mutates, contributes to the phenotype. question. Emmanouil Dermitzakis emphasizes as follows: "We needed to design a model to precisely link variants to a particular disease. Our goal, to simplify, was to locate the exact nucleotide that, in case of mutation, increases the risk of a disease, rather than the associated region or gene.
To build a solid model, scientists performed eQTL analyzes of hundreds of samples and identified thousands of causal variations in the non-coding genome. Using this dataset, they began building models to recognize these variations from DNA sequences, without linking them to existing phenotypes. As described by Andrew A. Brown, assistant professor in the Department of Genetic Medicine and Development of UNIGE’s Faculty of Medicine and one of the first authors of these studies: "We wanted to recognize pathogenic variants without any other information than this. sequence. If our model is confirmed, we will solve one of the major problems of modern genomics: by simply reading non-coding DNA sequences, we will be able to identify their pathogenic effects. This is the real future of predictive medicine.

University of Geneva
www.unige.ch/medecine/fr/carrousel/la-lecture-des-variants-genomique-ouvre-la-voie-a-la-medecine-predictive/