TUESDAY 21 MAY, 2024
WEDNESDAY 22 MAY, 2024
THURSDAY 23 MAY, 2024
FRIDAY 24 MAY, 2024
TUESDAY 21 MAY, 2024
02:00 pm
Registration
02:00 pm – 03:00 pm
1st dedicated poster session
03:00 pm – 03:30 pm
WELCOME
Chairs : Sofia Siest, Bernécourt, France / Tomris Ozben, Antalya, Turkey
03:00 pm – 03:10 pm
Sofia Siest, Bernécourt, France – SCs President
03:10 pm – 03:20 pm
Tomris Ozben, Antalya, Turkey – IFCC President
03:20 pm – 03:30 pm
Mario Plebani, Padova, Italy – EFLM President
03:30 pm – 04:30 pm
KEYNOTE LECTURE
Chairs: Sofia Siest, Bernécourt, France / Tomris Ozben, Antalya, Turkey
Reference Interval Harmonization: Harnessing the Power of Big Data Analytics to Derive Common Reference Intervals Across Populations and Testing Platforms
Khosrow Adeli, Toronto, Ontario, Canada
Reference Interval Harmonization: Harnessing the Power of Big Data Analytics to Derive
Common Reference Intervals Across Populations and Testing Platforms
Khosrow Adeli,
Ph.D., FCACB, DABCC, FADLM
Head and Professor, Clinical Biochemistry and Senior Scientist, Research Institute,
The Hospital for Sick Children, University of Toronto, Toronto, Canada
Several national surveys have reported wide variation in reference intervals across healthcare centres in certain regions, even those using the same analytical platform and reagents for the same assay. There is a high risk of inappropriate test result interpretation when reference intervals are not appropriately harmonized. The Canadian Society for Clinical Chemistry (CSCC) Working Group on Reference Interval Harmonization was established in 2015 to develop evidence-based harmonized/common reference intervals and support their implementation in laboratories across Canada. Harnessing the power of big data, laboratory results were collected across populations and testing platforms to derive common adult RIs for 16 biochemical markers. A novel comprehensive approach was established, including: (1) analysis of big data from community laboratories across Canada; (2) statistical evaluation of age, sex, and analytical differences; (3) derivation of hRIs using the refineR method; and (4) verification of proposed harmonized reference intervals across nine laboratories with different instrumentation using serum and plasma samples collected from healthy Canadian adults. Harmonized RIs were calculated for all assays using the refineR method, except free thyroxine. Derived harmonized reference intervals met proposed verification criterion across nine laboratories and five manufacturers for alkaline phosphatase, albumin (BCG), chloride, LDH, magnesium, phosphate, potassium (serum), total protein (serum). Further investigation is needed for select analytes due to lower verification in one or more laboratory (albumin (BCP), calcium, total CO2, total bilirubin, sodium) or concern regarding harmonized reference intervals that were considered too wide (alanine aminotransferase, creatinine, TSH). In this presentation, we will discuss the work completed by the Working Group on Reference Interval Harmonization in Canada, challenges encountered, and future plans to support implementation.
Reference Interval Harmonization: Harnessing the Power of Big Data Analytics to Derive Common Reference Intervals Across Populations and Testing Platforms
Professor Khosrow Adeli PhD, FCACB, DABCC, FAACC
Professor and Head, Clinical Biochemistry, The Hospital for Sick Children,
University of Toronto, Toronto, ON, Canada
President, International Federation of Clinical Chemistry & Laboratory Medicine
Harmonization in laboratory medicine from specimen collection to result reporting is critical to ensure consistent and accurate clinical decision-making. Harmonized or common RIs refer to using one interpretative recommendation for an analyte across several laboratories, regardless of analytical assay or patient population. Harmonized or common RIs should therefore only be considered for assays that demonstrate minimal bias across considered methodologies. Several national surveys have reported wide variation in reference intervals across healthcare centres in certain regions, even those using the same analytical platform for test measurement. There is a high risk of inappropriate test result interpretation when reference intervals are not appropriately harmonized. The Canadian Society for Clinical Chemistry (CSCC) Working Group on Reference Interval Harmonization was established in 2015 to develop evidence-based harmonized/common reference intervals (hRIs) and support their implementation in laboratories across Canada. Harnessing the power of big data, laboratory results were collected across populations and testing platforms to derive common adult RIs for 16 biochemical markers. A novel comprehensive approach was established, including: (1) analysis of big data from community laboratories across Canada; (2) statistical evaluation of age, sex, and analytical differences; (3) derivation of hRIs using the refineR method; and (4) verification of proposed hRIs across nine laboratories with different instrumentation using serum and plasma samples collected from healthy Canadian adults. Harmonized RIs were calculated for all assays using the refineR method, except free thyroxine. Derived hRIs met proposed verification criterion across nine laboratories and five manufacturers for alkaline phosphatase, albumin (BCG), chloride, LDH, magnesium, phosphate, potassium (serum), total protein (serum). Further investigation is needed for select analytes due to lower verification in one or more laboratory (albumin (BCP), calcium, total CO2, total bilirubin, sodium) or concern regarding too wide hRIs (alanine aminotransferase, creatinine, TSH). In this presentation, we will discuss the work completed by the Working Group on Reference Interval Harmonization in Canada, challenges encountered, and future plans to support implementation.
04:30 pm – 04:45 pm
INTRODUCTION TO THE CONFERENCE
Sofia Siest, Bernécourt, France
04:45 pm – 05:30 pm
PLENARY LECTURE
Multi-omics profiling in the era of cancer precision medicine
Tomris Ozben, Antalya, Turkey
Multi-omics profiling in the era of cancer precision medicine
Prof. Dr Tomris Ozben
IFCC President; EFLM, Past-President; Akdeniz University, Medical Faculty, Dept. of Medical Biochemistry, Antalya Turkey; University of Modena and Reggio Emilia, Medical Faculty, Clinical and Experimental Medicine, Ph.D. Program, Modena, Italy
Precision Medicine uses a deep knowledge of disease pathogenesis to tailor therapy for an individual cancer patient based on the tumour characteristics. Precision Medicine is an effective method of targeting and treating certain cancer types, providing a revolutionary treatment in oncology. Tumor heterogeneity remains a hurdle to understand tumor biology. There are variations in response to treatment among patients with the same cancers. For the same tumor type, there is a wide variation in clinical evolution of patients, highlighting differences in tumor cells’ progression or mutation. These differences are barriers to develop efficient therapies. Researchers are using molecular data available to characterize tumors, identify therapeutic targets, and make precision medicine more precise. Cancer hallmarks requires molecular alterations at multiple levels including genome, epigenome, transcriptome, proteome, and metabolome. Numerous attempts using single-level OMICS approaches lack the resolving-power to establish the casual relationship between molecular signatures and the phenotypic manifestation of cancer hallmarks. The multi-OMICS approaches have the potential to uncover the intricate molecular mechanism underlying different phenotypic manifestations of cancer hallmarks. Moreover, multi-OMICS approaches can be used to dissect the cellular response to chemo- or immunotherapy as well as discover molecular candidates with diagnostic/prognostic value. Each type of omics data adds to the list of molecular differences associated with cancer, revealing useful markers of disease processes, and providing insights into biological pathways. Multi-omics and Bioinformatics are the driving forces of a revolution in diagnostic and prognostic testing. Multi-omics methods generate vast amounts and different kinds of data. Integrating them to obtain biologically meaningful insights is one of the biggest challenges. As Precision Medicine in oncology expands to include big data, omics data, and molecular imaging, there are serious challenges ahead to translate them into meaningful healthcare for patients that will enable precision medicine as an individualized approach to medicine that considers biological variation among individuals in designing treatment strategies.
Mobile Health (mHealth) and Internet of Things (IoT)
Dr. Alexander Haliassos,
MD, PhD, EurSpLM ESEAP, the Greek Proficiency Testing Scheme for Clinical Laboratories. Athens, Grece.
05:30 pm – 07:00 pm
General Assembly of the Santorini Conferences (SCs) Association
WEDNESDAY 22 MAY, 2024
09:00 am – 11:00 am
SESSION I
COMMON DENOMINATORS OF CHRONIC DISEASES – DIAGNOSTICS, WHERE WE ARE
Chairs: John Lamont, Antrim, United Kingdom / Stavroula Kanoni, London, United Kingdom
09:00 am – 09:30 am
Denominators of long-term outcomes in chronic diseases and their implications in personalised medicine
Behrooz Alizadeh, Gröningen, The Netherlands
09:30 am – 10:00 am
VEGF-A a potential biomarker for personalised medicine in chronic diseases
Helena Murray, Antrim, United Kingdom
10:00 am – 10:30 am
Early inflammatory and fibrotic biomarkers of NAFLD and NASH
Mark Ruddock, Antrim, United Kingdom
10:30 am – 11:00 am
The quest for missing heritability: role of rare variant and gene-environment interactions
Guillaume Paré, Hamilton, Canada
The quest for missing heritability: role of rare variant and gene-environment interactions
Guillaume Pare, MD
McMaster University, Ontario, Canada
Biobank-scale genotyping has enabled the routine use of statistical genetics applications, such as Mendelian randomization, polygenic scores and heritability estimations. However, many questions remain less well explored, such as the contribution of gene-by-environment interactions (GxE) and the role of rare coding variants (RV) in complex traits. Leveraging the speed, versatility and robustness of large linear models, we sought to address these two questions. First, we introduce MonsterLM, a multiple linear regression method that does not rely on model specification and provides unbiased estimates of variance explained by GxE. Identification of GxE is crucial to understand the interplay of environmental effects on complex traits. However, current methods evaluating GxE on biobank-scale datasets have limitations. We demonstrate robustness of MonsterLM through comprehensive genome-wide simulations using real genetic data from 325K UK Biobank participants. We estimate GxE using waist-to-hip-ratio, smoking, and exercise as the environmental variables on 13 outcomes and find significant GxE for 8 environment-outcome pairs. The majority of GxE variance involves SNPs without strong marginal or interaction associations. Second, we developed a novel framework, the Rare variant heritability (RARity) estimator, to assess RV heritability (h2RV) without assuming a particular genetic architecture. We applied RARity to 31 complex traits in the UK Biobank (N=167K) and showed that gene-level RV aggregation suffers from 79% (95% CI: 68-93%) loss of h2RV. Using unaggregated variants, 27 traits had h2RV>5%, with height having the highest h2RV at 21.9% (95% CI: 19.0-24.8%). The total heritability, including common and rare variants, recovered pedigree-based estimates for 11 traits. We also used RARity to reveal 11 novel gene-phenotype relationships. Finally, we demonstrated that in silico pathogenicity prediction (variant-level) and gene-level annotations do not generally enrich for RVs that over-contribute to complex trait variance, and thus, novel methods are needed to predict RV functionality.
11:00 am – 11:30 am
COFFEE BREAK
11:30 am – 12:30 pm
SESSION II
FLASH COMMUNICATIONS
Chairs: Candan Hizel Perry, Montreal, Canada / Alexander Haushofer, Wels, Austria
11:30 am – 11:50 am
Genetic diagnosis and multi-omics clustering for diabetes precision medicine
Philippe Froguel, Lille, France
11:50 am – 12:10 pm
Needs of the scientific community: Trust in nutrition!
American Society for Nutrition (ASN) – Dante Preciado, Rockville,United States
12:10 pm – 12:30 pm
Personalised nutrition. The paradigm of obesity.
Georges Dedoussis, Athens, Greece
12:30 pm – 01:30 pm
SESSION III
ADVANCES IN CANCER DETECTION AND TREATMENT WITH LIQUID BIOPSY
Chairs: Candan Hizel Perry, Montreal, Canada / Sanja Stankovic, Belgrade, Serbia
12:30 pm – 01:00 pm
Liquid biopsy for early detection of cancer and minimal residual disease
Klaus Pantel, Hamburg, Germany
01:00 pm – 01:30 pm
The power of circulating tumor cells in immuno-oncology
Catherine Alix-Panabières, Montpellier, France
01:30 pm – 02:30 pm
LUNCH TIME
02:30 pm – 04:30 pm
SESSION IV
OMICS + DATA SCIENCE A MATCH MADE IN HEAVEN
Chairs: Panos Deloukas, London, United Kingdom / Alexander Haliassos, Athens, Greece
02:30 pm – 03:00 pm
Functional Analysis of Cardiovascular Disease Risk Variants
Panos Deloukas, London, United Kingdom
03:00 pm – 03:30 pm
Omics and personalized addiction care
Wei Deng, Hamilton, Canada
03:30 pm – 04:00 pm
Can we predict the future? The utility of genetic risk scores for classification and prediction of autoimmune disease
Richard Oram, Exeter, United Kingdom
04:00 pm – 04:30 pm
Artificial intelligence in external quality assessment – proficiency testing schemes in Laboratory Medicine
Alexander Haliassos, Athens, Greece
04:30 pm – 05:30 pm
2nd dedicated poster session
THURSDAY 23 MAY, 2024
09:00 am – 10:00 am
SESSION V
IMMUNOLOGY VERSUS GENOMICS: A MARRIAGE NEVER HAPPENED
Chairs: Sanja Stankovic, Belgrade, Serbia / Markus Paulmichl, Salzburg, Austria
09:00 am – 09:30 am
Cardiac inflammation: the relative contribution of autoimmunity and genes
Federica Marelli-Berg, London, United Kingdom
Cardiac inflammation: the relative contribution of autoimmunity and genes
Federica M Marelli-Berg1,
Silvia Fanti1*, Edward Stephenson1,2*, Etel Rocha-Vieira1,3, Alexandros Protonotarios2,4, Stavroula Kanoni1, Perry Elliott2,4, Saidi A Mohiddin1,2*,
1William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
2Barts Heart Centre, Barts Health NHS Trust, St Bartholomew’s Hospital, West Smithfield, London EC1A 7BE
3Federal University of Vales do Jequitinhonha e Mucuri, Diamantina, Minas Gerais, Brazil
4Institute of Cardiovascular Science, University College London, 72 Huntley Street, London WC1E 6AG
Autoimmunity is increasingly recognized as a key contributing factor in heart muscle diseases. The functional features of cardiac autoimmunity in humans remain undefined, due to the challenge of studying immune responses in-situ. We have previously described a subset of cMet-expressing memory T-lymphocytes, which preferentially migrate to cardiac tissue in mice and humans.
In-depth phenotyping of peripheral blood T-cells, including cMet+ T-cells, was undertaken in groups of patients with inflammatory and non-inflammatory cardiomyopathies, patients with non-cardiac autoimmunity and healthy controls. Validation studies were carried out using human cardiac tissue and in an experimental model of cardiac inflammation.
We show that cMet+ T-cells are selectively increased in the circulation and in the heart of patients with inflammatory cardiomyopathies. cMet+ T-cells display distinct phenotype and function compared to cMet-negative T-cells, including preferential proliferation to cardiac myosin and co-production of multiple cytokines (IL-4, IL-17 and IL-22). Further, circulating cMet+ T-cell subpopulations in different heart muscle diseases identify distinct and overlapping mechanisms of heart inflammation including in genetic cardiomyopathies.
In experimental autoimmune myocarditis, rise of autoantigen-specific cMet+ T-cells in peripheral blood marks the loss of immune tolerance to the heart. Importantly, disease development can be halted by pharmacological cMet inhibition, indicating a causative role for cMet+ T-cells.
09:30 am – 10:00 am
Myocarditis: The challenge of diagnosis and the opportunities for treatment
Perry Elliott, London, United Kingdom
10:00 am – 11:00 am
SESSION VI
IMMUNOLOGY BIOMARKERS IN ONCOLOGY PRECISION
Chairs: Eric Quemeneur, Strasbourg, France / Helena Murray, Antrim, United Kingdom
10:00 am – 10:30 am
Direct and indirect markers of response to anti-tumor vaccines or oncolytic virotherapy
Eric Quemeneur, Strasbourg, France
10:30 am – 11:00 am
The importance of blood biomarkers in Oncology
Mark Ruddock, Antrim, United Kingdom
11:00 am – 11:30 am
COFFEE BREAK
11:30 am – 12:30 pm
SESSION VII
AI-FACILITATED INTEGRATED RISK SCORES: FROM BENCH TO BEDSIDE FOR PERSONALIZED MEDICINE
Chairs: Stavroula Kanoni, London, United Kingdom / Alexander Haliassos, Athens, Greece
11:30 am – 12:00 pm
Integrated Risk Scores (IRS) for cardiovascular disease risk prediction – Advances towards precision medicine
Stavroula Kanoni, London, United Kingdom
12:00 pm – 12:30 pm
Digital Twins in Precision Medicine and Personalized Nutrition
Aristides Eliopoulos, Athens, Greece
12:30 pm – 01:30 pm
SELECTED ABSTRACTS – ORAL COMMUNICATIONS SESSION – 1st part
01:30 pm – 02:30 pm
LUNCH TIME
02:30 pm – 04:30 pm
SELECTED ABSTRACTS – ORAL COMMUNICATIONS SESSION – 2nd part
04:30 pm – 05:30 pm
VEGF CONSORTIUM
FRIDAY 24 MAY, 2024
09:00 am – 10:20 am
SESSION VIII
PHARMACOGENOMICS: CLINICAL TRANSLATION – NOW AND FUTURE – PART I
Chairs: Ron Van Schaik, Rotterdam, The Netherlands / Charity Nofziger, Anif/Niederalm, Austria
09:00 am – 09:20 am
Trends in precision medicine, pharmacogenetics as adjuvant in establishing a correct immunosuppressive therapy of kidney transplant
Sergio Bernardini, Rome, Italy
Trends in precision medicine, pharmacogenetics as adjuvant in establishing a correct immunosuppressive therapy of kidney transplant
Sergio Bernardini,
Dept. of Experimental Medicine, University of Tor Vergata, Rome, IT
Allogenic transplant of solid organ is now considered the election clinical procedure in patients with organ failure. Indeed, in the last decades important milestones have been reached especially in kidney transplant. Although the transplanted organ can compensate the function of original one, the main problem remains the immune response by the host organism that can lead to a possible rejection. The management of the immune response is at the basis for a long-life successful organ transplantation. To achieve this objective, drugs targeting the key immunological players of the immunological pathways, fundamental in graft rejection mechanisms have been developed. These can be now used in clinical management of transplanted patients. It is important to note that the wide inter and intra-patient variability of both the pharmacokinetics (PK) and pharmacodynamics (PD) represent the major clinical problem. Although the plasma concentrations of drugs are constantly monitored, variation of these parameters mainly due to the polymorphic status (genetic heterogeneity) of the genes involved in xenobiotic-metabolizing enzymes, transport proteins, and in some cases drug targets, can affects metabolite concentrations in each specific patient. This can induce an important toxicity or loss of efficacy. Numerous studies have been recently conducted to examine the relationship among genetic factors, drug pharmacokinetics, and therapy outcomes. Now several polymorphic genes, influencing drug’s efficacy have been catalogued, and they are now easily detected using Next generation sequencing (NGS) methods. Further research, and new investment in creating validated NGS commercial panel for the analysis of pharmacogenetics in renal transplant recipients will represent the future of precision medicine in the management of immunosuppressive therapy.
09:20 am – 09:40 am
From Pharmacogenomics to Polygenic Risk Score (PRS) – Are We There Yet?
Candan Hizel Perry, Montreal, Canada
09:40 am – 10:00 am
Charity Nofziger, Anif/Niederalm, Austria
10:00 am – 10:20 am
Interindividual variability and pharmacogenomics: possible ways forward
Munir Pirmohamed, Liverpool, United Kingdom
Interindividual variability and pharmacogenomics: possible ways forward
Munir Pirmohamed,
Department of Pharmacology and Therapeutics, The Wolfson Centre for Personalised Medicine, University of Liverpool, L69 3GL, UK
Interindividual variability in drug response (efficacy and/or safety) is the rule rather than the exception in clinical practice. This can be due to a number of clinical factors and genomic factors. While a genomic variant may play a major role in determining drug response, it is important not to forget about the clinical factors which also contribute. Our approach at present is unimodal (i.e. we look at one factor at a time), and we need to move to more multimodal approaches (combining genetic and clinical factors). This becomes even more important as our population grows older (with decreasing renal and hepatic function) and there is an increasing prevalence of multimorbidity and consequently polypharmacy. This puts them at higher risk of adverse drug reactions, drug interactions, and worse clinical outcomes. Tackling this will be a challenge, but genomics will add value to the usual approach of undertaking medicines reviews. In such populations, panel genotyping is likely to be the most pragmatic, and will enable us to move from reactive to pre-emptive genotyping approaches. This will be more convenient for the clinician and for the patient, as it fits in seamlessly with the current clinical pathways. The questions which need to be evaluated is when people should have panel genotyping undertaken, and which will be the most clinically-effective and cost-effective approach.
10:20 am – 11:00 am
COFFEE BREAK
11:00 am – 12:20 pm
SESSION VIII
PHARMACOGENOMICS: CLINICAL TRANSLATION – NOW AND FUTURE – PART II
Chairs: Candan Hizel Perry, Montreal, Canada/ Alexander Haushofer, Wels, Austria
11:00 am – 11:20 am
Pharmacogenetics in clinical practice: experiences and challenges
Ron Van Schaik, Rotterdam, The Netherlands
Tracking T cell-mediated autoimmunity in the heart.
11:20 am – 11:40 am
Pharmacogenetics clinical implementation: challenges and barriers
Adrian LLerena, Badajoz, Spain
Tracking T cell-mediated autoimmunity in the heart.
11:40 am – 12:00 pm
Markus Paulmichl, Salzburg, Austria
Tracking T cell-mediated autoimmunity in the heart.
12:00 pm – 12:20 pm
Pharmacogenetics and its appliance in clinical daily life
Andrea Griesmacher, Innsbrück, Austria
Tracking T cell-mediated autoimmunity in the heart.
12:20 pm – 01:00 pm
GENERAL DISCUSSION ON PHARMACOGENOMICS
moderated by specialists of pharmacogenomics interpretation
01:00 pm – 02:00 pm
CLOSING SESSION
Sofia Siest, Bernécourt, France