Scientific Workshops will be held on Sunday, June 18:
Sunday June 18 Morning Part 1 – 0800-0930
- W180800-A The “whats,” “whys,” and “hows” of critical values
- W180800-B An update on fluid-based biomarkers for the diagnosis of neurodegenerative disorders; where do we stand?
Sunday June 18 Morning Part 2 – 0945-1115
- W180945-A Laboratory standardization: bringing order to chaos?
- W180945-B The usefulness of comprehensive serological testing in the diagnosis of paraneoplastic neurologic syndromes (PNS) and autoimmune encephalitis autoantibodies
Sunday June 18 Afternoon – 1300-1615
- W181300-A Messaging for the media – A special workshop to learn how to balance the integrity of scientific terminology while simplifying your message. Through interactive case studies, mock interviews, and interactive discussions, you will be equipped to confidently interact with media and non-scientific personnel!
W180800-A The “whats,” “whys,” and “hows” of critical values Sunday June 18, 0800-0930
Lawrence de Koning, University of Calgary and Alberta Precision Laboratories
Allison Venner, Alberta Precision Laboratories and University of Calgary
Learning Objectives:
At the end of the session, the participants will be able to:
- Describe basic principles underlying the use of critical values.
- List common clinical biochemistry tests that have critical values, and the actual thresholds set.
- Explain the clinical rational for specific critical values as well as the clinical responses to results that exceed these thresholds.
- Discuss different methods of reporting critical results.
- Describe workload considerations and outcome-based approaches in setting critical values.
Clinical lab results that exceed critical values (critical result thresholds) should be quickly communicated to clinicians so that lifesaving care can be provided. However it is often unclear what tests should have critical values, why values are set at specific thresholds, and how clinicians respond to results that exceed critical values. This workshop will shed light on these important issues, both within the core laboratory and in the point of care setting.
W180800-B An update on fluid-based biomarkers for the diagnosis of neurodegenerative disorders; where do we stand? Sunday June 18, 0800-0930
Hans Frykman, University of British Columbia, BC Neuroimmunology Lab and US Neurocode Lab
Pankaj Kumar, University of British Columbia and BC Neuroimmunology Lab
Ali Mousavi, University of British Columbia, BC Neuroimmunology Lab and US Neurocode Lab
Learning Objectives:
At the end of the session, the participants will be able to:
- Recognize recent technologies and protocols for the detection of biofluid biomarkers in NDD and AD.
- Discuss the diagnostic performance and limitations in analytical and clinical validation of different testing platforms.
- Explain the clinical utility of different biomarkers in the diagnosis of different neurodegenerative diseases.
Neurodegenerative diseases (NDDs) of the central nervous system (CNS) are broad-spectrum disorders. Although they usually encompass specific diseases such as Alzheimer’s disease (AD), Motor neuron disease (ALS), Parkinson’s disease (PD), neurodegeneration is also accompanying the process with other neurological diseases especially inflammatory and demyelinating diseases such as multiple sclerosis (MS). They can be distinguished based on their severity, clinical course, distribution of lesion, and their imaging, pathological and laboratory findings. The foremost NDDs are defined by misfolding the normal proteins and accumulation of them in the CNS which makes the possibility for a mechanism-based proteomic biomarker to check in biofluids. On the other hand, the broad clinical presentations of NDDs result in the overlapping of their clinical features with other neurological disorders. Therefore, the discovery and detection of specific biomarker/s for different NDDs has potential to improve their clinical diagnosis. It also could help to facilitate the development and monitoring of effective disease-modifying therapies.
AD is the most common type of NDD with a long preclinical and progressive course its underline pathology is more defined. AD is a double proteinopathy and its fundamental pathological features are the aggregation of amyloid beta and tau in the form of neurotic plaques and neurofibrillary tangles. In 2018, the US National Institute on Aging (NIA) and the Alzheimer’s Association changed the diagnostic platform of AD to ATN including a research profile with β amyloid deposition, pathologic tau, and neurodegeneration. This reform has provided opportunities for moving from a clinical pathological diagnosis of AD to a clinical biological and biological definition of AD.
PD is the second most common NDD which is characterized by the deposition of alpha-synuclein in the form of inclusions of Lewy bodies in neurons and Lewy neuritis in axons, and dendrites. Because the pathological process in PD starts years before the beginning of its clinical symptoms, relying on clinical findings for its diagnosis is accompanied by substantial and irreversible neuronal degeneration. Therefore, finding a blood–based biomarker to allow the identification of the disease in the early stage of pathological changes is an urgent need.
Several studies have led to the emergence of α-synuclein as a readily discoverable biomarker and therapeutic target in PD.
Other biomarkers such as Blood-based markers of general neurodegeneration and glial activation such as neurofilament light chain protein (NFL) and glial acidotic fibrillary protein (GFAP) have emerged for clinical and therapeutic monitoring of demyelination and neurodegeneration.
Recently several studies showed that elevated NfL levels in CSF and serum/plasma of patients with multiple sclerosis and ALS at diagnosis are predictive factors for prognosis and clinical course of the disease. The recent development of ultrasensitive technologies such as the Single-molecule Array (Simoa) facilitated the early detection of biofluid biomarkers such as plasma tau or phosphorylated tau with the highest accuracy. These emerging technologies and novel neurodegenerative biomarkers in the simple Blood-based test offer a unique advantage to use them in clinical testing, and drug development trials for the diagnosis and management of AD and other neurodegenerative diseases. These easily accessible and cost-effective Blood-based biomarkers detecting the AD and other NDD pathologies have been developed, which might revolutionize the diagnostic workup of NDDs in the future.
In this workshop, we present an overview of the latest advances in the field of biomarkers for neurodegenerative diseases. We will discuss the diagnostic performance and limitations in analytical and clinical validation for some of the commonly used testing platforms. We also will discuss the pros and cons of the usefulness of different biomarkers in the diagnosis of NDDs particularly in the diagnosis of AD as the most common and prodromic type of NDD.
W180945-A Laboratory standardization: bringing order to chaos? Sunday June 18, 0945-1115
Jessica Gifford, DynaLIFE Medical Labs and University of Calgary
Learning Objectives:
At the end of the session, the participants will be able to:
- Describe issues and challenges associated with standardization.
- Discuss strategies to successfully implement laboratory standardization in the following areas:
- pre-analytical factors: test directory, test requisition, specimen routing.
- analytical factors: instrumentation, including lessons learned from a provincial RFP for general chemistry instrumentation.
- post-analytical factors: reference interval harmonization, and provincial LIS implementation.
Standardization of laboratory services is becoming a common theme in Canada due to budgetary restriction and regional consolidation of laboratory services. However, standardization is often initially met with fierce resistance due to concerns of job losses, vendor monopolies, reagent shortages or changes specific to one vendor, IT limitations, and inability to troubleshoot problem specimens or meet the needs of the local population. If done properly however, standardization can offer many opportunities to improve patient care through equalizing access to services and a continuity in results produced by laboratories within a city, zone, province or even country.
Over the last five years, laboratory service in Alberta at both the acute care and community level has been brought under the respective umbrellas of Alberta Precision Laboratories and DynaLIFE Medical Labs, with both organizations mandating provincial standardization of laboratory services. These efforts have included changes at the pre-analytical, analytical, and post-analytical levels.
In this workshop we will address important issues related to and lessons learned from the consolidation of laboratory services in Alberta, specifically from a clinical chemistry perspective. Topics discussed will include standardization of laboratory requisition forms and test directory, provincial requests for proposals for general chemistry/immunoassay instrumentation vendors, provincial efforts to standardize troponin testing, reference interval harmonization, and the standardization of the laboratory information system (LIS). The impact of these changes on both medical and operations staff will be addressed. This workshop provides a unique learning opportunity that is otherwise not available to clinical laboratorians. Real-life experiences in standardization will be shared, emphasizing the challenges and resource commitments that were required to meet these goals. This workshop is aimed at clinical biochemists, general pathologists, clinical biochemistry fellows, general pathology residents, medical laboratory technologists, and laboratory administrators.
W180945-B The usefulness of comprehensive serological testing in the diagnosis of paraneoplastic neurologic syndromes (PNS) and autoimmune encephalitis autoantibodies Sunday June 18, 0945-1115
Hans Frykman, University of British Columbia, BC Neuroimmunology Lab and US Neurocode Lab
Pankaj Kumar, University of British Columbia and BC Neuroimmunology Lab
Ali Mousavi, University of British Columbia, BC Neuroimmunology Lab and US Neurocode Lab
Learning Objectives:
At the end of the session, the participants will be able to:
- Recognize the most common clinical and AAbs associated features of AE and PNS.
- Identify the limitations in diagnostics accuracy when using commercial assay alone.
- Explain the advantages of comprehensive laboratory testing and our recommendations on optimizing turn around time for the detection of PNS and AE AAbs.
Paraneoplastic neurological syndromes (PNS) are a group of immune-mediated neurological conditions resulting from the remote effects of cancers. Autoimmune encephalitis (AE) is a heterogeneous group of serious non-infectious immune-mediated, inflammatory conditions of the central nervous system, mostly the parenchymal of the brain. PNS and AE are associated with auto antibodies that target intracellular antigens, synaptic receptors, or cell-surface proteins in the nervous system. Moreover, serological features, in a particular patient, are important determinators alongside clinical and oncological findings for the diagnosis and management of PNS. In this regard, in 2021, the PNS criteria were revised by a panel of international experts (PNS-Care panel) for clinical decision-making and research purposes. The panel introduced the new concept of “high-risk” and “intermediate-risk” phenotypes as well as their accompanying autoantibodies (AAbs), into “high-risk,” “intermediate-risk,” and “low-risk.” The “high-risk AAbs” (the older term “onconeural antibodies or classic PNS”) are >70% of the time associated with cancer include Hu, CV2, YO, PCA2/MAP1B, SOX1, Amphiphysin, RI/ANNA2, MA2, Tr (DNER), and KLH11. The “intermediate-risk AAbs,” where 30%–70% of cases being associated with cancer are; NMDAR, GABAbR, AMPAR, mGLuR5, VGCC, and CASPR2 (with Morvan syndrome), and the “low-risk AAbs” associated with cancer in <30% cases are; LGI1, DPPX, mGluR1, GABAaR, GFAP, GAD65, and CASPR2 (without Morvan syndrome).
Despite the gold standard diagnostics techniques recommended by PNS-Care ((i.e., screening with snap-frozen rodent brain immunohistochemistry/immunofluorescence assays, IHC/IFA) followed by confirmatory Cell-Based assays (CBA) with fixed or live cells and/or immunoblots (IB)), only a very few highly specialized neuroimmunology laboratories offer both techniques. More commonly, clinical laboratories use commercial fixed CBAs for detecting AE AAbs, however, these commercial kits when used alone lack the necessary sensitivity and specificity and have an increased risk for overdiagnosis. On the other hand, the number of false positives with commercial line blots has shown to be extremely high, up to 70% particularly for well-established “high-risk AAbs” that can lead to overdiagnosis, unwarranted workups, and unnecessary treatments. In this workshop we will explain the limited diagnostic accuracy that any commercial assay offers for AE and PNS AAbs detection if used alone. We will then discuss our laboratory experience on the usefulness of a comprehensive orthogonal testing algorithm involving different preparations of snap-frozen rat brain sections and numerous live and fixed Cell-Based assays to confirm any positive result. Moreover, we will discuss on how to optimize turn around time when using a comprehensive panel testing. At the end, we will discuss the timing and indication of cerebrospinal fluid (CSF) testing in patients with PNS and AE and provide our recommendations on when to choose serum and/or CSF samples.
W181300-A Messaging for the media Sunday June 18, 1300-1615
Rob Wozny, Sound Strategy Communications Ltd.
As PhD level scientists, communicating with the appropriate technical language to other professionals ensures that medical laboratory test results are delivered and understood. While the lexicon of the laboratory professionals ultimately serves the highest standards of quality care for the patient, the terminology and jargon utilized can make it difficult to understand for the mainstream media – an essential stakeholder that often disseminates initiatives to the public. In this hands-on workshop, you will learn how to confidently participate in a media interview, balance the integrity of scientific terminology while simplifying your messaging, tell your stories through channels of communication that engage mainstream and non-traditional media, and much more! This will be accomplished through interactive discussions, cases studies, and mock interviews to reinforce learning. This is an excellent opportunity for anyone looking to refine their communication skills. Mock-interview volunteers are encouraged and welcome!