Clinical Diagnostics & Research 2020

With QCI services your clinical lab can enable a seamless fastq to clinical report workflow. We provide services such as cloud based variant calling and automated upload of the data to the QCI platform by utilizing our APIs . In the QCI platform services are available for customized automated reporting of variants to reduce manual review. The final clinical report can also be customized with respect to design and data presented on the report.

Learning Objectives:

1. Learn about various clinical services that can take you from raw sequencing data to a final clinical report 

2. Get informed about API integration/Consultation services for the QCI I platform

3. Get informed about QCI reporting services like custom PDF report design and automated variant reporting policies

Today's presentation will cover the following topics from the perspective of a NYC based Laboratory:

• What have we learned year to date about CoV-2 and specifically how diagnostic testing has impacted where we are at today
• Review role of  Molecular / Antigen testing (In lab and POC) for Covid-19
• Experience with Serology testing YTD
• What's needed moving forward

Learning Objectives:

1. Gain additional understanding on current testing options for Covid-19

2. Understand options and pro's / con's for Covid-19 Antigen testing solutions

As many parts of the northern hemisphere move into the colder months and indoors, SARS CoV-2 has begun a second infection wave that has exceeded the first surge of cases in many global regions. This will likely be complicated by the upcoming flu season and underlines the requirement for effective testing to specifically assess and quantify the protective neutralizing antibody response post SARS CoV-2 infection or vaccination. The quantification of differential immune response levels and longevity between individuals for large populations remains elusive and constrained by the current neutralizing antibody test methods that require live cells and virus with tedious, costly and time consuming procedures. A newly available assay termed cPass SARS-Cov-2 Virus Neutralization Test (also known as Surrogate Virus Neutralization assay) permits the quantitative evaluation of protective neutralizing antibodies in a simple, cost-effective and high-throughput test amenable that mirrors the data from live cell assays. Samples from SARS CoV-2 recovered individuals exhibited differences up to 400-fold in neutralizing antibody titers raising questions around the: 1) strength of immune response between both infected and vaccinated individuals; 2) level of protection against re-infection and 3) duration of protection post infection/vaccination. All of which can be answered using the cPassTM sVNT.

Learning Objectives:

1. Brief overview of SARS CoV-2 infection mechanism

2. Description of cPassTM sVNT, its advantages and comparative qualitative data with live cell neutralization and serology tests

3. Quantitative protocol for cPassTM sVNT and its application to samples from recovered SARS CoV-2 individuals

Cell-free DNA (cfDNA) is a key analyte for liquid biopsy samples. Due to extremely low concentration and high degree of fragmentation, the extraction of cfDNA is technically challenging. Here, the efficiency of the automated large volume cfDNA extraction method was evaluated with regard to different performance parameters like quantitative cfDNA extraction for total and low-abundant biomarkers with focus on small fragments, precision, linearity for a broad range of input volumes and compatibility to downstream assays.

Learning Objectives:

1. Handling & challenges with cfDNA

2. Embedment of cfDNA extraction workflow into customized downstream assay

3. Quality control of extracted cfDNA

In 2012, the Choosing Wisely initiative was commenced by the ABIM with numerous societies putting forward lists of overused tests or procedures. The Choosing Wisely movement has spread to numerous countries including the UK, Canada, and Australia. The movement has spurred 1000s of quality improvement projects worldwide. Improving utilization and/or efficiency in the laboratory includes: curtailing inappropriate laboratory tests from being ordered, electronically stopping unnecessary duplicate tests, automating manual processes, eliminating paper-based processes, implementing testing cascades, and curtailing unnecessary transfusions. Since the choice of quality improvement projects appears limitless, it makes it difficult to know where to get started! If you elect to address overuse of a common laboratory test, numerous avenues are available to assist you with narrowing your list: ask your clinicians which tests your hospital is overusing (they know!), look at variability of test use by clinicians within the same area, consult the quality improvement literature for analytes that others have addressed, and sift through the choosing wisely statements for items you have not addressed. There are also numerous system levers you can pull to bring utilization under control: education (grand rounds, screen savers on computers, alerts on the log-in page of your EMR or landing page for the hospital internet), computerized provider order entry controls, middleware controls allowing identification of duplicate tests, removal of overused tests from requisitions and ordersets, implementation of criteria for certain test types, and audit and feedback to high users. Evaluation of success should be measured in repeated quality improvement cycles of plan-do-study-act (PDSA). Never be surprised if your first attempt fails to improve utilization. Lastly, don’t forget to share your successes by publishing your results – this will assist with more rapid improvement in healthcare.

Learning Objectives:

1. Identify areas of inefficiency in the lab that need improving

2. Identify tests that are commonly overused Evaluate system changes necessary to bring utilization down

3. Assess how to know if your system change was successful

The nuclear proliferation biomarker Ki-67 has multiple potential roles in breast and other cancers, both as a prognostic but also predictive marker. However, several studies have shown that the assessment of Ki-67 with immunohistochemistry (IHC) suffers from both intra-and inter-observer variability and low reproducibility. On top of that it is still being debated what the most appropriate way of scoring Ki-67 IHC is - should one use global scoring or the hot spot scoring method? In this webinar we will look into how Visiopharm CE-IVD APPs can be used for standardizing the assessment of Ki-67 IHC. We will also show how the APPs can accommodate both the global scoring method and the hot spot scoring method allowing for a tailored solution that fits the diagnostic workflow in your laboratory. We will focus on the clinically validated APPs, but will also reveal some of the AI technologies we have for research use.

Learning Objectives:

1. Understand the limitations of manual biomarker assessment in image analysis

2. Learn how CE-IVD APPs can used for standardization of Ki-67 scoring

3. Get a glimpse of the future AI-powered workflows for biomarker analysis

Cases of traumatic brain injury (TBI) have been steadily rising over the past decade with most common causes of injury observed among participants in contact sports, combat military personnel, and unintentional falls occurring in children and the elderly. These events can range from mild-to-severe injury in the affected individual. Brain imaging using computed tomography (CT) scan is the current gold standard for TBI testing and diagnosis. Mild TBI (mTBI), or concussion injury, is often the most difficult of these to detect because injury to the head region may not be observed on CT scan. Furthermore, CT scanners are not readily available outside of medical institutions. Functional scoring methods, like SCAT5 and Glasgow Coma Scale, may provide the clinician with some evidence of TBI at off-site locations (e.g., on the sports field or in combat zones). Biomarker testing for evidence of TBI has gained popularity as another means towards achieving a reliable diagnosis. A goal of this presentation is to describe TBI, summarize serum biomarkers tests that are used in both clinical and research settings, and suggest alternative means of test interpretation. Concussion biomarkers have shown good promise for ruling out injury (high negative predictive value), while positive test results are often equivocal. The classical way to interpret a biomarker test result is by comparing it to a population-based reference interval established in healthy individuals; the so-called “normal range”.  A potential remedy to improve positive diagnoses is to establish an individual’s own baseline concentration, then compare it with that person’s biomarker concentration after suspected TBI. Serial sampling is used to describe the comparison of two consecutive test results from separate blood draws. Establishing normal biological variation of the biomarker, along with statistical calculation of a “reference change value”, offers an alternative diagnostic strategy for interpreting serial sampling results.

Learning Objectives:

1. Identify current diagnostic tools for assessment of acute concussion/traumatic brain injury (TBI)

2. Describe clinical utility of serum biomarker proteins for detecting concussion injury in human subjects

3. Discuss serial sampling strategy, and reference change value (RCV), to identify a significant change in biomarker test results

Clinical Laboratories have the opportunity to support value based health care by aligning with organizational strategies that focus on population health and creating meaningful insights using real time longitudinal laboratory data.  To provide diagnostic insights, laboratorians must move from providing results for a single patient, to a population focus for groups of patients.  The presentation will include examples on how data can be positioned to support the screening, diagnosis, monitoring and intervention management for groups of patients with chronic and high cost health conditions. The use of Clinical Lab 2.0 concepts to frame the development of these population based initiatives will be discussed.   Key components that will be highlighted are leadership, selecting population based initiatives, and items to consider when building an evidence base. Examples discussed will include risk stratification and identification of gaps in care. Partnerships, both inside and outside the laboratory, essential for these efforts will be described.   Partner relationships with data analytics will be covered as one of the most important components to successfully deliver insights to a variety of stakeholders including clinical providers, healthcare administrators and health plans. Measuring the success of laboratory driven population health initiatives can be challenging and complex.  This presentation will describe several measures that can be used to demonstrate value both clinically and financially.  Barriers to population health initiatives will also be included in the presentation.

Learning Objectives:

1. At the end of the presentation audience members will be able to identify several Clinical Lab 2.0 components that should be included when developing population health initiatives from laboratory data

2. At the end of the presentation audience members will be able to explain the role of key partnerships both inside and outside the laboratory

3. At the end of the presentation audience members will be able to describe at least 2 examples of how clinical laboratory data can be used to provide meaningful insights supporting population health.

Biomarkers play a vital role in disease detection and treatment follow-up. It is important to note that the diseases in the early stage are typically treated with the greatest probability of success. Therefore, the early detection of biomarkers is very important in the case of cancer, cardiovascular disorders, and other pathological conditions. Biomarkers may includes antigens, DNA, mRNA, and enzymes. Cardiac biomarkers are part of the standards of care and guidelines for myocardial infarction and heart failure. Cardiac biomarkers represent also an evolving field of innovations to improve the prevention, diagnosis and monitoring of cardiovascular disorders. The ultimate goal behind the use of biomarkers for diagnosis is to develop reliable and cost-effective powerful detection tools for early diagnosis of diseases and disorders. A serial combination testing of a sensitive early marker (e.g., H-FABP, myoglobin, or CK-MB isoforms) and one of the cardiac-specific troponins (cTnT or cTnI) offers the best approach. Identifying the needs of physicians and potential new candidates for routine requires both multidisciplinary exchanges and translational research. Data mining and machine learning offer now more possibilities for this quest. Laboratorians play a key role after that to implement new biomarkers in routine practices and check the performances according to practices and accreditation specifications. Education and its continuing cycle is glue for an efficient integration in clinical practices and appropriate use by health care professionals. Thus, biomarker detection platforms must therefore be adapted for a rapid and sensitive point-of-care testing.

Learning ObjectivesL

1. Describe the value of cardiac biomarkers in emergency settings

2. Artificial Intelligence (AI) and its applications in cardiovascular early risk prediction

3. Present the needs for training and continuing education of health care professionals

The opioid crisis has put significant strain on the healthcare system and resources, including the clinical laboratory which has seen significant increases in requests for urine drug screening. Setting up and selecting tests for urine drug screening can be challenging even for experienced laboratories. Many labs rely on a screen and confirm approach, combining immunoassay screens with definitive mass spectrometry analysis. However, selection of appropriate tests and cutoffs depends on the patient population and type of service. In addition, interpretation of this testing can be very challenging as laboratory staff and clinicians require knowledge of drug metabolism, drug windows of detection and analytical detection and performance. In this presentation, Dr. Boyd will give an overview of options for opioid testing including immunoassay and MS testing, and the interpretive challenges of each. She will also show how her lab has changed their urine drug screen workflow to address the challenges of the opioid epidemic.

Learning Objectives:

1. Discuss the impact of the opioid crisis on the clinical laboratory

2. Discuss important factors in setting up a urine drug screening program

3. Compare available techniques for urine drug screening for opioids and challenges in interpretation

Point-of-care testing (POCT) is destined to play a much greater role in chronic disease diagnosis and management. Advanced POCT systems are being developed to deliver less costly and more acute healthcare in a patient’s home, but remain scarce. Especially lacking are miniature devices, similar to the commonly used blood glucose meter, to quantitatively detect low concentrations of protein biomarkers in blood. Here, a unique integrated system solution is presented, which represents a significant step beyond proof-of-concept high sensitivity nanosensors, for quantitative reading of b-type natriuretic peptide (BNP) in outpatient blood. BNP is an established biomarker for early heart failure (HF) diagnosis and prognosis. HF is an epidemic affecting more than 26 million people worldwide and a chronic disease with ever increasing prevalence. Currently, accurate and quantitative BNP blood tests are only available in central laboratory and emergency room using venous blood. Highly sensitive carbon nanotube thin film (CNT-TF) impedance sensors are integrated into a user-friendly POCT system, NanoBot, which consists of two parts: a disposable test strip and a miniature electrical readout unit. Using electrochemical impedance spectroscopy (EIS), combined with standard addition, NanoBot is demonstrated to detect blood BNP with a limit of detection (LOD), precision, and accuracy comparable to those of a standard immunofluorescence assay (IFA) and a commercial emergency room POCT device. A pilot clinical study with patient-derived blood plasma validates that NanoBot has not only strong performance, but also other advantages such as low sample volume, label-free and wash-free detection. Collectively, NanoBot’s performance and operational characteristics signify its promising potential as a POCT device for home-use heart failure diagnosis.

Learning Objectives:

1. Various aspects of electrochemical immunosensors for high-sensitivity detection of protein biomarkers

2. Recent advances and challenges in developing nano-biosensors

3. The need for disruptive technology to make the change from centralized healthcare to distributed healthcare

Patient laboratory test results are significantly over-represented in electronic medical records, but significantly under-utilized in research. An important application of laboratory data is to help improve laboratory testing and operational processes in order to benefit patient care. In this presentation, Dr. de Koning will review several laboratory data-based quality improvement initiatives and the resulting benefit to patients. Dr. de Koning will also review how laboratory data can be used to develop and validate patient risk scores for clinical decision support.

Learning Objectives:

1. Understand several applications of laboratory data to quality improvement studies

2. Describe how laboratory data should be processed and analyzed in order to create prognostic risk scores