Showing papers in "Critical Reviews in Clinical Laboratory Sciences in 2020"

Biomarkers associated with COVID-19 disease progression.

Abstract: The coronavirus disease 2019 (COVID-19) pandemic is a scientific, medical, and social challenge. The complexity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is centered on the unpredictable clinical course of the disease that can rapidly develop, causing severe and deadly complications. The identification of effective laboratory biomarkers able to classify patients based on their risk is imperative in being able to guarantee prompt treatment. The analysis of recently published studies highlights the role of systemic vasculitis and cytokine mediated coagulation disorders as the principal actors of multi organ failure in patients with severe COVID-19 complications. The following biomarkers have been identified: hematological (lymphocyte count, neutrophil count, neutrophil-lymphocyte ratio (NLR)), inflammatory (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT)), immunological (interleukin (IL)-6 and biochemical (D-dimer, troponin, creatine kinase (CK), aspartate aminotransferase (AST)), especially those related to coagulation cascades in disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). New laboratory biomarkers could be identified through the accurate analysis of multicentric case series; in particular, homocysteine and angiotensin II could play a significant role.

The COVID-19 pandemic

Abstract: In December 2019, an outbreak of pneumonia of unknown origin was reported in Wuhan, Hubei Province, China. Pneumonia cases were epidemiologically linked to the Huanan Seafood Wholesale Market. Inoculation of respiratory samples into human airway epithelial cells, Vero E6 and Huh7 cell lines, led to the isolation of a novel respiratory virus whose genome analysis showed it to be a novel coronavirus related to SARS-CoV, and therefore named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus belonging to the subgenus Sarbecovirus. The global spread of SARS-CoV-2 and the thousands of deaths caused by coronavirus disease (COVID-19) led the World Health Organization to declare a pandemic on 12 March 2020. To date, the world has paid a high toll in this pandemic in terms of human lives lost, economic repercussions and increased poverty. In this review, we provide information regarding the epidemiology, serological and molecular diagnosis, origin of SARS-CoV-2 and its ability to infect human cells, and safety issues. Then we focus on the available therapies to fight COVID-19, the development of vaccines, the role of artificial intelligence in the management of the pandemic and limiting the spread of the virus, the impact of the COVID-19 epidemic on our lifestyle, and preparation for a possible second wave.

Fructose and hepatic insulin resistance.

Abstract: Excessive caloric intake in a form of high-fat diet (HFD) was long thought to be the major risk factor for development of obesity and its complications, such as fatty liver disease and insulin resistance. Recently, there has been a paradigm shift and more attention is attributed to the effects of sugar-sweetened beverages (SSBs) as one of the culprits of the obesity epidemic. In this review, we present the data invoking fructose intake with development of hepatic insulin resistance in human studies and discuss the pathways by which fructose impairs hepatic insulin action in experimental animal models. First, we described well-characterized pathways by which fructose metabolism indirectly leads to hepatic insulin resistance. These include unequivocal effects of fructose to promote de novo lipogenesis (DNL), impair fatty acid oxidation (FAO), induce endoplasmic reticulum (ER) stress and trigger hepatic inflammation. Additionally, we entertained the hypothesis that fructose can directly impede insulin signaling in the liver. This appears to be mediated by reduced insulin receptor and insulin receptor substrate 2 (IRS2) expression, increased protein-tyrosine phosphatase 1B (PTP1b) activity, whereas knockdown of ketohexokinase (KHK), the rate-limiting enzyme of fructose metabolism, increased insulin sensitivity. In summary, dietary fructose intake strongly promotes hepatic insulin resistance via complex interplay of several metabolic pathways, at least some of which are independent of increased weight gain and caloric intake. The current evidence shows that the fructose, but not glucose, component of dietary sugar drives metabolic complications and contradicts the notion that fructose is merely a source of palatable calories that leads to increased weight gain and insulin resistance.

A summary of the diagnostic and prognostic value of hemocytometry markers in COVID-19 patients.

Abstract: Many studies have reported hemocytometric changes in COVID-19 infection at admission and during the course of disease, but an overview is lacking We provide a summary of the literature of hemocytometric changes and evaluate whether these changes may assist clinicians in diagnosing and predicting disease progression of COVID-19 Eighty-three out of 250 articles from December 2019 to 20 May 2020 were included from the databases, PubMed, Web of Science Core Collection, Embase, Cochrane and MedRxiv Our review of the literature indicates that lymphopenia and an elevated neutrophil/lymphocyte ratio are the most consistent abnormal hemocytometric findings and that these alterations may augment in the course of time, especially in those with severe disease

Preanalytical variables that affect the outcome of cell-free DNA measurements.

Abstract: Fragments of cell-free DNA (cfDNA) in human body fluids often carry disease-specific alterations and are now widely recognized as ideal biomarkers for the detection and monitoring of genomic disorders, especially cancer, that are normally difficult to examine noninvasively. However, the conversion of promising research findings into tools useful in routine clinical testing of cancer has been a slow-moving process. A major reason is that the diagnostic sensitivity and specificity of cfDNA-based clinical assays are negatively impacted by a combination of suboptimal and inter-institutional differences in preanalytical procedures. The most prominent factors include: (i) a poor understanding of the biological factors that determine the characteristics of the cfDNA population in a biospecimen prior to collection, (ii) inattention to how cfDNA with different structures and physical properties are affected differently by a given preanalytical step, and (iii) the sheer number of possible conditions that can be selected from for each preanalytical step along with a continually expanding menu of commercial products that often show varying degrees of bias and efficiency. The convergence of these variables makes it difficult for research groups and institutions to reach a consensus on optimal preanalytical procedures and a challenging task to establish widely applied standards, which ultimately hamper the development of cfDNA assays that are fit for broad clinical implementation. In this review, we follow a systematic approach to explore the most confounding preanalytical factors that affect the outcome of cfDNA measurements.

Diagnostic utility of protein to creatinine ratio (P/C ratio) in spot urine sample within routine clinical practice.

Abstract: The spot (random) urine protein to creatinine ratio (P/C ratio) is an alternative, fast and simple method of detecting and estimating the quantitative assessment of proteinuria. The aim of the work...

Managing hemolyzed samples in clinical laboratories.

Abstract: Hemolysis is conventionally defined as membrane disruption of red blood cells and other blood cells that is accompanied by subsequent release of intracellular components into the serum or plasma. It accounts for over 60% of blood sample rejections in the laboratory and is the most common preanalytical error in laboratory medicine. Hemolysis can occur both in vivo and in vitro. Intravascular hemolysis (in vivo) is always associated with an underlying pathological condition or disease, and thus careful steps should always be taken by the laboratory to exclude in vivo hemolysis with confidence. In vitro hemolysis, on the other hand, is highly preventable. It may occur at all stages of the preanalytical phase (i.e. sample collection, transport, handling and storage), and may lead to clinically relevant, yet spurious, changes in patient results by interfering with laboratory measurements. Hemolysis interference is exerted through several mechanisms: (1) spectrophotometric interference, (2) release of intracellular components, (3) sample dilution and (4) chemical interference. The degree of interference observed depends on the level of hemolysis and also on the assay methodology. Recent evidence shows that preanalytical practices related to detection and management of hemolyzed samples are highly heterogeneous and need to be standardized. The Working Group for Preanalytical Phase (WG-PRE) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has published many recommendations for facilitating standardization and improvement of this important preanalytical issue. Some key EFLM WG-PRE publications related to hemolysis involve: (i) a call for more transparency and some practical recommendations for improving the harmonization of the automatic assessment of serum indices and their clinical usefulness, specifically the hemolysis index (H-index), (ii) recommendations on how to manage local quality assurance of serum or plasma hemolysis/icterus/lipemia-indices (HIL-indices) and (iii) recommendations on how to detect and manage hemolyzed samples in clinical chemistry testing. In this review we provide a comprehensive overview of hemolysis, including its causes and effects on clinical laboratory assays. Furthermore, we list and discuss the most recent recommendations aimed at managing hemolyzed samples in everyday practice. Given the high prevalence of hemolyzed blood samples, the associated costs, the great heterogeneity in how hemolysis is handled across healthcare settings, countries and continents, and increasing patient cross-border mobility, standardization and quality improvement processes aimed at combatting this important preanalytical problem are clearly warranted.

Cerebrospinal fluid proteomics and biological heterogeneity in Alzheimer's disease: A literature review.

Abstract: Alzheimer's disease (AD) is the most common cause of dementia and is characterized by aggregation of amyloid and tau proteins in the brain. Results from genetic studies suggest that the pathophysiology underlying AD is complex, but studying this complexity in patients remains difficult. The cerebrospinal fluid (CSF) proteome contains a large number of proteins that can reflect ongoing biological processes. Proteomics techniques can be used to measure many proteins simultaneously in individual patients and may therefore provide an opportunity to study AD disease mechanisms. Here, we review the CSF proteomics literature to identify proteins consistently associated with AD, and perform pathway analyses on these proteins to study which biological processes may be involved in the disease.We performed a literature search of studies that investigated CSF proteomic alterations related to AD. We included original research articles when they measured at least 10 proteins in (antemortem) CSF in at least 10 individuals with AD, mild cognitive impairment (MCI) or controls. We examined if proteins were consistently related to AD, defined as consistent increase or decrease in AD vs. controls across studies. Next, we used the proteins identified as input to pathway analyses using Reactome to investigate which biological processes were enriched.In total, 29 studies were included that investigated AD-related changes to the CSF proteome, including a total of 1434 individuals with AD (of whom 47.1% had a CSF biomarker profile and 9.6% a postmortem examination consistent with AD) and 1380 controls. The studies reported 1 to 138 proteins associated with AD, of which 97 proteins were reported by two or more studies. Among proteins that were measured in more than one study, 27 (27.8%) showed consistent increases, 15 (15.5%) consistent decreases and 55 (56.7%) had contrasting results. Pathway analyses showed that AD-related proteins were enriched for hemostasis, lipoprotein and extracellular matrix pathways.These results indicate that proteomic alterations in CSF associated with AD reflect involvement of various biological pathways. The frequent occurrence of inconsistent protein level changes reported by different studies suggests that additional biological and/or (pre)analytical factors may influence the CSF proteome in AD, which should be further investigated in order to improve understanding of the biological complexity underlying AD.

The laboratory's role in combating COVID-19.

Abstract: Since Coronavirus Disease 2019 (COVID-19) first emerged in December 2019, the disease has rapidly evolved into a pandemic that threatens societies around the world As soon as the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified and its genome sequence determined, a laboratory diagnosis based on nucleic acid amplification technologies was quickly established and has played essential roles in the confirmation of a clinical diagnosis Serological testing for antibodies against SARS-CoV-2 is becoming available for complementary diagnosis, identification of convalescent plasma, and epidemiologic studies Additional laboratory biochemical tests, including monitoring the change in blood cells, blood gas, coagulation, liver function, cardiac markers, and inflammatory responses such as cytokine levels in plasma, are also critical in combating COVID-19 Nevertheless, with overwhelming numbers of patients and potentially large numbers of asymptomatic cases, clinical laboratories encounter enormous challenges in diagnostic approaches that can rapidly and accurately identify infected persons Strategies that can effectively detect disease progression in order to stratify patients for appropriate care, and that can thereby prevent exacerbation of the disease, are urgently needed This review discusses the laboratory's role and challenges in combating COVID-19

Early detection of cancer using circulating tumor DNA: biological, physiological and analytical considerations.

Abstract: Early diagnosis of cancer improves the efficacy of curative therapies. However, due to the difficulties involved in distinguishing between small early-stage tumors and normal biological variation, ...

Extracellular vesicles and their role in glioblastoma

Abstract: Research on the role of extracellular vesicles (EVs) in disease pathogenesis has been rapidly growing over the last two decades. As EVs can mediate intercellular communication, they can ultimately ...

The clinical impact of growth differentiation factor-15 in heart disease: A 2019 update

Abstract: Growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1) or non-steroidal anti-inflammatory drug-activated gene (NAG-1) has been identified as a biomarker of response to treatment and prognosis in cardiovascular diseases. GDF-15 is a member of the transforming growth factor-β superfamily and is involved in several pathological conditions such as inflammation, cancer, cardiovascular, pulmonary and renal diseases. Cardiac myocytes produce and secrete GDF-15 in response to oxidative stress, stimulation with angiotensin II or proinflammatory cytokines, ischemia, and mechanical stretch. Other cellular sources of GDF-15 production are macrophages, vascular smooth muscle cells, endothelial cells, and adipocytes, which secrete GDF-15 in response to oxidative or metabolic stress or stimulation of proinflammatory cytokines. GDF-15 is induced in hypertrophic and dilated cardiomyopathy after volume overload, ischemia, and heart failure. GDF-15 can be used as a marker of prognosis in patients with cardiovascular disorders, in combination with conventional prognostic factors, such as N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT).

Polypharmacy: a healthcare conundrum with a pharmacogenetic solution

Abstract: The use of multiple medications is growing at an alarming rate with some reports documenting an average of 12–22 prescriptions being used by individuals ≥50 years of age. The indirect consequences ...

Detection of amyloid beta peptides in body fluids for the diagnosis of alzheimer's disease: Where do we stand?

Abstract: Alzheimer's disease (AD) is an incurable neurodegenerative disease characterized by progressive decline of cognitive abilities. Amyloid beta peptides (Aβ), Tau proteins and the phosphorylated form of the Tau protein, p-Tau, are the core pathological biomarkers of the disease, and their detection for the diagnosis of patients is progressively being implemented. However, to date, their quantification is mostly performed on cerebrospinal fluid (CSF), the collection of which requires an invasive lumbar puncture. Early diagnosis has been shown to be important for disease-modifying treatment, which is currently in development, to limit the progression of the disease. Nevertheless, the diagnosis is often delayed to the point where the disease has already progressed, and the tools currently available do not allow for a systematic follow-up of patients. Thus, the search for a molecular signature of AD in a body fluid such as blood or saliva that can be collected in a minimally invasive way offers hope. A number of methods have been developed for the quantification of core biomarkers, especially in easily accessible fluids such as the blood, that improve their accuracy, specificity and sensitivity. This review summarizes and compares these approaches, focusing in particular on their use for Aβ detection, the earliest biomarker to be modified in the course of AD. The review also discusses biomarker quantification in CSF, blood and saliva and their clinical applications.

Perspectives on the role of PTEN in diabetic nephropathy: an update

Abstract: Phosphatase and tensin homolog (PTEN) is a potent tumor suppressor gene that antagonizes the proto-oncogenic phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway and governs basic cellular metabolic processes. Recently, its role in cell growth, metabolism, architecture, and motility as an intramolecular and regulatory mediator has gained widespread research interest as it applies to non-tumorous diseases, such as insulin resistance (IR) and diabetic nephropathy (DN). DN is characterized by renal tubulointerstitial fibrosis (TIF) and epithelial-mesenchymal transition (EMT), and PTEN plays a significant role in the regulation of both. Epigenetics and microRNAs (miRNAs) are novel players in post-transcriptional regulation and research evidence demonstrates that they reduce the expression of PTEN by acting as key regulators of autophagy and TIF through activation of the Akt/mammalian target of rapamycin (mTOR) signaling pathway. These regulatory processes might play an important role in solving the complexities of DN pathogenesis and IR, as well as the therapeutic management of DN with the help of PTEN K27-linked polyubiquitination. Currently, there are no comprehensive reviews citing the role PTEN plays in the development of DN and its regulation via miRNA and epigenetic modifications. The present review explores these facets of PTEN in the pathogenesis of IR and DN.

Acetylation and insulin resistance: a focus on metabolic and mitogenic cascades of insulin signaling.

Abstract: Insulin resistance is associated with an increased risk of several metabolic disorders including type 2 diabetes, hypertension and cardiovascular diseases. Advances over the last decade have expanded our understanding of the molecular mechanisms underlying insulin resistance; however, many details of the mechanisms causing insulin resistance remain unknown. Recently, attention has shifted toward the role of epigenetics in insulin resistance. In this regard, acetylation of the histone tails has been widely investigated for its role in influencing both metabolic and mitogenic cascades of insulin signaling. More specifically, histone acetyltransferases and histone deacetylases, as major modulators of chromatin accessibility and gene expression, have been studied to determine a possible interconnectivity between the special effects of lysine acetylation status and tyrosine phosphorylation networks on the target proteins of downstream pathways involved in both metabolic and mitogenic cascades of insulin signaling. There is accumulating evidence for the post-translational modification effects of IGFR, InsR, IRS1/2, PI3K, Akt, GLUT4, FoxO, PGC-1α, PPAR, AMPK and MAPKs on insulin resistance and glucose homeostasis. In this paper, we review the importance of acetylation of these factors in the regulation of insulin signaling and glucose metabolism, with a primary focus on the target proteins of downstream signaling of insulin. We also provide an update on the interplay between epigenetic modification and the cellular genome in the context of insulin signaling and describe the possible effect of the environment on this epigenetic regulation.

The potential of ctDNA analysis in breast cancer.

Abstract: Breast cancer is a highly heterogeneous and dynamic disease, exhibiting unique somatic alterations that lead to disease recurrence and resistance. Tumor biopsy and conventional imaging approaches are not able to provide sufficient information regarding the early detection of recurrence and real time monitoring through tracking sensitive or resistance mechanisms to treatment. Circulating tumor DNA (ctDNA) analysis has emerged as an attractive noninvasive methodology to detect cancer-specific genetic aberrations in plasma including DNA mutations and DNA methylation patterns. Numerous studies have reported on the potential of ctDNA analysis in the management of early and advanced stages of breast cancer. Advances in high-throughput technologies, especially next generation sequencing and PCR-based assays, were highly important for the successful application of ctDNA analysis. However, before being integrated into clinical practice, ctDNA analysis needs to be standardized and validated through the performance of multicenter prospective and well-designed clinical studies. This review is focused on the clinical utility of ctDNA analysis, especially at the DNA mutation and methylation level, in breast cancer patients, incorporating the latest advances in technological approaches and involving key studies in the early and metastatic setting.

Single-molecule measurements in microwells for clinical applications.

Abstract: The ability to detect and analyze proteins, nucleic acids, and other biomolecules is critical for clinical diagnostics and for understanding the underlying mechanisms of disease. Current detection methods in clinical and research laboratories rely upon bulk measurement techniques such as immunoassays, polymerase chain reaction, and mass spectrometry to detect these biomarkers. However, many potentially useful protein or nucleic acid biomarkers in blood, saliva, or other biofluids exist at concentrations well below the detection limits of current methods, necessitating the development of more sensitive technologies. Single-molecule measurements are poised to address this challenge, vastly improving sensitivity for detecting low abundance biomarkers and rare events within a population. Microwell arrays have emerged as a powerful tool for single-molecule measurements, enabling ultrasensitive detection of disease-relevant biomolecules in easily accessible biofluids. This review discusses the development, fundamentals, and clinical applications of microwell-based single-molecule methods, as well as challenges and future directions for translating these methods to the clinic.

Immunoscore: a novel prognostic tool. Association with clinical outcome, response to treatment and survival in several malignancies.

Abstract: The predictive accuracy of the traditional staging system for cancer, the American Joint Committee on Cancer/Union Internationale Centre le Cancer (AJCC/UICC) classification of malignant tumors, is...

What the lab can and cannot do: clinical interpretation of drug testing results

Abstract: Urine drug testing is one of the objective tools available to assess adherence. To monitor adherence, quantitative urinary results can assist in differentiating "new" drug use from "previous" (historical) drug use. "Spikes" in urinary concentration can assist in identifying patterns of drug use. Coupled chromatographic-mass spectrometric methods are capable of identifying very small amounts of analyte and can make clinical interpretation rather challenging, specifically for drugs that have a longer half-life. Polypharmacy is common in treatment and rehabilitation programs because of co-morbidities. Medications prescribed for comorbidities can cause drug-drug interaction and phenoconversion of genotypic extensive metabolizers into phenotypic poor metabolizers of the treatment drug. This can have significant impact on both pharmacokinetic (PK) and pharmacodynamic properties of the treatment drug. Therapeutic drug monitoring (TDM) coupled with PKs can assist in interpreting the effects of phenoconversion. TDM-PKs reflects the cumulative effects of pathophysiological changes in the patient as well as drug-drug interactions and should be considered for treatment medications/drugs used to manage pain and treat substance abuse. Since only a few enzyme immunoassays for TDM are available, this is a unique opportunity for clinical laboratory scientists to develop TDM-PK protocols that can have a significant impact on patient care and personalized medicine. Interpretation of drug screening results should be done with caution while considering pharmacological properties and the presence or absence of the parent drug and its metabolites. The objective of this manuscript is to review and address the variables that influence interpretation of different drugs analyzed from a rehabilitation and treatment programs perspective.

Methods for detecting toxic α-synuclein species as a biomarker for Parkinson's disease.

Abstract: Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the accumulation of α-synuclein (α-syn) into insoluble aggregates known as Lewy bodies and Lewy neurites in the brain. However, prior to the formation of these large aggregates, α-syn forms oligomers and small fibrils, which are believed to be the pathogenic species leading to the death of neurons in the substantia nigra in disease. The majority of aggregated α-syn is phosphorylated, and it is thought that this post-translational modification may be critical in disease pathogenesis. Thus, early detection of the toxic forms of α-syn may provide a window of opportunity for an intervention to halt or slow the progression of neurodegeneration in PD. Expression of α-syn is not restricted to the central nervous system and the protein can be found elsewhere, including bodily fluids and peripheral tissues. This review will examine current methods for detecting toxic forms of α-syn in accessible biospecimens and outline emerging techniques that may provide reliable identification of biomarkers for PD.

Implementation of patient-based real-time quality control

Abstract: The quest to use patient results as quality control for routine clinical chemistry testing has long been driven by issues of the unavailability and cost of suitable quality control material and the matrix effects of synthetic material. Hematology laboratories were early adopters of average of normals techniques, primarily because of the difficulty in acquiring appropriate, stable quality control material, while in the chemistry laboratories, the perceived advantages and availability of synthetic material outweighed the disadvantages. However, the increasing volume of testing in clinical chemistry plus the capability of computer systems to deal with large and complex calculations has now made the use of patient-based quality control algorithms feasible. The desire to use patient-based quality control is also driven by increasing awareness that common quality control rules and frequency of analysis may fail to detect clinically significant assay biases. The non-commutability of quality control material has also become a problem as laboratories seek to harmonize results across regions and indeed globally. This review describes the history of patient-based quality control in clinical chemistry, summarizes the various approaches that can be implemented by laboratory professionals, and discusses how patient-based quality control can be integrated with traditional quality control techniques.

Inter-assay variability in automated serum free light chain assays and their use in the clinical laboratory

Abstract: Serum κ and λ free light chain levels are markers of plasma cell proliferation, and their measurements have been included in recent guidelines by the International Myeloma Working Group for the management of patients with plasma cellular dyscrasias. Five in vitro diagnostic methods for the immunochemical quantification of serum free light chains (FLC) are available, three based on polyclonal antibodies (Freelite®, The Binding Site; FLC ELISA κ and λ, Sebia; human κ and λ FLC, Diazyme Laboratories) and two on monoclonal antibodies (N Latex FLC, Siemens Healthineers; Seralite®, Sebia). Several studies have shown that these methods cannot be used interchangeably for the follow-up of patients because measured κ and λ FLC concentrations may differ significantly, especially at high levels. Because no international reference material for the measurement of FLC is available, it is not possible to establish which method is the most accurate. For this reason, knowledge about the analytical and diagnostic performances of the assays used is important. The aim of this review is to describe the main analytical features of the κ and λ FLC assays and how they may influence the clinical use of these parameters.

Aptamers as potential recognition elements for detection of vitamins and minerals: a systematic and critical review.

Abstract: Background: Vitamin and mineral deficiencies are prevalent globally, and extensive efforts have been made to assess their status. Most traditional methods are expensive and time-consuming; therefor...

Colorectal carcinoma screening: Established methods and emerging technology.

Abstract: Colorectal carcinoma screening programs have shown success in lowering both the incidence and mortality rate of colorectal carcinoma at a population level, in part because this carcinoma is relatively slow growing and has an identifiable premalignant lesion. Still, many patients do not undergo the recommended screening for colorectal carcinoma, and of those who do, a subset may be over- or under-diagnosed by the currently available testing methods. The primary purpose of this article is to review the data regarding currently available colorectal cancer screening modalities, which include fecal occult blood testing, direct colonic visualization, and noninvasive imaging techniques. In addition, readers will be introduced to a variety of biomarkers that may serve as stand-alone or adjunct tests in the future. Finally, there is a brief discussion of the current epidemiologic considerations that public health officials must address as they create population screening guidelines. The data we provide as laboratory physicians and scientists are critical to the construction of appropriate recommendations that ultimately decrease the burden of disease from colorectal carcinoma.

Clinical applications of extracellular vesicle long RNAs

Abstract: Extracellular vesicles (EVs), primarily exosomes and microvesicles, are critical intercellular mediators of communication. Over the past decade, improved knowledge and methodologies have enabled the detection and quantification of RNA species in EVs, despite their extremely low levels. Recently, EV-associated long RNAs (exLRs) have been drawing much attention. Delivered by EVs, they have higher stability, greater difference in temporal and spatial expression, and the capacity to remodel both proximal and distal recipient cells. These properties guarantee their roles as biomarkers, therapeutic targets, vaccines, and gene therapy agents in a wide range of human diseases. Despite the progress in this area of research, limitations in both knowledge and methodologies have hindered its further development. Herein, we comprehensively reviewed studies related to exLRs, including protein-coding messenger RNAs (mRNAs) and noncoding RNAs (long noncoding RNAs and circular RNAs) in EVs to indicate their value in the diagnosis and treatment of human diseases; we also present a series of yet unsettled issues in this novel area, hence providing insights for future studies.

The clinical and laboratory investigation of dysbetalipoproteinemia

Abstract: Familial dysbetalipoproteinemia (type III hyperlipoproteinemia) is a potentially underdiagnosed inherited dyslipidemia associated with greatly increased risk of coronary and peripheral vascular disease. The mixed hyperlipidemia observed in this disorder usually responds well to appropriate medical therapy and lifestyle modification. Although there are characteristic clinical features such as palmar and tuberous xanthomata, associated with dysbetalipoproteinemia, they are not always present, and their absence cannot be used to exclude the disorder. The routine lipid profile cannot distinguish dysbetalipoproteinemia from other causes of mixed hyperlipidemia and so additional investigations are required for confident diagnosis or exclusion. A range of investigations that have been proposed as potential diagnostic tests are discussed in this review, but the definitive biochemical test for dysbetalipoproteinemia is widely considered to be beta quantification. Beta quantification can determine the presence of "β-VLDL" in the supernatant following ultracentrifugation and whether the VLDL cholesterol to triglyceride ratio is elevated. Both features are considered hallmarks of the disease. However, beta quantification and other specialist tests are not widely available and are not high-throughput tests that can practically be applied to all patients with mixed hyperlipidemia. Using apolipoprotein B (as a ratio either to total or non-HDL cholesterol or as part of a multi-step algorithm) as an initial test to select patients for further investigation is a promising approach. Several studies have demonstrated a high degree of diagnostic sensitivity and specificity using these approaches and apolipoprotein B is a relatively low-cost test that is widely available on high-throughput platforms. Genetic testing is also important in the diagnosis, but it should be noted that most individuals with an E2/2 genotype do not suffer from remnant hyperlipidemia and around 10% of familial dysbetalipoproteinemia cases are caused by rarer, autosomal dominant mutations in APOE that will only be detected if the gene is fully sequenced. Wider implementation of diagnostic pathways utilizing apo B could lead to more rational use of specialist investigations and more consistent detection of patients with dysbetalipoproteinemia. Without the application of a consistent evidence-based approach to identifying dysbetalipoproteinemia, many cases are likely to remain undiagnosed.

Novel biomarkers in Alzheimer's disease using high resolution proteomics and metabolomics: miRNAS, proteins and metabolites.

Abstract: Alzheimer’s disease (AD) is the most common form of dementia. It affects approximately 6% of people over the age of 65 years. It is a clinicopathological, degenerative, chronical and progressive di...

Bone health and hyperglycemia in pediatric populations.

Abstract: The impact of prediabetes and diabetes on skeletal health in the context of increased risk of fragility fractures in adults has been studied recently. However, the prevalence of diabetes, overweight, and obesity have also increased in younger subjects. Current data concerning bone metabolism based on assessment of markers for bone turnover and of bone quality in diabetes patients in diverse age groups appears to be inconsistent. This review synthesizes the current data on the assessment of bone turnover based on the use of circulating bone markers recommended by international organizations; the effects of age, gender, and other factors on the interpretation of the data; and the effects of type 1 and type 2 diabetes as well as hyperglycemia on bone quality and turnover with particular emphasis on the pediatric population. Early intervention in the pediatric population is necessary to prevent the progression of metabolic disturbances that accompany prediabetes and diabetes in the context of common low vitamin D status that may interfere with bone growth.

Essential role of laboratory physicians in transformation of laboratory practice and management to a value-based patient-centric model

Abstract: The laboratory is a vital part of the continuum of patient care. In fact, there are few programs in the healthcare system that do not rely on ready access and availability of complex diagnostic laboratory services. The existing transactional model of laboratory "medical practice" will not be able to meet the needs of the healthcare system as it rapidly shifts toward value-based care and precision medicine, which demands that practice be based on total system indicators, clinical effectiveness, and patient outcomes. Laboratory "value" will no longer be focused primarily on internal testing quality and efficiencies but rather on the relative cost of diagnostic testing compared to direct improvement in clinical and system outcomes. The medical laboratory as a "business" focused on operational efficiency and cost-controls must transform to become an essential clinical service that is a tightly integrated equal partner in direct patient care. We would argue that this paradigm shift would not be necessary if laboratory services had remained a "patient-centric" medical practice throughout the last few decades. This review is focused on the essential role of laboratory physicians in transforming laboratory practice and management to a value-based patient-centric model. Value-based practice is necessary not only to meet the challenges of the new precision medicine world order but also to bring about sustainable healthcare service delivery.