Critical reviews in clinical laboratory sciences最新文献

Parapneumonic pleural effusion (PPE) is a common complication in patients with pneumonia. Timely and accurate diagnosis of PPE is of great value for its management. Measurement of biomarkers in circulating and pleural fluid have the advantages of easy accessibility, short turn-around time, objectiveness and low cost and thus have utility for PPE diagnosis and stratification. To date, many biomarkers have been reported to be of value for the management of PPE. Here, we review the values of pleural fluid and circulating biomarkers for the diagnosis and stratification PPE. The biomarkers discussed are C-reactive protein, procalcitonin, presepsin, soluble triggering receptor expressed on myeloid cells 1, lipopolysaccharide-binding protein, inflammatory markers, serum amyloid A, soluble urokinase plasminogen activator receptor, matrix metalloproteinases, pentraxin-3 and cell-free DNA. We found that none of the available biomarkers has adequate performance for diagnosing and stratifying PPE. Therefore, further work is needed to identify and validate novel biomarkers, and their combinations, for the management of PPE.

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy of CD4⁺ T lymphocytes caused by human T lymphotropic virus type-1 (HTLV-1) infection. HTLV-1 was brought to the World Health Organization (WHO) and researchers to address its impact on global public health, oncogenicity, and deterioration of the host immune system toward autoimmunity. In a minority of the infected population (3-5%), it can induce inflammatory networks toward HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), or hijacking the infected CD4⁺ T lymphocytes into T regulatory subpopulation, stimulating anti-inflammatory signaling networks, and prompting ATLL development. This review critically discusses the complex signaling networks in ATLL pathogenesis during virus-host interactions for better interpretation of oncogenicity and introduces the main candidates in the pathogenesis of ATLL. At least two viral factors, HTLV-1 trans-activator protein (TAX) and HTLV-1 basic leucine zipper factor (HBZ), are implicated in ATLL manifestation, interacting with host responses and deregulating cell signaling in favor of infected cell survival and virus dissemination. Such molecules can be used as potential novel biomarkers for ATLL prognosis or targets for therapy. Moreover, the challenging aspects of HTLV-1 oncogenesis introduced in this review could open new venues for further studies on acute leukemia pathogenesis. These features can aid in the discovery of effective immunotherapies when reversing the gene expression profile toward appropriate immune responses gradually becomes attainable.

Otitis media (OM) is an umbrella term for a number of conditions associated with middle ear inflammation. Chronic suppurative otitis media (CSOM), a type of OM, is characterized by long-term middle ear infection with perforated ear drum and otorrhea. The most common outcome associated with it is acquired hearing impairment in infected individuals which ultimately affects their cognitive and scholastic developments. Clinically, CSOM is thought to be a sequel of re-occurring episodes of Acute otitis media (AOM). Pseudomonas aeruginosa and Staphylococcus aureus are found to be the predominant pathogenic isolates in these patients. However, with the emergence of antibiotic resistance amongst these pathogens, the adequate evaluation and treatment of this condition has become more problematic. The disease has also been recognized as one of the neglected tropical clinical manifestations with high prevalence in school-age children, especially in poor or underprivileged countries. Moreover, untreated cases have further worsened the situation by contributing to various life-threatening complications. Thus, effective treatment and surgical strategies, as well as strengthening of hearing care algorithms along with the discovery of novel animal models for advanced clinical research, can jointly help to fight this disease. In this regard, mapping of the audiological analysis with microbiological findings in CSOM patients may help elucidate the frequency that favors growth of specific pathogens. Knowledge about this potential correlation can then support timely detection of the infection, which is perceived as one of the emerging approaches for its management. In addition to these strategies, creating a true sense of awareness among people can also help mitigate this pathological condition by facilitating early identification, prevention, and treatment. This review discusses the incidence, pathogenesis, investigations, complications, and available treatment modalities associated with CSOM.

The term frontotemporal dementia (FTD) refers to a group of progressive neurodegenerative disorders characterized mainly by atrophy of the frontal and anterior temporal lobes. Based on clinical presentation, three main clinical syndromes have traditionally been described: behavioral variant frontotemporal dementia (bvFTD), non-fluent/agrammatic primary progressive aphasia (nfPPA), and semantic variant PPA (svPPA). However, over the last 20 years, it has been recognized that cognitive phenotypes often overlap with motor phenotypes, either motor neuron diseases or parkinsonian signs and/or syndromes like progressive supranuclear palsy (PSP) and cortico-basal syndrome (CBS). Furthermore, FTD-related genes are characterized by genetic pleiotropy and can cause, even in the same family, pure motor phenotypes, findings that underlie the clinical continuum of the spectrum, which has pure cognitive and pure motor phenotypes as the extremes. The genotype-phenotype correlation of the spectrum, FTD-motor neuron disease, has been well defined and extensively investigated, while the continuum, FTD-parkinsonism, lacks a comprehensive review. In this narrative review, we describe the current knowledge about the genotype-phenotype correlation of the spectrum, FTD-parkinsonism, focusing on the phenotypes that are less frequent than bvFTD, namely nfPPA, svPPA, PSP, CBS, and cognitive-motor overlapping phenotypes (i.e. PPA + PSP). From a pathological point of view, they are characterized mainly by the presence of phosphorylated-tau inclusions, either 4 R or 3 R. The genetic correlate of the spectrum can be heterogeneous, although some variants seem to lead preferentially to specific clinical syndromes. Furthermore, we critically review the contribution of genome-wide association studies (GWAS) and next-generation sequencing (NGS) in disentangling the complex heritability of the FTD-parkinsonism spectrum and in defining the genotype-phenotype correlation of the entire clinical scenario, owing to the ability of these techniques to test multiple genes, and so to allow detailed investigations of the overlapping phenotypes. Finally, we conclude with the importance of a detailed genetic characterization and we offer to patients and families the chance to be included in future randomized clinical trials focused on autosomal dominant forms of FTLD.

Thyroid dysfunctions are among the most common endocrine disorders and accurate biochemical testing is needed to confirm or rule out a diagnosis. Notably, true hyperthyroidism and hypothyroidism in the setting of a normal thyroid-stimulating hormone level are highly unlikely, making the assessment of free thyroxine (FT4) inappropriate in most new cases. However, FT4 measurement is integral in both the diagnosis and management of relevant central dysfunctions (central hypothyroidism and central hyperthyroidism) as well as for monitoring therapy in hyperthyroid patients treated with anti-thyroid drugs or radioiodine. In such settings, accurate FT4 quantification is required. Global standardization will improve the comparability of the results across laboratories and allow the development of common clinical decision limits in evidence-based guidelines. The International Federation of Clinical Chemistry and Laboratory Medicine Committee for Standardization of Thyroid Function Tests has undertaken FT4 immunoassay method comparison and recalibration studies and developed a reference measurement procedure that is currently being validated. However, technical and implementation challenges, including the establishment of different clinical decision limits for distinct patient groups, still remain. Accordingly, different assays and reference values cannot be interchanged. Two-way communication between the laboratory and clinical specialists is pivotal to properly select a reliable FT4 assay, establish reference intervals, investigate discordant results, and monitor the analytical and clinical performance of the method over time.

The two common progressive lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are the leading causes of morbidity and mortality worldwide. Asthma-COPD overlap, referred to as ACO, is another complex pulmonary disease that manifests itself with features of both asthma and COPD. The disease has no clear diagnostic or therapeutic guidelines, thereby making both diagnosis and treatment challenging. Though a number of studies on ACO have been documented, gaps in knowledge regarding the pathophysiologic mechanism of this disorder exist. Addressing this issue is an urgent need for improved diagnostic and therapeutic management of the disease. Metabolomics, an increasingly popular technique, reveals the pathogenesis of complex diseases and holds promise in biomarker discovery. This comprehensive narrative review, comprising 99 original research articles in the last five years (2017-2022), summarizes the scientific advances in terms of metabolic alterations in patients with asthma, COPD, and ACO. The analytical tools, nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS), commonly used to study the expression of the metabolome, are discussed. Challenges frequently encountered during metabolite identification and quality assessment are highlighted. Bridging the gap between phenotype and metabotype is envisioned in the future.

Circulating cell-free microRNAs (miRNAs) represent a major reservoir for biomarker discovery. Unfortunately, their implementation in clinical practice is limited due to a profound lack of reproducibility. The great technical variability linked to major pre-analytical and analytical caveats makes the interpretation of circulating cell-free miRNA data challenging and leads to inconsistent findings. Additional efforts directed to standardization are fundamental. Several well-established protocols are currently used by independent groups worldwide. Nonetheless, there are some specific aspects in specimen collection and processing, sample handling, miRNA quantification, and data analysis that should be considered to ensure reproducibility of results. Here, we have addressed this challenge using an alternative approach. We have highlighted and discussed common pitfalls that negatively impact the robustness of circulating miRNA quantification and their application for clinical decision-making. Furthermore, we provide a checklist usable by investigators to facilitate and ensure the control of the whole miRNA quantification and analytical process. We expect that these recommendations improve the reproducibility of findings, and ultimately, facilitate the incorporation of circulating miRNA profiles into clinical practice as the next generation of disease biomarkers.

The diagnosis of leukemic B-cell lymphoproliferative disorders (B-LPDs) is made by integrating clinical, cytological, cytometric, cytogenetic, and molecular data. This leaves room for differences and inconsistencies between experts. In this study, we examine methodological and conceptual aspects of the flow cytometric classification of leukemic B-LPDs that could explain them. Among methodological aspects, we discuss (1) the different statistical tests used to select and evaluate markers, (2) how these markers are analyzed, (3) how scores are interpreted, (4) different degrees to which diagnostic information is used, and (5) and the impact of differences in study populations. Among conceptual aspects, we discuss (1) challenges to integrating different biological data points, (2) the under examination of the costs of misclassification (false positives and false negatives), and finally, (3) we delve into the impact of the lack of a true diagnostic gold standard and the indirect evidence suggesting poor reproducibility in the diagnosis of leukemic B-LPDs. We then outline current harmonization efforts and our personal approach. We conclude that numerous flow cytometry scores and diagnostic systems are now available; however, as long as the considerations discussed remain unaddressed, external reproducibility and interobserver agreement will not be achieved, and the field will not be able to move forward if a true gold standard is not found.

Processes to enhance customer-related services in healthcare organizations are complex and it can be difficult to achieve efficient patient-focused services. Laboratories make an integral part of the healthcare service industry where healthcare providers deal with critical patient results. Errors in these processes may cost a human life, create a negative impact on an organization's reputation, cause revenue loss, and open doors for expensive lawsuits. To overcome these complexities, healthcare organizations must implement an approach that helps healthcare service providers to reduce waste, variation, and work imbalance in the service processes. Lean and Six Sigma are used as continuous process improvement frameworks in laboratory medicine. Six Sigma uses an approach that involves problem-solving, continuous improvement and quantitative statistical process control. Six Sigma is a technique based on the DMAIC process (Define, Measure, Analyze, Improve, and Control) to improve quality performance. Application of DMAIC in a healthcare organization provides guidance on how to handle quality that is directed toward patient satisfaction in a healthcare service industry. The Lean process is a technique for process management in which waste reduction is the primary purpose; this is accomplished by implementing waste mitigation practices and methodologies for quality improvement. Overall, this article outlines the frameworks for continuous quality and process improvement in healthcare organizations, with a focus on the impacts of Lean and Six Sigma on the performance and quality service delivery system in clinical laboratories. It also examines the role of utilization management and challenges that impact the implementation of Lean and Six Sigma in clinical laboratories.

For decades, blood testing has been an integral part of routine doping controls. The breadth of information contained in blood samples has become considerably more accessible for anti-doping purposes over the last 10 years through technological advancements regarding analytical instrumentation as well as enhanced sample collection systems. Particularly, microsampling of whole blood and serum, for instance as dried blood spots (DBS), has opened new avenues in sports drug testing and substantially increased the availability and cost-effectiveness of doping control specimens. Thus, microvolume blood specimens possess the potential to improve monitoring of blood hormone and drug levels, support evaluation of circulating drug concentrations in competition, and enhance the stability of labile markers and target analytes in blood passport analyses as well as peptide hormone and steroid ester detection. Further, the availability of the fraction of lysed erythrocytes for anti-doping purposes warrants additional investigation, considering the sequestering capability of red blood cells (RBCs) for certain substances, as a complementary approach in support of the clean sport.