Critical reviews in clinical laboratory sciences最新文献

Allergic bronchopulmonary aspergillosis (ABPA), a severe inflammatory respiratory disease, is caused by a hypersensitivity reaction to the colonization of the airways with Aspergillus fumigatus. It is most often described in patients with asthma or cystic fibrosis. The diagnosis of ABPA is based on a combination of clinical, radiological, and immunological findings that have been included in different diagnostic criteria over the years. In this paper, we review the biomarkers included in these diagnostic criteria and novel research biomarkers that may be used in the diagnosis and treatment follow-up of ABPA in cystic fibrosis.

While coronavirus disease 2019 (COVID-19) begins as a respiratory infection, it progresses as a systemic disease involving multiorgan microthromboses that underly the pathology. SARS-CoV-2 enters host cells via attachment to the angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is widely expressed in a multitude of tissues, including the lung (alveolar cells), heart, intestine, kidney, testis, gallbladder, vasculature (endothelial cells), and immune cells. Interference in ACE2 signaling could drive the aforementioned systemic pathologies, such as endothelial dysfunction, microthromboses, and systemic inflammation, that are typically seen in patients with severe COVID-19. ACE2 is a component of the renin-angiotensin system (RAS) and is intimately associated with the plasma kallikrein-kinin system (KKS). As many papers are published on the role of ACE and ACE2 in COVID-19, we will review the role of bradykinin, and more broadly the KSS, in SARS-CoV-2-induced vascular dysfunction. Furthermore, we will discuss the possible therapeutic interventions that are approved and in development for the following targets: coagulation factor XII (FXII), tissue kallikrein (KLK1), plasma kallikrein (KLKB1), bradykinin (BK), plasminogen activator inhibitor (PAI-1), bradykinin B1 receptor (BKB1R), bradykinin B2 receptor (BKB2R), ACE, furin, and the NLRP3 inflammasome. Understanding these targets may prove of value in the treatment of COVID-19 as well as in other virus-induced coagulopathies in the future.

Vitamin D has a well-known role in the calcium homeostasis associated with the maintenance of healthy bones. It increases the efficiency of the intestinal absorption of dietary calcium, reduces calcium losses in urine, and mobilizes calcium stored in the skeleton. However, vitamin D receptors are present ubiquitously in the human body and indeed, vitamin D has a plethora of non-calcemic functions. In contrast to most vitamins, sufficient vitamin D can be synthesized in human skin. However, its production can be markedly decreased due to factors such as clothing, sunscreens, intentional avoidance of the direct sunlight, or the high latitude of the residence. Indeed, more than one billion people worldwide are vitamin D deficient, and the deficiency is frequently undiagnosed. The chronic deficiency is not only associated with rickets/osteomalacia/osteoporosis but it is also linked to a higher risk of hypertension, type 1 diabetes, multiple sclerosis, or cancer. Supplementation of vitamin D may be hence beneficial, but the intake of vitamin D should be under the supervision of health professionals because overdosing leads to intoxication with severe health consequences. For monitoring vitamin D, several analytical methods are employed, and their advantages and disadvantages are discussed in detail in this review.

Technical quality assurance (QA) and quality control (QA/QC) are important activities within medical laboratories to ensure the adequate quality of obtained test results. QA/QC tools available at medical laboratories include external QC and internal QC, patient-based real-time quality control (PBRTQC) tools such as moving average quality control (MAQC), limit checks, delta checks, and multivariate checks, and finally, analyzer flagging. Recently, for PBRTQC tools, new optimization and validation methods based on error detection simulation have been developed to obtain laboratory-specific insights into PBRTQC error detection. These developments have enabled implementation and application of these individual tools in routine clinical practice. As a next step, they also enable performance comparison of the individual QA/QC tools and integration of all the individual QA/QC tools in order to obtain the most powerful and efficient QA/QC plans. In this review, a brief overview of the individual QA/QC tools and their characteristics is provided and the error detection simulation approaches are explained. Finally, a new concept entitled integrated quality assurance and control (IQAC) is presented. To enable IQAC, a conceptual framework is suggested and demonstrated for sodium, based on available published data. The proposed IQAC framework provides ways and tools by which the performance of different QA/QC tools can be compared in a so-called QA/QC error detection table to enable optimization and validation of the overall QA/QC plan in terms of alarm rate as well as pre-analytical, analytical, and post-analytical error detection performance.

Viral respiratory infections are common and serious diseases. Because there is no effective treatment method or vaccine for respiratory tract infection, early diagnosis is vital to identify the pathogen so as to determine the infectivity of the patient and to quickly take measures to curb the spread of the virus, if warranted, to avoid serious public health problems. Real-time reverse transcriptase PCR (rRT-PCR), which has high sensitivity and specificity, is the best approach for early diagnosis. Among rRT-PCR methods, multiplex rRT-PCR can resolve issues arising from various types of viruses, high mutation frequency, coinfection, and low concentrations of virus. However, the design, optimization, and validation of multiplex rRT-PCR are more complicated than singleplex rRT-PCR, and comprehensive research on multiplex rRT-PCR methodology is lacking. This review summarizes recent progress in multiplex rRT-PCR methodology, outlines the principles of design, optimization and validation, and describes a scheme to help diagnostic companies to design and optimize their multiplex rRT-PCR detection panel and to assist laboratory staff to solve problems in their daily work. In addition, the analytical validity, clinical validity and clinical utility of multiplex rRT-PCR in viral respiratory tract infection diagnosis are assessed to provide theoretical guidance and useful information for physicians to understand the test results.

The urocortins are polypeptides belonging to the corticotropin-releasing hormone family, known to modulate stress responses in mammals. Stress, whether induced physically or psychologically, is an underlying cause or consequence of numerous clinical syndromes. Identifying biological markers associated with the homeostatic regulation of stress could provide a clinical laboratory approach for the management of stress-related disorders. The neuropeptide, urocortin 3 (UCN3), and the corticotropin-releasing hormone receptor 2 (CRHR2) constitute a regulatory axis known to mediate stress homeostasis. Dysregulation of this peptide/receptor axis is believed to play a role in several clinical conditions including post-traumatic stress, sleep apnea, cardiovascular disease, and other health problems related to stress. Understanding the physiology and measurement of the UCN3/CRHR2 axis is important for establishing a viable clinical laboratory diagnostic. In this article, we focus on evidence supporting the role of UCN3 and its receptor in stress-related clinical syndromes. We also provide insight into the measurements of UCN3 in blood and urine. These potential biomarkers provide new opportunities for clinical research and applications of laboratory medicine diagnostics in stress management.

A plethora of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostic tests are available, each with different performance specifications, detection methods, and targets. This narrative review aims to summarize the diagnostic technologies available and how they are best selected to tackle SARS-CoV-2 infection as the pandemic evolves. Seven key settings have been identified where diagnostic tests are being deployed: symptomatic individuals presenting for diagnostic testing and/or treatment of COVID-19 symptoms; asymptomatic individuals accessing healthcare for planned non-COVID-19-related reasons; patients needing to access emergency care (symptom status unknown); patients being discharged from healthcare following hospitalization for COVID-19; healthy individuals in both single event settings (e.g. airports, restaurants, hotels, concerts, and sporting events) and repeat access settings (e.g. workplaces, schools, and universities); and vaccinated individuals. While molecular diagnostics remain central to SARS-CoV-2 testing strategies, we have offered some discussion on the considerations for when other tools and technologies may be useful, when centralized/point-of-care testing is appropriate, and how the various additional diagnostics can be deployed in differently resourced settings. As the pandemic evolves, molecular testing remains important for definitive diagnosis, but increasingly widespread point-of-care testing is essential to the re-opening of society.

Thyroid hormones are primarily responsible for regulating the basal metabolic rate but also make important contributions to reproductive function and fetal development. Both hyper- and hypothyroidism in pregnancy have been associated with increased risks of complications that include preeclampsia and low birth weight, among others. Furthermore, thyroid hormone deficiency in the developing fetus results in neurodevelopmental delay. As the fetus is exclusively reliant on maternal thyroid hormone for most of the first trimester and requires continued maternal supply until birth, identifying maternal thyroid dysfunction is critically important. However, evaluating thyroid function in pregnancy is challenging because of the many physiological changes that affect concentrations of thyroid-related analytes. Increasing plasma human chorionic gonadotropin (hCG) concentrations in the second half of the first trimester elicit a corresponding transient decrease in thyroid-stimulating hormone (TSH), and continually increasing estradiol concentrations throughout pregnancy cause substantial increases in thyroxine-binding globulin (TBG) and total thyroxine (T4) relative to the nonpregnant state. Lastly, free T4 concentrations gradually decrease with increasing gestational age. For these reasons, it is essential to interpret thyroid function test results in the context of trimester-specific reference intervals to avoid misclassification of thyroid status. This review summarizes the effects of thyroid dysfunction prior to conception and during pregnancy and describes considerations for the laboratory assessment of thyroid function in pregnant women.

Inflammation is an enabling characteristic of the hallmarks of cancer. There has therefore been increasing interest in the clinical value of circulating inflammatory biomarkers in cancer. In this review, we summarize results on C-reactive protein (CRP), alone or as part of the Glasgow Prognostic Score (GPS, composed of CRP and serum albumin), as a biomarker of prognosis or prediction and monitoring of therapeutic response in patients with breast cancer. A systematic literature search was performed in Medline and Embase from 1990 to August 2021. The association of serum CRP and overall survival and disease/progression-free survival was summarized in meta-analyses using a random effects model. The results from a total of 35 included studies (20,936 patients) were divided according to three identified patient settings (metastatic, non-metastatic, and general setting). Most of the studies examined prognostic utility. Several larger studies observed associations between high serum CRP and poor survival, but the meta-analyses suggested a limited value in a non-metastatic and general breast cancer setting (populations with unknown or varied disease stage). In metastatic patients, however, more consistent findings supported an association between serum CRP and prognosis (hazard ratio for overall survival: 1.87 (95% CI 1.31-2.67). Only five studies examined a role in prediction or monitoring of therapeutic response. One study reported a significant association between serum CRP levels and response to chemotherapy. Findings regarding serum CRP as a biomarker in breast cancer appear inconsistent, particularly in non-metastatic and general breast cancer, where the prognostic value could not be confirmed. In patients with metastatic breast cancer we suggest that high serum CRP is an indicator of poor prognosis. Too few studies assessed the role of serum CRP in prediction or monitoring of treatment response to allow conclusions.

Using laboratory test results for diagnosis and monitoring requires a reliable reference to which the results can be compared. Currently, most reference data is derived from the population, and patients in this context are considered members of a population group rather than individuals. However, such reference data has limitations when used as the reference for an individual. A patient's test results preferably should be compared with their own, individualized reference intervals (RI), i.e. a personalized RI (prRI).The prRI is based on the homeostatic model and can be calculated using an individual's previous test results obtained in a steady-state situation and estimates of analytical (CV_A) and biological variation (BV). BV used to calculate the prRI can be obtained from the population (within-subject biological variation, CV_I) or an individual's own data (within-person biological variation, CV_P). Statistically, the prediction interval provides a useful tool to calculate the interval (i.e. prRI) for future observation based on previous measurements. With the development of information technology, the data of millions of patients is stored and processed in medical laboratories, allowing the implementation of personalized laboratory medicine. PrRI for each individual should be made available as part of the laboratory information system and should be continually updated as new test results become available.In this review, we summarize the limitations of population-based RI for the diagnosis and monitoring of disease, provide an outline of the prRI concept and different approaches to its determination, including statistical considerations for deriving prRI, and discuss aspects which must be further investigated prior to implementation of prRI in clinical practice.