Critical reviews in clinical laboratory sciences最新文献

Pulmonary arterial hypertension (PAH), one subtype of pulmonary hypertension (PH), is a life-threatening condition characterized by pulmonary arterial remodeling, elevated pulmonary vascular resistance, and blood pressure in the pulmonary arteries, leading to right heart failure and increased mortality. The disease is marked by endothelial dysfunction, vasoconstriction, and vascular remodeling. The role of Sodium-Glucose Co-Transporter-2 (SGLT2) inhibitors, a class of medications originally developed for diabetes management, is increasingly being explored in the context of cardiovascular diseases, including PAH, due to their potential to modulate these pathophysiological processes. In this review, we systematically examine the burgeoning evidence from both basic and clinical studies that describe the effects of SGLT2 inhibitors on cardiovascular health, with a special emphasis on PAH. By delving into the complex interactions between these drugs and the potential pathobiology that underpins PH, this study seeks to uncover the mechanistic underpinnings that could justify the use of SGLT2 inhibitors as a novel therapeutic approach for PAH. We collate findings that illustrate how SGLT2 inhibitors may influence the normal function of pulmonary arteries, possibly alleviating the pathological hallmarks of PAH such as inflammation, oxidative stress, aberrant cellular proliferation, and so on. Our review thereby outlines a potential paradigm shift in PAH management, suggesting that these inhibitors could play a crucial role in modulating the disease's progression by targeting the potential dysfunctions that drive it. This comprehensive synthesis of existing research underscores the imperative need for further clinical trials to validate the efficacy of SGLT2 inhibitors in PAH and to integrate them into the therapeutic agents used against this challenging disease.

Transthyretin (TTR), a homotetrameric protein found in plasma, cerebrospinal fluid, and the eye, plays a pivotal role in the onset of several amyloid diseases with high morbidity and mortality. Protein aggregation and fibril formation by wild-type TTR and its natural more amyloidogenic variants are hallmarks of ATTRwt and ATTRv amyloidosis, respectively. The formation of soluble amyloid aggregates and the accumulation of insoluble amyloid fibrils and deposits in multiple tissues can lead to organ dysfunction and cell death. The most frequent manifestations of ATTR are polyneuropathies and cardiomyopathies. However, clinical manifestations such as carpal tunnel syndrome, leptomeningeal, and ocular amyloidosis, among several others may also occur. This review provides an up-to-date listing of all single amino-acid mutations in TTR known to date. Of approximately 220 single-point mutations, 93% are considered pathogenic. Aspartic acid is the residue mutated with the highest frequency, whereas tryptophan is highly conserved. "Hot spot" mutation regions are mainly assigned to β-strands B, C, and D. This manuscript also reviews the protein aggregation models that have been proposed for TTR amyloid fibril formation and the transient conformational states that convert native TTR into aggregation-prone molecular species. Finally, it compiles the various in vitro TTR aggregation protocols currently in use for research and drug development purposes. In short, this article reviews and discusses TTR mutagenesis and amyloidogenesis, and their implications in disease onset.

Circulating tumor DNA (ctDNA, DNA shed by cancer cells) is emerging as one of the most transformative cancer biomarkers discovered to-date. Although potentially useful at all the phases of cancer detection and patient management, one of its most exciting possibilities is as a relatively noninvasive pan-cancer screening test. Preliminary findings with ctDNA tests such as Galleri or CancerSEEK suggest that they have high specificity (> 99.0%) for malignancy. Their sensitivity varies depending on the type of cancer and stage of disease but it is generally low in patients with stage I disease. A major advantage of ctDNA over existing screening strategies is the potential ability to detect multiple cancer types in a single test. A limitation of most studies published to-date is that they are predominantly case-control investigations that were carried out in patients with a previous diagnosis of malignancy and that used apparently healthy subjects as controls. Consequently, the reported sensitivities, specificities and positive predictive values might be lower if the tests are used for screening in asymptomatic populations, that is, in the population where these tests are likely be employed. To demonstrate clinical utility in an asymptomatic population, these tests must be shown to reduce cancer mortality without causing excessive overdiagnosis in a large randomized prospective randomized trial. Such trials are currently ongoing for Galleri and CancerSEEK.

Haptoglobin (Hp) is a polymorphic protein that was initially described as a hemoglobin (Hb)-binding protein. The major functions of Hp are to scavenge Hb, prevent iron loss, and prevent heme-based oxidation. Hp regulates angiogenesis, nitric oxide homeostasis, immune responses, and prostaglandin synthesis. Genetic polymorphisms in the Hp gene give rise to different phenotypes, including Hp 1-1, Hp 2-1, and Hp 2-2. Extensive research has been conducted to investigate the association between Hp polymorphisms and several medical conditions including cardiovascular disease, inflammatory bowel disease, cancer, transplantation, and hemoglobinopathies. Generally, the Hp 2-2 phenotype is associated with increased disease risk and poor outcomes. Over the years, the Hp 2 allele has spread under genetic pressures. Individuals with the Hp 2-2 phenotype generally exhibit lower levels of CD163 expression in macrophages. The decreased expression of CD163 may be associated with the poor antioxidant capacity in the serum of subjects carrying the Hp 2-2 phenotype. However, the Hp 1-1 phenotype may confer protection in some cases. The Hp1 allele has strong antioxidant, anti-inflammatory, and immunomodulatory properties. It is important to note that the benefits of the Hp1 allele may vary depending on genetic and environmental factors as well as the specific disease or condition under consideration. Therefore, the Hp1 allele may not necessarily confer advantages in all situations, and its effects may be context-dependent. This review highlights the current understanding of the role of Hp polymorphisms in cardiovascular disease, inflammatory bowel disease, cancer, transplantation, hemoglobinopathies, and polyuria.

Point-of-care testing (POCT) is the fastest-growing segment of laboratory medicine. This review focuses on the essential aspects of setting analytical performance specifications (APS) and performing quality assurance for POCT in primary healthcare. In-vitro diagnostic medical devices for POCT are typically small and easy to operate. Users often have little to no laboratory experience and may not necessarily see the value of conducting quality assurance on their devices. Therefore, training, guidance, and motivation should be integral parts of the total quality management system, as they are vital for managing errors and ensuring reliable results. It is common to believe that the analytical quality of POCT should be comparable to that of laboratory testing, and as a result, APS should be the same. This paper challenges this concept. The APS for POCT can often be less stringent compared to those used in a central laboratory because the requester is closer to both the analytical and clinical situation. Point-of-care instruments should be selected based on clinical needs, the required analytical quality and user-friendliness in the intended usage setting.Quality assurance should include both internal quality control (IQC) and external quality assessment (EQA). It is recommended that IQC protocols should be dependent on the complexity of the POCT device. A scoring system to determine how frequent IQC should be analyzed in primary healthcare on different types of POCT devices has been suggested. The main challenge in EQA for POCT involves using suitable control materials that reflect instrument performance on patient samples. Obtaining commutable control materials for POCT is difficult since the matrix often is whole blood. An essential aspect of EQA for POCT is that feedback reports should be easily interpretable. Users should receive advice from the EQA organizer regarding the root causes of deviating results. Quality assurance for POCT is not an easy task and presents numerous challenges. However, there is evidence that quality assurance improves the quality of POCT measurements and, consequently, can enhance patient outcomes.

Endometriosis, an enigmatic and chronic disorder, is considered a debilitating condition despite being benign. Globally, this gynecologic disorder affects up to 10% of females of reproductive age, impacting almost 190 million individuals. A variety of genetic and environmental factors are involved in endometriosis development, hence the pathophysiology and etiology of endometriosis remain unclear. The uncertainty of the etiology of the disease and its complexity along with nonspecific symptoms have led to misdiagnosis or lack of diagnosis of affected people. Biopsy and laparoscopy are referred to as the gold standard for endometriosis diagnosis. However, the invasiveness of the procedure, the unnecessary operation in disease-free women, and the dependence of the reliability of diagnosis on experience in this area are considered the most significant limitations. Therefore, continuous studies have attempted to offer a noninvasive and reliable approach. The recent advances in modern technologies have led to the generation of large-scale biological data sets, known as -omics data, resulting in the proceeding of the -omics century in biomedical sciences. Thereby, the present study critically reviews novel and noninvasive biomarkers that are based on -omics approaches from 2020 onward. The findings reveal that biomarkers identified based on genomics, epigenomics, transcriptomics, proteomics, and metabolomics are potentially able to diagnose endometriosis, predict prognosis, and stage patients, and potentially, in the near future, a multi-panel of these biomarkers will generate clinical benefits.

Serum protein electrophoresis (SPEP) is a valuable laboratory test that separates proteins from the blood based on their electrical charge and size. The test can detect and analyze various protein abnormalities, and the interpretation of graphic SPEP features plays a crucial role in the diagnosis and monitoring of conditions, such as myeloma. Furthermore, the advancement of artificial intelligence (AI) technology presents an opportunity to enhance the organization and optimization of analytical procedures by streamlining the process and reducing the potential for human error in SPEP analysis, thereby making the process more efficient and reliable. For instance, AI can assist in the identification of protein peaks, the calculation of their relative proportions, and the detection of abnormalities or inconsistencies. This review explores the characteristics and limitations of AI in SPEP, and the role of standardization in improving its clinical utility. It also offers guidance on the rational ordering and interpreting of SPEP results in conjunction with AI. Such integration can effectively reduce the time and resources required for manual analysis while improving the accuracy and consistency of the results.