查看更多>>摘要：? 2022 Elsevier B.V.Background and aims: The concentration of glycated hemoglobin (HbA1c) is an essential diagnostic and therapeutic biomarker in diabetes mellitus. However, it is known that Hb structural variants and synthesis disorders, can affect the HbA1c measurement in different assays. Although the analytical interference of various hemoglobinopathies on the chromatographic measurement of HbA1c using HPLC has been well studied, data on the interference on the enzymatic assay are few. Materials and methods: In this multi-center study, a large number (n = 104) of 33 different hemoglobin variants were collected over a period of one year and compared between an HPLC (Tosoh G8 and G11) and an enzymatic assay (Abbott Alinity c). Results: A good comparability between ion-exchange HPLC and the Alinity assay for most Hb variants was found. However, we were able to determine for the first time that certain Hb variants (Hb Okayama, HbAE, Hb Lepore) can lead to clinically relevant discordant results. HbF (>5%) can already cause a relevant aberration. Conclusions: Overall, using the Abbott HbA1c assay in the presence of certain hemoglobin variants can induce clinically relevant interference that can affect diagnosis and therapy monitoring decisions, mainly because the enzymatic assay cannot provide any information about Hb variants.
查看更多>>摘要：? 2022 The AuthorsBackground: Cytological analysis of body fluids (BF) provides important information for diagnosis in various medical conditions. We evaluated the analytical performance of the UF-4000 BF mode for ascitic, cerebrospinal, pleural, synovial and continuous ambulatory peritoneal dialysis fluids compared to light microscopy counting (LM). Materials and methods: 223 consecutive BF were analyzed by UF-4000 and results were compared using Pearson's correlation, Bland-Altman analysis, and contingence tests at relevant cut-off values. This study also included the evaluation of precision, linearity, and carryover. Results: For white and red blood cells (WBC, RBC) counts in all BF, correlation was excellent with Pearson's coefficients R2 > 0,98. Bland-Altman analysis didn't reveal significant differences with limited bias for WBC ranging from ?10 to ?1 WBC/μL and bias ranging from ?43 to ?6/μL for RBC. At specific cut-off values for WBC, Se and Spe were 100% except for ascites (Spe = 98%) due to two false positive. Precision evaluated at three concentration levels was good for each parameter (WBC < 10%). Linearity was excellent for WBC (R2 > 0,99) and carryover negligible (<0,004%). Conclusion: UF-4000 BF mode is a good alternative to manual LM for BF cell counting. This automated method gives rapid and accurate results which is important for therapeutic decisions.
查看更多>>摘要：? 2022 Elsevier B.V.Non-transferrin-bound iron (NTBI) is an important biomarker related to the iron loading status of patients with certain diseases. NTBI is a highly toxic form of iron capable of generating free radicals and can lead to oxidative damage of various tissues. It is critical to quantify NTBI in blood to ensure personalised patient chelation management and to prevent high iron concentrations that can lead to toxicity and organ failure. Different analytical methods for the direct quantification of NTBI are described in the literature, but none have been translated for use in clinical laboratories. This review provides a critical discussion on the recent breakthroughs and remaining challenges for the direct quantification of NTBI. Most of the developed methods involve lengthy and complex sample preparation, use of expensive reagents and equipment while lacking the required accuracy and reproducibility. Collectively, these factors have limited the clinical translation of the developed methods, and therefore, the need for a reliable and widely accepted analytical method to quantify NTBI remains. Finally, this review explores the potential of rapid and accurate electrochemical techniques that have been demonstrated for environmental samples but are yet to be applied to detect NTBI in human blood plasma/serum and translation to widespread routine clinical use.
查看更多>>摘要：? 2022 Elsevier B.V.Background: Over the last 3 decades, there has been a steady rise in global mortality due to cardiovascular diseases (CVDs). Therefore, timely diagnosis of CVDs is paramount. Low-Density Lipoprotein-cholesterol (LDL-C) in blood serum is one of the biomarkers for the risk assessment of CVDs, measured by direct assays and indirect approaches. The indirect method of LDL-C quantification by Friedewald's formula is more widely used in Indian clinical settings than direct assays due to its time and cost-effectiveness. However, its accuracy has been questioned for a long. We tried to find the formula that work in best agreement with the direct method. Methods: Lipid profiling was done following a direct homogenous method (LDL-C_M) and LDL-C was calculated by 3 formula. The LDL-C values were categorized into groups based on TG. All the formula were statistically correlated with LDL-C_M. Results: Teerakanchana's formula has shown a strong positive correlation (r = 0.914) and good agreement M (Lin's CCC = 0.929, CI = 0.918–0.939) with LDL-C_M, followed by Vujovic's formula (r = 0.903, Lin's CCC = 0.925, CI = 0.912–0.936). Conclusions: Teerakanchana and Vujovic's formula may replace Friedewald to quantify LDL-C in the public health care settings of the North Indian population.
查看更多>>摘要：? 2022 Elsevier B.V.Double stranded DNA (dsDNA) is known to act as a damage‐associated molecular pattern (DAMP) that stimulates the body's innate immune response. In general, cyclic GMP-AMP (cGAMP) synthase (cGAS), a DNA sensor, detects these disease‐causing DNA and activates the stimulator of interferon gene (STING), which in turn phosphorylates interferon regulatory factor 3 (IRF3), triggering the synthesis of type I interferon (IFN). During this process, the cGAS‐STING pathway interacts with different modes of cell death, including autophagy, apoptosis, pyroptosis, and necroptosis. Importantly, cGAS might get stimulated by self‐DNA, such as nuclear DNA (nuDNA) and mitochondrial DNA (mtDNA), which ensures a close association between the cGAS‐STING signaling pathway and autoimmune responses. Following an ischemic attack, damaged or necrotic cells release large amounts of self‐DNA that subsequently activate cGAS, resulting in a range of consequences related to an injury. The present study presents an overview of studies focused on cGAS‐STING signaling and cell death, and summarizes the findings of this pathway with regard to ischemia or ischemia/reperfusion (I/R) in different organs of the body, including heart, brain, liver, kidney, and intestine.
查看更多>>摘要：? 2022 Elsevier B.V.Background: Clozapine (CLO) is an atypical antipsychotic used in management of treatment-resistant schizophrenia. Adverse drug reactions are caused by both CLO and its primary metabolite, norclozapine (NCLO). We defined the biological variability of CLO, NCLO, and the CLO to NCLO ratio (CNR) as well as assess the impact of reporting CLO and NCLO routinely. Methods: The CVi and CVg were calculated from 1904 results from 247 patients by CV-ANOVA, and ANOVA, respectively, for CLO, NCLO, and the CNR. Association between each were also analyzed against a number of parameters including age and gender, complete blood count (CBC), kidney and liver function tests, lipids, and glucose within 24 h of CLO measurement. Results: For CLO, NCLO and CNR, the CVi was calculated as 19.3%, 19.2%, and 14.7%, and the CVg was 46.9%, 51.4%, and 36.3%, respectively. A total of 87 patients (19.7%) demonstrated higher NCLO results than CLO, with a ratio as low as 0.47. Kidney function was also found to have a statistically significant relationship to CLO and NCLO levels. Conclusions: We provide data for biological variability of CLO metabolism as well as while providing some evidence for reporting NCLO values clinically.
查看更多>>摘要：? 2022 Elsevier B.V.Pyroptosis is identified as a pro-inflammatory programmed cell death, mediated by gasdermins (GSDMs) family of proteins accompanied by pro-inflammatory signals release. As essential players in innate immunity, inflammasomes are intracellular protein complexes which cleave gasdermin D (GSDMD), forming structurally stable pores in the cell membrane, subsequently inducing pyroptosis. Extensive evidence indicates that inflammasomes and pyroptosis contributes to tumors, nerve injury, inflammatory diseases and metabolic disorders. As a metabolic disorder, diabetes is characterized with hyperglycemia, insulin resistance and chronic inflammation. Meanwhile, aberrant pyroptosis exerts a key role in the occurrence and progression of diabetes and its common complication, diabetic nephropathy (DN). Furthermore, evidence has shown that DN patients and animal models exhibit increased circulating IL-1β and inflammasome, while decreasing the expression of key components of the inflammasome mitigates kidney damage and delays progression. Current research has reported that non-coding RNAs (ncRNAs) are involved in activation of inflammasomes and play a crucial role in the control of pyroptosis in DN pathogenesis. In addition, studies have indicated that some natural plant compounds have therapeutic potential via regulation of inflammasomes and pyroptosis to prevent and potentially treat DN. This mini-review examines the molecular mechanism of inflammasome activation and pyroptosis, highlights the critical roles of ncRNA and explores potential therapeutics to regulate pyroptosis in DN.
查看更多>>摘要：? 2022 Elsevier B.V.Here we reported a pedigree that gave birth to two characteristic clinical signs of Kabuki syndrome daughters. They had an intellectual disability with special facial features. Their eyebrows were relatively wide and the rear 1/3 of the eyebrows were light and sparse. Their eyes were long, narrow, valgus and strabismus. Their noses were broad at the root and flat at the tip. They also had skeletal dysplasia, mainly manifested in the short second knuckle of the little fingers of both hands. Genetic studies showed a novel de novo KMT2D variant (c.16343G > C; p.R5448P) as a cause of Kabuki syndrome. It was very unlikely that the same de novo mutation occurred in two members of a family. Gonadal mosaicism in one of the parents was suspected. Haplotype construction and clone sequencing were used for mutation source analysis. Finally, we inferred that the haplotype from the mother (Gdel-G-C-T-A) contained the pathogenic mutation. A gonadal mosaicism novel KMT2D mutation was identified in their mother.
查看更多>>摘要：? 2022Background: To select and standardize point-of-care (POC) glucose meters across a multi-hospital system. Methods: We formed a multidisciplinary POC glucose standardization working group including key stakeholders from each site. A set of selection criteria: usability, clinical and laboratory performance, indications for use, interface connectivity, ease of implementation and ongoing operational costs were used to develop a scoring schema to facilitate a consensus-driven selection process. Results: Method comparison and consensus error grid evaluation against the clinically validated reference methods demonstrated that the analytical performance for all candidate meters was comparable for both the laboratory and clinical evaluation. However, Meter 1 ranked highest in usability evaluations, implementation and streamlined interface connectivity. The meter selection process and implementation were staggered across sites due to complexity of transitioning to a new manufacturer's meter and limitations in vendor support for training and ongoing troubleshooting of interface connectivity. Conclusions: Standardization of POC glucose meters in a large multi-hospital system is a complex undertaking requiring robust, multidisciplinary organizational structure both system-wide and locally, development of consensus-driven selection tools, usability evaluation by end-users, laboratory and clinical evaluation of the analytical performance, and a strong vendor-laboratory partnership during the implementation process.
查看更多>>摘要：? 2022 Elsevier B.V.Historically, Youden plots are made of a scatter plot of the results of two EQA samples with an elliptical confidence area around them. Because Youden plots compare individual laboratory results with respect to other laboratories, they intrinsically evaluate with state of the art. In the field of medical laboratory science, analytical performance specifications have been proposed and various EQA providers show these limits on Youden plots by horizontal and vertical lines near the limits of total error. This study shows the weaknesses of these limits of total error and proposes a new approach for drawing acceptance areas on Youden plots. The classical Youden plot is extended with two acceptance areas: A first acceptance area evaluates the reported results with respect to maximum allowed variability, a second acceptance area evaluates the results with respect to maximum allowed variability and bias. The ellipses are calculated using quantiles of the Chi-square and noncentral Chi-square distribution. Results show that the new approach allows evaluating results from individual laboratories and from measurement procedures by comparing the position and overlap of the confidence area and the acceptance areas. It is demonstrated that his approach controls the type I error better than the rectangular limits.
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