查看更多>>摘要：? 2021Background and aims: As numerous studies have reported the concentration-exposure relationships of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), therapeutic drug monitoring is a promising approach in lung cancer treatment, aiming to avoid treatment failure or toxicity. A new method for the simultaneous analysis of five EGFR-TKIs (afatinib, erlotinib, gefitinib, icotinib and osimertinib) and their metabolites in human plasma samples was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Materials and methods: Afatinib-d6, erlotinib-d6, OSI-420-d4, gefitinib-d6 and osimertinib-C13,d3 were used as internal standards (ISs). The samples were prepared by liquid-liquid extraction using tert-butyl methyl ether. Chromatographic separation was undertaken on an XBridge C18 column using a linear gradient elution. LC-MS/MS was conducted in positive ionization mode with multiple reaction monitoring. Results: The proposed method showed satisfactory results in terms of linearity, sensitivity, specificity, precision (intra- and inter-day coefficients of variation ranged from 1.1 to 13.9%), and accuracy (from 93.3 to 111.1%). The IS-normalized matrix factors were below 15%. The sensitivity and linearity were highly appropriate for the expected concentrations according to the analysis of samples from non-small cell lung caner (NSCLC) patients who received EGFR-TKIs. Conclusions: The proposed method showed an acceptable reproducibility, high sensitivity and selectivity, and low matrix effects. This method could be significant for monitoring plasma concentrations of the mentioned EGFR-TKIs in NSCLC patients, aiming to improve the efficacy and safety of targeted therapies.
查看更多>>摘要：? 2022 Elsevier B.V.Background and aims: Monoclonal/biclonalgammopathy of unknown significance (MGUS/BGUS) is observed in COVID-19. This study was conducted to determine the changes in serum protein electrophoresis (SPEP) in COVID-19. Materials and methods: In this descriptive (cross-sectional) study, serum inflammatory markers (CRP, IL-6 and ferritin) were measured and SPEP was carried out by capillary electrophoresis method in 35 controls and 30 moderate & 58 severe COVID-19 cases. Results: Serum inflammatory markers were increased in COVID-19 cases with severity. M?band(s), β-γ bridging and pre-albumin band(s) on SPEP were observed in 15.5, 11 & 12% of severe cases and 3, 4 & 0% moderate COVID-19 cases respectively. Area under curve (AUC) of α 1 and α 2 bands of SPEP increased significantly in severe COVID-19. Conclusions: We conclude that SPEP changes like the appearance of M?band(s) indicating MGUS(BGUS), β- γ bridging indicating the presence of fast-moving immunoglobulins, pre-albumin band indicating the rise in serum transthyretin level and the increase in AUC of α 1 and α 2 bands indicating the rise in positive acute phase reactants occur in COVID-19. The occurrence and magnitude of these changes are higher in severe COVID-19 than that in moderate COVID-19. The diagnostic and prognostic significance of these SPEP changes are worth exploring.
查看更多>>摘要：? 2022 Elsevier B.V.Background: Voltage-gated calcium channel subunit α2δ-1 plays an important role in acute brain injury. We attempted to investigate whether serum α2δ-1 subunit concentrations are correlated with severity and prognosis following intracerebral hemorrhage (ICH). Methods: Serum α2δ-1 subunit concentrations were quantified in 103 ICH patients and 103 healthy controls. National Institutes of Health Stroke Scale (NIHSS) score and hematoma volume were estimated for assessing illness severity. Modified Rankin scale score of 3–6 at 90 days after stroke onset was defined as a worse outcome. Results: Serum α2δ-1 subunit concentrations were markedly higher in patients than in controls (median, 875.1 vs. 209.3 pg/ml). Serum α2δ-1 subunit concentrations of patients were tightly correlated with NIHSS score (r = 0.589) and hematoma volume (r = 0.594). Serum α2δ-1 subunit concentrations ≥ 875.1 pg/ml independently discriminated development of 90-day poor outcome with odds ratio of 5.228 (95% CI, 2.201–12.418) and area under the receiver operating characteristic curve of 0.794 (95% CI, 0.703–0.867). Serum α2δ-1 subunit concentrations > 973.4 pg/ml predicted 90-day poor outcome with 64.0% sensitivity and 90.6% specificity. The prognostic predictive ability of serum α2δ-1 concentrations was equivalent to those of NIHSS score and hematoma volume (both P > 0.05), and serum α2δ-1 concentrations also significantly improved the prognostic predictive capabilities of NIHSS score and hematoma volume (both P < 0.05). Conclusions: Serum α2δ-1 subunit concentrations are intimately correlated with illness severity and are independently associated with poor 90-day outcome, substantializing serum α2δ-1 subunit as a potential prognostic biomarker for ICH.
查看更多>>摘要：? 2022 Elsevier B.V.Although reference intervals (RIs) play an important role in clinical diagnosis, there remain significant differences with respect to race, gender, age and geographic location. Accordingly, the Clinical Laboratory Standards Institute (CLSI) EP28-A3c has recommended that clinical laboratories establish RIs appropriate to their subject population. Unfortunately, the traditional and direct approach to establish RIs relies on the recruitment of a sufficient number of healthy individuals of various age groups, collection and testing of large numbers of specimens and accurate data interpretation. The advent of the big data era has, however, created a unique opportunity to “mine” laboratory information. Unfortunately, this indirect method lacks standardization, consensus support and CLSI guidance. In this review we provide a historical perspective, comprehensively assess data processing and statistical methods, and post-verification analysis to validate this big data approach in establishing laboratory specific RIs.
查看更多>>摘要：? 2021Background: Although cardiac troponin T (cTnT) and troponin I(cTnI) are expressed to similar amount in cardiac tissue, cTnI often reach ten-times higher peak levels compared to cTnT in patients with myocardial necrosis such as in acute myocardial infarction (MI). In contrast, similar levels of cTnT and cTnI are observed in other situations such as stable atrial fibrillation and after strenuous exercise. Objective: Examine cTnT and cTnI levels in relation to COVID-19 disease and MI. Methods: Clinical and laboratory data from the local hospital from an observational cohort study of 27 patients admitted with COVID-19 and 15 patients with myocardial infarction (MI) that were analyzed with paired cTnT and cTnI measurement during hospital care. Results: Levels of cTnI were lower than cTnT in COVID-19 patients (TnI/TnT ratio 0.3, IQR: 0.1–0.6). In contrast, levels of cTnI were 11 times higher compared to cTnT in 15 patients with MI (TnI/TnT ratio 11, IQR: 7–14). The peak cTnI/cTnT ratio among the patients with MI following successful percutaneous intervention were 14 (TnI/TnT ratio 14, IQR: 12–23). The 5 COVID-19 patient samples collected under possible necrotic events had a cTnI/cTnT ratio of 5,5 (IQR: 1,9–8,3). Conclusions: In patients with COVID-19, cTnT is often elevated to higher levels than cTnI in sharp contrast to patients with MI, indicating that the release of cardiac troponin has a different cause in COVID-19 patients.
查看更多>>摘要：? 2022 Elsevier B.V.Background: Epidemiological studies suggest that increases in red blood cell distribution width (RDW) and decreases in albumin level can independently predict adverse cardiovascular outcomes. The prognostic value of RDW-albumin ratio (RAR), an innovate biomarker of inflammation, in heart failure (HF) patients has not been assessed. This study aimed to explore the association between RAR and mortality of HF patients. Methods: Data on patients diagnosed with HF were extracted from MIMIC-III database version 1.4. Cox proportional hazards models were used to investigate the associations between RAR and mortality of HF patients. HF patients admitted to the Second Affiliated Hospital of Wenzhou Medical University were also enrolled to explore the relationship between RAR and existing indicators of HF. Results: For 90-day mortality, the HR (95% CI) for the second (4.33＜RAR＜5.44) and the third (RAR＞5.44) tertiles were 2.00 (1.58, 2.54) and 3.63 (2.91, 4.53), respectively, compared to the first tertile (RAR＜4.33). When adjusted for age, gender and ethnicity in Model 1, the adjusted HR (95% CI) value of third tertiles was 3.66 (2.93, 4.56). Further adjust the vital signs, blood biochemical indicators, SOFA score and other parameters in Model II, the adjusted HR value of third tertiles was still statistically significant (HR: 2.70, 95% CI: 2.07–3.51, P < 0.0001). A similar trend was observed for 30-day, one-year mortality. For HF patients, high RAR significantly increased the risk of sepsis and requirement for renal replacement therapy. Additionally, there is a positive correlation between RAR, CRP levels, and NT-proBNP respectively. Conclusion: High level of RAR is associated with increased short- and long-term mortality of patients with heart failure. The RAR is a promising biomarker that is easy to obtain and readily predicts mortality in heart failure patients.
查看更多>>摘要：? 2022 Elsevier B.V.Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder with elevated LDL-C levels which can ultimately lead to premature Coronary Artery Disease (CAD). Objectives: In presence of limited genetic data on FH in India, the present study was aimed to determine the mutation spectrum in Indian FH patients using a targeted exome sequencing. Methods: 54 FH cases (31 index cases + 23 extended family members) were categorized according to Dutch Lipid Clinic Network Criteria (DLCNC). Targeted exome sequencing was performed using 23 gene panel associated with lipid metabolism. Results: All subjects showed the presence of family history of CAD, 38(70%) patients had corneal arcus whereas only 06(11%) subjects had xanthomas. As per the DLCNC, definite, probable, possible and unlikely FH were 48%, 30%, 11% and 11% respectively. Mutations were observed in 12 of the 23 gene panel with CETP, APOA5, EPHX2 and SREBP2 genes were identified for the first time in Indian FH patients. All 19 mutations including a novel frame-shift mutation in LDLR gene were reported for the first time in Indian FH patients. These mutations were identified in 28(52%) subjects and interestingly ～73% of the clinically identified FH patients didn't harbour mutations in FH classical genes (LDLR, ApoB, PCSK9). Conclusion: This is the first study in the South Indian FH patients to perform targeted exome sequencing. Absence of mutations in the FH classical genes strongly indicates the polygenic nature of FH, further underscoring the importance of targeted exome sequencing for identifying mutations in genetically diverse Indian population.
查看更多>>摘要：? 2022 Elsevier B.V.Background and aims: Investigations in pregnancy should be interpreted using pregnancy-specific reference intervals (RIs). However, because of the progressive nature of pregnancy, even pregnancy-specific RIs may not be equally representative at different gestations. We proposed that gestational age-specific RIs may increase diagnostic accuracy over those with fixed limits. Materials and methods: The trajectory of platelets was mapped in 32,778 pregnant women, using 116,798 results. Then we evaluated the accuracy with which a low measurement in early pregnancy (<3rd centile) predicted thrombocytopaenia at term, compared to the existing limit (<150 × 109/L). Results: Platelets fell by 14.8% between 8 and 40 weeks. Platelets below the 3rd centile before 20 weeks predicted thrombocytopaenia at term (<100 × 109/L) with a significantly greater degree of accuracy than a fixed limit (AUC 0.86 vs. 0.76, p = 0.004). Conclusion: Pregnancy-specific RIs can be defined using routinely collected hospital data, and the abundance of such freely available data enables a detailed investigation of temporal changes throughout gestation. Individualised RIs offer improved accuracy profiles, over and above those already derived specifically from pregnant populations. Clinicians should consider how this may be used to improve diagnostic accuracy for biomarkers used in current clinical practice, and those yet to be defined.
查看更多>>摘要：? 2022 Elsevier B.V.Hypothyroidism is closely associated with increased serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG). The thyroid gland plays an important role in this process because thyroid hormones (THs) modulate cholesterol production, transformation and clearance. Although recent evidence suggests that thyroid-stimulating hormone (TSH) itself also participates in hyperlipidemia, the underlying mechanism remains unclear. Others demonstrated that the pathologic development of hypothyroidism-related hyperlipidemia was associated with down-regulated THs and up-regulated TSH in serum. This finding suggests a role for hypothyroidism in hyperlipidemia and potentially in related cardio-metabolic disease. Multiple newly identified modulatory biomarkers, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), angiopoietin-like protein (ANGPTLs), and fibroblast growth factors (FGFs), might play a role in modulating the risk of hyperlipidemia induced by hypothyroidism. Moreover, hypothyroidism also contributes to the production of dysfunctional high-density lipoprotein (HDL) particles. In the present review, we examine the relationship between hypothyroidism with the risk and pathologic development of hyperlipidemia. We explore mechanisms by which hypothyroidism promotes hyperlipidemia in general and its contribution to cardio-metabolic disease specifically.
查看更多>>摘要：? 2022 Elsevier B.V.Background and aims: No clear rules about the optimal frequency of organizing External Quality Assessment (EQA) rounds exist. More frequent challenges will facilitate faster responses and more reliable statistics. Adding extra samples leads to extra information, but the correlation between results from different samples reduces the extra information from additional samples. Materials and Methods: Data were used for ALT and Albumin from the RCPAQAP EQA scheme. Every two weeks, laboratories analysed two samples. Correlation between results of different samples was calculated to determine the power of distinguishing poorly from well-performing laboratories. The power was compared to hypothetical cases of no correlation and one-sample-per-week to estimate the number of samples negated due to correlation. Results: Correlation leads to negation of a number of samples, but not more than 50% of samples were negated. The number of negated samples was positively related with the correlation between EQA results. Conclusions: The proposed framework provides a quantitative evaluation of the impact of adding more EQA rounds or samples. A correlation exists and is higher for analyses performed closer in time, but the examples shown here did not show a detrimental effect on correctly evaluating laboratories.
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