Clinical biochemistry最新文献

Background

Sub-clinical inflammation in hyperglycemia is tied to the pathogenesis of diabetic kidney disease (DKD). Though well known for its immunostimulatory function, the significance of extracellular heat shock protein 72 (eHSP72) in DKD is not well studied. We aimed to determine the association of extracellular HSP72 with systemic inflammation and the progression of DKD, and explore its possible clinical significance in DKD.

Methods

160 type 2 diabetic individuals were enrolled in the study. Their anthropometric data, routine biochemical parameters, urinary renal function parameters, and blood count parameters were estimated. Plasma from patients’ blood samples were used to estimate HSP72 and interleukin 1β (IL-1β) using sandwich immunoassays.

Results

Plasma eHSP72 is elevated in DKD. Pairwise comparisons showed the drastic elevation of eHSP72 in the presence of albuminuria. A significant positive relationship was observed between plasma levels of eHSP72 and IL-1β. eHSP72 levels did not statistically differ between micro and macro-albuminuric DKD. However, it was inversely associated with estimated glomerular filtration rate, the index of disease severity, independent of age, gender, diabetes duration and absolute monocyte count. At a cutoff of 0.52 ng/ml, with sensitivity of 64.1 % and specificity of 69.2 %, plasma eHSP72 differentiated the presence of DKD in type 2 diabetics with statistical significance.

Conclusion

The positive relationship of eHSP72 and IL-1β with worsening DKD likely indicates their participation in immunostimulatory pathways of renal fibrosis. eHSP72 may be closely linked to albuminuria-induced tubular injury and likely contributes to fibrotic changes in the progression of DKD. From our study, we infer the possible clinical significance of eHSP72 as a marker of sub-clinical renal damage in DKD, and the implication of IL-1β-associated mechanisms in DKD progression.

The clinical utility of a diagnostic test refers to its usefulness in improving patient outcomes, informing clinical decision-making, and optimizing healthcare resources. A diagnostic test with high clinical utility provides accurate, reliable, and actionable information that can guide appropriate treatment decisions, monitor treatment response, and identify potential adverse events or complications.

Ultimately, the clinical utility of a diagnostic test depends on how well it can improve patient outcomes by guiding appropriate treatment decisions, improving clinical outcomes, and optimizing healthcare resource utilization. Healthcare providers need to weigh the benefits and drawbacks of using a particular diagnostic test in their clinical practice to determine its clinical utility.

Introduction

In this study, we aimed to create reference intervals (RI) using a large Canadian population-based cohort, for plasma protein biomarkers with potential utility to screen, diagnosis, prognosticate and manage a variety of neurological diseases and disorders. RIs were generated for: the ratio of amyloid beta 42 over 40 (Aβ42/40), phosphorylated tau-181 (p-tau-181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP).

Methods

900 plasma specimens from male and female participants aged 3–79 years old were obtained from the Statistics Canada Biobank, which holds specimens from the Canadian Health Measures Survey. Analysis of Aβ42/40, p-tau-181, NfL and GFAP was performed on the Quanterix Simoa HD-X analyzer using the Neurology 4-plex E and p-tau-181 assays. Discrete RIs were produced according to Clinical Laboratory Standards Institute guidelines (EP28-A3c). Continuous RIs were created using quantile regression.

Results

For discrete RIs, significant age partitions were determined for each biomarker. No significant sex partitions were found. The following ranges and age partitions were determined: Aβ42/40: 3–<55y = 0.053–0.098, 55–<80y = 0.040–0.090; p-tau-181: 3–<12y = 1.4–5.6 pg/ml, 12–<60y = 0.8–3.1 pg/ml, 60–<80y = 0.9–4.0 pg/ml; NfL: 3–<40y = 2.6–11.3 pg/ml, 40–<60y = 4.6–17.7 pg/ml, 60–<80y = 8.1–47.1 pg/ml; GFAP; 3–<10y = 47.0–226 pg/ml, 10–<60y = 21.2–91.9 pg/ml, 60–<80y = 40.7–228 pg/ml. Continuous RIs produced smooth centile curves across the age range, from which point estimates for each year of age were calculated.

Conclusions

Discrete and continuous RIs for neurological plasma biomarkers will help refine normative cut-offs across the lifespan and improve the precision of interpretating biomarker levels. Continuous RIs are recommended for use in age groups, such as pediatrics and older adults, that experience rapid concentration changes by age.

Background

Hemodialysis patients exhibit variable immunogenicity following administration of the SARS-CoV-2 mRNA vaccine. The aim of the current study was to evaluate the use of two commercial assays in the assessment of SARS-CoV-2 antibody response in hemodialysis patients and to compare their utility to commonly used SARS-CoV-2 serological assays developed in Canada.

Methods

We evaluated serologic antibody response in 85 hemodialysis patients up to 6 months after receiving both doses of the Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine. In addition, antibody response was assessed in 46 chronic kidney disease patients and 40 COVID-19 naïve health care workers (HCW) up to 3 months and 9 months, respectively. Anti-spike (S) and anti-nucleocapsid (N) levels were measured using Elecsys anti-SARS-CoV-2 immunoassays on the Roche analyzer and compared to ELISA-based detection of anti-S, anti-receptor binding domain (RBD), and anti-N.

Results

The Elecsys anti-N immunoassay showed 93 % concordance with the anti-N ELISA. The Elecsys anti-S immunoassay showed 97 % concordance with the anti-S ELISA and 89 % concordance with the anti-RBD ELISA. HCWs exhibited significantly higher anti-S levels relative to hemodialysis patients. Anti-S levels decreased significantly over a 6-month period (p < 0.001) in patients receiving maintenance hemodialysis. In addition, anti-S levels decreased significantly over a 9-month (p < 0.001) and 3-month period (p < 0.001) in HCWs and CKD patients, respectively.

Conclusions

There is high concordance between commercial SARS-CoV-2 serological assays and SARS-CoV-2 serological assays developed in Canada. Hemodialysis patients exhibited varying immunogenicity following two doses of the COVID-19 mRNA vaccine with anti-S levels decreasing over time.

Background

Therapeutic monoclonal antibodies (tmabs) have been hypothesized to interfere with immunoassay measurements, although studies investigating this potential new class of interference are lacking. This study evaluated the effects of tmabs used in cancers ipilimumab (Bristol Myers Squibb), nivolumab (Bristol Myers Squibb), pembrolizumab (Merck) and autoimmune disorders adalimumab (AbbVie), infliximab (Janssen) and vedolizumab (Takeda) in common immunoassays used in the clinical laboratory.

Methods

Residual sera from 10 randomly chosen patients were split into two tubes and spiked with same volume (approximately 5 % final volume) of either saline (control) or 6 tmabs (final concentration of 100 μg/mL each). Concentrations from sixteen analytes in 19 different assays were assessed: TSH (Roche and Beckman), free thyroxine (Roche and Siemens), cortisol (Beckman), Cancer Antigens (CA): CA19-9 (Beckman), CA15-3 (Roche), CA125 (Roche), and CA27.29 (Siemens), carcinoembryonic antigen (Beckman), alpha-fetoprotein (Beckman), thyroglobulin (Beckman) and thyroglobulin antibodies (Beckman), thyroid peroxidase antibody (Beckman), beta-human chorionic gonadotropin (Roche and Beckman), total prostate-specific antigen (Roche), parathyroid hormone (Roche) and antinuclear antibodies IgG (Werfen). The tmab spiked residual sera were compared with matched saline spiked sera and percent error was assessed against allowable total error defined from biological variation or CLIA limits.

Results

None of the tested immunoassays were affected by the presence of the tmabs, in samples within or outside assay reference intervals. The median % error among all immunoassays ranged between −2.0% (for TSH) to 2.7% (for TPO Ab assay).

Conclusion

These findings demonstrate no detectable tmab interference for the assessed immunoassays using spiked preparations of the tmabs in residual human sera. The findings are limited to the tmabs and immunoassays studied here.

Measuring the clinical utility of a diagnostic test involves evaluating its impact on patient outcomes, clinical decision-making, and healthcare resource utilization. Determining clinical utility requires accessing patient medical history and outcomes data. These studies involve enrolling patients undergoing diagnostic tests and tracking their clinical outcomes. Researchers can determine the test's clinical utility by comparing the outcomes of patients who receive the diagnostic test to those who do not. These outcomes include benefits and harm. The highest level of evidence to support clinical utility determinations may be obtained from clinical trials. However, clinical laboratories are often not involved in clinical trials, and laboratory specialists may not be experienced in conducting such trials. Many established laboratory tests have never had clinical utility determined. Prospective studies assessing a diagnostic test's impact on clinical outcomes may require long-term patient monitoring, which is problematic.

This paper presents methods that may be used to assess clinical utility.

Sudden sensorineural hearing loss (SSNHL) is defined as hearing loss of more than 30 dB in less than 72 h. SSNHL is a frequent complaint and an emergency in otolaryngology. Various biomarkers have been used to determine the prognosis of SSNHL. This systematic review and meta-analysis aims to evaluate the relationship between the different biomarkers and the prognosis of SSNHL. We searched English-language literature up to October 2022 in four databases, including PubMed, Google Scholar, Cochrane, and Science Direct. This search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. This study was reported in the International Prospective Register of Systematic Reviews (PROSPERO) database (ID = CRD42022369538). All studies examining the role of neutrophil to lymphocyte ratio (NLR) concluded that higher NLR is associated with a worse prognosis. The results of studies regarding the relationship between platelet to lymphocyte ratio (PLR) and tumor necrosis factor (TNF) are controversial. Other factors shown to be associated with SSNHL include Glycated hemoglobin (HbA1C), blood glucose, iron levels, serum endocan, salusin-beta, and bone turnover biomarkers. This meta-analysis showed that PLR, NLR, and neutrophils were significantly different between recovered and non-recovered patients. PLR, NLR, and neutrophil count are reliable tools to assess the prognosis of patients with SSNHL.

This study aimed to quantitatively estimate the correlation between systemic inflammation with cognitive function, as well as glycemic and lipid profiles in patients with type 2 diabetes mellitus (T2DM). The PubMed, Web of Science, EMBASE, SCOPUS, CNKI, Wanfang, VIP, and CBM databases were searched from its inception until June 2023 (PROSPERO registration: CRD42022356889). We analyzed data extracted from observational studies to quantify the correlations (r) as the pooled effect size and further performed subgroup analyses and sensitivity analyses. A total of 32 studies involving 7,483 patients with T2DM were included. The findings revealed a significant moderate negative correlation between interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) levels with Montreal Cognitive Assessment scores. TNF-α levels also had moderate negative correlation with Mini-Mental State Examination scores. For glycemic and lipid profiles, there was a significant moderate positive correlation between CRP and TNF-α levels and glycated hemoglobin (HbA1c), and TNF-α levels were also found to be lowly positively correlated with fasting blood glucose (FBG). CRP levels were found to have a low positive correlation with total cholesterol (TC), and IL-6 levels were found to be lowly positively correlated with triglycerides. The results indicate that elevated levels of IL-6, CRP, and TNF-α are significantly associated with cognitive impairment in patients with T2DM and may serve as inflammatory markers for T2DM with mild cognitive impairment. The CRP and TNF-α levels were more strongly correlated with HbA1c than with FBG and TC. Further research is needed to determine the clinical value of these inflammatory biomarkers and to investigate potential causal mechanisms underlying this association.