Analytical performance evaluation of a new integrated clinical chemistry and immunoassay analyzer.

Background: Clinical laboratories perform a wide range of tests that are used by healthcare professionals to guide medical decision making. Use of automated analyzers in the clinical laboratory can improve patient care by not only reducing the turn-around-time (TAT) of results but also improving accuracy of the reported results by reducing human error. The aim of this study was to evaluate the performance characteristics of a new automated laboratory instrument, the Atellica® CI Analyzer, Model 1900, over a 3-month period in a European laboratory setting.

Feasibility of using real-world free thyroxine data from the US and Europe to enable fast and efficient transfer of reference intervals from one population to another.

Objectives: The direct approach for determining reference intervals (RIs) is not always practical. This study aimed to generate evidence that a real-world data (RWD) approach could be applied to transfer free thyroxine RIs determined in one population to a second population, presenting an alternative to performing multiple RI determinations.

Design And Methods: Two datasets (US, n = 10,000; Europe, n = 10,000) were created from existing RWD.

Highly sensitive therapeutic drug monitoring of infliximab in serum by targeted mass spectrometry in comparison to ELISA data.

Background: Presently, antibody concentration measurements for patients undergoing treatment are predominantly determined by ELISA, which still comes with known disadvantages. Therefore, our aim was to establish a targeted mass-spectrometric assay enabling the reproducible absolute quantification of peptides from the hypervariable and interaction regions of infliximab.

Methods: Peptides of infliximab were measured post-trypsin digestion and subsequent separation on a Vanquish Horizon UHPLC coupled to a TSQ Altis Triple-Quad mass spectrometer.

Krebs von den Lungen-6 as a Potential Predictive Biomarker in Fibrosing Interstitial Lung Diseases.

Background: As fibrosing interstitial lung diseases (fILDs) are associated with high mortality, monitoring of disease activity under treatment is highly relevant. Krebs von den Lungen-6 (KL-6) is associated with the presence and severity of different fILDs, mainly in Asian patient populations.

Objectives: Our aim was to evaluate KL-6 as a predictive biomarker in fILDs in Caucasian patients.

Rapid Detection of Lithium Concentrations in Oral Fluid.

Background: Lithium medication is considered to be the first-line treatment for bipolar disorder as a monotherapy, and for treatment-resistant depression with lithium augmentation. However, because of potential toxicity, lithium levels must be monitored frequently. Recent studies have demonstrated a significant correlation between lithium levels measured in serum and those detected in oral fluid, suggesting that oral fluid analysis may represent an easy, noninvasive means to monitor lithium levels.

Fluoxetine Enhances Synaptic Vesicle Trafficking and Energy Metabolism in the Hippocampus of Socially Isolated Rats.

Chronic social isolation (CSIS)-induced alternation in synaptic and mitochondrial function of specific brain regions is associated with major depressive disorder (MDD). Despite the wide number of available medications, treating MDD remains an important challenge. Although fluoxetine (Flx) is the most frequently prescribed antidepressant, its mode of action is still unknown.

A multicenter performance evaluation of the new Elecsys Vitamin D total III assay versus reference isotope dilution liquid chromatography tandem mass spectrometry and commercially available comparators.

Background: Vitamin D deficiency/insufficiency and toxicity are worldwide issues; thus, accurate diagnostic assays are required to measure vitamin D. We evaluated the performance of the new Elecsys Vitamin D total III assay (Roche Diagnostics International Ltd).

Methods: Repeatability and intermediate precision of the Elecsys Vitamin D total III assay (cobas e 601 analyzer) were evaluated at three sites using five human serum pools (HSPs) and two PreciControls (five-day model, one reagent lot [CLSI-EP05-A3]) and compared against prespecified acceptance criteria.

Dickkopf 3-A New Indicator for the Deterioration of Allograft Function After Kidney Transplantation.

Evidence of tubular atrophy and interstitial fibrosis is prognostically unfavorable and associated with a premature graft loss after kidney transplantation. Recently, Dickkopf 3 (DKK3), a profibrotic glycoprotein released by stressed tubular epithelial cells, has been identified to cause IF/TA by regulating the Wnt/β-catenin signaling and seems to engage a T-cell response. The aim of our study was to determine if a correlation between DKK3 and graft function exists and if DKK3 could be a new indicator to identify patients at risk for a deterioration in graft function.

Multicenter Evaluation of a New, Fully Automated Androstenedione Electrochemiluminescence Immunoassay: Precision Analysis, Method Comparison, and Determination of Reference Ranges.

Background: Androstenedione (ASD) levels can aid diagnosis of hyperandrogenism together with other clinical/laboratory findings. We evaluated performance of the new, automated Elecsys® ASD assay vs an ASD isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) reference measurement procedure and determined reference ranges.

Methods: Repeatability/intermediate precision were assessed using 3 control levels and 5 human serum pools (n = 75 each; Clinical and Laboratory Standards Institute EP05-A3).

Tianeptine modulates synaptic vesicle dynamics and favors synaptic mitochondria processes in socially isolated rats.

Deregulation of synaptic function and neurotransmission has been linked with the development of major depression disorder (MDD). Tianeptine (Tian) has been used as antidepressant with anxiolytic properties and recently as a nootropic to improve cognitive performance, but its mechanism of action is unknown. We conducted a proteomic study on the hippocampal synaptosomal fractions of adult male Wistar rats exposed to chronic social isolation (CSIS, 6 weeks), an animal model of depression and after chronic Tian treatment in controls (nootropic effect) and CSIS-exposed rats (lasting 3 weeks of 6-week CSIS) (therapeutic effect).

Performance evaluation of the Roche Elecsys Anti-SARS-CoV-2 S immunoassay.

The Elecsys® Anti-SARS-CoV-2 S immunoassay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) has been developed for the detection of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein. We evaluated the assay performance using samples from seven sites in Germany, Austria, and Switzerland. For specificity and sensitivity analyses, 7880 presumed negative pre-pandemic samples and 827 SARS-CoV-2 PCR-confirmed single or sequential samples from 272 different patients were tested, respectively.

Multicentre Performance Evaluation of the Elecsys Anti-SARS-CoV-2 Immunoassay as an Aid in Determining Previous Exposure to SARS-CoV-2.

Introduction: We performed a multicentre evaluation of the Elecsys Anti-SARS-CoV-2 immunoassay (Roche Diagnostics), an assay utilising a recombinant protein representing the nucleocapsid (N) antigen, for the in vitro qualitative detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: Specificity was evaluated using serum/plasma samples from blood donors and routine diagnostic specimens collected before September 2019 (i.e.

Intraocular epidermal growth factor concentration, axial length, and high axial myopia.

Purpose: Various molecules such as dopamine have been found to be associated with axial elongation in experimental studies. Here, we examined whether intraocular EGF is associated with axial length in myopic patients.

Methods: The hospital-based investigation included patients of European descent without optic nerve, retinal, or macular diseases except for myopic maculopathy.

Specificity testing by point prevalence as a simple assessment strategy using the Roche Elecsys® anti-SARS-CoV-2 immunoassay.

Background: The detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mandatory for the diagnosis, retrospective assessment of disease progression, and correct evaluation of the current infection situation in the population. Many such assays have been launched by various manufacturers. Unfortunately, the new US Food and Drug Administration emergency use regulations have resulted in a situation where laboratories have to perform their own validation studies but many of these laboratories do not have the biobank needed to conduct the studies.

Clinical evaluation of commercial automated SARS-CoV-2 immunoassays.

Objective: Numerous immunoassays for detecting antibodies directed against SARS-CoV-2 have been rapidly developed and released. Validations of these have been performed with a limited number of samples. The lack of standardisation might lead to significantly different results.

Hippocampal synaptoproteomic changes of susceptibility and resilience of male rats to chronic social isolation.

The susceptibility of an individual to chronic social isolation (CSIS) stress may cause major depression (MD) whereby some individuals are resistant to the stress. Recent studies relate MD with altered expression of synaptic proteins in specific brain regions. To explore the neurobiological underpinnings and identify candidate biomarkers of susceptibility or resilience to CSIS, a comparative proteomic approach was used to map hippocampal synaptic protein alterations of rats exposed to 6 weeks of CSIS, an animal model of depression.

Clinical performance evaluation of a SARS-CoV-2 Rapid Antibody Test for determining past exposure to SARS-CoV-2.

Objectives: Due to the number of asymptomatic infections and limited access to high-performance antibody tests, the true prevalence and seropositivity of SARS-CoV-2 infection remains unknown. To fill this gap, the clinical performance of a point-of-care SARS-CoV-2 Rapid Antibody Assay, a chromatographic immunoassay for detecting IgM/IgG antibodies, in near patient settings was assessed.

Methods: Forty-two anti-SARS-Cov-2 positive (CoV+) and 92 anti-SARS-Cov-2 negative (CoV-) leftover samples from before December 2019 were assessed; the Elecsys® Anti-SARS-CoV-2 was used as the reference assay.

Tianeptine Enhances Energy-related Processes in the Hippocampal Non-synaptic Mitochondria in a Rat Model of Depression.

Tianeptine (Tian) has been widely used in treating mood and anxiety disorders, and recently as a nootropic to improve cognitive performance. However, its mechanisms of action are insufficiently clear. We used a comparative proteomic approach to identify sub-proteome changes in hippocampal cytosol and non-synaptic mitochondria (NSM) following chronic Tian treatment (3 weeks, 10 mg/kg/day) of adult male Wistar rats and rats exposed to chronic social isolation stress (CSIS) (6 weeks), an animal model of depression.

Social isolation stress-resilient rats reveal energy shift from glycolysis to oxidative phosphorylation in hippocampal nonsynaptic mitochondria.

Aims: To examine the differences in the hippocampal proteome profiles of resilience or susceptibility to chronic social isolation (CSIS), animal model of depression, and to identify biomarkers that can distinguish the two.

Main Methods: Comparative subproteomic approach was used to identify changes in hippocampal cytosol and nonsynaptic mitochondria (NSM) of CSIS-resilient compared to CSIS-sensitive or control rats. The resilient and sensitive phenotypes of CSIS rats were distinguished based on their sucrose preference values.

Development of a Mass Spectrometry-Based Method for Quantification of Ustekinumab in Serum Specimens.

Background: Ustekinumab (UST) is a human monoclonal antibody used to treat moderate-to-severe Crohn disease by blocking the interleukin-12/23 pathway. Although an optimized therapeutic concentration of UST is associated with clinical response and improved prognosis, the availability of clinical laboratory methods for UST monitoring is limited. Furthermore, the commercially available methods are immunoassays that are prone to interference of antidrug antibodies.

Quantitative Mass Spectrometry Imaging Reveals Mutation Status-independent Lack of Imatinib in Liver Metastases of Gastrointestinal Stromal Tumors.

Mass spectrometry imaging (MSI) is an enabling technology for label-free drug disposition studies at high spatial resolution in life science- and pharmaceutical research. We present the first extensive clinical matrix-assisted laser desorption/ionization (MALDI) quantitative mass spectrometry imaging (qMSI) study of drug uptake and distribution in clinical specimen, analyzing 56 specimens of tumor and corresponding non-tumor tissues from 27 imatinib-treated patients with the biopsy-proven rare disease gastrointestinal stromal tumors (GIST). For validation, we compared MALDI-TOF-qMSI with conventional UPLC-ESI-QTOF-MS-based quantification from tissue extracts and with ultra-high resolution MALDI-FTICR-qMSI.

Multicentre evaluation of the Roche Elecsys® Active B (holotranscobalamin) electro-chemiluminescence immunoassay.

Background: Vitamin B deficiency is a common disorder. In circulation, vitamin B is bound to transcobalamin (holotranscobalamin), which is considered the active form of cobalamin. The objective of this study was to evaluate the analytical performance of the Roche Elecsys Active B immunoassay.

Immediate Neutrophil-Variable-T Cell Receptor Host Response in Bacterial Meningitis.

Bacterial meningitis is a life-threatening disease that evokes an intense neutrophil-dominated host response to microbes invading the subarachnoid space. Recent evidence indicates the existence of combinatorial V(D)J immune receptors in neutrophils that are based on the T cell receptor (TCR). Here, we investigated expression of the novel neutrophil TCRαβ-based V(D)J receptors in cerebrospinal fluid (CSF) from human patients with acute-phase bacterial meningitis using immunocytochemical, genetic immunoprofiling, cell biological, and mass spectrometric techniques.