Unraveling the unexpected: Interference in iron assay leads to diagnosis of multiple myeloma.

BACKGROUND: Iron studies are critical for diagnosing iron deficiency and hemochromatosis. We present a case exhibiting macrocytic anemia with perplexingly high plasma iron concentrations. METHODS AND RESULTS: The initial clinical presentation with significantly elevated iron results raised concerns for hemochromatosis. However, inconsistent results in dilution studies suggested the presence of an interfering substance. Inspection of the reaction curves from the instrument revealed very high background absorption in the 800 nm channel. This, coupled with the observation of an insoluble precipitate upon mixing the acid buffer reagent with the patient's serum, as well as the patient's high total protein and low albumin levels, suggested immunoglobulin overproduction. Serum protein electrophoresis confirmed a monoclonal gammopathy with a subsequent diagnosis of multiple myeloma. CONCLUSION: Excessive monoclonal immunoglobulins can precipitate in acidic buffers and interfere with spectrophotometric measurements in iron testing. Although challenging, investigating an interference and determining its cause can uncover underlying diseases that have yet to be diagnosed.

Establishing hemolysis, icterus, and lipemia interference limits for body fluid chemistry analytes measured on the Roche cobas instrument.

OBJECTIVES: The aims of this study were to (1) establish the maximum allowable interference limits for hemolysis, lipemia, and icterus for chemistry analytes tested in body fluid samples and (2) assess the effectiveness of serial dilution to mitigate spectral interferences. METHODS: Residual body fluids from clinically ordered testing were mixed (<10% by volume) with stock solutions of interferent (spiked) and compared with a control spiked with an equal volume of 0.9% saline. The analytes were measured on the Roche cobas c501 instrument. Difference and percentage difference were calculated and compared with allowable total error limits. A subset of samples were serially diluted with 0.9% saline. Mean (SD) difference and percentage difference were calculated. RESULTS: The interference thresholds were lower than the package insert for lactate dehydrogenase, cholesterol, triglycerides, and total protein for hemolysis; amylase, cholesterol, and total protein for icterus; and albumin for lipemia. Only cholesterol and triglyceride results returned to baseline upon dilution of icteric samples. CONCLUSIONS: Interference thresholds in body fluids were lower than blood for 6 analytes. Diluting interferences that surpass these limits does not produce reliable results that are comparable to the baseline results before spiking in the interferent.

Unclassified green dots on nucleated red blood cells (nRBC) plot in DxH900 from a patient with hyperviscosity syndrome.

OBJECTIVES: Analytical interferences, caused by antibodies, often go unnoticed and require a deep understanding of analyzer principles in the correct clinical context. METHODS: A case report details a 56-year-old man with symptoms of hyperviscosity syndrome (HVS) due to multiple myeloma. RESULTS: The DxH 900 analyzer revealed abnormalities in the nucleated red blood cell (nRBC) graph, attributed to a high concentration of IgA kappa. Immediate plasmapheresis successfully treated HVS, reducing the monoclonal component and eliminating the aberrant green signal. CONCLUSIONS: In the appropriate clinical context, the recognition of analytical interferences is necessary for accurate clinical interpretation, and it is only possible with knowledge of the analytical principles of the instruments. In this case, the high concentration of IgA kappa generated an aberrant green signal in the VCSm.

[Factor XI deficiency: actuality and review of the literature]. / Déficit en facteur XI : actualités et revue de littérature.

Although two clusters have been identified in France, constitutional factor XI deficiency is a rare disorder. Acquired factor XI deficiency is extremely rare. The management of factor XI deficiency is not staightforward because of the unpredictable bleeding tendency that does not clearly relate to the factor XI level. Other haemostastis parameters have to be taken into account to evaluate the bleeding tendency. We report the cases of a congenital factor XI deficiency, an acquired factor XI deficiency and a von Willebrand disease associated to a factor XI deficiency. On the other hand, some interferences can lead to underestimation of factor XI and we report the case of an interference by lupus anticoagulant. The objective of this review is to better understand how to manage a reduced factor XI level.

Using analytical performance specifications in a medical laboratory.

Analytical performance specifications (APS) are used for the quantitative assessment of assay analytical performance, with the aim of providing information appropriate for clinical care of patients. One of the major locations where APS are used is in the routine clinical laboratory. These may be used to assess and monitor assays in a range of settings including method selection, method verification or validation, external quality assurance, internal quality control and assessment of measurement uncertainty. The aspects of assays that may be assessed include imprecision, bias, selectivity, sample type, analyte stability and interferences. This paper reviews the practical use of APS in a routine clinical laboratory, using the laboratory I supervise as an example.

Optically Controlled Gain Modulation for Microwave Metasurface Antennas.

Over the past decade, metasurfaces (MTSs) have emerged as a highly promising platform for the development of next-generation, miniaturized, planar devices across a wide spectrum of microwave frequencies. Among their various applications, the concept of MTS-based antennas, particularly those that are based on surface wave excitation, represents a groundbreaking advancement with significant implications for communication technologies. However, existing literature primarily focuses on MTS configurations printed on traditional substrates, largely overlooking the potential benefits of employing photosensitive substrates. This paper endeavors to pioneer this novel path. We present a specialized design of a modulated MTS printed on a silicon substrate, which acts as a photosensitive Ka-band surface wave antenna. Remarkably, the gain of this antenna can be time-modulated, achieving a variance of up to 15 dB, under low-power (below 1 W/cm²) optical illumination at a wavelength of 971 nm. This innovative approach positions the antenna as a direct transducer, capable of converting an optically modulated signal into a microwave-modulated radiated signal, thus offering a new dimension in antenna technology and functionality.

Double trouble: Unmasking two hook effects on Siemens Atellica® - Total PSA and total hCG assays.

The "hook effect" or "prozone phenomenon" occurs when the concentration of a particular analyte saturates the antibodies used in the test, resulting in falsely low or negative results despite the presence of high analyte concentrations. We report two recent cases of hook effect encountered with a widely used immunoassay analyzer, the Siemens Atellica® IM1600. The first case involves a patient with advanced metastatic prostate cancer whose total PSA (tPSA) concentration dropped dramatically from his last biological control. The second case concerns a pregnant woman whose total HCG (ThCG) levels were also subject to the hook effect and who was found to have a molar pregnancy. In both cases, a dilution step enabled to overcome this analytical concern and to obtain a correct result. In addition, a comparison of the sensitivity of different immunoassay analyzers to this phenomenon was carried out. To avoid this analytical error, an additional dilution step should automatically be performed when there is a clinical suspicion of elevated levels of tumor or hormone markers. Finally, the most affected manufacturers should adapt their assays, accordingly.

Profiling dynamics of the Southeast Asia's largest lake, Tonle Sap Lake.

Lakes, as vital components of the Earth's ecosystem with crucial roles in global biogeochemical cycles, are experiencing pervasive and irreparable worldwide losses due to natural factors and intensive anthropogenic interferences. In this study, we investigated the long-term dynamic patterns of the Tonle Sap Lake, the largest freshwater lake in the Mekong River Basin, using a series of hydrological data and remote sensing images between 2000 and 2020. Our findings revealed a significant decline in the annual average water level of the lake by approximately 2.1 m over 20 years, accompanied by an annual average reduction in surface area of about 1400 km2. The Tonle Sap Lake exhibited episodic declines in water level and surface area, characterized by the absence of flooding during the flood season and increasing aridity during the dry season. Furthermore, the shoreline of the lake has significantly advanced towards the lake in the northwestern and southern regions during the dry season, primarily due to sedimentation-induced shallowing of the lake edge depth and decreased water levels. In contrast, lake shorelines in the eastern region remained relatively stable due to the constructed embankments for the protection of the cultivated farmland. While the seasonal fluctuations of the Tonle Sap Lake are regulated by regional precipitation in the Mekong River Basin, the prolonged shrinking of the lake can be mainly ascribed to intensive anthropogenic activities. The interception of dams along the upper Mekong River has resulted in a decrease in the inflow to Tonle Sap Lake, exacerbating its shrinkage. Moreover, there are minor impacts from agricultural land expansion and irrigation on the lake. This study highlights the driving forces behind the evolution of Tonle Sap Lake, providing valuable information for lake managers to develop strategies aimed at conserving and restoring the ecological integrity of the Tonle Sap Lake.

Glucose measurements with accu check inform II versus hexokinase plasma method during surgery under general anesthesia, an observational cohort study.

PURPOSE: Limited research exists on translation of in-vitro glucose measurement interfering compounds to the in-vivo situation. We investigated whether Point-of-Care glucose measurements by Accu Chek Inform II (ACI II) were accurate to monitor glucose concentrations during surgery with general anesthesia by comparing with the reference laboratory hexokinase plasma glucose test. METHOD: Patients undergoing surgery with general anesthesia were included. Anesthesia was maintained with either Sevoflurane or Total intravenous anesthesia (TIVA). Prior to and after induction, blood glucose was measured with ACI II and the hexokinase test. Bland-Altman analysis was performed to assess method agreement. Subgroup analyses on glucose measurement differences per type of maintenance anesthesia were performed. RESULTS: Thirty-nine patients were included, and 78 measurements were performed. All paired measurements had clinically acceptable agreement with a percentage error of 10.0% (95% CI 8.0 to 11.9). The mean difference (95% limits of agreement) between ACI II and hexokinase for all measurements was 0.0 mmol/L (-0.7 to 0.7 mmol/L). Before induction (n = 39), mean difference was -0.1 mmol/L (-0.6 to 0.4 mmol/L), and after induction (n = 39), mean difference was 0.1 mmol/L (-0.8 to 0.9 mmol/L). Further investigation showed the difference varied per test for patients receiving Sevoflurane compared to patients receiving TIVA (-0.2 ± 0.4 mmol/L vs. 0.4 ± 0.3 mmol/L, p < 0.001). Before and after induction, the difference between ACI II and hexokinase measurements increased for patients receiving Sevoflurane compared to patients receiving TIVA (0.4 ± 0.4 mmol/L vs. -0.4 ± 0.3 mmol/L, p < 0.001). CONCLUSION: The agreement between glucose measurements using ACI II and the reference laboratory hexokinase test was clinically acceptable with a percentage error of 10.0% (95% CI 8.0 to 11.9). The use of TIVA may negatively affect the measurement performance of the ACI II.

Performance evaluation of a novel platelet count parameter, hybrid platelet count, on the BC-780 automated hematology analyzer.

OBJECTIVES: Automated hematology analysis is expected to improve the performance of platelet counting. We evaluated the performance of a new platelet counting, hybrid (PLT-H) and also impedance (PLT-I) and optical (PLT-O) on the BC-780 automated hematology analyzer compared to the international reference method (IRM) in blood samples with thrombocytopenic and platelet interference. METHODS: The basic platelet count performance of the BC-780 automated hematology analyzer was evaluated according to the requirements of the Clinical Laboratory and Standards Institute (CLSI) Document H26-A2. Additionally, the thrombocytopenic (low PLT count) blood samples and the platelet interference blood samples including fragmented red blood cells (RBCs), microcytes or small RBCs, and giant platelets were determined with the BC-780 hematology analyzer compared to the IRM. RESULTS: Blank counting and the carry-over contamination rate of platelet count using the BC-780 both met the manufacturers' claim. For both 123 thrombocytopenic and 232 platelet interference blood samples (72 fragmented RBCs, 91 microcytes and 51 giant platelets), all three platelet counting methods exhibited high comparability with the IRM (the lowest correlation (r)=0.916). Interestingly, the comparability of PLT-H (r=0.928-0.986) with the IRM was better than that of PLT-I (r=0.916-0.979). CONCLUSIONS: The performance of PLT-H in the BC-780 met the manufacturer's specifications. PLT-H exhibits better reproducibility than did PLT-I, correlates well with the PLT-O for thrombocytopenic samples and demonstrates good anti-interference ability. PLT-H counting is therefore recommended as a zero-cost alternative platelet counting method for platelet interference samples in clinical settings.

Voltammetry in Determination of Trace Amounts of Lanthanides-A Review.

This paper presents an overview of approaches proposed in the scientific literature for the voltammetric determination of rare earth elements (mainly cerium and europium individually, as well as various lanthanides simultaneously) in manifold kinds of samples. The work is divided into chapters describing the most important aspects affecting the sensitivity of the proposed methods: the technique adopted (AdSV, ASV, CSV), complexing agents used, the kind of working electrode (mercury-based, noble metal or carbon electrodes) and the most popular electrode modifiers (e.g., metal film, carbon nanotubes, molecularly imprinted polymers). Analytical parameters of the procedures presented in the paper are collected in tables. The subsequent chapters are devoted to a detailed discussion of potential inorganic and organic interfering factors. The possibilities of simultaneous determination of several lanthanides in one sample and the influence of other lanthanides on the determined rare earth element were also discussed. Finally, the applications of the voltammetric procedures to the determination of rare earth metals in real samples with miscellaneous matrix is described. All analytical results were tabulated in order to compare the analytical suitability of the proposed procedures.

Hyperglycaemia and Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) may coexist with type 2 diabetes mellitus (T2DM). Patients with COPD have an increased risk of developing T2DM compared with a control but, on the other side, hyperglycaemia and DM have been associated with reduced predicted levels of lung function. The mechanistic relationships between these two diseases are complicated, multifaceted, and little understood, yet they can impact treatment strategy. The potential risks and benefits for patients with T2DM treated with pulmonary drugs and the potential pulmonary risks and benefits for patients with COPD when taking antidiabetic drugs should always be considered. The interaction between the presence and/or treatment of COPD, risk of infection, presence and/or treatment of T2DM and risk of acute exacerbations of COPD (AECOPDs) can be represented as a vicious circle; however, several strategies may help to break this circle. The most effective approach to simultaneously treating T2DM and COPD is to interfere with the shared inflammatory substrate, thus targeting both lung inflammation (COPD) and vascular inflammation (DM). In any case, it is always crucial to establish glycaemic management since the reduction in lung function found in people with diabetes might decrease the threshold for clinical manifestations of COPD. In this article, we examine possible connections between COPD and T2DM as well as pharmacological strategies that could focus on these connections.

Lack of observed interference by therapeutic monoclonal antibodies in select commonly utilized immunoassays.

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.

An ICP-MS-Based Analytical Strategy for Assessing Compliance with the Ban of E 171 as a Food Additive on the EU Market.

A method was developed for the determination of total titanium in food and food supplements by inductively coupled plasma mass spectrometry (ICP-MS) after microwave-assisted acid digestion of samples. Five food supplements, including one certified reference material, and 15 food products were used for method development. Key factors affecting the analytical results, such as the composition of the acid mixture for sample digestion and the bias from spectral interferences on the different titanium isotopes, were investigated. Resolution of interferences was achieved by ICP-MS/MS with ammonia adduct formation and viable conditions for control laboratories equipped with standard quadrupole instruments were identified. The method was successfully validated and enables rapid screening of samples subject to confirmatory analysis for the presence of TiO2 particles. For the latter, single-particle ICP-MS (spICP-MS) analysis after chemical extraction of the particles was used. The two methods establish a viable analytical strategy for assessing the absence of titania particles in food products on the EU market following the E 171 ban as a food additive.

Best Practice for Identification of Classical 21-Hydroxylase Deficiency Should Include 21 Deoxycortisol Analysis with Appropriate Isomeric Steroid Separation.

There are mixed reports on the inclusion and use of 21 deoxycortisol (21DF) as the primary decision marker for classical 21-hydroxylase deficiency. We hypothesize that this may be due to insufficient recognition of the presence and chromatographic separation of isomeric steroids. The aim of this study was to determine the comparative utility of 21DF for screening and diagnosis of CAH due to classical 21-hydroxylase deficiency using a second-tier LC-MS/MS method that included the separation of isomeric steroids to 17OHP and 21DF. For each baby sample, one 3.2 mm dried blood spot was eluted in a methanolic solution containing isotopically matched internal standards. Data were interrogated by univariate and receiver operator characteristic analysis. Steroid profile results were generated for 924 non-CAH baby samples (median gestational age 37 weeks, range 22 to 43 weeks) and 17 babies with 21-hydroxylase deficiency. The ROC curves demonstrated 21DF to have the best sensitivity and specificity for the diagnosis of classical 21-hydroxylase deficiency with an AUC = 1.0. The heatmap showed the very strong correlation (r = 0.83) between 17OHP and 21DF. Our data support 21DF as a robust marker for CAH due to 21-hydroxylase deficiency. We recommend that 21DF be incorporated into routine newborn screening panels as part of the second-tier LC-MS/MS method, follow-up plasma steroid panels, and external quality assurance material.

Evusheld, a SARS-CoV-2 spike protein-directed attachment inhibitor, appears in serum protein electrophoresis and immunofixation: a case study.

Serum protein electrophoresis (SPE) and immunofixation (IFE) assays are commonly used to diagnose and monitor patients with multiple myeloma (MM). Identifying analytical interferences in SPE and IFE caused by therapeutic monoclonal antibodies (tmAbs) can be challenging. Here we report the case of a 72-year-old male with a long history of relapsed immunoglobulin (Ig)G kappa MM. A follow-up SPE showed the original peak plus 2 additional cathode peaks. Immunofixation was ordered as a reflex test to investigate the new peaks that showed initial patient monoclonal IgG kappa in addition to 2 restricted bands of the IgG kappa type. Therapeutic monoclonal antibody interference was suspected and the patient's chart was reviewed. The patient was not on any antimyeloma monoclonal antibody therapy. However, preexposure prophylaxis therapeutic monoclonal antibodies tixagevimab plus cilgavimab (Evusheld) for severe acute SARS-CoV-2 was administered approximately 45 minutes before sample collection, which led to the identifiable spikes and correlated bands. After 2 days, the IgG kappa bands disappeared, confirming this therapy's effect on SPE and IFE. Therefore, clinical pathologists should be aware of when providers prescribe new monoclonal antibody therapy and become familiar with the position of commonly prescribed (tmAbs) therapies at their institutions.

The Role of Supraerupted and Distoverted Maxillary Third Molars in the Treatment of Temporomandibular Disorder: A Randomised Controlled Trial.

Objective Temporomandibular disorder (TMD) is a multifactorial disease that is classified into muscular and joint disorders. The etiology of TMD is unknown but it is related to various factors such as bruxism, uncorrected high dental restorations, and occlusal prematurities. This study aims to provide treatment modalities for TMD patients with supraerupted and/or distoverted maxillary third molars that have premature contact with the opposing arch. Methods A total of 430 subjects diagnosed with TMD were included in the study and randomized into study and control groups based on their treatment needs. A detailed case history was taken, and findings of intra and extra oral examination were recorded along with other investigations such as study model analysis, orthopantomogram (OPG), cone-beam computed tomography (CBCT), and MRI. The multiphase treatment included counseling in phase I, extraction in phase II (only for the study group), and oral appliance in the third phase. The final phase involved the restoration of edentulous areas or reduced vertical dimension. Results Extraction of supraerupted and/or distoverted maxillary third molars in the study group during phase II showed a 96% reduction in TMD when compared to the control group who did not undergo extraction. Conclusion TMD is a repetitive motion disorder, and the success of treatment relies on the elimination of causative factors, the type of appliance used, and the establishment of ideal occlusion. This study suggests that the extraction of supraerupted and/or distoverted maxillary third molars is a prerequisite for treating TMD patients.

Determination of lipemia acceptance thresholds for 31 immunoassay analytes.

BACKGROUND: Lipemia is one of common endogenous interferences that can compromises sample quality and potentially influence results of various laboratory methods. Determination of the lipemic index or triglyceride concentrations are used to define the degree of lipemia. This study was aimed to establish lipemic index (LI) and triglyceride thresholds above where significant interference exists for 31 immunoassay analytes measured on Roche Cobas 6000. MATERIALS AND METHODS: The study was carried out following CLSI C56-A and EP07-ED3:2018 guidelines using sample pools spiked with increasing concentrations of lipid emulsion solution, reaching 70 mmol/L. To define the LI and triglyceride thresholds, the bias from concentration in the native sample was calculated at different lipemia degree and compared with allowable error limits based on biological variation or state-of-the-art technology. RESULTS: No lipemia interference was observed for 27 out of 31 analytes even at the highest concentrations of lipid emulsion (LI ranging from 1737 to 2086 mg/dL, triglyceride concentration 60.34-73.99 mmol/L). However, progesterone, 25-OH vitamin D, testosterone, and estradiol were negatively affected by lipemia at 217 mg/dL (9.58 mmol/L), 222 mg/dL (10.66 mmol/L), 478 mg/dL (18.81 mmol/L), and 941 mg/dL (35.82 mmol/L) of the LI (triglyceride concentration), respectively. CONCLUSION: Most immunoassays evaluated in this study were found to be robust to lipemia interference. By using these thresholds, laboratories can report the immunoassay results from analyzing a lipemic patient sample in many cases.