bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter Laboratory Comparison of Iohexol Measurement
Authors: Schwartz George J , Wang Hongyue , Erway Brian , Nordin Gunnar , Seegmiller Jesse , Lieske John C , Bäck Sten-Erik , Miller W Greg , Eckfeldt John H 
Published: July 2018

Abstract

Background
Iohexol is used for measurement of kidney glomerular filtration rate (GFR). Until recently, there have not been available proficiency standards to assist in calibrating a laboratory's results. In view of a shift in calibration at the University of Rochester Medical Center (URMC) laboratory, serving as Central Biochemistry Laboratory for the CKiD study, we performed a multicentered laboratory comparison.

Methods
Two batches of 30 fortified sera and patient samples from serum or heparinized plasma were sent for duplicate analysis to URMC, University of Minnesota (UMN), Mayo Clinic, and University of Lund. Five proficiency testing materials from Equalis AB were also provided. Iohexol calibration was performed using dilutions of OmnipaqueTM 300 and concentrations measured by HPLC or LC-MS/MS (Mayo).

Results
The 2 batches sent to UMN and University of Lund agreed well. URMC calibration was 11%–13% lower, and Mayo was 4%–8% lower for fortified samples. URMC corrected calibration was 3%–8% higher for these samples. When measured values were adjusted for the results of the Equalis samples, all laboratories agreed within 1%–2% on all iohexol concentrations.

Conclusions
For 12 URMC calibrator lots from November 2006 to March 2016, the factor quantifying the underestimation of measured to true iohexol concentration was 0.89. If each concentration was divided by 0.89, the calculated GFRs would be reduced by 10%–11%. GFR results for CKiD were adjusted for this shift in calibration. Regular examination of iohexol proficiency testing materials, free exchange of samples among laboratories, and standardized dilution of the stock iohexol for calibration would help to bring more universal agreement to this assay.
Severe Isotype-Matched Immunosuppression (IMI) as a Potential Risk Factor for Progression of MGUS Patients
Authors: Jiménez Juana J , Pais Tiago M , Barbosa Nuno , Campos Maria Luisa , Díaz Maria Antonia Peñalver , de Larramendi Carmen H 
Published: July 2018

AbstractBackgroundMonoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma in virtually every case. However, only a small percentage will progress and at very different rates. In addition, recent data have suggested that MGUS is associated with other comorbidities including infections, suggesting impaired immune function in some MGUS patients. Therefore, we aimed at assessing the value of isotype-matched immunosuppression (IMI; e.g., suppression of an IgAκ in an IgAλ patient), a type of immunosuppression more specific than classical immunoparesis (IP; e.g., IgG and/or IgM suppression in an IgA patient), as a prognostic marker for MGUS progression.MethodsThe Hevylite assay was used to assess IMI and immunoglobulin ratios in 307 serum samples from a cohort of 248 MGUS patients. Follow-up clinical records were available for 154 individuals.ResultsA greater incidence of IMI (51%) over classical IP (37%) was observed, although both show a progressive increase with higher risk groups. Survival analysis of 154 patients showed that severe IMI (&gt;50% suppression) differentiates 2 groups with significantly different time to progression (P = 0.024) while severe IP does not (P = 0.48). Also, a combination of severe IMI and involved monoclonal immunoglobulin &gt;1.5g/dL by Hevylite (both variables found to be independent prognostic markers in multivariate analysis) identified a group of patients with a median time to progression 6-fold shorter than the remaining group (P &lt; 0.0001).ConclusionsThese findings indicate a possible role for IMI in the malignant transformation of MGUS patients and a potential utility as a new risk factor.
Simple HPLC Method with Internal Standard for Evaluation of Vitamin B1 Status By Use of Whole Blood
Authors: Zhang Xiaochun , Tang Xiaoying , Gibson Bill , Daly Thomas M 
Published: July 2018

Abstract

Background
Two primary assays are routinely used for evaluating a patient's vitamin B1 status: plasma free thiamine and whole blood thiamine diphosphate (TDP). TDP is the bioactive form of vitamin B1 and best reflects body stores. Plasma free thiamine levels are driven by recent dietary intake. The objective of this study was to develop a simple HPLC method with an internal standard (IS) that simultaneously measures TDP and thiamine in whole blood, and to assess the use of this single-tube assay to provide comprehensive evaluation of vitamin B1 status.

Methods
The final assay used amprolium thiochrome as an IS, and the sample preparation procedure takes approximately 1 h. Whole blood thiamine and plasma thiamine were concurrently measured for 126 subjects.

Results
The analytical measurement range was 1.7 to 442.3 nmol/L (TDP) and 1.7 to 375.4 nmol/L (thiamine), with interassay precisions of 4.0% to 4.8% (TDP) and 2.9% to 8.0% (thiamine), respectively. Method comparison with a reference laboratory HPLC method showed r = 0.9625, slope = 1.021, and intercept = 0.982 (n = 53) for TDP quantification. Whole blood thiamine correlated closely with plasma thiamine levels but were slightly higher with a mean difference of 1.0 nmol/L (range: −3.0 to 5.0 nmol/L). The reference interval for whole blood TDP and thiamine was 84.3 to 213.3 nmol/L and 1.7 to 21.9 nmol/L, respectively.

Conclusions
This assay provides a simple and reliable HPLC method with a suitable IS for quantification of both TDP and thiamine from whole blood. It also eliminates the need for separate samples for TDP and thiamine measurement, which will allow both short-term and long-term vitamin B1 status to be assessed from a single sample.
Quantitation of Infliximab and Detection of Antidrug Antibodies in Serum by Use of Surface Plasmon Resonance
Authors: Thoren Katie L , Pasi Brian , Delgado Julio C , Wu Alan H B , Lynch Kara L 
Published: July 2018

Abstract

Background
Monitoring infliximab (IFX) concentrations and the presence of antidrug antibodies (ADA) is important for patient management. We developed a method to measure IFX and ADA in serum in a single injection using surface plasmon resonance (SPR).

Methods
Using the Bio-Rad ProteOn XPR36, tumor necrosis factor-α and IFX were covalently immobilized onto separate lanes of a chip surface. Diluted serum was injected over both lanes, followed by an injection of goat antihuman antibody. The binding response was used to quantify IFX or detect ADA. The analytical performance of the assay was determined. Using 50 patient samples, SPR results were compared with results from a reporter gene assay (RGA).

Results
For the quantification of IFX, the functional sensitivity was 0.5 μg/mL. The total precision was &lt;10% for all concentrations tested. IFX concentrations measured by SPR correlated well with RGA (R = 0.862), but a bias was observed (slope = 0.61). SPR detected 14 ADA-positive samples. Compared with RGA for ADA detection, there were 6 true-positive, 8 false-positive, 5 false-negative, and 31 true-negative findings.

Conclusion
SPR can be used to measure biological drug concentrations and detect ADA in serum. This technique may provide complementary information to current methods used to detect ADA.
Comparison of Point-of-Care Activated Clotting Time Methods in Different Clinical Settings in a Large Academic Medical Center
Authors: Korpi-Steiner Nichole L , Walz J Matthias , Schanzer Andres , Rao Lokinendi V 
Published: July 2018

AbstractObjectivesThis study is a comparative analysis of measured activated clotting time (ACT) values by use of 5 different point-of-care (POC) ACT methods spanning the range detected during different clinical procedures at our institution.MethodsWe determined the correlation, imprecision, and differences in measured ACT values with use of 4 POC ACT methods compared with a reference ACT method in 41 venous whole blood samples collected from 25 adult patients undergoing interventional procedures. The POC ACT methods evaluated included the i-STAT with kaolin activator in prewarm mode, i-STAT with Celite activator in prewarm and nonprewarm modes, ACTPlus, and HMSPlus, which was designated the reference method. Each venous whole blood patient sample was tested in duplicate on each POC ACT test system (total n = 410 ACT measurements). Analyses of imprecision and differences in measured ACT values were stratified by moderate (100–299 s) and high (≥300 s) ACT ranges.ResultsIn this study population, measured ACT values ranged from 100–835 s with use of the HMSPlus. All methods demonstrated good correlation (r ≥ 0.95) in ACT values compared to the reference method. Imprecision varied by method with ranges of 1.7%–2.7% CV in the moderate ACT range and 2.5%–4.8% CV in the high ACT range. ACTPlus and i-STAT-Celite-prewarm methods exhibited proportional differences in measured ACT values whereas the i-STAT-Celite-nonprewarm and i-STAT-kaolin-prewarm demonstrated constant differences in measured ACT values compared to HMSPlus.ConclusionsACT values correlate well between POC methods. Imprecision and difference profiles vary by method; notably, imprecision exceeds systematic differences in the high ACT range and contributes to intermethod differences that are limitations worthy of consideration when contemplating a change in ACT methods.
Accuracy of Two Progesterone Immunoassays for Monitoring In Vitro Fertilization
Authors: Roper Stephen M , Rubin Jessica R , Ali Mahesheema , Gibbons William E , Zarutskie Paul W , Devaraj Sridevi 
Published: July 2018

Abstract

Background
Progesterone concentrations are routinely monitored during in vitro fertilization cycles. Immunoassay-based platforms are used most often in this setting because they are simple to use and amenable to same-day sample collection and result-reporting. However, immunoassay methods are subject to variation in specificity between different assay manufacturers. In this study, a set of unexpectedly high progesterone concentrations led to a method comparison between two in-house immunoassay platforms relative to the reference method.

Methods
Progesterone was measured in 28 serum samples from women undergoing IVF cycles using the Siemens ADVIA Centaur Immunoassay system and the Abbott Architect i1000SR analyzer. A subset of these samples was selected for progesterone measurement by liquid chromatography–tandem mass spectrometry to define the accuracy of each immunoassay.

Results
The Siemens ADVIA Centaur immunoassay system overestimated progesterone concentrations by 19% and the Abbott Architect overestimated progesterone concentrations by 5%.

Conclusions
The Abbott Architect progesterone immunoassay provides a more accurate measurement of serum progesterone than the Centaur immunoassay at concentrations relevant for monitoring in vitro fertilization populations.
Transplant Virus Detection Using Multiplex Targeted Sequencing
Authors: Tan Susanna K , Shen Peidong , Lefterova Martina I , Sahoo Malaya K , Fung Eula , Odegaard Justin I , Davis Ronald W , Pinsky Benjamin A , Scharfe Curt 
Published: July 2018

Abstract

Background
Viral infections are a major cause of complications and death in solid organ and hematopoietic cell transplantation.

Methods
We developed a multiplex viral sequencing assay (mVseq) to simultaneously detect 20 transplant-relevant DNA viruses from small clinical samples. The assay uses a single-tube multiplex PCR to amplify highly conserved virus genomic regions without the need for previous virus enrichment or host nucleic acid subtraction. Multiplex sample sequencing was performed using Illumina MiSeq, and reads were aligned to a database of target sequences. Analytical and clinical performance was evaluated using reference viruses spiked into human plasma, as well as patient plasma and nonplasma samples, including bronchoalveolar lavage fluid, cerebrospinal fluid, urine, and tissue from immunocompromised transplant recipients.

Results
For the virus spike-in samples, mVseq's analytical sensitivity and dynamic range were similar to quantitative PCR (qPCR). In clinical specimens, mVseq showed substantial agreement with single-target qPCR (92%; κ statistic, 0.77; 259 of 282 viral tests); however, clinical sensitivity was reduced (81%), ranging from 62% to 100% for specific viruses. In 12 of the 47 patients tested, mVseq identified previously unknown BK virus, human herpesvirus-7, and Epstein–Barr virus infections that were confirmed by qPCR.

Conclusions
Our results reveal factors that can influence clinical sensitivity, such as high levels of host DNA background and loss of detection in coinfections when 1 virus was at much higher concentration than the others. The mVseq assay is flexible and scalable to incorporate RNA viruses, emerging viruses of interest, and other pathogens important in transplant recipients.
Improved Clinical Sensitivity of a Reflexive Algorithm to Minimize False-Negative Test Results by a Urine Benzodiazepine Immunoassay Screen
Authors: Mullins Garrett R , Reeves Amanda , Yu Min , Goldberger Bruce A , Bazydlo Lindsay A L 
Published: July 2018

Abstract

Background
Urine drug testing is an essential component of treating patients for chronic pain and/or anxiety and is used to monitor compliance during treatment. A common algorithm is to use an immunoassay as a urine drug screen (UDS), followed by mass spectrometry to confirm all presumptive positive samples. Many UDSs, however, have significant limitations, and false-negative test results can be common due to lack of antibody specificity.

Methods
Urine samples were screened by a benzodiazepine immunoassay followed by confirmatory testing using LC-MS/MS to determine an initial false-negative test rate for the screen. Attempts to improve the false-negative test rate included hydrolysis before screening and optimization of the absorbance cutoff required for a positive result.

Results
Hydrolysis corrected 41% of false-negative test results in samples containing parent benzodiazepines and/or metabolites but had no effect on samples containing only clonazepam. Of the confirmed false-negative test results, 85% (17 of 20) demonstrated absorbance values between 20 and 100, with 100 being the cutoff for a positive result. Implementing an optimized absorbance cutoff of 20, rather than 100, for a reflexive confirmation testing algorithm decreases the false-negative test rate of detecting benzodiazepine from 47% to 2%.

Conclusions
Hydrolyzing samples before the benzodiazepine screen provided a modest improvement in the false-negative test rate; however, the screen still missed samples containing clonazepam. Optimization of the absorbance cutoff to reflex samples to LC-MS/MS markedly improved the false-negative test rate for all benzodiazepines.
Sample Type and Storage Conditions Affect Calprotectin Measurements in Blood
Authors: Pedersen Lise , Birkemose Erling , Gils Charlotte , Safi Sara , Nybo Mads 
Published: July 2018

Abstract

Background
Calprotectin, a complex of calcium-binding proteins, is abundant in granulocytes. Increased levels of plasma calprotectin have been found in patients with inflammatory and autoimmune diseases. However, a number of preanalytical factors may affect calprotectin measurement in blood samples.

Methods
Twelve blood samples [4 tubes, 1 each of lithium-heparin (Li-heparin), EDTA, and serum] were drawn from each of 14 healthy individuals. To evaluate the effect of temperature and storage time in the lag time between collection and centrifugation, samples were kept for 2 h at 4 °C, 20 °C, or 37 °C, before centrifugation. Leukocyte, neutrophil, and monocyte counts were measured in EDTA samples on a Sysmex XN-10 hematology analyzer to investigate the relationship between calprotectin concentrations and the granulocyte count.

Results
Calprotectin measurements in EDTA samples were not influenced by temperature or time lag between collection and analysis. Compared to EDTA plasma, significantly higher calprotectin concentrations were found in serum and Li-heparin plasma samples. Furthermore, calprotectin concentrations increased in serum and Li-heparin samples when stored at higher temperatures. There was a linear relationship between the serum calprotectin concentration and neutrophil count in EDTA whole blood.

Conclusions
EDTA is the most suitable anticoagulant for determination of calprotectin in plasma, as this sample matrix does not seem to be affected by temperature or time between sample collection and analysis. Of particular note, neutrophil activation by either clotting or centrifugation should be avoided during the preanalytical process.
Interpretation of Pain Management Testing Results Using Case Examples
Authors: Sobolesky Philip M , Smith Breland E , Pesce Amadeo J , Fitzgerald Robert L 
Published: July 2018

Abstract

Background
Because of the increasing volume of opiate-related overdoses, clinical testing of urine for drugs and related compounds in pain management clinics has become increasingly important. Interpreting findings of drugs present in urine specimens requires knowledge of pharmacokinetics, metabolism, drug purity, and cutoff concentrations used to report a positive result.

Content
This case-based mini-review provides examples of how to interpret immunoassay and quantitative confirmatory urine drug-testing results. Particular emphasis is placed on interpretation of opiate and benzodiazepine results, as these drugs have complicated metabolic profiles.

Summary
Both determining patient medication compliance and identifying the presence of additional drugs provides important information to the treating physician involved in managing pain. Mass spectrometry-based methods are required to identify specific drugs present and can provide important quantitative data for interpreting opiate medication compliance.
Adjusted Plasma Chloride and Bicarbonate Concentrations: An Approach to Identifying Acid–Base Disorders
Authors: Feldman Mark , Dickson Beverly 
Published: July 2018

Abstract

Background
Chloride disorders (hypochloremia, hyperchloremia) and bicarbonate disorders (hypobicarbonatemia, hyperbicarbonatemia) are common in clinical medicine and indicate metabolic and/or respiratory acid–base disorders. The normally inverse relationship between chloride and bicarbonate concentrations in the blood is altered, however, by changes in fluid balance, i.e., water excess or deficit, with resulting changes in sodium and other electrolyte concentrations and by anion gap metabolic acidosis, which lowers bicarbonate concentrations but not the chloride concentrations.

Methods
We used formulas derived over a decade ago that utilize dry slide laboratory technology to adjust plasma chloride and bicarbonate concentrations for changes in water balance, as reflected in changes in plasma sodium concentrations and in the plasma anion gap. We then prospectively validated these formulas in 736 consecutive adults, 499 having abnormal basic metabolic panel results and 237 having normal panel results, using modern wet laboratory technology.

Results
Plasma chloride and bicarbonate concentrations were inversely correlated (2-tailed P-value &lt;0.0001), but the correlations were only modest (Spearman r: −0.48 for the abnormal group and −0.41 for the normal group). After adjusting the plasma chloride and bicarbonate concentrations using the 2 prior formulas, the inverse correlations were very high, with Spearman r: −0.998 for the abnormal group and −0.999 for the normal group.

Conclusions
Adjusting plasma chloride and bicarbonate concentrations for any water imbalance and anion gap alterations leads to very high inverse correlations between these 2 anions, allowing accurate assessment of either subtle or overt acid–base disorders.
Development of a Novel Homogeneous Assay for Remnant Lipoprotein Particle Cholesterol
Authors: Hirao Yuhko , Nakajima Katsuyuki , Machida Tetsuo , Murakami Masami , Ito Yasuki 
Published: July 2018

Abstract

Background
Quantification of remnant lipoprotein particle cholesterol (RLP-C) by automated assay is useful in routine clinical laboratories to assess coronary artery disease risk and diagnose type III hyperlipoproteinemia.

Methods
Enzymes and surfactants were screened to establish a homogeneous RLP-C assay using the chylomicron-VLDL, LDL, and HDL fractions isolated by ultracentrifugation, along with the RLP fraction isolated by immunoaffinity gel. All data were generated using a Hitachi analyzer.

Results
A specific cholesterol esterase with a polyoxyethelene styrenated phenyl ether derivative (surfactant) was used for the establishment of a homogeneous RLP-C assay. This cholesterol esterase with subunits of &gt;40 kDa (H-CE) was found to react with lipoproteins other than RLP, whereas this enzyme with subunits of &lt;40 kDa (L-CE) reacted with RLP. H-CE was applied for the first reaction step with the specific surfactant to decompose non-RLP lipoproteins, degrading non-RLP cholesterol into water and oxygen in the presence of cholesterol oxidase and catalase. For the second step, L-CE was applied to release cholesterol from RLP, and then the released RLP-C was determined in a standard cholesterol oxidase and peroxidase system. This new homogeneous assay exhibited good correlation with the RLP-C immunoseparation method.

Conclusions
We established a simple, rapid, automated homogeneous assay for RLP-C. The assay can determine RLP-C levels in 10 min in a fully automated manner, processing a large number of samples in routine clinical laboratories.
The Becton Dickinson Barricor Tube Does Not Introduce Isobaric Interferences in Mass Spectrometry-based Measurements of Testosterone
Authors: Mazur Chase , Hayden Joshua 
Published: July 2018

Abstract

Background
Testosterone analysis by mass spectrometry is essential for accurate low-level results. Unfortunately, the commonly used gel-based separator tubes introduce an intense, isobaric interference that can coelute with testosterone and impede analysis. The new Becton Dickinson (BD) BarricorTM tube (BT) uses an elastomer separator that might not introduce such interferences.

Methods
Testosterone concentrations and chromatograms were obtained for plasma samples from plasma separator tubes (PSTs) and the new BTs using a laboratory-developed liquid chromatography–tandem mass spectrometry (LC-MS/MS) method.

Results
Intense signals close to the testosterone retention time were observed in the testosterone quantifier transition (289.2→97.0) from the PSTs; resolving these signals required longer chromatographic run times. No isobaric interferences were introduced by the BTs, allowing for shorter chromatographic run times and faster inject-to-inject times.

Conclusion
BTs do not introduce the interferences observed in PSTs in LC-MS/MS testosterone analysis. These tubes can be used as a single tube that both separates cells and is amenable to LC-MS/MS testosterone analysis without additional chromatographic run times.