bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Center-Wide Study of D-Dimer Testing for Pulmonary Embolism in the ED Setting
Authors: Balakrishnan Ridin , Hu Shaomin , Gil Morayma Reyes 
Published: September 2019

Abstract
Pulmonary embolism (PE) is a life-threatening condition associated with a very high mortality. While its diagnosis remains challenging, the use of diagnostic tests has increased tremendously. There are many different guidelines used to work up suspected PE. The Wells and/or Geneva scores are used to estimate the pretest probability (PTP) of PE before any complementary testing is done. While a CT pulmonary angiography (CTPA) should not be performed in individuals with a low/intermediate PTP and a negative D-dimer (DD), some data suggest that up to 55% of patients with low PTP undergo a CTPA, even though they might not have had a DD or had a negative DD. As such, in this study, we wanted to evaluate the use of DD in our emergency department (ED). A pilot study was conducted using an interactive software developed in-house for the evaluation of health care quality, efficiency, and effectiveness. The EMR database (EPIC) we use consists of laboratory, clinical, pathological, and radiological reports, allowing us to use different search criteria and to outline cutoff values for continuous and categorical variables while permitting us to define a timeframe for the different observations. We looked at all ED visits in the period from 2014 to 2018 in which CTPAs were done for suspected PE. A total of 8,873 ED visits from 2014 to 2018 had a CTPA done for suspected PE. Of these, 6,117 cases had no DD done and 1,812 had a DD done along with CTPA. The high percent of visits with imaging done without a DD (69%) is justified if these are all cases with a high PTP (DD not indicated). If this assumption was true, then we expected a high percent of positive confirmation of PE by imaging. However, only 11% of these cases showed positive findings of PE. This rate is similar to published studies in many US hospitals that demonstrate overuse of CT owing to a lack of using the PTP-based approach. On the other hand, a vast majority of cases in our study with normal DD (<0.5 μg/L) had negative CT results (98%). Interestingly, all four cases that had positive PE findings by CT despite a negative DD (2%) were women (three below the age of 62 with chronic and/or subsegmental PE and one 47-year-old with a DD = 0.49 μg/L). This finding calls for consideration of age and possibly gender-based DD reference ranges. Lastly, while CTPA is considered the gold standard for PE diagnosis, it has limitations: cost, increased length of stay, unnecessary exposure of radiation, contrast, and unnecessary treatment of subsegmental PE. Therefore, an approach using PTP and using DD appropriately is warranted in order to prevent patients from being exposed to unnecessary risks and also to reduce costs.
Effects of Biotin Supplements Ingestion on Beckman Biotinylated Immunoassays
Authors: Cao Liyun , Scott Donna , Hardy Robert 
Published: September 2019

Abstract

Background
Biotin is a water-soluble B vitamin with high affinity for streptavidin binding. The biotin-streptavidin amplification strategy is widely used to increase the analytical sensitivity of clinical laboratory tests, which are also vulnerable to biotin interference. The aim of this study is to evaluate the effects of the orally taken biotin supplements on Beckman biotinylated immunoassays.

Methods
Twelve volunteers were recruited to ingest a single dose of 10 mg biotin after fasting of multivitamin supplements for 3 days. Blood samples were collected at 0, 0.5, 1, 2, and 4 hours postingestion. Eleven biotinylated and nonbiotinylated immunoassays were performed on Beckman DXI and on Abbott Architect as a comparison.

Results
Ingestion of a single dose of 10 mg biotin caused falsely high values in biotinylated competitive immunoassays such as free triiodothyronine (fT3), total T3 (TT3), and free thyroxine (fT4) assays and falsely low values in biotinylated sandwich immunoassays such as thyroglobulin (Tg) and GI 19-9. The interference started at 0.5 hour postingestion, peaked at 1 hour postingestion, and continued at 4 hours postingestion. The extent of interference is different among these analytes. TT3 showed a maximum of a 219% increase of concentration, while GI 19-9 showed a maximum of a 25% decrease of concentration. fT3, fT4, and Tg showed intermediate changes of concentrations. The interference was not seen in nonbiotinylated immunoassays performed on Beckman DXI or Abbott Architect.

Conclusions
Single dose of biotin ingestion at the dosage of over-the-counter supplements can induce significant interference in certain biotinylated immunoassays and lead to incorrect test results.
A Laboratory Investigation in Response to Clinical Concern Regarding Heparin-PF4 ELISA Accuracy
Authors: Carll Timothy , Wool Geoffrey 
Published: September 2019

Abstract
Heparin-induced thrombocytopenia (HIT) is an immune-mediated disease that confers increased risk of thromboembolism to some patients receiving heparin. Usual evaluation of HIT entails a combination of clinical assessment (“4T” score), screening assay for anti-PF4 antibodies, and confirmatory functional assays, most commonly 14C-serotonin release assays (SRAs). At this academic medical center, clinician perception of increasing positivity on the screening ELISA raised concern for testing false positivity or a locoregional increase in HIT incidence. In response, we reviewed all anti-PF4 IgG/A/M ELISA testing for UChicago Medicine patients in a 3.5-year period in order to assess the accuracy of this assay in comparison to gold-standard SRA testing. ELISA results were categorized as negative (<0.400 OD), weakly positive (≥0.400 but <1.000 OD), or strongly positive (≥1.000 OD). During the same interval, all instances of confirmatory testing in a heparin-induced serotonin release system were compiled and scored by result as negative (<20% release difference with low-dose [0.1 U/mL] heparin and no apparent inhibition by high-dose [100 U/mL] heparin), borderline (<20% release difference with low-dose heparin, with 8% or more inhibition by high-dose heparin), and positive (>20% release with low-dose heparin, together with inhibition of release [<20%] with high-dose heparin). Both ELISA and SRA testing were stratified by month of order to highlight temporal trends. In total, 1,657 instances of anti-PF4 ELISA testing were studied, of which 298 were weakly positive and 166 were strongly positive (464 total abnormal ELISA). There were 348 instances of SRA testing, of which 50 were positive and 7 were borderline (57 total abnormal SRA). Of note, there were no instances wherein a negative ELISA test was followed by a borderline or positive SRA test. Over the most recent 4-month interval, a slight increase in the percentage of ELISA positivity was observed. A concordant increase in the number of positive SRA tests was also observed. There was no evidence of an increased rate of discrepancy between the two testing platforms, suggesting that this change does represent a locoregional increase in HIT cases. We took this opportunity to evaluate our ELISA testing sensitivity, specificity, and positive and negative predictive values and found them to be similar to previously published metrics. Given SRA testing as a gold-standard metric, this suggests a local sensitivity and negative predictive value of 100%. As expected, a strongly positive PF4 result was found to be a stronger predictor of a borderline or positive SRA result (39.8% PPV) than was a weakly positive PF4 result (4.5% PPV). As a note of caution, however, one patient had a weakly positive PF4 ELISA result and 100% release on SRA testing.
Metagenomic Characterization of Influenza Virus: Bacteria Super-Infections Associated With Death and Survival
Authors: Klonoski Josh , Williams Matthew , Huber Victor 
Published: September 2019

Abstract
Bacterial super-infections (BSIs) increase morbidity and mortality during influenza epidemics and pandemics, but not all strains of influenza virus uniformly increase host susceptibility to BSIs. Infection of mice with a swine virus isolate, A/swine/Texas/4199-2/98-H3N2 (TX98), did not significantly predispose the host to BSI mortality regardless of whether the BSI was caused by S aureus, S pneumoniae, or S pyogenes. Comparison of this survival phenotype with the laboratory influenza virus strain A/Puerto Rico/3/1934-H1N1, which demonstrates lethal synergism, showed that cellular recruitment profiles and cytokine responses differ between the two viruses in a manner that implicates host responses against the invading virus as a contributor to secondary infection severity. To better understand host, viral, and bacterial responses underlying disparate outcomes, we utilized metagenomic analysis of 559 genes, the NanoString nCounter Immunology Panel-Plus kit and FFPE mouse lungs from a published BSI time course. Results show an overall increased level of gene expression during BSIs associated with survival when compared to peak viral titers. Early viral clearance and the presence of S pyogenes in the lungs of TX98-infected lungs 24 hours after BSI was confirmed. Host responses tied to differences in early viral detection and clearance consisted of RIG-I, OAS, TLR3, TLR8, and TLR9. Key changes were noted in the expression of type I and II interferons, complement proteins, cytokines, chemokines, Fc receptors, scavenger receptors, the immunoproteasome, and genes associated with T, B, Treg, and NK cell activation. Interestingly, there was no significant increase in host antimicrobial peptides during BSIs associated with survival while CAMP and Nos2 were significantly increased 24 hours prior to death in lethal BSIs. To our knowledge, this is the first side-by-side metagenomics study of influenza BSIs associated with death and survival. Results offer mechanistic insight into clinical outcomes.
Assessing Propylene Glycol Interference at Concentrations Relevant to Serum Levels With Electronic Cigarette Use in an Enzymatic Ethylene Glycol Assay
Authors: Calvaresi Emilia , Wyness Sara , Jackson Alexandria , Genzen Jon , Johnson-Davis Kamisha 
Published: September 2019

Abstract

Introduction
Clinical laboratory measurement of ethylene glycol (ETG) by enzymatic methods is known to be subject to interference with high (several hundred milligrams/deciliter) concentrations of propylene glycol (PG). An estimated 10.8 million people in the United States, or almost 1 in 20 Americans, are reported to use electronic cigarettes (e-cigarettes; ie, “vaping”), in which PG is frequently used as a liquid solvent. No published reports exist investigating whether serum concentrations of PG that may be seen with e-cigarette use (generally, concentrations of 10-15 mg/dL in moderate users and up to 30 mg/dL in heavy users) can lead to either interference flags in analytical ETG measurement or falsely positive ethylene glycol concentrations being reported.

Methods
Studies were conducted to assess PG interference on enzymatic ETG measurement. Commercially acquired human AB serum (catalog # 35-060-CI; Corning Life Sciences) was spiked with various amounts of PG (catalog #158720010; Acros Organics/Thermo Fisher Scientific) to achieve both concentrations of PG expected with e-cigarette use (0-30 mg/dL) and supra-physiological concentrations (>30 mg/dL) for comparative purposes. PG-spiked sera were tested using a quantitative enzymatic ETG assay (Quantitative Ethylene Glycol kit, catalog #C504-0A; Catachem) previously validated as a laboratory-developed test on an AU5810 automated chemistry analyzer (Beckman Coulter).

Results
None of the tested PG concentrations designed to mimic physiological levels expected with e-cigarette use (0, 5, 10, 15, 20, 25, and 30 mg/dL) caused falsely positive quantitative ETG results, defined as values above the ETG limit of quantitation (LOQ) of 5 mg/dL. At these low concentrations, interference patterns neither were observed in reaction monitors, nor were instrument interference error flags triggered. As concentrations of PG approached 50 mg/dL, abnormal curve appearances were observed in the instrument reaction monitor, although this neither resulted in interference error flags nor false detection of ETG. However, as PG concentrations approached and exceeded ≥100 mg/dL, both interference flags and falsely positive ETG results were observed.

Conclusion
Results from the present experiments demonstrate that serum concentrations of PG expected with e-cigarette use did not cause interference with enzymatic ethylene glycol detection in this assay.
Automated Calculation of Turnaround Times Using Data Warehouses for Publication in Online Test Menus
Authors: Simonson Paul , Hoffman Noah , Mathias Patrick 
Published: September 2019

Abstract
Awareness of turnaround times (TATs) is important for time-sensitive clinical decision making and setting expectations for timing communications with patients. In fact, a significant number of clinicians consider the TAT as the most important measure of laboratory quality (PMID 24839360). TAT definitions vary considerably, ranging from rough estimates to more precisely defined statistics based on historical data, the former more typically provided in online test catalogs and the latter usually reserved for a limited number of tests for internal quality assurance and improvement. As data warehousing of laboratory information is becoming more commonplace, calculation of TATs can more easily be performed. Our goal in this project was to develop a generalized, automated approach to calculate expected TATs for publication in our online test catalog. We began by defining TAT as the amount of time between receipt of the specimen by the laboratory and the reporting of the finalized result in the laboratory information system (using specimen collection time increased median TATs by 21 minutes). The TAT of an order set/panel of tests was calculated using the time stamp of the last finalized test result of the set. For development purposes, a subset of warehouse data corresponding to all tests within a 1-month period was selected (170,363 accession numbers, 2,206,311 total test results). All accessions with “add-on requests” (tests requested by physicians using specimens collected for prior tests) were removed. The median and 90th percentile TATs were calculated using R for each test and panel, as these values are commonly used in quality assurance programs and are thought to be intuitively easy to understand in a test menu. Values were not reported if fewer than 100 test results were available for a given test. A summary table and TAT distribution graphs are provided for review by laboratory personnel before being published in the online test menu. Categorizing tests ordered “stat” versus “nonstat” generated some interesting insights, the most obvious being that, for the majority of our tests, the difference in median TATs is very small. In some cases, however, the median stat TAT was actually longer (eg, hemoglobin A1C), which might be due to blood draws at irregular hours by phlebotomists, then batching of samples with specimens collected later at regular blood draw times, suggesting that elimination of the stat option was appropriate. Distinct advantages of using data warehouses to calculate TATs include being able to provide clinicians with data-driven estimates of expected lab result TATs. Such data can also be used for internal quality assurance purposes. Areas of further development include developing a more rigorous mathematical theory of the precision associated with our median and 90th percentile TATs and tuning the frequency of data query and TAT recalculation.
Reduction in False-Positive PF4/Heparin Antibody Testing Following Implementation of a Latex Immunoturbidimetric Assay
Authors: Gangahar Chiraag , Webber Daniel , Jackups Ronald 
Published: September 2019

Abstract

Background
Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of exposure to heparin that is caused by autoantibodies against heparin-PF4 complexes. We recently changed our in-house HIT screening platform from a manual, daily batched ELISA (Stago-Asserochrom HPIA Immunoassay) to an automated, on-demand latex immunoturbidimetric assay (LIA, HemosIL HIT-Ab) and have also implemented a reflex from a positive LIA result to the confirmatory serotonin release assay (SRA). We compared the two methods in terms of utilization, test performance, and turnaround time.

Methods
Data were collected retrospectively from a 7-month period before (June-December 2017) and after (June-December 2018) implementation of the HemosIL LIA in the clinical laboratory at a large academic institution. This study includes consecutive test results from adults (median age: 64 years, range: 19-98 years) seen at our 1,300-bed main hospital. Test utilization, turnaround time (sample receipt to verification), and test performance characteristics were compared between the two methods. Repeat testing was excluded from the analysis. Samples with a positive result on the HemosIL LIA were reflexed to a serotonin release assay (SRA), performed at a large reference laboratory, whereas samples tested with the earlier ELISA assay were referred for SRA testing based upon clinical judgment. When performed, SRA was considered the gold standard for diagnosis of HIT.

Results
During the 7 months before and after switching methods, there were 109 of 594 (18.4%) positive ELISA results and 45 of 523 (8.6%) positive LIA results. Only 90 of 109 (82%) of the positive results from the ELISA HIT Ab test were sent out by clinicians for SRA testing, whereas 45 of 45 (100%) of the positive results from LIA testing were reflexed to SRA per protocol. Although fewer LIA tests were sent out for SRA testing, there were an equal number of SRA-confirmed cases of HIT with the ELISA (PPV: 16/90 [17.8%]) and LIA methods (PPV: 16/45 [35.6%]), resulting in a high positive predictive value (PPV) with the newly implemented method. Not only was the PPV higher with the LIA test, but it had a significantly shorter mean turnaround time of 96 minutes compared to the ELISA TAT of 1,234 minutes (P < .0001).

Conclusions
With the new testing protocol, patients received results faster (average 96-minute TAT) and had fewer false-positive results (74/594 pre vs 29/523 post), with no apparent reduction in detection of true-positive cases of HIT (16/594 pre vs 16/523 post).
PT and aPTT Are Not Predictors of Thromboembolic Events
Authors: Shervinrad Mohammadreza , Tormey Christopher , Siddon Alexa 
Published: September 2019

Abstract

Background
VTEs remain a common occurrence in both ambulatory and hospitalized patients, with over 900,000 VTEs in the United States annually, of which almost 300,000 are fatal. Besides the factors of Virchow’s triad (trauma, stasis, and endothelial activation), it has been recognized that intrinsic abnormalities of the clotting cascade may lead to a predisposition to clot. Recently, it has been noted that elevated levels of normal procoagulant factors can predispose to hypercoagulability and have been associated with an increase in VTEs; also, a shortened time in the aPTT test has been associated with an increase in “idiopathic” VTEs.
One of the foremost goals of thrombosis research is to develop simple and inexpensive test systems to estimate the likelihood for a future VTE. A strong association between an increased risk for VTE and a short activated partial thromboplastin time (APTT) was found in several studies.
The aim of our study is to evaluate relationship between shortened PT and aPTT with thrombotic events in broad random population; we conducted a retrospective analysis of aPTT and PT at our institution. Using a computer system, results from our facility’s central laboratory were reviewed for PT and aPTT blood samples that were collected from our hospital and surrounding afﬁliated clinics over a 5-year period. Our population was composed of retired service members and their dependents (ie, spouse and children). The samples included both outpatients and hospitalized patients. A short aPTT and PT was deﬁned as aPTT and PT less than the lower limit of normal in our laboratory.

Results
We reviewed results from 239 activated partial thromboplastin times and prothrombin time during the study period. Nine percent of our patients were female and 91% were male. The means of age, aPTT, PT, and INR of patients were 58.87, 30.79, 10.01, and 0.89, respectively. We did not find any history of thromboembolic events in our patient population with shortened PT and aPTT.

Discussion
Shortened aPTT and PT are more and more being known as a potential risk factors for developing VTEs. Many studies showed shortened aPTT and PT are associated with thromboembolic events. To the best of our knowledge, this is the first study that has shown there is no relationship between shortened aPTT and PT and thromboembolic events.
To evaluate whether a shortened aPTT and PT represent an increased risk of VTEs, we would need to include patient clinical factors. Additionally, evaluating for increased levels of factors II, VIII, IX, XI, and ﬁbrinogen and factor VII would also be worthful since increased levels of any of these can shorten the aPTT and PT. Following a patient population prospectively would enable us to characterize the natural history of patients with shortened aPTT and PT.
Endocervical Adenocarcinoma With Skip Lesion in a Fundal Endometrial Polyp Mimicking Endometrioid Adenocarcinoma Arising From Endometrial Polyp
Authors: Aakash Nfn , Murzabdillaeva Albina , Lin Mei , Zhang Songlin 
Published: September 2019

Abstract
Human papillomavirus–related adenocarcinomas account for approximately 20% of all cervical cancers. Most of them arise in the transformation zone but may be found exclusively in endocervical canal. Contiguous spread into the lower uterine segment is known to occur, but finding a “skip” lesion in a fundal endometrial polyp poses an interesting pathologic conundrum. We present a case of a 57-year-old woman with a history of postcoital bleeding and abnormal cervical smear. Cervical exam showed a 2-cm exophytic mass on anterior cervix. Biopsy revealed invasive endocervical adenocarcinoma. Patient underwent radical hysterectomy. Gross examination revealed large cervical mass without involvement of low uterine segment and a benign-appearing small uterine fundal polyp. Microscopic examination confirmed the deeply invasive endocervical adenocarcinoma, and the benign-appearing endometrial polyp had similar atypical glands on the polyp surface and admixed with benign endometrial glands. Both cervical tumor and the carcinoma involving endometrial polyp demonstrated identical immunohistochemistry showing diffuse positive p16 and CEA(m) and negative for ER and vimentin. The authors report a rare case of endocervical adenocarcinoma with skip lesion in the endometrial fundal polyp, and rare cases with skip lesion in the fallopian tubes from endocervical adenocarcinoma have been reported in the literature. High clinical suspicion and ancillary immunohistochemistry are necessary to differentiate the lesion from endometrioid or papillary carcinoma arising from endometrial polyp.