bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying unnecessary duplicate genetic testing in a large medical center
Authors: Lee Edward , Goldstein D Yitzchak , Naeem Rizwan 
Published: October 2021

Abstract

Introduction
Genetic testing has become ubiquitous in clinical medicine and plays an important role in making diagnoses and guiding treatment plans. Indiscriminate use of these tests can cause duplicate testing, which is typically not indicated because results from repeated constitutional molecular genetic testing should not change over time. Thus, duplicate genetic testing often represents inappropriate test utilization that can contribute an unnecessary burden on the laboratory and health care system.

Objective
The purpose of our study is to determine the incidence of duplicate testing of in-house genetic testing offered at a large medical center, which includes cystic fibrosis, factor V Leiden, prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T, and MTHFR A1298C, and to develop a tool to identify and block duplicate testing.

Methods
We retrospectively analyzed internal laboratory databases of all cystic fibrosis (n = 36164), factor V Leiden (n = 3264), prothrombin G20210A (n = 2890), MTHFR C667T (n = 1451), and MTHFR A1293C (n = 1290) testing performed at the molecular pathology laboratory at a large medical center from either January 2010 or January 2014 to July 2019. We analyzed and cleaned the databases with the R programming language, and we developed a prototype web-based app to proactively identify duplicate test requests with the Shiny R package.

Results
From January 2010 to July 2019, 3535 (9.8%) of the 36164 cystic fibrosis tests performed were duplicate tests for 3257 unique patients. Of these duplicate cystic fibrosis tests, 2997 were repeated once in the same patient, 244 were repeated twice in the same patient, 14 were repeated three times in the same patient, and 2 were repeated four times in the same patient. From January 2014 to July 2019, 99 (3.0%) of the 3264 factor V Leiden tests, 86 (3.0%) of the 2890 prothrombin G20210A tests, 49 (3.4%) of the 1451 MTHFR C667T, and 46 (3.6%) of the 1290 MTHFR A1298C tests performed were duplicate tests.
We developed a proof-of-concept Shiny web-browser app that provides a user-friendly interface to determine if a patient has been previously tested in the molecular pathology lab. This app operates locally on a laboratory computer and uses spreadsheets automatically exported from the electronic medical record. These features allow for the app to be deployed quickly without needing to be integrated into the electronic medical record.

Conclusions
The results of this study indicate that unnecessary duplicate testing represents a small but significant proportion of genetic testing performed by the molecular pathology laboratory. Duplicate testing occurred more frequently with cystic fibrosis testing, which reflects its high volume at the medical center. Deployment of web-based apps using Shiny can provide straightforward and efficient tools for reducing duplicate tests.
Evaluating the reference range of a new high-sensitivity troponin assay using retrospective review of laboratory data
Authors: Reinhart Alexandria , Mathias Patrick , Hoofnagle Andrew 
Published: October 2021

Abstract
Rapid diagnosis of myocardial infarction (MI) in the emergency department (ED) is critical for proper patient management and optimal patient outcomes. High-sensitivity plasma troponin assays may help identify cardiac injury sooner by having better analytical sensitivity. When our institution first adopted the Beckman-Coulter high-sensitivity troponin I assay (hsTnI), cardiologists were hesitant to use the upper reference limit (URL) provided by the manufacturer (&lt; 0.0136 ng/mL for female patients, &lt; 0.0198 ng/mL for male patients), due to concerns regarding assay specificity at the URL. To help transition to the new high-sensitivity assay and its potential benefits, we began using the new hsTnI assay, but maintained the URL of the previous automated immunoassay, which was based on the 99th percentile of a healthy population (&lt; 0.04 ng/mL = negative; 0.04 - 0.4 ng/mL = suspected MI, above the 99th percentile; &gt; 0.4 ng/mL = likely MI). The purpose of the current study was to assess the suitability of the manufacturer’s URL for the new hsTnI assay for our health system’s patient population. To do this, we extracted patient encounter ICD-10 diagnosis codes, diagnosis-related groups (DRGs), and hsTnI results from our institution’s enterprise data warehouse and the laboratory information system for patients seen between Jan 2, 2020 and Aug 31, 2020. We included all patients who presented to the ED and received hsTnI testing. Each patient encounter was subsequently categorized as having MI or no-MI, based on diagnosis codes and DRGs. The first troponin test for each encounter was selected for analysis. The URL recommended by the manufacturer identified 92% and 100% of female and male patients with MI, respectively. Furthermore, 5.1% of 1947 female patients without MI and 9.9% of 1976 male patients without MI were above the manufacturer’s URL (female = 0.0136 ng/mL; male = 0.0198 mg/mL) but below 0.04 ng/mL. These results are lower than the false-positive rate of 12% observed in a separate study cited by the assay manufacturer. These data suggest that the manufacturer’s range is applicable to our patient population.
Why get tested? Linking Intentions for Seeking SARS-CoV-2 Testing with RT-PCR Results and Cycle Threshold Values at Community Testing Sites
Authors: Laitman Andrew , Greninger Alex , Mathias Patrick , Hoffman Noah 
Published: October 2021

Abstract
During the SARS-CoV-2 pandemic, community-based testing sites have provided free COVID testing to millions of people who would have otherwise faced substantial barriers. In one metropolitan area, over 700,000 tests were performed from September 2020 through February 2021. To make appointments online, people not only provided basic demographic information such as age, gender, and address but also free-text reasons for seeking testing. We sought to examine how reason for testing, coded as free text, in combination with other collected demographic information, correlated with rates of SARS-CoV-2 positivity and measures of infectiousness such as the Real-Time Polymerase Chain Reaction (RT-PCR) Cycle Threshold (Ct) value. Data from the scheduling software used to coordinate the on site testing workflow was extracted and linked to SARS-CoV-2 PCR assay metadata stored in a laboratory data warehouse, including Ct values. We categorized individual text responses into 3 separate categories: symptomatic, exposed but asymptomatic, and asymptomatic without exposure. Symptomatic individuals were identified based on the presence of common keywords and phrases like “symptom”, “fever”, “cough”, and “sore throat.” Similarly, exposed individuals were identified by keywords such as “exposed”, “exposure”, and “roommate.” All others were categorized as asymptomatic. We found that symptomatic individuals had the highest frequency of testing positive at 11.6% (21,150/181,868). Exposed individuals and asymptomatic individuals had lower rates of detection with frequencies of 7.4% (10,266/138,721) and 4.9% (8,987/185,026) respectively. Repeat testing represented 29.9% of the results and positivity rates were calculated using the first result for each individual. In addition, among those who tested positive, symptomatic individuals exhibited the lowest average Ct values, while those who are asymptomatic exhibit the highest average Ct values. Among those who self-reported duration of symptoms, recent onset of symptoms was strongly correlated with lower Ct values. Across more than 700,000 results, self-reported symptomatic people, based on free text responses, have a higher likelihood of testing positive for SARS-CoV-2. People who claim a more recent onset of symptoms are more likely to exhibit higher concentrations of viral RNA.
Comparative Evaluation of Three Serologic Assays for the Identification of SARS-CoV-2 Antibodies
Authors: Hogan Keenan , Klippel Dave , Plapp Fred , Liesman Rachael 
Published: October 2021

Abstract
Serologic assays for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies continue to be developed and approved rapidly with limited external validation. Accurate diagnostics are an essential component of pandemic management and public health. Residual serum samples (N=113) from patients who were evaluated for SARS-CoV-2 infection status by polymerase chain reaction (PCR) were retrospectively tested in parallel across three automated SARS-CoV-2 serologic assays: Liaison SARS-CoV-2 S1/S2 IgG, Elecsys anti-SARS-CoV-2 total antibody, and Access SARS-CoV-2 IgG. Testing of 51 PCR-positive and 62 PCR-negative patients demonstrated qualitative inter-test agreement of 96% overall, 100% in PCR-negative patients, 88% in early positive samples (0-13 days post positive PCR), and 100% in convalescent samples (14+ days post positive PCR). Calculated kappa values for paired inter-test agreement ranged 0.93-0.96. Compared to PCR, overall percent positive agreement ranged from 82-86% (100% for convalescent samples) and percent negative agreement was 100% for each assay. This study demonstrates high diagnostic accuracy and inter-test agreement for three automated SARS-CoV-2 serologic assays. External validation of serologic assays is critical to ensure diagnostic accuracy and appropriate utilization of critical resources.
A rare autopsy case of pentalogy of Cantrell with tetralogy of Fallot and olfactory bulb agenesis
Authors: Akinsanya A O , Inman A 
Published: October 2021

Abstract

Introduction/Objective
Pentalogy of Cantrell is an uncommon congenital disorder characterized by sternal, diaphragmatic, pericardial, intracardiac and supraumbilical abdominal or chest wall defects. It is usually associated with other abnormalities and thus poses a therapeutic challenge, with a high mortality rate despite early diagnosis.

Methods/Case Report
This is an autopsy case of a 1 day old, former 37-week-old male infant with a prenatal diagnosis of incomplete pentalogy of Cantrell including omphalocele, ectopia cordis, pleural effusions, cardiac anomalies and polyhydramnios who was delivered via elective cesarean section. Maternal history included tobacco use during pregnancy, multiple psychiatric disorders, and a family history of an unbalanced translocation. The infant required intubation, ventilation, and chest tube insertion at birth due to respiratory distress. He also developed pneumoperitoneum which had to be decompressed. Within 24 hours the infant passed, despite advanced care. On autopsy, external examination showed central and peripheral cyanosis and a large omphalocele containing the heart, parts of the liver and intestines. Initial internal examination revealed a hypoplastic left lung, anterior diaphragmatic defect and absence of the pericardium. Organ dissection post-fixation showed an overriding aorta, pulmonic stenosis, subaortic valve ventricular septal defect and right ventricular hypertrophy, all components of tetralogy of Fallot. On brain examination, the olfactory groove and bulb were both absent. Examination of the placenta and 3 vessel cord revealed no abnormalities. Chromosomal microarray analysis on cord blood was normal.

Conclusion
The spectrum of defects seen in this disease complex has been postulated to be due to failure of differentiation or migration of mesenchymal structures during embryonic development but ultimately, this entity is not well understood. Identifying various disease associations through autopsies can help to establish possible etiologies, and options for therapeutic interventions or screening.
Postmortem Findings in Patients with COVID19 Using Multiple Organ Core Needle Biopsies
Authors: Harb Z F , Mueller J , Khan A , Ravikumar N , Tidswell M 
Published: October 2021

Abstract

Introduction/Objective
The coronavirus disease 2019 (COVID19) pandemic had caused more than 500,000 deaths in the United States. Although it mainly manifests with respiratory symptoms, postmortem examination reveals that it is more of a systemic disease affecting mutliple body organs.

Methods/Case Report
Postmortem needle core biopsies from multiple organs were obtained from 9 patients who died at our institution in the months of April and May of 2020 due to a confirmed SARS-CoV-2 infection by RT-PCR testing of nasopharyngeal swabs. The core biopsies from body organs included lungs (8), liver (7), kidneys (5), heart (2), spleen (2), and brain (2). Histopathological examination was performed in conjunction with a set of special and immunohistochemical stains. Electron microscopy examination was also done in 4 cases.

Results (if a Case Study enter NA)
The cohort consisted of 6 males and 3 females with a mean age of 70.4 years (range: 68–79). The majority had comorbidities (8/9) and presented with respiratory symptoms (9/9). The most significant postmortem findings were mainly in the lungs, including alveolar hemorrhage, hyaline membranes, fibrin thrombi, intraalveolar macrophages, type-2 pneumocyte hyperplasia, and interstitial myofibroblast reaction and collagen deposition. Immunohistochemical stains showed predominance of T-lymphocytes with a mixture of CD4 and CD8 positive cells. Examination of liver showed minimal to marked microvesicular and macrovesicular steatosis and centrilobular congestion and necrosis. Tissue from kidneys revealed mild to severe acute tubular injury. Microglial activation and Alzheimer type-II astrocytosis were noted in brain, and mild white pulp depletion was seen in the spleen. Electron microscopy showed the presence of foreign bodies suspicious for viral particles ranging in size from 52.6 to 97.9 nm in 2/4 cases.

Conclusion
Our findings based on postmortem core needle biopsies confirm the observation that most severely affected patients have significant pulmonary pathology. However, other organs show findings that may lead to a better understanding of this disease. Postmortem examination will continue to be an invaluable tool for studying the pathologic manifestations of COVID-19.
To evaluate if ultrasound gel or water-based media affects ER/PR staining patterns on breast core biopsy specimens
Authors: Chng J K , Mihir G , Lee Y , Tan C , Mansor S 
Published: October 2021

Abstract

Introduction/Objective
IHC staining for biomarkers ER, PR and HER-2 (CerB2) forms an essential component of breast cancer management and prognostication. Staining for these biomarkers is dependent on optimal fixation of the specimen in formalin. Scoring systems employed for ER and PR grade the intensity of the nuclear staining along with the percentage of the cells stained. This study aims to determine if ultrasound gel used during core biopsy as opposed to water affects immunohistochemical staining of biomarkers ER and PR in breast cancer specimens, following an observation that ultrasound gel assisted core biopsies may affect ER/PR nuclear staining scores through excess cytoplasmic staining.

Methods/Case Report
We included a total of 50 cases of invasive breast carcinoma diagnosed on core biopsy from KK Women’s and Children’s Hospital from February 2019 to July 2020. These included 25 cases with gel and 25 cases with water applied to the breast prior to the procedure. All biopsies were optimally fixed in formalin as per recommended latest ASCO/CAP guidelines. The control group included 25 resection cases of invasive breast carcinoma which had neither gel nor water and had been optimally fixed in formalin. Cytoplasmic staining for ER and PR was graded as being present or absent and was compared against the excision specimens (control group) to determine if using the gel was significant in producing cytoplasmic staining. The data was analyzed on SPSS using multiple logistic regression.

Results (if a Case Study enter NA)
Using the gel appeared to be statistically significant in producing cytoplasmic staining for ER (p=0.042) as opposed to using water (p=0.274). For PR staining, both gel-based (p=0.250) and water-based media (p=0.286) were not statistically significant in causing cytoplasmic staining.

Conclusion
The preliminary findings of this small retrospective case-control study gives an insight that gel-based media may have a role in causing cytoplasmic staining for oestrogen receptor in breast cancer biopsy specimens which may interfere with accurate scoring and impact results of external quality assurance schemes to which laboratories subscribe to. However the study is limited by the small sample size and exclusion of any other pre- analytical factors like needle bore or number of cores taken which may have had an impact on the staining.
Analytical and Clinical Performance Evaluation of ARK Fentanyl II Assay on Beckman Coulter AU System
Authors: Larsen N , Smothers C , Martin D , Moore A , Lima J , Cao L 
Published: October 2021

Abstract

Introduction/Objective
Drugs of abuse, specifically opioids, have been in recent years an important focus in both medicine and media due to the ‘opioid epidemic’ and large numbers of overdose deaths. Synthetic opioids such as fentanyl have contributed to this epidemic. The CDC reports that of roughly 50,000 opioid overdose deaths in 2019, nearly 73% were due to synthetic opioids. The objective of this study is to assess the analytical and clinical performance of the Fentanyl II Assay by ARK Diagnostics, Inc.

Methods/Case Report
Fentanyl was qualitatively determined by the ARK Fentanyl II Assay, a homogenous enzyme immunoassay based on competition between drug in the specimen and drug labeled with recombinant glucose-6- phosphate dehydrogenase (rG6PDH) for antibody binding sites. The presence of drug in urine increases enzyme activity, which converts nicotinamide adenine dinucleotide (NAD) to NADH in the presence of glucose-6-phosphate, resulting in an absorbance change measured by spectrophotometry. The evaluation was performed following CLSI guidelines. The analytical performance was evaluated for accuracy and precision.

Results (if a Case Study enter NA)
To evaluate the accuracy, twelve positive and eight negative specimens were tested by the ARK immunoassay performed on two Beckman Coulter instruments (AU480 and AU680) and by LC- MS/MS. The results from both instruments showed 100% agreement with the results from LC-MS/MS. On instrument AU480, the within-run CVs were 18.0% at the level of 22.510 ng/mL and 0.8% at the level of 552.628 ng/mL. The between-run CVs were 8.8% at the level of 68.928 ng/mL and 3.7% at the level of 158.947 ng/mL. On instrument AU680, the within-run CVs were 273.4% at the level of 1.052 ng/mL and 0.8% at the level of 523.788 ng/mL. The between-run CVs were 7.8% at the level of 53.779 ng/mL and 3.1% at the level of 145.263 ng/mL. In May 2021, 2,075 fentanyl assays were run at UAB. Of those, 476 returned a positive result with a positive rate of 22.9%, and 1,599 were negative with a negative rate of 77.1%. One positive result was confirmed by LC-MS/MS as negative for fentanyl but positive for norfentanyl, a metabolite of fentanyl. The clinical specificity was 99.9% and sensitivity was 100%.

Conclusion
In Conclusion, the ARK fentanyl Assay II on Beckman Coulter AU system has good accuracy, sensitivity and specificity. The precision at medium and high levels are good. However, the precision at low level needs to be improved.
Difference in hemoglobin %A2 between homozygous hemoglobin A and hemoglobin S-trait patients as measured by capillary electrophoresis
Authors: Tucker C M , Stickle D 
Published: October 2021

Abstract

Introduction/Objective
Quantitation by high-performance liquid chromatography (HPLC) of hemoglobin %A2 is often not used in evaluation for thalassemia of hemoglobin S-trait patients, due to analytical interference from glycated hemoglobin S1d to increase %A2. In contrast, an increase in %A2 for S-trait when measured by capillary electrophoresis (CE) has been reported, without known analytical interference. This observation has not been re- evaluated in modern versions of CE, however. For validation exercises associated with startup of CE at our institution, we compared distributions of %A2 among A patients and S-trait patients using Sebia “Capillarys® 2” CE.

Methods/Case Report
%A2 is provided in two Sebia “Capillarys® 2” methods: analysis of A1c (method 1, M1) and analysis of hemoglobin variants (method 2, M2). To minimize effect of potential preselection for thalassemia among M2 samples, we first evaluated distributions of %A2 for A and S-trait among M1 samples. We then evaluated correlation of A2 measurements between M1 and M2. Statistical analyses were conducted using R programming.

Results (if a Case Study enter NA)
Using M1, %A2 for S-trait patients (2.61±0.31%, n=116) was higher than for A patients (2.11±0.27%, n=108) (p&lt;0.001), with difference=0.42-0.57 %A2 (95% confidence interval, CI). %A2 by M1 was consistently less than %A2 by M2, for both A and S-trait (p&gt;0.25): for A, M1/M2=0.89±0.05 (n=35); for S-trait, M1/M2=0.88±0.05 (n=32). Decreased %A2 by M1 compared to M2 may in part be due to separation in M1 of a glycated form of A2. Using M2, %A2 for S-trait patients (3.05±0.29%, n=32) was higher than for A patients (2.41±0.29%, n=35) (p&lt;0.001), with difference=0.50-0.76 %A2 (CI). M2 results were consistent with M1 data when combined with the observed M1/M2 ratios.

Conclusion
Results suggest a physiological increase in %A2 in S-trait patients compared to A patients, not likely to be attributable to thalassemia. The average increase is ~0.6 %A2 for hemoglobin variant analysis by CE.
The Diagnostic Predictive Value of Aspartate Aminotransferase/Platelet Ratio Index (APRI) in Assessing the Disease Severity of Filipino Dengue Patients in Pampanga, Philippines: A Multicenter Study
Authors: Serrano S S , Yambao D C , Sarile C M , Torres P B , Tranquilino A M , Umali M T , Umipig J C , Sison R G , Nieto X A 
Published: October 2021

Abstract

Introduction/Objective
Lack of good predictive biomarkers tied with its widely varying clinical manifestation make DENV infection a major public health concern especially in developing countries like the Philippines. Liver involvement is found to be a common manifestation among severe dengue patients hence enzymes such as aspartate aminotransferase (AST) is used in determining dengue severity. This study aims to evaluate the predictive value of AST/platelet ratio index (APRI) in assessing disease severity among Filipino dengue patients upon admission.

Methods/Case Report
Clinical data of 16 dengue patients from two hospitals in Pampanga were analyzed retrospectively. Results for NS1 antigen test, CBC, and AST along with signs and symptoms of patients upon admission were reviewed. ANCOVA was used to compare AST and APRI between the groups while ROC regression and Youden’s index were utilized in identifying severe dengue using AST and APRI.

Results (if a Case Study enter NA)
Among the 16 patients, 10 were male and 6 were females with a mean age of 17.9 years (range, 6 to 34). There was no evidence that AST (p=0.223) significantly differed between severe and non- severe dengue, with a mean of 131.0±24.5 and 78.5±24.5, respectively. Calculated APRI scores (p=0.604) did not show significant difference between SD and NSD, with a mean of 3.8± 4.1 and 3.7±4.1, respectively. The obtained AST cutoff for SD was 119 U/L; while the APRI cutoff for SD is 4.03. However, considering the age of patients as covariate, both AST [AUC = 0.55 (95% CI: 0.15 to 0.86)] and APRI [AUC = 0.69 (95% CI: 0.27 to 1.00)] was not able to differentiate patients with SD and NSD.

Conclusion
The parameters AST and APRI were not able to differentiate and predict severity between SD and NSD. A larger cohort with a more specific age group, and collection of samples throughout the course of illness are needed to further substantiate the results.