bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensitivity of Automated Urine Chemstrip Analysis for Detecting Microscopic Abnormalities
Authors: Robertson-Patera Jessica , Nakashima Megan 
Published: September 2019

Abstract

Objectives
Urinalysis (UA) is used to screen for multiple medical abnormalities. Microscopic analysis of urine requires trained morphologists and can be time-consuming; therefore, a reflex strategy where microscopic analysis is only performed when the chemstrip is positive is an attractive strategy. We previously described the retrospective performance of the iChem VELOCITY (Beckman Coulter, CA, USA) and CLINITEK Novus strip cassettes (Siemens, Munich, DE) for detecting microscopic abnormalities. The iRICELL is iQ microscopic and is now paired with the AX-4030 (Arkray, JP). During our validation of the new workcell, we tested the sensitivity and specificity of the chemstrip results for microscopic abnormalities.

Methods
A total of 60 samples were analyzed on both the VELOCITY and AX-4030. Microscopic evaluation was performed by centrifuging the urine and examining by light microscope. Sensitivity and specificity for each chemstrip result were calculated and compared.

Results
Looking at sensitivity of any chemistry abnormality for any microscopic abnormality, the AX-4030 was 90.2% sensitive compared to 80.5% on the VELOCITY. The AX-4030 leukocyte esterase result was slightly less sensitive but more specific than the VELOCITY for presence of leukocytes (94.7% sensitivity and 95.1% specificity compared to 100% sensitivity and 87.8% specificity). The AX-4030 blood results were slightly more sensitive for detection of RBC (77.8% vs 72.2%) and more specific (100% vs 92.9%), perhaps related to the known interference of ascorbic acid with the VELOCITY strips.

Conclusion
Overall, the AX-4030 chemstrip results were more sensitive for microscopic abnormalities than the VELOCITY, although 10% of cases would still be missed. For a general population, a reflex methodology may be adequate. However, in patients with a higher likelihood of microscopic abnormalities, performing routine microscopic analysis may still be prudent.
Discovery of Enteric Pathogens in the Alaskan Subsistence Diet
Authors: Leu-Burke Grace , Beacham Robert , Bennetts Courtney 
Published: September 2019

Abstract

Objectives
Transmission of enteric pathogens from food ingestion is an ongoing public health concern, with commensal bacteria in ruminant animal species causing human disease. Enteric pathogens Salmonella, Shigella, and Shiga toxin producing Escherichia coli (STEC) have been isolated from domesticated animals. However, the Alaskan subsistence diet relies on wild game, such as reindeer, caribou, and moose for their food supply. Research concerning enteric pathogens in wildlife has not established. Therefore, we conducted a pilot survey on moose and reindeer to determine potential enteric pathogen transfer risk.

Methods
Between July 2018 and January 2019, we collected 72 fecal samples from reindeer and moose migrating in Fairbanks, Anchorage, and the Matanuska Valley. Samples were cultured for enteric pathogens, including E coli 0157, using standard clinical microbial process. Phenotypic Shiga toxin production was verified by enzyme immunoassay.

Results
Reindeer were statistically significant for enteric pathogens when compared to moose (P < .05) Eighty percent of the reindeer population were colonized for either Shigella, Yersinia, or Shiga toxin-producing E coli, with 20% positive for multiple pathogens. Non-0157 Shiga toxin production was observed in 30% of reindeer samples, generated by a sorbitol fermenting E coli. In contrast, moose population showed a near absence of enteric pathogens with only 5% positive for Shigella. Salmonella was not identified in either animal.

Conclusion
Reindeer, moose, and caribou meat are prominent in the Alaskan subsistence diet. Although moose had limited enteric pathogen colonization, reindeer were significant for transmission risk, including non-0157 Shiga toxin producing E coli, which has been linked to hemolytic uremic syndrome. Isolation of a non-0157 STEC in wildlife indicates environmental colonization. Because reindeer and caribou are closely linked in diet and migration, Alaska clinical laboratories should screen for enteric pathogens, including non-0157 Shiga toxins.
Reducing Culture Reporting Errors in the Microbiology Laboratory
Authors: Hogan Kathryn , Umar Beena , Alhamar Mohamed , Callahan Kathleen , Samuel Linoj 
Published: September 2019

Abstract

Objectives
There are few papers that characterize types of errors in microbiology laboratories and scant research demonstrating the effects of interventions on microbiology lab errors. This study aims to categorize types of culture reporting errors found in microbiology labs and to document the error rates before and after interventions designed to reduce errors and improve overall laboratory quality.

Methods
To improve documentation of error incidence, a self-reporting system was changed to an automatic reporting system. Errors were categorized into five

types
Gram stain (misinterpretations), identification (incorrect analysis), set up labeling (incorrect patient labels), procedures (not followed), and miscellaneous. Error rates were tracked according to technologist, and technologists were given real-time feedback by a manager. Error rates were also monitored in the daily quality meeting and frequently detected errors were discussed at staff meetings. Technologists attended a year-end review with a manager to improve their performance. To maintain these changes, policies were developed to monitor technologist error rate and to define corrective measures. If a certain number of errors per month was reached, technologists were required to undergo retraining by a manager. If a technologist failed to correct any error according to protocol, they were also potentially subject to corrective measures.

Results
In 2013, we recorded 0.5 errors per 1,000 tests. By 2018, we recorded only 0.1 errors per 1,000 tests, an 80% decrease. The yearly culture volume from 2013 to 2018 increased by 32%, while the yearly error rate went from 0.05% per year to 0.01% per year, a statistically significant decrease (P = .0007).

Conclusion
This study supports the effectiveness of the changes implemented to decrease errors in culture reporting. By tracking errors in real time and using a standardized process that involved timely follow-up, technologists were educated on error prevention. This practice increased safety awareness in our micro lab.
Clinical Validation of the Lymph3Cx Assay to Distinguish Primary Mediastinal Large B-Cell Lymphoma From Diffuse Large B-Cell Lymphoma
Authors: Ramsower Colleen , Yip Tameson , Glinsmann-Gibson Betty , Robetorye Ryan , Rimsza Lisa 
Published: September 2019

Abstract

Introduction
Primary mediastinal large B-cell lymphoma (PMLBCL) is recognized as a distinct lymphoid neoplasm. However, differentiation from diffuse large B-cell lymphoma (DLBCL) can be difficult due to the need for close clinicopathologic correlation and variability in morphology and immunophenotype. In addition, a recent study identified lymphomas that share molecular and morphological features with PMBCL, yet do not involve the mediastinum. Correct classification of PMBCL may impact therapeutic decision making, increasing the demand for more accurate diagnostic methods. Recent research identified a new gene expression signature that robustly differentiated PMLBCL from DLBCL in both training and independent validation cohorts using RNA isolated from routinely available formalin-fixed, paraffin-embedded (FFPE) tissues.

Methods
This assay, known as the “Lymph3Cx,” utilizes the nCounter platform (NanoString Technologies, Seattle, WA) and consists of probes for 58 target genes (including both discriminatory and housekeeping genes) that can distinguish PMLBCL cases from DLBCL as well as the “cell-of-origin” subtypes of DLBCL. In the current study reported here, the Molecular Diagnostics–Arizona Laboratory (MDAZL) performed a full validation of the Lymph3Cx assay for use in our clinical diagnostic laboratory.

Results
Assay performance

included
accuracy (92.9%), precision (100%), analytical sensitivity (100 ng RNA limit of detection), analytical specificity (measures are in place to prevent interfering substances), reproducibility between technologists and technical replicates (100%), specimen stability (18 months for unstained tissue sections), and RNA Isolation Kit Utility (two kits with equal performance) in order to become the first CLIA-certified, CAP-accredited clinical diagnostics laboratory to offer a molecular assay for distinction of PMLBCL from DLBCL.

Conclusion
The Lymph3Cx assay will be prospectively used for evaluation of Mayo Clinic patients and for use as an integrated biomarker in clinical trials.
Laboratory-Diagnosed Gonorrhea and Chlamydia Infection Rate in the Veteran Population: The Corporal Michael J. Crescenz Veteran Affairs Medical Center (CMCVAMC) Experience
Authors: Petersen Jeffrey , Patel Sahil , Dalal Sharvari , Jhala Darshana 
Published: September 2019

Abstract

Introduction
Sexually transmitted infections (STIs) due to gonorrhea and/or chlamydia remain a major public health problem. Previously, it has been documented in the literature that active duty/deployed military personnel may have a higher incidence of STI infections compared with the general population; however, similar studies for the veteran population (after discharge from military service) appear sparse. For facilities that diagnose gonorrhea and chlamydia by a real-time polymerase chain reaction (PCR) assay, an understanding of the expected rate of gonorrhea and chlamydia is helpful for monitoring the assay, both for epidemiological purposes and as a check on assay to detect abnormal trends; therefore, we present the unique experience of the CMCVAMC.

Method
Quality assurance/improvement quarterly data from October 1, 2013, to December 31, 2018, were reviewed to obtain both the test volume of PCR for gonorrhea and chlamydia as well as the number of positive test results at the CMCVAMC. Testing had been performed using the Abbott m2000 RealTime System (Abbott Park, Illinois).

Results
A total of 12,856 PCR tests for gonorrhea and chlamydia had been performed on the veteran population; of these, 257 were positive for gonorrhea and 410 were positive for chlamydia. Quarterly percentage rates on a quarterly basis ranged from 1.67% to 5.30% (chlamydia) and 1.01% to 3.25% (gonorrhea) with average rates of 3.29% and 2.01% for chlamydia and gonorrhea, respectively, and expected rates <6% at the CMCVAMC.

Conclusions
The establishment of the average expected rate of positive laboratory-diagnosed chlamydia and gonorrhea at the CMCVAMC makes a significant contribution to the epidemiological data concerning veterans and provides a valuable benchmark for similar facilities performing quality assurance of their PCR assay for these STIs.
Bioinformatics Model of Serum Biomarkers to Prognosticate the Response to Programmed Death-1/Ligand-1 Targeted Immunotherapy in Metastatic Non–Small Cell Lung Cancer
Authors: Tarhoni Imad , Multani Maneet , Fughhi Ibtihaj , Gerard David , Fidler Mary , Batus Marta , Bonomi Philip , Borgia Jeffrey 
Published: September 2019

Abstract

Introduction
Immune-checkpoint inhibitors revolutionized the therapeutic paradigm for metastatic non–small cell lung cancer (NSCLC). The average response, however, still hovers at 20%, demonstrating the urgent need for biomarkers predictive of response. High-throughput laboratory technology promises to serve as an insightful and robust tool to recognize and select patterns of biomarkers in serum. We applied machine learning on serum immune-checkpoint biomarkers for prognostication of response to immunotherapy in advanced NSCLC.

Method
Pretreatment sera from 106 advanced NSCLC cases who failed frontline chemotherapy were evaluated for 16 soluble immune-checkpoint molecules using the Human Immuno-Oncology Checkpoint Protein Panel (MilliporeSigma). This panel constituted BTLA, CD27, CD28, TIM-3, HVEM, CD40, GITR, GITRL, LAG-3, TLR-2, PD-1, PD-L1, CTLA-4, CD80, CD86, and ICOS. Primary data points were collected and calculated via a Luminex FLEXMAP 3D system (xPONENT v4.0.3 Luminex Corp). The minimum follow-up after treatment was 12 months. Response patterns were categorized based on their overall survival (OS) as long-term responders (>12 months) or short-term responders (<12 months). Values were analyzed with the clinical outcomes using “Survminer” and “survival” R packages to determine the log-rank-based cutoff values associated with overall survival. Finally, machine learning methods were implemented using “caret” and “rpart” R packages to fit a classification model to predict the response pattern. The model was trained and tested on random fractions of the cohort.

Results
BTLA4, HVEM, CD40, GITRL, LAG-3, PD-1, CD80, and CD86 serum levels significantly correlated with OS (all P values ≤.02 and HR of 0.27, 0.5, 4.59, 0.17, 0.12, 0.48, 3.64, and 0.37, respectively). The algorithm composing PD-1, LAG-3, CD86, and CTLA4 predicted the response pattern with PPV of 81%, specificity of 87%, and accuracy of 75%.

Conclusion
The serum immune-checkpoint predictive model might assist in the tissue and gene-based profiling of immune-checkpoints to predict the benefit from immunotherapy.
Importance of Predictive Biomarkers and Epigenetics in Health: Novel Solutions in Clinical Care
Authors: Jaffe Russell , Mani Jayashree 
Published: September 2019

Abstract

Introduction/Objective
Chronic health issues precipitate from a myriad of origins. We underline three common underlying causes: cumulative repair deficits, oxidative damage and metabolic acidosis. A unique set of predictive biomarkers (PBs) addressing these aspects is presented that has been developed on the premise that epigenetics influence 92% and genetics influence the remaining 8% of health. Together with an individualized and personalized treatment plan, this approach has shown to provide best health outcomes.

Methods
(1) To tailor therapeutic management of chronic conditions, predictive tests that have a variance of 5% or less are used and their “least risk, most gain” goal values are adhered to instead of usual or normal statistical ranges. This helps confirm specific individual need and facilitates effective monitoring of outcome results. Repair deficit is measured by hsCRP, oxidative damage measured by homocysteine, Omega 3 index, and 8OhdG; immune intolerance indicated by lymphocyte response assays and metabolic acidosis indicated by urine pH assessment. (2) Individualized nutrient protocols are formulated based on predictive biomarker results. (3) A metabolically alkalinizing diet is initiated with the goal to providing a buffering effect on cellular chemistry. For example, dietary sugars and refined flours are the single biggest triggers of inflammation driving hyperinsulinemia leading to a biochemical cascade that alters gene expression promoting inflammation.

Results
This proactive approach is evidence based and has been shown to lower costs while enhancing individual outcomes when compared to current best standards of care, reducing risks, and adding “years to life and life to years.”

Conclusion
There is a difference between known tests and functional predictive tests—identifies individual epigenetic risks better. Least risk-highest gain goal values are more relevant than normal lab values. Choosing the right kind of high-sensitivity biomarkers and adopting an associated lifestyle plan can improve quality of clinical care.
Evaluation of the Proliferation of Breast Cancer Cells Among Women in Osun State, Southwest Nigeria
Authors: Iyiola Sina , Ifeoma Enweani , Ngokere Anthony , Avwioro Godwin , Komolafe Akinwumi 
Published: September 2019

Abstract

Objectives
Nigeria has one of the highest morbidity rates from breast cancer; therefore, this work examined the proliferation rate of breast cancer and the hospital presentation time lag among women in Osun State, Nigeria.

Methods
This cross-sectional study was carried out in Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife and Ladoke Akintola University Teaching Hospital, Oshogbo, Nigeria. The request cards and tissue blocks were sorted from the year 2014 to 2017. The time lag it took the patients to report at the hospitals was retrieved from the request cards. The breast tissue blocks were sectioned, stained with H&E, and graded. A representative tissue block was selected for each patient. Sections obtained from the blocks were stained with Mki67 antibody using a diaminobenzidine horseradish peroxidase technique. The cells were semiquantitatively scored as percentage of tumor cells stained brown. The mean ± SD was calculated.

Results
Out of 240 breast cancer patients sampled, 6 (2.5%), 97 (40.4), and 137 (57.1%), respectively, were grades 1, 2, and 3. The mean value of MKi67 was 23.90 ± 20.38, median 16.00. The mean value for grade 2 cancer was 15.31 ± 14.34; grade 3 cancer was 37.95 ± 22.47. Only 21.9% of breast cancer patients came to clinic within 3 months of lumps awareness in their breasts while 64.5% attended clinic after 6 months.

Conclusions
Breast cancer among the Osun State women was not very aggressive when comparing the Mki67 values obtained in this study with the values obtained in the developed world. Greater percentages of women with breast cancer waited too long before presenting themselves at the hospital. Thus, a high morbidity rate was recorded.
CDC and Clinical Laboratory Partners: Analysis of Biosafety Gaps Revealed During the Ebola Outbreak
Authors: Cornish Nancy , Campbell Sheldon , Weirich Elizabeth 
Published: September 2019

Abstract

Objectives
Patient care and public health in the United States depend on timely and reliable clinical laboratory testing. A third of the roughly 500 million yearly patient visits to health care providers involve at least one laboratory test, and approximately 70% of medical decisions are based upon test results. However, the performance of clinical laboratory testing could be compromised by patient specimens potentially contaminated with highly infectious materials. The importance of biosafety in clinical laboratories was highlighted during the 2014 Ebola crisis, where fears about safety resulted in some institutions refusing or delaying tests on patient specimens, which resulted in delayed diagnoses and contributed to patient deaths.

Methods
In collaboration with subject matter experts from academia, medical centers, and federal institutions, the Centers for Disease Control and Prevention has reviewed the capability of clinical laboratories to safely test patient specimens potentially contaminated with highly infectious materials, like Ebola. Current biosafety guidance for clinical laboratories has been largely based on biosafety practices in research laboratories, so the guidelines do not always correspond to clinical laboratories and may be incomplete or occasionally inconsistent. While essential to patient care, clinical laboratories are also unique environments with specialized equipment, processes, and therefore distinct challenges. Here we discuss the complexity of clinical laboratories and describe how applying current biosafety guidance to clinical laboratories may be difficult and confusing at best or inappropriate and harmful at worst. We describe biosafety gaps and opportunities for improvement in the areas of ethics; risk assessment and management; automated and manual laboratory disciplines; specimen collection, processing, and storage; test utilization; waste management; laboratory personnel training and competency assessment; and accreditation processes.

Conclusion
These identified gaps in knowledge and practice could inform future research and education in clinical laboratory biosafety.
An Institutional Review of Pathologist Approval of Send-Out Testing: A Look at Financial Impact
Authors: Peterson Daniel , Foulis Philip , Agosti Steven 
Published: September 2019

Abstract

Introduction
Beginning in 2012, the Choosing Wisely campaign sought to identify tests or procedures whose necessity should be questioned to ensure that they are truly necessary. This study aims to look at the inappropriate usage of relatively uncommon “send-out” laboratory tests that, although rare for the majority of patients, carry a much higher financial cost than more common “in-house” tests. The study objective is to gain an understanding of the fiscal impact of pathology approval of send-out test orders.

Methods
The laboratory records of send-out tests that were either approved or cancelled by the pathology department based on explicit test specific criteria were reviewed from 2004 to May 8, 2018. This review totaled 49,935 unique patients, 115,484 unique accessions for a send-out test order, and 588 unique send-out tests that did not meet criteria encompassing a menu of 725 send-out tests. The cost of each send-out test, number of cancelled tests, and number of approved tests were examined to reveal which cancelled test orders accounted for the most savings.

Conclusion
This study showed that, with no policy in place for pathology approval of send-out testing, inappropriate test orders may contribute to 30% of the cost of all send-out testing. The three areas of testing that contributed to the costliest amount of inappropriate ordering (41% of overall savings) were cytogenetics, FISH, and HIV/HCV treatment susceptibility testing. This information may be used to address the root cause of the issue by educating clinicians as to the appropriate clinical indications of certain send-out tests, the tests most commonly inappropriately ordered, and the tests that require the greatest discretion when ordering. Further study is necessary to address possible interventions that may resolve the root cause of inappropriate send-out test orders.
Implementation of an Algorithmic Approach to Molecular Infectious Disease Laboratory Testing on Cerebrospinal Fluid Samples
Authors: Maris Alexander , Hughes Caitlin , Antoine-Reid Thessicar , Schmitz Jonathan 
Published: September 2019

Abstract
Rapid turnaround time for infectious disease laboratory testing is critical for the encephalitic/meningitic patient. Clinicians and emergency medicine providers often will bundle cerebrospinal fluid (CSF) studies (cell counts, glucose, protein) with molecular infectious disease laboratory (MIDL) assays, up front, to expedite clinical decision making about antimicrobial therapy and hospital admission. Many patients, however, ultimately do not have CSF pleocytosis and, predictably, have negative MIDL results. We quantified patients who had MIDL testing ordered, without concurrent CSF pleocytosis, to justify a mandated algorithm for CSF MIDL testing. Four months of MIDL CSF results were reviewed (viral monoplex PCRs); 274 patients were identified. Forty-seven percent of patients (128/274) were neonates (<2 months old) and thus may not have had the immunologic capacity to mount a pleocytosis to CNS infection. Of the remaining 53% of patients (>2 months old), who would have been expected to generate a CSF pleocytosis, 55% (81/146) had one or more MIDL studies ordered without CSF pleocytosis; 3.4% of these patients (5/146) did not have CSF cell counts ordered. Among all patients, 7.7% (21/274) had positive MIDL results (1 HSV1; 2 HSV2; 18 enterovirus). Seventeen patients had CSF pleocytosis; the 4 patients without CSF pleocytosis were neonates (3) or had no cell counts ordered (1). A ratio of 700 RBC to 1 WBC was used to approximate the expected number of CSF WBC in bloody taps (10%; 28/274). We show that over half of patients >2 months old had MIDL studies ordered without CSF pleocytosis; all patients with positive MIDL results had CSF pleocytosis or were neonates or had no cell counts ordered. An algorithm will be implemented in which all neonates with concern for CNS infection will have CSF MIDL tests ordered; among nonneonates, only those with documented CSF pleocytosis may have MIDL assays ordered (with rare exceptions; eg, leukopenia).