bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Utilization of Next-Generation Sequencing-Based Clonality Assays for Immunoglobulin Heavy Chain in Evaluating Suspected B-Cell Proliferation
Authors: Katerji Hani , Katerji Roula , Campbell Andrew , Rothberg Paul , Ding Yi 
Published: September 2019

Abstract

Objectives
B-cell clonality assays of the immunoglobulin heavy chain (IGH) and light chain (IGK) genes have been used widely in the workup of B-cell neoplasms. PCR is the current gold standard test for clonality. Recently, NGS has been suggested to both improve sensitivity and identify the specific V-(D-)J sequence required to track clones. Here we report our experience with using NGS for complementing our current procedures.

Methods
Our validated NGS test is performed by amplifying patients’ DNA using IGH-FR1 assay panel. Pooled amplicons get sequenced. The sequence data then get analyzed using in-house bioinformatics software, which sorts sequences and generates frequency distributions. Each sequence is ranked by its frequency. A clonal population is designated if the top sequence read is at least 1% of the total reads. For the standard PCR gene rearrangement test, we use a BIOMED-2 PCR-based B-cell assay.

Results
We retrospectively searched our database for all cases in which IGH and IGK clonality was tested by either standard PCR or NGS from 8/2016 to 7/2017. A total of 253 cases were tested by PCR while 21 cases were tested by NGS, which showed higher success rates. Of the 253 cases tested by conventional PCR, 39% (n = 98) were clonal (either IGH, IGK, or both), 34% (n = 86) were polyclonal, and the rest 28% (n = 69) showed a weak inconclusive signal or failed. Of the 21 cases analyzed by NGS, 71% (n = 15) were clonal, 24% (n = 5) were polyclonal, and just 5% (n = 1) failed.

Conclusion
Our experience indicates that NGS for IGH clonality, even more expensive, is an effective and more sensitive tool that produces higher informational content and yields higher success rates when compared to conventional PCR assay. NGS captures multidimensional data and provides a more precise determination of the clonal relationship between different lymphoid proliferations, which also is essential for the detection and measurement of minimal residual disease.
Quantification of BCR-ABL1 Fusion Transcripts in Patients With Acute B Lymphoblastic Leukemia by Multiplex Droplet Digital PCR
Authors: Martinez Ryan , Nennig Davis , Mroz Pawel 
Published: September 2019

Abstract
Droplet digital PCR (ddPCR) is a novel PCR platform that provides quantification of amplification targets by massive sample partitioning and analysis in a single sample. These results are independent of a calibration curve and may increase detection when compared to quantitative RT-PCR (qRT-PCR). The t(9;22)(BCR-ABL1) translocation is associated with chronic myelogenous leukemia (CML) and a subset of acute B lymphoblastic leukemias (B-ALLs). Several studies have demonstrated the clinical utility of quantifying BCR-ABL1 fusion transcript levels for detecting minimal residual disease (MRD). qRT-PCR is a well-established method for MRD monitoring but has inherent limitations with regard to lower limit of detection and quantification (LOD and LOQ). Here we report the results of a pilot project to compare and evaluate ddPCR and qRT-PCR in detecting BCR-ABL1 e1a2 transcripts for MRD monitoring in B-ALL. We developed and optimized a single-step, multiplexed ddPCR assay for detecting BCR-ABL1 e1a2 and ABL1 e10 from RNA. Droplets were prepared using a QX100 or QX200 droplet generator (Bio-Rad, Hercules, California), and PCR products were run on a QX100 droplet reader and analyzed with QuantaSoft software. Method comparison of droplet generation was assessed between manual and automated methods, finding automated methods gave an 8.2% increase in total droplets generated (15,082 vs 13,940). Next, assay performance was evaluated using the Invivoscribe BCR-ABL1 e1a2 RNA dilution set and t(9;22)-positive SUPB15 cell line. ddPCR demonstrates a limit of detection to 10–6 dilution in the Invoscribe kit and a minimum input of 10–3 to 10–4 ng of RNA from the SUPB15 cell line. Future studies will include multiplexed ddPCR in BCR-ABL1-positive B-ALL patients at time points day 0 (diagnostic sample) and days 33 and 78 postinduction for MRD determination. The performance of ddPCR will be compared with standard qPCR along with clinicopathologic correlation to determine if ddPCR can improve MRD and clinical outcomes of patients with t(9;22)+ B-ALL.
Relationship Between Gene Polymorphism and Type 2 Diabetes in a Palestinian Population: A Study of Five Gene Polymorphisms
Authors: Najjar Mahmoud 
Published: September 2019

Abstract

Objectives
To investigate the association between KCNQ1 rs2237892, KLF14 rs972283, ZBED3 rs4457053, COL8A1 rs792837, and FTO rs8050136; gene polymorphisms; and T2DM in the male Palestinian population.

Methods
In this case-control study, 100 T2DM male patients and 100 control men were examined. The two groups were genotyped for the five gene polymorphisms using restriction fragment length polymorphism–PCR (RFLP-PCR) and allele-specific (AS-PCR) techniques. Body mass index (BMI), glycated hemoglobin (HbA1c), insulin (C-peptide), total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) were measured for all the study participants. The relation between the five gene polymorphisms, T2DM, and the measured clinical parameters were statistically analyzed using appropriate tests.

Results
Among the tested polymorphisms, significant associations were evident between KLF14 “GG” genotype (P = .014), FTO “CC” genotype (P = .043), and COL8A1 TC genotype (P = .015) and increased risk of T2DM. The KLF14 G-containing genotypes exerted a significant effect on lowering HDL-c (P = .026) and on elevating LDL-c (P = .045) and cholesterol level (P = .042) in the control group. The FTO “CC” genotype showed a significant effect on raising HbA1c level in the patients (P = .007). KCNQ1 (rs2237892 T>C), ZBED3 (rs4457053 A>G), and COL8A1 (rs792837 T>C) genotypes did not reveal significant effects on the tested parameters.

Conclusion
KLF14 “GG,” FTO “CC,” and COL8A1 C allele and “TC” genotypes are significantly associated with T2DM in the investigated population. KLF14 “GG” and “AG” have an association with the levels of HDL-c, LDL-c, and cholesterol in control subjects. The HbA1c level was significantly higher in patients with the FTO “CC” genotype. The study recommends confirming the obtained results on a larger sample and examining the association of other gene polymorphisms with T2DM in the Palestinian population.
Clinicopathologic Features of Uterine Fibroids in a Private Gynecologic Setting in Calabar, Nigeria
Authors: Ekanem Ima-Obong , Ekanem Ima-Obong , Ekanem Odudu , Ekanem Chinweoke 
Published: September 2019

Abstract

Introduction
Uterine fibroid is a common gynecologic problem among adult females in Nigeria with variable clinical presentations. Unfortunately, these patients often seek medical attention very late after having consulted nonorthodox and/or traditional health practitioners.

Objectives
To assess the clinical outcome of patients diagnosed with uterine fibroids and review the pathologic features of specimens obtained from such patients managed over a 48-months period at Davis Medical Centre, a specialist gynecologic private health facility in Calabar, Nigeria.

Methods
This retrospective study was conducted at Davis Medical Centre, located in a semirural community in Calabar Municipality. It involved the extraction of data from case notes of patients and review of laboratory reports and H&E-stained histopathologic slides of surgical specimens removed from patients who presented with abdominal mass/swelling, heavy menstrual bleeding, abdominal pain, and inability to get pregnant having excluded other causes of infertility and ultrasonographic features suggestive of leiomyoma.

Results
A total of 82 patients aged between 26 and 54 years (mean age 36 ± 2 SD) were seen, giving an annual rate of about 20 cases yearly in the 4-year period (2015-2018) studied. Forty-eight (58.5%) had giant uterine fibroids with uterine size between 16 and 28 weeks. Myomectomy was the mainstay of treatment in 93.9% while 6.1% had abdominal hysterectomy. Histologically, the number of fibroid nodules ranged from 1 to 60 nodules with the largest weighing 4,097 g. All had the typical whorled grayish-tan gross appearance of leiomyoma uteri with a large proportion histologically showing degenerative changes of the hyaline type (39%) and few having features suggestive of adenomyosis.

Conclusion
Despite the grotesque, unusual macroscopic and characteristic microscopic findings, timely and careful surgical intervention can remedy the reproductive outcome and save lives of the affected patients when seen and managed by an experienced specialist gynecologist.
Bridging the Gap With Choosing Wisely Recommendations: What Laboratory Topics Matter Most to Other Medical Specialty Societies?
Authors: Caldwell Barbara 
Published: September 2019

Abstract

Introduction
This study sought to evaluate the nature and frequency of laboratory recommendations made by medical societies other than ASCP.

Methods
Review of all 2012 to 2018 ABIM Choosing Wisely (CW) non-ASCP laboratory recommendations and categorization of recommendations per topic area.

Results
There are 107 total recommendations made by other medical specialties that involve laboratory medicine. The most common recommendations are (1) Transfusion Medicine: to minimize transfusion of PRCs (19 recommendations, 18%); (2) Women’s Health: Pap smear testing, other women’s health testing (18 recommendations, 17%); and (3) General Laboratory: reducing repetitive routine laboratory tests (10 recommendations, 9%). Most (64, 60%) recommendations addressed screening while 29 (27%) focused on treatment and 14 (13%) were related to monitoring disease.

Conclusion
Almost one-half (44%) of all recommendations fell into three common areas and there were more recommendations related to screening for disease than for treatment or monitoring. For Choosing Wisely to achieve increasing success, increasing efforts are needed to disseminate this information, promote multidisciplinary effective test utilization, and encourage continued laboratory medicine recommendations from all medical stakeholders.
Observational Study of Tissue Acquisition Turnaround Time for Commercial Comprehensive Genomic Profiling in Solid Tumors
Authors: Krigsfeld Gabriel , Roth Aleeza , Cooper Maureen , Smith Liisa , Iyer Radhika , Brown Adam , Pratt James , Truesdell John , Schwartz Joshua 
Published: September 2019

Abstract

Introduction
Increased development and use of next-generation sequencing in clinical diagnostics has revolutionized precision medicine. Steps prior to a specimen arriving at a diagnostic facility, including pathological evaluation, are crucial parameters determining specimen quality and success of comprehensive genomic profiling (CGP). This observational study identified factors that may influence tissue acquisition for commercial CGP in clinical oncology.

Methods
Data were collected from deidentified patients (n = 63) from select US pathology labs enrolled in a Foundation Medicine (FMI) early access program for the CGP test FoundationOne CDx (Foundation Medicine). A representative substudy cohort (n = 20) with qualitative information available was selected. Lab visit frequency by FMI was monitored for 42 cases. Tissue acquisition turnaround time (TA-TAT) was separated into stages: (1) tissue request to pathology lab acknowledgment, (2) pathology lab acknowledgment to tissue pathology review, (3) tissue pathology review to packaging, and (4) packaging to tissue arriving at FMI.

Results
Median TA-TAT for the total population was 5.0 days (range, 0-27.0) and 3.5 days for the substudy cohort (range, 1.0-11.0). The duration of each TA-TAT stage was evaluated separately and varied between labs (0%-71.4% of total TA-TAT). TA-TAT was longer for unstained slides compared with formalin-fixed, paraffin-embedded (FFPE) tissue blocks. There was a trend for decreased TA-TAT when stages 1 and 2 occurred on the same day versus different days. For the cases with lab-visit frequency reported, those with biweekly visits had shorter TA-TAT (biweekly: n = 12, median = 2.0, 2.5th-97.5th percentile range, 0.3-5.7 days; single visit: n = 30, median = 5.5, 2.5th-97.5th percentile range, 0.7-13.1 days).

Conclusions
Understanding and optimizing the tissue acquisition workflow may reduce TA-TAT, thereby facilitating report delivery and subsequent treatment guidance to patients.

Funding
Bristol-Myers Squibb. Professional medical writing and editorial assistance was provided by Katerina Pipili, PhD, and Jay Rathi, MA, of Spark Medica Inc, funded by Bristol-Myers Squibb.
The Utilization of JAK2 Molecular Testing at the University of Minnesota Medical Center
Authors: Mroz Pawel , Arries Cade 
Published: September 2019

Abstract

Objectives
JAK2 gene mutation status is included in the 2017 WHO diagnostic criteria of a myeloproliferative neoplasm (MPN) and therefore indicated in the diagnostic workup. Overutilization and inappropriate testing, however, can cause harm and lead to medical errors, and most importantly, it can significantly drive up the costs of patients’ care. Here we report an attempt to evaluate the success rate and the associated costs of JAK2 testing as well as to correlate it with clinical indications and patient presentation.

Methods
We conducted the analysis of next-generation testing orders/results performed at out institution between 9/2/2015 and 7/13/2018. We reviewed the rate of positive results as well as the type of order submitted to laboratory and compared the costs of individual tests.

Results
We analyzed 3,474 NGS orders/results performed at our institution. Of those, 1,203 were submitted for JAK2 testing, making this the most commonly ordered NGS test. Out of 1,203 results, there were 820 unique patient specimens and 118 tested positive (15%). The JAK2 testing was primarily ordered as part of the NGS MPN panel, which includes JAK2, CALR, and MPL mutation hotspots (70%), the custom panel (23%), JAK2 single gene (5%), or as part of comprehensive myeloid panel (2%). The mutation detection rate was 15%, 12%, 11%, and 15%, respectively.

Conclusion
Testing for JAK2 gene mutation status is the most commonly ordered NGS test in our laboratory. The detection rate for pathogenic mutation, irrespective of the type of genetic panel ordered, was 11% to 15%. Our analysis of the JAK2 ordering and reporting suggests that the JAK2 testing may be somewhat overutilized at our institution. An ongoing analysis of clinical indications, patient presentation, and associated costs will help to fully elucidate the true utility of this testing and will be included in the poster presentation.
An Integrated Approach to Genetic Test Stewardship: The Role of Laboratory Genetic Counselors in Test Preauthorization and Ordering
Authors: Conta Jessie , Sternen Darci , Stasi Shannon , Candadai Sarah Clowes , Wellner Monica , Dickerson Jane 
Published: September 2019

Abstract

Introduction
The complexity and relative high cost of genetic tests combined with stringent administrative and medical coverage policies can negatively impact test accessibility and, ultimately, patient care. The burden of test preauthorization typically falls on the ordering provider and team, and is particularly cumbersome for specialists that do not have genetics expertise. As part of the Seattle Children’s laboratory stewardship program, we integrated laboratory genetic counselors (GCs) in a hospital-wide genetic test preauthorization and order review process to support efficient test authorization and ensure appropriate genetic test utilization.

Methods
A rotating team of laboratory GCs reviews all genetic test requests at the time of preauthorization for medical necessity, optimal test selection, and CPT coding. This information is triaged to our centralized insurance processing department for submission to payers. Lab GCs review test orders for the same elements, preauthorization status, and supporting paperwork.

Conclusions
The 7,889 preauth requests and 7,177 test orders have been reviewed in our institution since implementing this two-phase review process in January 2016. Twenty-eight percent of requests were modified or cancelled at the time of preauth review, with the majority of modifications related to test optimization and improved necessity documentation. Additionally, 21% of requests were modified or cancelled when reviewed at the time of order. The intervention resulted in $1.5M cost-avoidance accrued since 2016. A recent provider survey revealed that 90% of providers are neutral, very, or extremely satisfied with the genetic test authorization process and support provided by the laboratory GC team. By integrating a laboratory GC case review process, we supported effective genetic test utilization at our institution, reduced collective provider and staff time and rework related to insurance authorization, and reduced financial liability for the patient/family and institution.
Laboratory Test Utilization in an Expanding Regional Laboratory Network: Past Successes and Future Opportunities
Authors: Paczos Tamera , Bell Phoenix 
Published: September 2019

Abstract

Introduction
The University of Rochester Medical Center developed a reference test utilization program implemented in 2011 to tackle increasing test volumes and costs. There was an initial >7,000 decrease in test volumes, which equated to >$1,000,000.00 in savings by year end 2012. Despite this, by the end of 2018, testing volumes had increased 34% and the cost had climbed 36%. Here we would like to discuss the methods implemented for initial success, potential reasons for continued increases in volumes and costs, and ideas to mitigate this trend in the future.

Methods
In 2010, the University of Rochester formed a laboratory diagnostics committee, which successfully decreased reference testing volumes and costs in both the inpatient and outpatient settings. They did this by developing a formulary for reference tests, which was divided into three tiers based on clinical utility and cost: tier 1 tests, unrestricted and available to all providers to order; tier 2 tests, restricted with only board-certified, subspecialty-trained physicians able to order; and tier 3 tests, off formulary and not available to order. The resident physician staff was also no longer allowed to order any reference testing on inpatients. Despite initial gains costs and volumes have climbed >36% and 34%, respectively, since implementation. Possible explanations for this include the addition of regional affiliate hospitals and reference clients that are not following these protocols, increased testing volumes, and increasing use of molecular testing.

Conclusion
Despite successful implementation of a reference test utilization program, close monitoring and adaptations are necessary in our continuously changing health care environment to remain effective. Implementation of the program at the regional affiliate hospitals and a more robust molecular testing menu in-house are potential options to control rising costs while providing high-quality patient care.
Blood Utilization at Regional Hospitals
Authors: Demkowicz Ryan , Dermawan Josephine , Shetty Sindu , Scarborough Richard , Lu Haiyan , Sardina Luis , Chong Yap-Yee 
Published: September 2019

Abstract

Introduction
Transfusion medicine is unique to lab medicine. While it still involves testing and reporting of results, it is one of the few areas where the laboratory is providing treatment. The risk of providing a blood product must be weighed against the benefit before the decision is made to transfuse a patient. Our study looked at blood utilization at our regional hospitals to assess if there were areas where we need to improve this decision process.

Methods
Chart reviews were performed for patients who received packed red blood cells (RBCs) in the regional hospitals over a 2-month period. Using the AABB and Choosing Wisely recommendations, we created two screening criteria: hemoglobin (Hb) >8 g/dL or greater than 1 unit RBC ordered when Hb is >6 g/dL to screen for outliers among RBC orders. A more in-depth chart review including information on clinical diagnosis, indications, bleeding status, and blood loss during surgery was performed on cases that met these criteria. Using this information, a decision was made on the appropriateness of the transfusion.

Results
In total, 1,592 RBC units were screened at eight regional hospitals. Sixty-eight (4%) were flagged as inappropriate, 57 (83.8%) due to multiple units, and 11 (16.2%) for an Hb >8 g/dL. The percentage of inappropriate transfusions at a hospital ranged from 5.2% to 13.6%. However, all hospitals except one were under 5.5%.

Discussion
In general, regional physicians are transfusing RBCs appropriately. When a unit is ordered inappropriately, it is most likely due to ordering multiple units upfront. To further improve blood utilization, these data were presented to hospital administration and a new alert in the EMR was created. A repeat study will be performed to see if the alerts and awareness of these data has had an effect on blood utilization.
Diagnosis of Rare Antibody Anti-Ata in Pregnancy: A Case Report
Authors: Taherian Mehran , Liu Zhonghua , Petras Melissa 
Published: September 2019

Abstract

Background
Anti-Augustine antigen (Ata) is a high-prevalence RBC antigen, and anti-Ata is an extremely rare RBC alloantibody. Anti-Ata is usually produced by an Ata (–) individual after alloimmunization by transfusion or during a pregnancy and is associated with immediate or delayed hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. We report the detection of a unique antibody to an antigen of high incidence, the anti-Ata.

Case Presentation
The patient was a 26-year-old African American pregnant female G7P2042 with a medical history of beta-thalassemia trait, presented at her second trimester for evaluation of abdominal cramping. The patient has had two prior ectopic pregnancies, managed surgically, and two healthy children delivered vaginally with no obstetric or congenital complications. She was treated for a pulmonary embolism a few months before while she was on OCPs. She had no prior transfusions. She also had anemia (RBC 4.1 × 1012/L, Hgb 9.7 g/dL, Hct 29.6%, MCV 72.2 fL). The patient’s blood sample was sent for type and screen, and it came positive for anti-Ata antibody. This test was performed at Memorial Blood Centers (a reference lab) and Kaleida Health Laboratories. The phenotype of our patient was c+ E+ e+ k+ Kpb+ Jsb+ Jka+ M+ N+ s+ U+ Lub+. The baby was followed with serial fetal middle cerebral arterial (MCA) Doppler assessment, without evidence of fetal anemia. The term infant was delivered by cesarean section without complications. Currently, both mother and baby are doing well.

Conclusion
Although anti-Ata is unlikely to cause hemolytic disease of the newborn, it is important to ensure that compatible blood is available should the mother require transfusion postdelivery.