bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tracking Blood Product Wastage over a 6-year Period in Virginia Commonwealth University Medical Center
Authors: Liu L , Shemenski J , Zmanovskaia S , Sanford K 
Published: October 2024

Abstract

Introduction/Objective
Blood transfusions are a necessary practice for hospital emergency and surgical department. In emergent situations, blood components are in unmonitored settings during transit of critically ill patients. Any unused blood products are returned to the blood banks outside of a controlled temperature environment and are no longer viable to use. This study seeks to collect the average amount of blood products wasted in the Emergency and Surgery Department at Virginia Commonwealth University’s (VCU) Main Hospital. In addition, the study intends to highlight the budget that is impacted by these wasted blood units.

Methods/Case Report
Emergency Stock Records of VCU’s Hospital Emergency Department, Operating Room, Children’s Hospital of Richmond’s (CHoR) Emergency Department, and the CHoR’s Operating Room were collected and accumulated by the Transfusion Service’s Quality Assurance Coordinator. VCU’s Main Hospital Emergency Department monitors blood unit viability with a sensitive temperature indicator on each unit of blood stored in unmonitored refrigerators. Blood units above 10 degrees Celsius trigger the indicator and are required to be discarded. Our study collected a tally of these discarded units due to a triggered temperature indicator from 2018 to 2023. Acquisition cost per blood unit was estimated to be approximately $250 and overhead cost per unit was estimated to be $760.

Results (if a Case Study enter NA)
From 2018 to 2023, VCU’s health system wasted an average of 89.16 blood units per year due to the triggered temperature indicators, with a total of 535 units wasted over six years. The average annual cost of the wasted units totaled $90,058.33 per year ($22,291.67 and $67,766.67 in acquisition and overhead costs, respectively); cumulative cost over the 6 years amounted to $540,350 ($133,750 and $406,600 in acquisition and overhead costs, respectively).

Conclusion
With a notable number of resources and funding lost in the process due to blood unit wastage, an administrative discussion should focus on the use of high-level remote- controlled automated refrigerators in lieu of manual temperature indicator to reduce the expenditure and wastage of blood products.
Copy Number Analysis of Whole Exome Sequencing Data
Authors: Madubata Chinwe , Bi Xin , Pang Jiuhong , Gu Yue , Koganti Lahari , Liao Jun , Hsiao Susan , Aggarwal Vimla , Mansukhani Mahesh , Jobanputra Vaidehi 
Published: October 2024

Abstract

Background
Genetic alterations implicated in constitutional disorders range in size from single nucleotide substitutions to losses and gains of millions of bases. Whole exome sequencing (WES) captures many clinically relevant variants, but an analytic pipeline optimized for detection of small substitutions, insertions, and deletions may miss pathogenic copy number variants (CNVs). Historically, our laboratory performed separate cytogenetic tests to evaluate for larger genomic imbalances. Addition of copy number analysis to our WES pipeline could improve the assay’s diagnostic yield. This study describes part of our strategy to validate copy number analysis of our constitutional whole exome sequencing data.

Methods
We identified 18 CNV specimens that underwent both chromosomal microarray analysis (CMA) and WES between 2017 and 2023. Variants included 13 deletions (size range 14Kb-2Mb) and 5 duplications (size range 325Kb-10Mb). The standard method of constitutional copy number analysis in our clinical laboratory is CMA using the Affymetrix Cytoscan HD Array and analysis software. CNVs identified on CMA were reviewed with reference to the Database of Genomic Variants and multiple academic hospital databases. WES was performed on an Illumina sequencing system following capture-based library enrichment with the Integrated DNA Technologies xGen Exome Research, CNV Backbone, Human mtDNA Research, and Human ID Research Panel probes. CNVs identified on WES were called using the Broad Institute’s Genomic Analysis Toolkit (GATK) with a quality score cutoff of 120. Whole exome sequencing data was visualized on the Integrative Genomics Viewer.

Results
14 out of 18 CNVs reported on CMA were also detected on WES with a quality score at or above 120 (78%). This includes 10 out of 13 deletions (77%) and 3 out of 5 duplications (60%). For both deletions and duplications, the size ranges of detected variants at or above the cutoff score and undetected variants overlapped. One duplication reported on CMA was detected on WES with a quality score below 120. Visualization of whole exome sequencing data showed variation in probe density that may have affected CNV calling.

Conclusions
The majority of CNVs reported after CMA (14/18, 78%) were also detected on WES data using a GATK quality score cutoff of 120. The data does not suggest an association between CNV size and detection by WES, although interpretation is limited by the small number of cases. Data visualization may be required to identify some CNVs. Future steps to characterize the limitations of copy number analysis of WES data include assessments of variance in probe density and read depth across the exome. Copy number analysis of WES data from cases with normal CMA results will also be performed for assay validation.
Estimation of Gestational Age-Specific Reference Intervals for Coagulation Assays in a Neonatal Intensive Care Unit Using Real-World Clinical Data
Authors: Spies Nicholas , Lalos Natasha , Vesoulis Zachary , Maucione Carly , Eby Charles , Dietzen Dennis , Roper Stephen 
Published: October 2024

Abstract
Interpretation of coagulation testing in neonates currently relies on reference intervals defined from adult cohorts. These likely do not reflect the normative values for neonates, in whom immature synthesis of vitamin K-dependent factors may contribute to this divergence. Direct reference interval estimation studies are difficult, particularly in neonatal populations; however, advances in indirect estimation may allow us to infer normative distributions from routinely collected clinical data. To accomplish this, initial coagulation testing results from all patients admitted to a level IV neonatal intensive care unit between 1/1/2018 - 1/1/2023 were extracted from the electronic health record and analyzed. Results prior to June 2021 were performed on the viscosity-based STA Compact Max (Diagnostica Stago. Parsippany, NJ, USA). Afterward, results were performed on a nephelometry-based ACL Top (Instrumentation Laboratory. Bedford, MA, USA). Specimens collected after transfusion of blood products were excluded. Prothrombin times (PT) and international normalized ratios (INR) were available for 1,117 neonates, while activated partial thromboplastin times (aPTT) were available for 790 neonates. The 95% confidence intervals (CI) of the median PT for extremely preterm, very preterm, preterm and term neonates were [19 - 21s], [18 - 22s], [17 - 19s] and [17 - 18s]. For INR, the CI were [1.6 - 1.8], [1.5 - 1.8], [1.4 - 1.6], and [1.4 - 1.5]. For aPTT, the CI were [51 - 61s], [47 - 58s], [45 - 50s], and [42 - 46s]. Indirect reference intervals (IRIs) were then estimated across gestational age groups (binning all patients delivered at less than 37 weeks into one preterm category) using refineR. The IRI for PT was 10 - 24s for preterm,10 - 22s for term, and 10 - 24s for all neonates. The IRI for INR was 0.7 - 2.1 for preterm, 0.8 - 1.8 for term, and 0.8 - 1.9 for all neonates. The IRI for aPTT was 24.5 - 68.4s for preterm, 24.7 - 58.2s for term, and 25 - 62.3s for all neonates. When compared to currently reported reference intervals, the lower limits of the IRI were similar to currently reported reference intervals; however, the upper limits of the IRIs were 1.3 - 1.8 times higher than current reference intervals. Theoretically, implementation of these IRIs would lead to a 3-fold decrease in the number of results flagged as abnormal. In conclusion, IRIs for coagulation assays estimated from neonates using routine clinical data show substantial divergence from current reference intervals in their upper limits, possibly due to the decreased factor concentrations seen prior to liver maturation. If implemented, these IRIs would substantially reduce the proportion of abnormal results. Future work will explore whether switching to these reference intervals could lead to a reduction in unnecessary transfusions or improved clinical outcomes.
Critical Value Reporting Performance Improvement Initiative: A Journey Towards Timely Patient Safety
Authors: Kuan Kevin , Forest Stefanie 
Published: October 2024

Abstract
Timely reporting of critical values serves as a quality indicator for the National Patient Safety Goal. Since the oncology inpatient unit at our institution has the highest number of critical values and often struggles to meet the targeted goal of timely results acknowledgement, this prompted a performance improvement initiative. By utilizing the Institute for Healthcare Improvement (IHI) Model for Improvement, the study aimed to decrease the time from specimen collection to acknowledgment of a complete blood count critical values (overall TAT). Three key metrics were monitored, including unit turnaround time (time from collection to receipt in laboratory; uTAT), laboratory turnaround time (time from receipt in laboratory to verified results) and timely critical value acknowledgment rate (% acknowledgement within 30 minutes). Quality improvement tools such as process maps and fishbone diagrams were employed, and two areas for improvement were identified. Firstly, it was observed that samples collected by the phlebotomists were delivered in batch to the laboratory via carts. However, samples collected by nurses were sent to the laboratory via a pneumatic tube. Hence, the uTAT varied drastically due to the different delivery methods. Secondly, the mode of alerting providers regarding critical values, which was via telephone calls from telecommunication staff, was deemed disruptive and redundant, as the providers often were already aware of the results from the electronic medical record (EPIC). Two multi-cycle Plan-Do-Study-Act (PDSA) interventions were implemented by a multidisciplinary team. The first focused on sending samples via pneumatic tube. The second PDSA intervention focused on a direct clinician acknowledgment of critical values within EPIC, by creating an auxiliary column on the EPIC patient list. Consequently, the overall TAT decreased from a median time of 167 minutes in July 2021 to 140 minutes by March 2022 in the oncology inpatient unit, with a sustained result (139 minutes) by October 2023. This reduction was driven by the standardization of pneumatic tube delivery system; the uTAT decreased from a median time of 104 minutes to 46 minutes by March 2022 and remained low at 52 minutes by January 2024. Notably, the rate of timely acknowledgment of critical value results worsened, dropping from 67% to as low as 51 % (March 2022) and improved to 64% by January 2024. It was realized that this unintended consequence was attributed to the decrease in uTAT, leading to more critical value results reported in early morning when there was less staffing. Despite the worsening in timely critical value acknowledgment, the overall TAT showed a discernible reduction. The application of IHI methodology played a pivotal role in expediting result reporting. Subsequent steps will focus on utilizing secure communication channels to augment the success rate of critical values acknowledgment within 30 minutes.
Evaluating RhD Assessment By Automated Methodology: A Potential ‘Blind Spot’ For RhD Variant Identification
Authors: Yurtsever Nalan , Tormey Chris , Bizzario Laurie , Lee Edward 
Published: October 2024

Abstract

Background
Automated blood typing platforms are ideal for blood donor centers, given their broad recognition of RhD antigen variants, resulting in products from such donors to be labeled as RhD positive. However, this ‘blind spot’ for variants may be problematic for hospital-based transfusion services, since RhD variants may require provision of RhD- RBC units and Rh immune globulin. The extent to which automated methods accurately characterize variant D antigen expression is not known. As such, the objective of our study was to assess D typing results, as well as RHD genotyping, among two automated testing platforms at our facility.

Methods
The study site is a single tertiary care center with analysis done from 12/2020-1/2024. At our facility, all females &lt;60 years of age with RhD antigen testing results of ≤2+ agglutination (0-4+ scale) via automated methods [solid phase testing 12/20-4/22 (Neo, Immucor, Norcross, GA) and gel testing 5/22-1/24 (Erytra, Grifols, Emeryville, CA)] are assessed by a tube RhD antigen test (Grifols reagents). If tube testing confirms a ≤2+ result (0-4+ scale), molecular variant D analysis is performed (Versiti, Milwaukee, WI). Patients typed as Rh negative with anti-D antibodies, or those with inconsistent D typing, are also subjected to genetic D testing. The Wilcoxon matched pairs signed rank test was employed for comparative data (P&lt; 0.05 was deemed significant).

Results
Amongst tested patients, 73 demonstrated ≤2+ agglutination via an automated typing method, leading to variant D genetic analysis. Of these, 71% (n=52) harbored variant D antigens. Within this subgroup, 29 (56%) subjects exhibited variants associated with potential allo-anti-D development (n=5 partial D variants; n=24 weak D variants). Notably, 4 patients with partial D and 1 with weak D demonstrated allo-anti-D antibodies. Of 23 patients with variant D who underwent automated gel testing, 20 concurrent tube testing results were available. Gel testing revealed significantly stronger agglutination compared to tube testing (p &lt; 0.001). In contrast, for paired solid phase and tube testing (n=11), there was no statistically significant difference in agglutination strength (p = 0.28).

Conclusion
Automated testing, particularly gel-based platforms, exhibits reduced sensitivity to RhD antigen variant identification when compared to tube testing, placing subsets of patients potentially at risk for forming allo-anti-D. Implementing protocols for verification of D status could enhance the sensitivity of variant D detection for facilities that largely rely on automated methods for antigen typing.
Conformal Prediction and Large Language Models for Medical Coding
Authors: Snyder Christopher , Brodsky Victor 
Published: October 2024

Abstract
The assignment of current procedure terminology (CPT) codes to medical events is a highly cumbersome, logistic challenge for many healthcare organizations, as well as a significant contributor to medical expenses. Improvement in the allocation of medical resources and expenses dedicated to such tasks can be achieved through automation. However, because of the complex nature of medical records, automation of procedure terminologies is just now developing with the advent of machine learning methods. In this study, we develop a fine-tuned large language model (LLaMA-3B) as a high-reliability predictor for CPT codes. As input, we use 2018 pathology report text data, including gross report, microscopic description, brief medical history, and final diagnosis. We define our dataset with the top five most common technical component CPT codes, which account for 85% of all samples. As a (meta) predictor of the veracity of the large language model itself, we use the prediction’s softmax scalar value of the classification model, borrowing from similar recent approaches in conformal prediction. Specifically, the validation set, which is distinct from both the train and test set, is used to establish a prediction threshold below which the model withholds judgement. We show that, by fine tuning an off-the-shelf language model on pathology report text alone, we can achieve 95% prediction accuracy of the top 5 most common CPT codes on our dataset. We also then demonstrate the utility of combining large language models with conformal prediction. The two in combination raise our accuracy to 99.5% when we allow the model to abstain on making a prediction on 30% of the data, as is determined by a separate threshold on the scalar value of the predictor from the aforementioned validation set. We therefore present a highly flexible model for medical coding, which is simultaneously provably-reliable. Large language models can as such serve as a powerful tool for overcoming challenges in medical billing, thereby improving healthcare efficiency and reducing medical costs.
The Predictive Value of sFlt-1/PlGF Ratio for Postpartum Preeclampsia
Authors: Li Yaxin , Cagino Kristen , Yee Jim , Andy Caroline , Grossman Tracy , Zhao Zhen 
Published: October 2024

Abstract

Background
Preeclampsia (PE) is a leading cause of maternal mortality, affecting 5% to 8% of pregnancies worldwide. Postpartum PE typically develops within the first 48 hours and can occur up to 6 weeks after childbirth and requires immediate clinical management. However, overdiagnosis may lead to unnecessary hospital admissions and overuse of medical resources. The ratio of soluble fms like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) has been evaluated as a tool to predict PE, but its utility in the postpartum setting is yet to be established.

Methods
In this study, we conducted a non-interventional, prospective study at NewYork-Presbysterian-Weill Cornell Hospital, measuring serum sFlt-1 and PlGF levels using Elecsys® and cobas e411 analyzer. The primary aim was to determine the predictive accuracy of the sFlt-1/PlGF ratio in postpartum PE, focusing on its sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) using a cutoff 38, as established in the PROGNOSIS study.

Results
Among 47 participants, 9 (19.1%) developed postpartum PE. The sFlt-1/PlGF ratio was significantly higher for the women who developed PE (55.9, IQR, 48.6-196.2) than for women without PE (19.9, IQR, 5.8-29.1). There was no significant difference in age, first-trimester body-mass index (BMI), gestational week of delivery, smoking status and nulliparous between PE and non-PE groups. Moreover, the sFlt-1/PlGF ratio at 38 cutoff point had a sensitivity of 77.8% (95% CI, 45.0-93.7) and a specificity of 81.6% (95% CI, 66.6-90.8), with a PPV of 50.0% (95% CI, 33.9-66.1). Notably, it demonstrated a high NPV of 93.9% (95% CI, 80.4-98.3).

Conclusion
Our findings suggest that the sFlt-1/PlGF ratio may be used as a predictor of postpartum PE, highlighting its significance in managing postpartum PE.
A Closer Look at the Newer GP1bM Assay Sheds Light on Unusual Findings
Authors: Asif Maryam , Tun Theingi , Sabath Daniel 
Published: October 2024

Abstract
Von Willibrand disease (VWD) is the most common inherited bleeding disorder. The 2021 Guidelines on VWD diagnosis recommend newer assays measuring the platelet-binding activity of von Willebrand factor (VWF), such as VWF: GPIbM and VWF: GPIbR, over the traditional ristocetin cofactor assay (VWF: RCo). Among these newer assays, the GP1bM INNOVANCE VWF Ac assay obtained de novo FDA approval in October 2022. Its ristocetin-independent activity distinguishes it from other assays. Our laboratory conducted a comprehensive validation on the Stago StaR-Max platform, utilizing Siemens Standard Plasma for calibration. The VWF activity measured by the GP1bM assay was compared with the existing VWF: Ab assay (IL, HemosIL® von Willebrand Factor Activity). The validation studies revealed a good correlation between the two assays. Since implementing the GP1bM assay in October 2023, our attention has been drawn to at least four cases exhibiting unexpectedly high activity levels compared to VWF antigen levels. On average, the activity-to-antigen ratio was 1.9. Notably, all these cases showed the presence of all multimers (low, intermediate, and high). Despite extensive investigation, encompassing considerations like heterophile antibody interference using scantibodies, retesting with different lot numbers of Innovance VWF Ac reagent, and rerunning tests at an outside laboratory, the cause of this anomaly remains elusive. A notable variable lies in the platform disparity between Siemens and Stago. Given the recent introduction of this assay, it has yet to gain widespread adoption in laboratories, resulting in a limited understanding of its practical variations. While recent studies affirm the overall superior performance of newer assays compared to the ristocetin cofactor assay, intricate details of each assay remain less explored. The novelty of the GP1bM assay and its limited usage in laboratories underscore the potential emergence of stable outliers as it becomes more widely adopted. The peculiar cases in our study pose an enigma as to why the reported activity is approximately double the antigen level. As laboratories increasingly embrace and integrate the GP1bM assay, a more complete understanding of its potential variations is expected to unfold. This may elucidate the mysteries surrounding these peculiar cases and ensure the assay’s robust interpretation in clinical settings.
Pediatric safety profile of low titer O whole blood with increasing Anti-A and Anti-B titers
Authors: Addams Joel , Stewart Collin , Conrad Hope 
Published: October 2024

Abstract

Objectives
To add additional evidence to the safety of using low-titer O whole blood (LTOWB) in the massively hemorrhaging pediatric population, even with increasing allowance of anti-A and anti-B titers, up to 200.

Methods
A retrospective review from December 2021 to March 2023 of the blood bank and surgical massive transfusion protocols was performed with IRB approval to identify patients less than 18 years old who had received LTOWB as part of trauma resuscitation. In addition to patient characteristics, volume of LTOWB and other components were assessed, as well as Day 1-3 of serum potassium, creatinine, and total bilirubin. Wilcoxon rank-sum tests were performed to compare continuous variables and Fisher’s exact tests were performed to compare categorical variables between group O blood groups patients and non-O blood group patients.

Results
Only ten patients were identified under 18 years of age who had received LTOWB during trauma resuscitation, with five being blood group O and five non-O. Patient characteristics were similar between the two groups; however, only 10% were female and 10% self-reported as Black or African American. Age in the non-O group was 15 +/- 3.0 and 16.2 +/- 1.3 in the O group, p=0.75. Weight was 56.16 kg +/- 7.17 in the non-O group and 64.02+/- 14.23 in the O group, p=0.35. LTOWB transfused was 10.46 mL/kg +/- 2.42 in the non-O group and 10.32 +/- 6.53 in the O group, p=0.25. Potassium, creatinine, and total bilirubin were similar on Days 1-3 in both groups, except a single high total bilirubin in the non-O group, and this value normalized on Day 3.

Conclusion
A small data set was extracted from the available massive transfusion protocol data, reflecting the small amount of pediatric patients requiring massive transfusion for trauma compared to adults. Moreover, the predominance of males requiring massive transfusion for trauma corresponds with general trauma trends in the United States. These data reflect and are similar to previous safety reviews of pediatric trauma patients receiving LTOWB. This retrospective review records, however, a time period when the titer of anti-A and anti-B had been relaxed to 200 (rather than 50 in previous studies). This study, although small, reflects an additional Level I trauma site delivering LTOWB at potentially higher titers without negative sequelae in potassium, creatinine, or total bilirubin. With upcoming randomized controlled trials, such as Massive Transfusion in Children (MATIC-2), these data continue to reassure that the practice of using LTOWB is likely safe during the resuscitation period.