bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myeloid/Lymphoid Neoplasms With Fibroblast Growth Factor Receptor 1 Rearrangement: A US Real-World Chart Review
Authors: Parasuraman S , Saverno K , Colucci P , Kish J , Zimmerman-Savill K 
Published: November 2023

Abstract

Introduction/Objective
Myeloid/lymphoid neoplasms (MLN) with fibroblast growth factor receptor 1 gene (FGFR1) rearrangement (MLNFGFR1) is a rare and aggressive hematologic malignancy characterized by molecular disruption of FGFR1 at the 8p11 locus. This real-world study describes demographic and clinical characteristics, diagnostic testing, and clinical outcomes in patients with MLNFGFR1 in the US.

Methods/Case Report
Probable MLNFGFR1 cases (n=51) were identified from a retrospective, physician-abstracted (5/29/2020-6/23/2020) chart review of patients within the US Cardinal Health Oncology Provider Extended Network (feasibility survey). In a subsequent full chart review (12/29/2020-3/4/2021), 33 of these probable MLNFGFR1 cases were considered to be confirmed based on additional 8p11/FGFR1 testing result data collected. Descriptive analyses of demographic/clinical characteristics, diagnostic testing, and clinical outcomes of patients with confirmed MLN FGFR1 were performed.

Results (if a Case Study enter NA)
The mean age at initial MLNFGFR1 diagnosis was 65.9 (SD 13.5) years, 60.6% patients were male, and 63.6% were white. Patients were managed by 12 physicians,10 in community practices.
FGFR1 translocations were identified by karyotyping in 72.7% of patients. Rearrangements in FGFR1 were detected by fluorescence in situ hybridization, next generation sequencing, and/or real-time polymerase chain reaction in 66.7%, 21.2% and 6.1% of patients, respectively. FGFR1 rearrangement was detected in bone marrow aspirate and peripheral blood in 90.9% and 9.1% of patients, respectively. Fusion partners ZMYM2 and CPSF6 were reported in 46.2% and 15.4% of patients, respectively, and BCR, CUX1, RANBP2, TPR, and MYO18A were reported in 7.7% of patients each.

Conclusion
Although rare, patients with MLNFGFR1 do present in US community practice settings. Conventional cytogenetics can identify FGFR1 translocations which can be confirmed by FISH with FGFR1 break-apart probes. NGS can be used to identify cryptic rearrangements when clinical suspicion is high but no rearrangement is present on FISH. In addition to diagnosis, RT-PCR is also useful to assess molecular response.
Nine-Gene Prognostic Signature for Myelodysplastic Syndrome
Authors: Lyapichev K , Kazacheuskaya L , Memon M D , Ong M , Cotelingam J , Beedupalli K , Centeno L , Patil A 
Published: November 2023

Abstract

Introduction/Objective
Myelodysplastic Syndrome (MDS) is a family of clonal hematopoietic malignancies found frequently in the seventh and eight decades, supporting that aging and acquired somatic mutations drive development of the disease. Without a cure, the prognosis is poor. Patient consideration for bone marrow transplantation remains low (&lt;5%), and enrollment in clinical trials is slightly better (25%). Information regarding MDS-specific whole genome sequencing, a prognostic prediction system, and overall survival is limited and may be beneficial in developing curative therapies. Hence, we aimed to analyze the genomic profile, epidemiology, and overall survival of MDS.

Methods/Case Report
We utilized cBioPortal cancer genomics [The Cancer Genome Atlas (TCGA) PanCancer Atlas, TCGA Firehose Legacy, and TCGA Nature 2013] to study the mutations associated with MDS. Epidemiological characteristics and genetic profiles available on cBioportal were evaluated. Gene mutations with the most statistically significant, shortest overall survival and survival in days were used for the gene query, and survival rate with the common mutations was calculated. Logrank test and Kaplan–Meier estimators were used in analyzing the survival function. Patients with two or more overlapping mutations were excluded.

Results (if a Case Study enter NA)
We identified 7,554 patients with MDS out of which 2,852 had a primary MDS. There were 3,323 patients who had gender and age data available. 26.5% were male, and most patients (600) were between the ages of 70-75 years. 1573 (20.8%) were alive and 1600 (21.2%) were deceased. The common mutations associated with reduced survival were ASXL1, NPM1, FLT3, TET2, SF3B1, SRSF2, STAG2, RUNX1, TP53. Median survival of patients with these mutations was 32.02, 27.32, 25.97, 64.21, 80.94, 46.82, 44.28, 16.21, and 10.52 months respectively in comparison with the unaltered mutation group (68.68) (p &lt; 0.0001). Survival was lowest amongst TP53 10.52 months and RUNX1 16.21 months. Leukemia free survival with ASXL1, NPM1, FLT3, TET2, SF3B1, SRSF2, STAG2, RUNX1, and TP53 mutations was 27.88, 13.02, 23.44, 56.52, 79.96, 37.32, 24.89, 14.86,
and 9.44 months respectfully in comparison to the unaltered mutation group (68.68) (p &lt; 0.0001).

Conclusion
Our study found that TP53 and RUNX1 genes were associated with the worst prognosis in MDS with median survival of 10.52 and 16.21 months, respectively. This study may provide insight for genetic predictors and targeted therapies for MDS, as well as provide better understanding of patient prognosis.
Validating Recorded EHR and Actual Weight: Single Institution Study
Authors: Yeon S , Turcios Escobar S E , Janiszewski S , Lauridsen L , Campbell-Lee S , Allison D 
Published: November 2023

Abstract

Introduction/Objective
Our hemapheresis clinic performs outpatient and inpatient therapeutic apheresis procedures including red blood cell exchange and therapeutic plasma exchange. Accurate height, weight, and hematocrit are required for calculating replacement fluid volumes for both procedures. Our practice has been using the patient’s most recent weight recorded in the EHR. The purpose of this quality improvement project is to validate concordance between patients’ actual body weight and documented body weight.

Methods/Case Report
STUDY DESIGN AND DATA COLLECTION
We performed this quality improvement project in our hemapheresis clinic. The study focused on weight variations impacting calculations for apheresis volume requirements. Data were collected from March 20th, 2023 – April 20th, 2023. Patients receiving red blood cell exchange or therapeutic plasma exchange were randomly selected and weighed prior to the procedure on a calibrated scale. The most recently recorded weight in the EHR was also collected. Non-ambulatory patients or patients receiving phlebotomy or stem cell collection were excluded from the study.
Statistical Analysis:
Statistical analyses were performed using R Statistical Software (Foundation for Statistical Computing, Vienna, Austria). We compared means of two observations using a paired t-test. P values less than 0.05 were considered to be statistically significant to test null hypothesis.

Results (if a Case Study enter NA)
A total of 40 patient data were collected. Seventeen male and 23 female patients were weighed and recorded. The mean value of EHR weight is 70.56kg and that of clinic weight is 71.41kg (P=0.08701). The weight discrepancy was calculated in comparison with EHR recorded weight and it was transformed to weight discrepancy by percentage using d(clinic weight -EHR weight)/clinic weight*100. Out of 40 patients, 33 patients had weight discrepancy by percentage between 0 to 4%.

Conclusion
Patient body weight is an important factor in calculating the replacement volume requirements in therapeutic apheresis. It is often prescribed based on the recorded EHR weight. In our data, we have shown that the weight discrepancy is not significant and therefore EHR recorded weight is reliable in replacement volume calculation. Our study is subject to several limitations that it was conducted for one month in a single institution and the sample size is not large. However, our study is novel in describing the relationship between recorded patient data and the actual patient data.
Unpredictable Blood Product Usage in Orthotropic Liver Transplantation: A Foregone Conclusion or A Problem Solved by Artificial Intelligence?
Authors: Gosnell H L , Barouqa M , Rashidi H , Reyes Gil M 
Published: November 2023

Abstract

Introduction/Objective
Orthotropic liver transplantation (OLT) is a complex procedure requiring coordination between operative and transfusion medicine staff. Unanticipated blood product demands during these surgeries strain blood bank inventory, especially when units are needed for patients with significant alloantibodies. Currently, transfusion medicine services issue set numbers of crossmatched red blood cell (RBC) units for these procedures. At our institution, 10 units are issued for each OLT. This project categorized OLT patients into three groups by RBC unit requirements: &lt;5 units, 5-9 units and &gt;10 units. Furthermore, we identified pre-operative clinical and lab factors predicting placement into each category. From this data, we developed an artificial intelligence platform (CCBBAI-1).

Methods/Case Report
We collected data from 474 adults (&gt;18 years old) that underwent OLT from Jan. 1, 2021, to Dec. 31, 2022. Demographic, anticoagulant, and lab testing data generated within 24 hours of admission were obtained. Data analysis was performed in R-studio. CCBBAI-1 was built using machine intelligence learning optimizer platform (MILO).

Results (if a Case Study enter NA)
Based on univariate regression analysis (p-value&lt;0.05, 95% confidence interval (CI)), the following lab variables were predictive of &gt;10 RBC units issued: high INR (OR 3.48 [CI 2.35-5.26]), admission heparin dosage (2.61 [1.56-4.31]), total bilirubin (1.06 [1.04-1.08]), conjugated bilirubin (1.08 [1.04-1.11]), PTT (1.04 [1.03-1.06]), BUN (1.03 [1.02-1.04]), and creatinine (1.55 [1.33-1.83]). Low albumin (1.50 [1.13-2.22]) and MCV (1.04 [1.02-1.07]) also projected a 10 RBC unit procedural requirement. The univariate regression analysis variables predictive in categorizing patients requiring 5-9 units vs &lt; 5 units were as follows: decreased albumin (2.17 [1.42-3.33]), decreased serum calcium level (1.72 [1.13-2.63]) and elevated INR (2.14 [1.36-3.40]). The mean number of units issued for each patient group including those requiring &gt;10, 5-9, and &lt;5 units were 22, 7, and 2 units, respectively. CCBBAI-1 achieved a sensitivity of 87.0% and specificity of 70.0% in classifying patients requiring &gt;10 RBC units. Patients needing &lt;10 units were analyzed in a second module to determine if they needed 5-9 units, achieving a sensitivity of 64.7% and a specificity of 62.4%.

Conclusion
Our study divided OLT patients into three categories and identified predictive laboratory values characterizing each group, a step towards improving transfusion medicine efficacy in this context.
Blood Shortage Monitoring: Comparison of the Supply Situation During the Omicron Surge and at the Tail End of the COVID-19 Pandemic this Year
Authors: Petersen J M , Jhala D 
Published: November 2023

Abstract

Introduction/Objective
The COVID-19 pandemic was marked by the first-ever declaration of a severe blood crisis by the American Red Cross in 2022. During this blood crisis, the, there were significant shortages of blood products that required precise monitoring of the current stock for communication and collaboration with the clinical team to ensure uninterrupted patient care. The blood supply gradually improved since 2022’s blood crisis, particularly as the public health emergency related to COVID-19 ended on May 11th, 2023. However, published literature on the comparison of the blood supply in the last calendar months of the public health emergency versus during the blood shortage is sparse.

Methods/Case Report
From January 28th, 2022, to February 28th, 2022, the amount of red blood cell (RBC) inventory was noted along with the percentage reduction from usual pre-crisis inventory level. This inventory information was communicated with the clinical services to coordinate clinical care during the blood supply crisis. Additionally, a separate inventory comparison to cover the last 5 calendar months (including May) until the end of the Public Health Emergency on May 11th, 2023, was performed from January 1st, 2023, to May 11th, 2023.

Results (if a Case Study enter NA)
During the crisis from January 28th, 2022, to February 28th, 2022, there were significant reductions in red blood cell inventory (up to 67% reduction in O+ units and 75% for A+ units). Collaboration with the clinical team and efforts to procure and conserve blood products enabled continuity of clinical care. On the other hand, there was documented improvement in the blood inventory at the tail end of the pandemic (January 1st, 2023, to May 11th, 2023) with average inventory reductions of only 19% in O+ units and 43% in A+ units.

Conclusion
There was a significant blood shortage during the Omicron surge of 2022 that required inventory monitoring, collaboration with the clinical team, and efforts to procure and conserve blood products to ensure continued successful clinical care. As the pandemic’s public health emergency neared its end, the blood supply situation has been improving substantially.
Trends in hematopoietic stem cell utilization and cost of cryopreservation
Authors: Jebackumar Travis , Soundar Esther 
Published: November 2023

Abstract
Autologous stem cell transplantation (ASCT) is the standard of care treatment for multiple myeloma. Standard ASCT procedures collect hematopoietic stem cells (HPSC) in excess for multiple transplants due to reports of high mobilization failure and unsuccessful ASCT collections following myeloablative treatments. Cost analysis studies estimate that one year of cryopreservation and one day of HPSC collection would each cost $5000 per patient. Limited data is available on the usage of the second transplant and the storage costs of non-transplanted products. This study evaluates the utilization of cryopreserved HPSC products and calculates the cost of cryopreservation. A retrospective chart review study of a cohort of 240 deceased MM patients, who received ASCT between January 2010 to December 2015. Demographic and clinical data were obtained from the laboratory and electronic medical record. The cohort was categorized into two groups, with 130 patients in Group 1 (≤60 years) and 110 patients in Group 2 (&gt;60 years). Cumulative incidence of a second transplant was computed from the life table using the Kaplan Meier method. The cost of cryopreservation was calculated based on the time HPSC products remained in the freezers before disposal. PBSC was mobilized using Granulocyte Colony Stimulating Factor (GCSF), or GCSF and Mozobil. The average age of patients at first collection is 61 (IQR: 54-66) years and the average age of death is 64 (IQR: 58 -70) years. The average life span of patients after receiving the first transplant is 3 (IQR: 2-5) years. The average number of collection days is 2 (IQR: 1-3). 65 patients had 1-day collections, 105 had 2-day collections and 70 had ≥3-day collections. 175 patients (73%) had &gt;1 day collection. Only 22 patients (9%) received a second transplant and 18 of them (82%) were in Group 1 (≤60). The cumulative incidence of a second transplant by 5 years is 23% for Group 1 and 4% for Group 2. Two-transplant collections required 492 days of apheresis with an overall cost of $2,500,000; however, one-transplant collections would cost $1,400,000 for 279 apheresis days. The median cost of cryopreservation for each patient who did not receive the second transplant is $15,000 (IQR: $8000 - $25,000). Therefore, the estimated cost for all patients in the study is $3,600,000 until the disposal of HPSC products. The incidence of a second transplant is low across all patients and significantly lower in patients greater than 60 years of age. Cryopreserved stem cell products remain under-utilized, leading to substantial financial burden. The duration of HPSC collection and cryopreservation must be re-evaluated for future treatment plans. Institutional policies should be revised based on the utilization trend to lower the operational cost of storage.
Lorazepam Detection with Urine Benzodiazepines Screening Tests: Not all Tests are Created Equal
Authors: Akter Tanjina , Babic Nikolina 
Published: November 2023

Abstract
Lorazepam belongs to the benzodiazepines family of drugs and is one of the commonly used anti-anxiety medications in the US. In clinical practice, immunoassay screening tests are used to monitor compliance, detect abuse and in cases of drug overdose. Many clinicians rely on benzodiazepine immunoassay screening tests to detect lorazepam due to the test availability on automated clinical analyzers, short turnaround time and cost efficiency. However, compromised test sensitivity often leads to erroneous results. In this study, we used mass spectrometry to establish the lorazepam cross-reactivity threshold in two commonly used benzodiazepine screening tests: the Abbott ARCHITECT cSystem 16000 and NexScreen Drug Screen Cup.
Methods: Mass spectrometry testing was performed at a major reference laboratory. Lorazepam-positive patient urine at concentrations of 320 ng/mL and 4,895 ng/mL were tested concurrently by two immunoassay methods. The Abbott ARCHITECT is a semi-quantitative assay with a positivity cut-off of 200 ng/mL. According to the manufacturer’s instructions for use (IFUs), the cross-reactivity threshold of the test is equivalent to a lorazepam concentration of 650 ng/mL. The NexScreen Drug Screen Cup is a lateral flow immunoassay used as a point-of-care (POC) test. The positivity cut-off of this test is 300 ng/mL; per IFUs, the cross-reactivity threshold of this test to lorazepam is 3,900 ng/mL, and 5,000 ng/mL for lorazepam-glucuronide, a drug metabolite. To determine the test sensitivity of the NexScreen test, patient specimen (4,895 ng/mL) was diluted at 1:5, 1:10, 1:20, 1:50, and 1:100, targeting the lorazepam concentrations of 979, 490, 245, 98 and 49 ng/mL respectively. To determine the sensitivity of the immunoassays to the parent molecule vs the metabolite, pre-screened negative urine was spiked with lorazepam or lorazepam-glucuronide at a concentration of 650 ng/mL, 5000 ng/mL, and 10000 ng/mL.
Results: Abbott ARCHITECT failed to detect lorazepam in both patients, while the NexScreen resulted in positive benzodiazepine screen results for both patient specimens. All lorazepam-spiked specimens tested positive on both methods. However, all lorazepam glucuronide-spiked specimens tested negative on Abbott ARCHITECT and positive on NexScreen cup. The highest dilution detected by NexScreen was 1: 20, equivalent to approximately 245 ng/mL of lorazepam.
Conclusion: Our findings suggest that the ARCHITECT benzodiazepine assay should not be used to screen patients on lorazepam, given its inability to detect the major metabolite, lorazepam glucuronide. Whenever available, a mass spectrometry method is always preferred. The results of our study demonstrated that in a specific patient population, where the likelihood of positive lorazepam test is high, the NexScreen cup is a viable, cost-effective alternative due to its excellent sensitivity.
Performance of a Modified ALLType NGS HLA Typing Assay with the Ion Chef/Ion S5/TypeStream Visual System
Authors: Shen Manli , Duffy Brian , Jennemann Jo-ellen , Willey Patricia , Tang Mei San , Brescia Peter , Lee Jar How , Liu Chang 
Published: November 2023

Abstract

OBJECTIVE
S: The commercial ALLType assay (One Lambda, West Hills, CA) enables accurate, high-resolution typing of 11 HLA genes using the Ion Chef/Ion S5/TypeStream Visual (TSV) system. The assay features a multiplexed PCR to enrich all target HLA genes in a sample, and up to 48 samples can be indexed and sequenced in a run. The assay is laborious due to the late pooling of indexed libraries. Early pooling significantly simplifies the workflow but may increase the background noise and typing errors. This project aims to examine the feasibility of early pooling immediately after the indexing step and evaluate the performance of such a modified ALLType protocol.

METHODS
A total of 75 unique samples with diverse HLA genotypes were included in this study, which comprised 52 proficiency testing samples of three different sources, 10 stem cell recipients, 7 stem cell donors (including 2 buccal swabs), and 6 deceased organ donors. Genomic DNA extracted from these samples was tested in four sequencing runs, with 15-31 samples per run, using the modified ALLType procedure (reagent lot: 15). The results were compared with the reference typings generated by the manufacturer-established protocol. All data were analyzed using TSV (version 3.0) and the IPD-IMGT/HLA library (version 3.47); the default analysis parameters were applied. The primary endpoint of the study was the concordance of 3-field typing results. The secondary endpoint was key health metrics, including allele balance, key-exon coverage, and background noise. We also evaluated the saving on hands-on time and reagents with the modified protocol.

RESULTS
The concordance rates of 3-field typing results were 100% for HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, and HLA-DRB1, and 96.2% for HLA-DRB3/4/5. The three discrepant HLA-DRB3/4/5 results with the modified protocol were false positive allele calls due to a small number of contaminating reads, which were corrected by increasing the threshold for HLA-DRB3/4/5 in TSV. The allele balance and exon 2 coverage across all samples and genes were comparable between the modified and reference protocols, with R-squared values of 0.83 and 0.81, respectively. High background signals in exons were observed in only 0.6% of all samples with both protocols. The modified protocol reduced the hands-on time by 15%, from 6.5 to 5.5 hours, and reduced the use of library preparation reagents by 30%.

CONCLUSION
It is feasible to pool indexed libraries early during the library preparation process without increasing the background noise in the sequencing data. The modified ALLType protocol showed typing accuracy and health metrics comparable to the original protocol, with significant savings on time and reagents.