bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Unusual Extramedullary Presentation of an NPM1-Mutated Acute Myeloid Leukemia (AML) in a Young Adult
Authors: Percy M C , Redemann J , Babu D , Marshall T 
Published: November 2022

Abstract

Introduction/Objective
Pleural effusion presentation of AML, particularly without leukemic disease, has been rarely described in the literature. This case serves to investigate the value of an identified NPM1 mutation.

Methods/Case Report
A 25-year-old male with Down syndrome presented with dyspnea. Computerized tomography scan identified a moderate pleural effusion and pelvic lytic bone lesions. A complete blood count was normal. Pleural fluid cytologic evaluation showed a spectrum of immature myeloid precursors, and flow cytometry identified a 23% CD117 positive myeloblast population expressing CD33, CD13, and dim CD45 but lacking CD34 and HLA-DR. Fluorescence in-situ hybridization testing was negative for a PML-RARA fusion. Given the phenotype, molecular testing was initiated and confirmed an NPM1 mutation. Testing revealed additional pathogenic variants in DNMT3A and IDH1 with no FLT3 mutations. Peripheral blood smear and bone marrow evaluations yielded no clear leukemic involvement, and cytogenetics from bone marrow showed 47,XY,+21c[20]. The significance of this myeloid infiltrate was initially not entirely clear with no established leukemic involvement or tumor-forming mass as required for the World Health Organization diagnosis of myeloid sarcoma. However, the finding of the NPM1 mutation lent high confidence for a diagnosis of an extramedullary presentation of acute myeloid leukemia, though the lytic bone lesions were not biopsied to possibly demonstrate a myeloid sarcoma.

Results (if a Case Study enter NA)
N/A.

Conclusion
The identified NPM1 mutation was instrumental in diagnosing an unusual presentation of AML where material was limited. Subsequent to this presentation the patient developed more overt leukemic disease at an outside institution, additionally supporting this diagnosis.
Whole Exome-Sequencing Identifies Variants Associated with Harris Platelet Syndrome
Authors: Das A , Naina H V , Venigalla S S 
Published: November 2022

Abstract

Introduction/Objective
Introduction: Harris platelet syndrome (HPS) is an autosomal dominant giant platelet disorder characterized by normal platelet function with varying degrees of thrombocytopenia. HPS was initially reported in healthy blood donors from West Bengal, and subsequent studies showed it is prevalent in healthy blood donors from the northeastern part of the Indian subcontinent. Objective: Whole-exome sequencing was performed to identify single-nucleotide polymorphisms in protein-coding genes and the associated pathways between the cases and controls.

Methods/Case Report
Methods: HPS is defined as healthy blood donors having a mean platelet volume (MPV) greater than 12 fL (normal &lt;10 fL) with or without concomitant thrombocytopenia in the absence of any significant past history of bleeding disorder in either themselves or their first-degree relatives. HPS and control healthy donors were enrolled in the study with proper consent. Plasma is extracted from 15 ml of blood samples that were drawn from subjects, and whole-exome sequencing was done on the samples. Pathway analysis of candidate genes and interaction mapping was done using Reactome Pathway Database and STRING, respectively.

Results (if a Case Study enter NA)
Results: Whole-exome sequencing from the plasma from HPS and non-HPS subjects (n=5 in each group) identified 1374 differentially expressed genes between the two groups. There was a total of 42 single nucleotide polymorphisms (SNPs), (5 deletions and 1 insertion) in the cases (either heterozygous or homozygous) but not in controls. 13 pathways were associated with these variants, and iron homeostasis and defective Cubulin (CUBN) were the top among the predicted pathways. HDL clearing, vitamin and cofactor transport, metabolism, and cardiac conduction defects were among the significantly predicted pathways affected by the variants in HPS patients. An interaction map of the 25 differentially expressed genes where the variants can be mapped is prepared.

Conclusion
Conclusion: This study shows that SNP variants in HPS may be associated with pathways related to iron homeostasis, HDL clearing, vitamin metabolism and transport and cardiac conduction defects. Phenomapping of HPS patients with detailed genotyping in large population cohort studies are necessary to validate and characterize the functional effect of HPS variants.
Clinical Application of Rapid PCR and Computational Digital Pathology for Cancer Diagnostics: A showcase for Advanced Lung Cancer Management
Authors: Hoo-Fatt N , Ullah A , Nam M 
Published: November 2022

Abstract

Introduction/Objective
While there has been a significant increase in our understanding of the molecular changes that occur during cancer growth, the clinical efficacy of molecular testing for cancer diagnosis treatment for advanced cancers has been limited .The objective of this project is to determine the use of rapid molecular tests with same-day turn-around-time (TAT) for tumor mutations and the application of objective AI-based digital scoring methods of Immunohistochemistry test for PD-L1 for Keytruda® (Pembrolizumab). These targeted therapies for various cancers will improve patient care by reducing turnaround time and increasing diagnostic accuracy of cancer biomarker testing.

Methods/Case Report
A combination of rapid EGFR assays, IHC for PDL1 and digital pathology scoring was used. The data received was then used for genome-wide correlation analysis of human gene CD274 and the RNA-seq dataset from The Cancer Genome Atlas (TCGA).

Results (if a Case Study enter NA)
Our preliminary study results showed that there is a correlation between Micro-RNA expression of PD-L1 and immunohistochemistry PD-L1 stains. Some micro-RNA expression showed over- expression of PD-L1, which resulted in high PD-L1 IHC score. This shows that there may be a case for more bio marker studies to aid in predicting of the response to PD-L1 pathway inhibitors. The rapid molecular testing results were also comparable to next gen sequencing (NGS) in determining the EGFR mutations. Future studies include the training of the PD-L1 AI algorithm for scoring to be used as a diagnostic companion and the use of immune based metrics to study the response and resistance to immunotherapy in non-small cell lung cancer(NSCLC).

Conclusion
We would like to showcase a combined modality diagnostic biomarker testing system that can allow the clinical decision on the targeted therapy in 24-48 hours. With the approval of Keytruda® (Pembrolizumab) in many advanced cancers, we believe that our approach for NSCLC will provide fast and high quality results for timely treatment of patients.
The Association Between Serum Hyaluronic Acid Levels and Routine Liver Function Tests in Liver Fibrotic HCV Patients
Authors: Abdelmonem M , Wasim H , Elhusseny A , Eldaly R , Saleh Abdelfattah M , Abdelmageed M 
Published: November 2022

Abstract

Introduction/Objective
Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, that occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension and often requires liver transplantation. Markers (NIM) of Liver Fibrosis, such as hyaluronic acid, help evaluate the stage of fibrosis in patients with liver fibrosis. This study aims to investigate whether or not there is a correlation between serum hyaluronic acid levels and liver function tests in patients who suffer from chronic HCV-induced liver fibrosis.

Methods/Case Report
This study was conducted on 118 (60 males and 58 females) patients recruited from Internal Medicine Dept., Mansoura University Hospitals, Egypt. The patients were diagnosed with chronic HCV-induced liver fibrosis. Also, we included 50 healthy comparable control subjects (27 males and 23 females). Routine laboratory tests such as AST, ALT, albumin, total bilirubin, and platelets count were performed. The APRI was calculated as [AST/ (upper limits of normal)/ platelets count 109/L]×100. The AST-ALT ratio was calculated as [AST/ ALT]. According to the manufacturer's instructions, the serum levels of hyaluronic acid were measured by radioimmunoassay.

Results (if a Case Study enter NA)
We observed a statistically significant positive correlation was found between serum hyaluronic acid levels and APRI (r=0.3, p=0.001), ALT (r=0.3, p=0.003), AST (r=0.3 and p=0.01), and total bilirubin (r=0.3 and p=0.002). Furthermore, there was a statistically significant negative correlation between serum hyaluronic acid levels and albumin (r= -0.43, p=0.0001), and platelets count (r= -0.4, p=0.0001).

Conclusion
The levels of hyaluronic acid in the body and the results of other liver function tests tend to rise in tandem, which suggests a significant relationship between the two. This may assist us in constructing an accurate picture of the patient's condition, which will lead to a more precise diagnosis.
Quality Improvement at the Laboratory’s Specimen Reception Station
Authors: Ong S , Pasaribu S , Tan S , Aw T , Huang J , Woo M , Koh S , Khoo K 
Published: November 2022

Abstract

Introduction/Objective
In our 1000-bed acute care tertiary hospital, physicians order laboratory tests via the computerized-provider-order-entry (CPOE) system and print barcode labels (patient demographics/tests ordered) at the computer-on-wheel printer. When tubes with unsuitable barcodes (misaligned, poor quality) are received at the laboratory specimen reception area a fresh barcode is re-printed by our laboratory staff. An incident involving a re- printed barcode label pasted on the wrong blood tube prompted an investigation into the quality of barcodes.

Methods/Case Report
We initiated ‘an opportunity for improvement (OFI) project’ at the laboratory specimen reception station. The OFI team involved Nursing, Information Technology (IT) and Pathology departments aimed to eliminate re-printing of barcode labels by 75% within 6 months. We collated and analyzed reasons for re-printing of barcodes on 3 separate 48-hour periods (27-28 April 2020, 24-25 June 2020, and 13-14 June 2022). A series of interventions and initiatives were implemented.

Results (if a Case Study enter NA)
Re-printed barcodes were from the Emergency Department (56%), Out-patient clinics (7%) and Wards (57%). Root cause analysis(RCA) using the “5 whys” technique categorized re-print causes into staff-related (misaligned barcodes) and printer-related (faint barcodes lines/truncated un-verifiable patient demographics). The team mass-emailed clinicians an educational “Do-You-Know” guide on proper pasting of barcodes on blood tubes and instructions on how to obtain help for printer rectification. These guide documents were placed in the hospital-wide document-sharing portal - Docupedia. Immediate close follow-up with sites that had poor barcodes was done in real-time. Barcode reprints decreased 83% within 2 months - from 174 (27-28 Apr 2020) to 30 (24-25 Jun 2020). A recent audit showed sustained elimination of barcode re-printing: 25 cases (13-14 Jun 2022).

Conclusion
The OFI project has successfully raised the quality of CPOE labels on specimen tubes contributing to process efficiency and safer patient care. Close communication with all care sites and their representatives on the OFI team are critical success factors.
Laboratory Testing for Obstetrics Patients at Academic and Non-Academic Health Systems
Authors: Windham A K , Staker C , Zhou Y , Whitted M , Brimhall B , Podichetty A 
Published: November 2022

Abstract

Introduction/Objective
Evaluation of obstetric clinical laboratory test utilization differences between academic and non-academic health systems would provide important benchmarking information for healthcare leaders and policy makers.

Methods/Case Report
Over a 3-year period (2019-2021), using the Vizient® Clinical Data Base with permission from Vizient, Inc. (All rights reserved.), we compared clinical laboratory utilization for adult obstetrics inpatients at mid-size (250-450 hospital beds) academic (N=9; 27,036 hospitalizations) and non-academic (N=17; 50,462 hospitalizations) hospitals across the US. We used Medicare Severity Diagnosis Related Groups (MSDRG), employed by the US Centers for Medicare and Medicaid Services (CMS), to identify Cesarean section (MSDRG triplet 786-788) and vaginal delivery (MSDGR triplet 805-807) patient groups. For both groups, we stratified by comorbid conditions and complications into high, moderate, and low severity subgroups. We compared the mean number of laboratory tests (CPT codes 80000-89999) per hospitalization and per hospital day. We measured aggregate Clinical Resource Intensity Weight (RIW) per hospitalization to quantify laboratory resource consumption for each encounter. The RIW is based on the CMS Ambulatory Payment Classification (APC) weights.

Results (if a Case Study enter NA)
Academic hospitals had a significantly (p&lt;.01) higher mean number of lab tests per Cesarean section hospitalization (20.3 vs. 10.3 tests, 97.1% higher) and hospital day (4.7 vs. 3.3 tests, 42.4% higher). Laboratory RIW per case was also significantly (p&lt;.01) higher at academic hospitals (4.8 vs. 3.6 RIW, 33.3% higher); however, RIW per day did not differ between academic and non-academic hospitals. Significant differences (p&lt;.01) persisted after adjusting for severity level. Although differences were smaller, academic hospitals had greater lab tests per case (12.1 vs. 8.1 tests, 49.4% higher) and day (4.3 vs. 3.6 tests, 19.4% higher) for vaginal delivery hospitalizations. Laboratory RIW per case was also significantly (p&lt;.01) higher at academic hospitals (3.4 vs. 2.8 RIW, 21.4% higher). Laboratory RIW per day did not differ significantly. Significant differences remained for the high and moderate severity vaginal delivery groups.

Conclusion
Academic hospitals have greater laboratory test utilization for obstetrics patients. This difference appears to be largely due to a longer mean length of stay as well as use of tests with higher RIW.
High-Volume Laboratory Tests as Baseline for Benchmarking Less-Common Tests
Authors: Windham A K , Zhou Y , Brimhall B , Podichetty A 
Published: November 2022

Abstract

Introduction/Objective
Benchmarking establishes baseline laboratory utilization patterns across health systems. Nicholas et al. (2021) recently evaluated the use of test volume ratios to identify utilization intervention targets at VA hospitals. We aim to investigate potential differences of reported test volume ratios with those of non-VA hospitals.

Methods/Case Report
Using the Vizient® Clinical Data Base with permission from Vizient, Inc. (All rights reserved.), we obtained aggregated annual test and patient volumes from 2019-2021. To assess the accuracy of high-volume tests as a surrogate for patient volumes, we compared mean annual sodium and MCV test volumes with mean annual number of patient encounters at 712 hospitals (7,685,149 mean annual patient volume). We then calculated test volume ratios for eight less common analytes (homocysteine, prolactin, vitamin D (25-OH), HCV viral load, HIV viral load, Lyme disease serology, CD4, and HSV serology) at hospitals with patient encounters greater than 10,000 (279 hospitals, 6,046,670 mean annual patient volume). We calculated ratios using mean annual number of 1) sodium tests and 2) patient encounters as the denominator for comparison to reported ratios. All analytes are included in Choosing Wisely™ guidelines.

Results (if a Case Study enter NA)
There was strong positive correlation between mean annual sodium and MCV test volumes and mean annual patient volume (R = 0.92 and R=0.96, respectively). Our analyte-to-sodium volume ratios were smaller than expected. However, the analyte-to-patient volume median ratios were similar to those reported. A comparison of the calculated ratios showed a strong positive correlation (R=0.90), but the sodium ratios were nearly 4x smaller than the patient volume ratios. On average, the two methods agreed nearly 70% of the time for institutions with ratios greater than the 90th percentile- the intervention threshold. In comparison to previously reported median ratios, five analytes (homocysteine, prolactin, vitamin D (25-OH), Lyme disease serology and HSV serology) showed a significant difference from previously published ratios.

Conclusion
In comparison to VA hospitals, significant differences in median ratios were found. For calculating test volume ratios, high-volume tests are an adequate surrogate for patient volumes but may pose a challenge for inter- institution comparisons. Standardization for quantifying high-volume tests would improve the use of test volume ratios for benchmarking.
Safety Concerns for Laboratory Professionals in Rural Practice Settings During Covid-19
Authors: Williams J , Nunez-Argote L , Campbell J L , Brooks J 
Published: November 2022

Abstract

Introduction/Objective
The COVID-19 pandemic exacerbated the health risks of laboratory professionals. This study aimed to understand the impact increased workload and decreased staffing levels have, specifically in rural areas where clinical laboratory testing is performed, and to document how these changes affect the wellbeing of laboratory professionals.

Methods/Case Report
The study integrated responses from a cross-sectional study of laboratory professionals which employed an anonymous electronic survey deployed between November of 2021 and February of 2022. Specific items asked if participants had worked in clinical laboratories since the public health emergency started, if they were concerned regarding Covid-19 transmission, adequate staffing, and support at their workplace. A subsequent qualitative study including focus groups and an interview questionnaire targeted laboratory professionals working in rural laboratories in four states of the Mid-west to further understand any immediate health impacts on wellbeing for these professionals.

Results (if a Case Study enter NA)
Among 438 participants in the survey that indicated they worked in the laboratory since March of 2020, 20% said they worked in non-metro US counties (RUCC 4-9). Among the non-metro laboratory professionals, 70% indicated that staffing levels in their laboratories were inadequate, with over 50% of them expressing concern about contracting Covid-19 at their workplace, and 53% saying they had been told to work despite a possible or confirmed exposure to the virus. The analysis of thirteen focus groups (N=59) and qualitative written interviews (n=15) found that workplace changes impacted the health of laboratory professionals in rural areas. These included lack of availability of laboratory equipment and increased work hours, which increased self-reported levels of stress. Recommendations for improvement included flexibility in scheduling of hours and proper compensation for overtime work.

Conclusion
Working in rural clinical laboratories during the Covid-19 pandemic exposed laboratory professionals to stress that was exacerbated by a work environment operating in scarcity.
Metastatic Common Bile Duct Melanoma Presenting as Obstructive Jaundice: A Case Report and Review
Authors: Kaur N , Rahmanov N , Varshney N , Tang S J 
Published: November 2022

Abstract

Introduction/Objective
Malignant melanomas (MM) account for 4-7% of all new cancer cases. The most common primary site is the skin, however, in 1.3% of cases, these tumors originate from the mucous membranes of the respiratory, genitourinary, and gastrointestinal tracts. The metastatic spread to the biliary system is extremely infrequent, with rare reports in the literature. Herein, we report a case of history of cutaneous MM with metastasis to the biliary tract.

Methods/Case Report
A 35-year-old Caucasian female presented with pruritis, dark urine, and jaundice. Laboratory results favored the cholestatic process (total bilirubin – 10 mg/dL, alkaline phosphatase – 500 U/L, AST- 400 U/L, ALT – 1000 U/L). She had a remote diagnosis of MM of the left chest with metastases to bilateral axillary and periclavicular lymph nodes 8 years ago. She underwent wide local excision of the skin lesion and lymph node dissection then. ERCP with direct cholangioscopy revealed a 3 x 2 cm obstructive mass in the common bile duct which was biopsied to reveal cohesive, pleomorphic, epithelioid cells containing black-brown pigment with enlarged, irregular, and hyperchromatic nuclei. These atypical cells stained strongly with SOX10 and Mart-1 immunohistochemical stains, confirming the diagnosis of metastatic malignant melanoma.

Results (if a Case Study enter NA)
NA.

Conclusion
MM is cancer that originates from melanocytes, derived from the neural crest during embryogenesis. The pathogenesis of metastatic spread to the biliary system is still unknown due to the paucity of literature describing this. Diagnosis is often difficult, with many patients completely asymptomatic or occasionally presenting with biliary symptoms. There should be a detailed history, and extensive clinical workup along with extensive histological and immunoprofile, esp. in cases with a history of cutaneous melanoma for early detection of a potential metastasis leading to adequate management.
Correlation of SARS-CoV2 Viral Growth on Cultures, Ct Values, SARS-CoV-2 Variant and Vaccination Status in Asymptomatic, Pre-Symptomatic and Post-Infection Asymptomatic COVID Patients
Authors: Kaur H , Morris C P , Gallagher N , Norton J , Eldesouki R , Mostafa H , Sachithanandham J , Pekosz A 
Published: November 2022

Abstract

Introduction/Objective
COVID-19 large scale immunizations have helped control the infectious spread, but breakthrough infections are still observed and some of these patients remain asymptomatic. In this study, we compared the viral growth characteristics with vaccination status in asymptomatic patients.

Methods/Case Report
We searched our institutional laboratory database for asymptomatic patients infected with delta variant (November-December 2021, n=65) and omicron variant (December 2021, n=68), that were further classified as “truly asymptomatic”, “pre-symptomatic” and “post-infection asymptomatic” based on detailed chart reviews. The patients’ left-over nasopharyngeal swab samples’ cycle threshold values and the recovery of infectious virus in cell culture were compared.

Results (if a Case Study enter NA)
In the delta cohort, out of 65 asymptomatic patients, 36 were truly asymptomatic, 26 presymptomatic and 3 post infection asymptomatic patients. In the omicron cohort, out of 68 asymptomatic patients, 45 were truly asymptomatic and 23 were presymptomatic patients. The vaccination rate was 59% in truly asymptomatic (delta cohort=56%, omicron cohort=62%), 55% in presymptomatic (delta cohort=50%, omicron cohort=61%) and 67% in post-infection patients (delta cohort only). There was no significant difference in the Ct values of truly asymptomatic (mean Ct=21.08), presymptomatic (mean Ct=20.30) and post-infection asymptomatic patients (mean Ct=20.84) in the combined cohort (p=0.78) and in the delta (p=0.95) or omicron (p=0.45) subcohorts. The Ct values were not correlated with the vaccination status of the patients (vaccinated patients mean Ct=20.56, non-vaccinated patients mean Ct=20.16, p=0.68). Samples with positive viral growth on cultures had significantly lower Ct values (mean Ct= 17.16), compared to samples with negative viral culture results (mean Ct= 24.61) (p&lt;0.0001). The viral growth on culture was not associated with the symptom status, SARS-CoV-2 variant type (delta vs omicron) and vaccination status of the patients in the delta and omicron subcohorts.

Conclusion
Our findings show that there is no significant correlation between vaccination status and viral loads and culture results in asymptomatic patients.