bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Synchronous Development of Acute Myeloid Leukemia and Multiple Myeloma: A Rare Case Presentation”
Authors: Alrammahi A , Ndam F , Snower D , Kapila N 
Published: October 2024

Abstract

Introduction/Objective
The co-occurrence of acute myeloid leukemia (AML) and multiple myeloma (MM) presents a diagnostic challenge, particularly when it arises without prior chemotherapy exposure. This study aims to elucidate the clinical characteristics, diagnostic approach, and management implications of such synchronous hematologic malignancies through a detailed case report.

Methods/Case Report
A 64-year-old female with no previous medical history presented with chest pain, shortness of breath, and hematologic abnormalities. Clinical evaluation revealed severe pancytopenia, cystic liver mass, enlarged retroperitoneal lymph nodes, and hypercalcemia. Peripheral blood smear indicated hematologic malignancy, prompting further investigation. Bone marrow aspirate analysis, including flow cytometry and immunohistochemical stains, was performed to confirm the dual cell populations of AML blasts and MM plasma cells.

Results (if a Case Study enter NA)
Flow cytometric analysis and immunohistochemical stains of the bone marrow aspirate confirmed the presence of distinct cell populations: blasts expressing markers consistent with AML and abundant plasma cells indicative of MM. Monotypism of plasma cells was established, with kappa predominance. Notably, there was no coexpression of markers between the AML blasts and MM plasma cells.

Conclusion
This case highlights the rare occurrence of synchronous AML and MM in a patient without prior chemotherapy exposure. The diagnostic approach involving flow cytometry and immunohistochemical stains proved essential in confirming the dual hematologic malignancies. Clinicians should be vigilant for such presentations, as timely diagnosis and appropriate management are crucial for optimizing patient outcomes in these complex cases.
Myeloid neoplasm with concurrent BCR::ABL1 translocation, and JAK2 and SF3B1 co-mutations with severe fibrosis: a case report
Authors: Hanan A , Safdar J , Khan A , Gur H , Lee J , Mahmood N , Karp L , Singh R , Shaham M , Spitzer S , Arif M , Cohen N 
Published: October 2024

Abstract

Introduction/Objective
Myeloproliferative neoplasms (MPNs) arise from hematopoietic stem cells with somatically altered tyrosine kinase signaling. Classification of MPNs is based on hematologic, histopathologic and molecular characteristics including the presence of BCR::ABL1 and JAK2 V617F.

Methods/Case Report
We present a 72-year-old male with a myeloid neoplasm and severe fibrosis, with concurrent BCR::ABL1 translocation, and co-mutations in JAK2 and SF3B1. Initially, the patient was diagnosed with anemia, thrombocytosis and folic acid deficiency and was prescribed supplemental folic acid. At follow up, normocytic anemia and thrombocytosis were seen. Bone marrow biopsy showed overtly fibrotic marrow with maturing trilineage hematopoiesis, markedly increased megakaryopoiesis and ring sideroblasts. Chromosome analysis and sequential GTG-fluorescence in situ hybridization (FISH) of metaphases using the dual-fusion three color probe BCR/ABL1- ASS1 revealed abnormal results. A t(9;22)(q34;q11.2) was detected along with an atypical FISH signal pattern with a single BCR::ABL1 fusion on the derivative chromosome 22 instead of the typical two fusions, resulting in loss of one BCR::ABL1 fusion signal including loss of the ASS1 on the derivative chromosome 9. Next-generation sequencing (NGS) analysis detected double driver mutations, JAK2 p. Val617Phe and SF3B1 p. Lys700Glu in the patient. JAK2 V617F mutation was further confirmed by real-time quantitative PCR (qPCR) with variant allele frequencies of 39.7%. Additionally, the patient was positive for BCR::ABL1 p190 fusion transcript (10%). The presence of JAK2 and SF3B1 co-mutations along with ring sideroblasts and the patient’s clinical presentation suggests the diagnosis of myelodysplastic/myeloproliferative neoplasm with thrombocytosis and SF3B1 mutation.

Results (if a Case Study enter NA)
NA

Conclusion
Although, the detection of t(9;22) by chromosome analysis is a diagnostic feature of chronic myeloid leukemia (CML), our case adds to the limited information on co-existence of BCR::ABL1 and JAK2 V617F with SF3B1 mutations in severe fibrosis. The frequency of co-occurrence, the temporal order of acquisition and clonal relationship of these alterations is poorly understood, and it is also unclear for this case since there is no prior bone marrow biopsy or diagnostic work up. Literature search of these rare cases show that some patients with similar findings progress to myelofibrosis as in this patient. It is possible that the presence of two mutated tyrosine kinase genes accelerates disease progression.
Ordering and Utilization of Peripheral Blood Flow Cytometry in an Academic Medical Center
Authors: Golab K E , Harrington A , Fydryszewski N , Schur C 
Published: October 2024

Abstract

Introduction/Objective
The American Society for Clinical Pathology and the American Board of Internal Medicine’s Choosing Wisely campaign have developed best practice utilization guidelines for laboratory testing. Wisconsin Diagnostic Laboratories and Medical College of Wisconsin leadership noticed an increase in inappropriate peripheral blood flow cytometry testing in the last two years. An intervention was developed to help reduce inappropriate testing requests.

Methods/Case Report
The laboratory implemented a clinical decision support tool in the electronic medical record system that looked at patient diagnosis, history of stem cell transplant, and recommendations from pathology to help improve utilization of peripheral blood flow cytometry testing. Based on patient history, flow cytometry testing would move forward, or an alternative order of a peripheral blood pathology smear review with reflex to flow cytometry was offered. Pathologists would reflex flow cytometry if abnormalities were present by light microscopy or predetermined reflexing criteria were met.

Results (if a Case Study enter NA)
314 cases were included for analysis. The intervention reduced volumes of peripheral blood flow cytometry in patients without a history of hematologic malignancy by 49.1% (p=&lt;0.001). Appropriate utilization increased from 47.0% in the pre-intervention period to 80.4% in the post intervention period (p=&lt;0.001). Significant diagnosis rate increased from 42.5% to 50.0% (p=.261). This resulted in a cost savings of $12,232 for the health system during the intervention period.

Conclusion
Clinical decision support based utilization efforts provide strong and consistent interventions to reduce the unnecessary and inappropriate ordering of peripheral blood flow cytometry.
Assessment of Molecular Response to Treatment of Chronic Myeloid Leukemia at Kigali University Teaching Hospital of Kigali
Authors: MUKANDEKEZI A 
Published: October 2024

Abstract

Introduction/Objective
Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative neoplasm that gives proliferation advantage to the granulocytes, it is one of the commonest chronic hematological malignancies and it is a burden to the world especially Rwanda. Since the introduction of Tyrosine Kinase Inhibitors (TKIs) especially the first line Imatinib in 2001, the outcomes of CML have been much improved and currently, in developed world, the life expectancy of patients with CML is almost the same as general population. However, it is not the case in developing world especially Rwanda due to limitation on access of all TKIs.
The aim of this study is to assess molecular response on Imatinib of patients with CML.

Methods/Case Report
This was a one arm open label prospective cohort study that recruited 31 patients with CML and on Imatinib for at least three months and followed for 11 months. The clinical features at diagnosis and recruitment were captured from the hospitals filing systems and investigator’s own assessment at the time of recruitment respectively. Information was filled to a well-structured questionnaire. Lab results at the time of diagnosis was obtained from laboratories reporting systems. Samples for full blood count and BCR-ABL1/ABL1 were withdrawn from the patients at the time of diagnosis and they were run at University Teaching Hospital of Kigali (CHUK). Data analysis was performed using Statistical Package for the Social Sciences (SPSS 28) and South Texas Art Therapy Association (STATA 15.0).

Results (if a Case Study enter NA)
Better response according to European LeukemiaNet (ELN) defined as optimal response was found among only 38.7% and resistance to imatinib defined by ELN as Failure and warning was found in 45.2% and 16.1% respectively. The eleven months survival rate was 93.5% in which it is 85.7% among those in treatment failure group. Late presentation showed by presence of very high White Blood Cells above 100x109/L and massive splenomegaly at diagnosis, and poor adherence to Imatinib according to Morsiky Medication Adherence Scale (MMAS-8) are associated with poor molecular response to Imatinib.

Conclusion
CML is a serious disease especially to those who suffer from it; on time diagnosis, access to all available lines of TKIs and better follow up are crucial for patients with CML to access the same life expectancy as general population as it is in developed world.
Can multiplexing Immunohistochemistry for PD-L1, CD68, and CD3 improve scoring for “Keytruda®” Indication?
Authors: Melvin S , Nam M 
Published: October 2024

Abstract

Introduction/Objective
FDA-approved companion diagnostics immunohistochemistry scoring for PD-L1 is essential for Keytruda ® treatment in patients with NSCLC. The challenge with PD-L1 testing alone is false positive PD-L1 expression score due to alveolar macrophage infiltration. Multiplexing with PD-L1, CD68, and CD3 could help alleviate this issue. By viewing PD-L1 expression on tumor cells, CD68 expression on macrophages, and the presence of CD3+ T cells on a single slide, pathologists will be able to see the presence of an immune microenvironment (high PD-L1 expression with abundant macrophages) and the potential for response to other types of Immunotherapies (presence of T cells).

Methods/Case Report
Positive NSCLC FFPE blocks were sectioned and stained using Agilent Dako Omnis. Two combinations of multiplex staining were prepared for each block by staining PD-L1 (brown) alone first followed by CD3 and CD68. First slide: CD3(Vina Green), CD68(Magenta); Second slide: CD3(Magenta), CD68(Vina Green). To prevent wash out, dehydration and clearing occurred with two changes of 100% alcohol and three changes of xylene for manual cover slipping.

Results (if a Case Study enter NA)
Manual scoring of PD-L1 alone vs two different multiplex combinations was compared to Agilent Proscia digital AI scoring using a preliminary study set (9 positives, 2 negatives). CD68-green and CD3-magenta showed better discrimination than CD68-magenta and CD3-green at a glance. This could be due to the staining intensity and nonspecific background staining of CD68-magenta. Manual scoring was higher compared to digital scoring, which could be due to the human error of positive bias. Digital scoring was significantly lower for PD-L1 alone vs both multiplex stains. The digital scoring for the multiplex stains showed a higher scoring percentage by removing false positive macrophages.

Conclusion
Reflex scoring workflow is being developed to focus on difficult cases using the multiplex triple stain, i.e. clear negative and clear &gt;50% with 3+ intensity. More cases will be collected and studied to further investigate the improved PD-L1 scoring with digital imaging assisted by artificial intelligence and to compare the multiplex color combinations.
P53 ABNORMAL ENDOMETRIAL CANCERS – ANALYSIS OF PD-1 CO-EXPRESSION BY CD4 HELPER AND CD8 CYTOTOXIC T-CELL SUBTYPES IN THE TUMOR MICROENVIRONMENT
Authors: Ariyanayagam S , Baksh D 
Published: October 2024

Abstract

Introduction/Objective
Endometrial cancer is classified into four molecular subtypes of which the p53 abnormal variant is biologically aggressive. Programmed cell death protein 1 (PD-1) is a cell surface receptor and a vital inhibitor of the immune response. Programmed death ligand 1 (PD-L1) is a trans-membrane co-inhibitory factor of the immune response. PD-1 / PDL-1 interaction inhibits the activation and survival of T cells and decreases cytokine secretion.
Some cancer cells express PD-L1, which then bind to PD-1 expressed on tumor specific T cells, and escape destruction by the T cells. The CD4/CD8 T cell immune response in the p53 abnormal variant has not been adequately evaluated with respect to the PD-1/PD-L1 pathway. Understanding this immune microenvironment is important to assess the potential use of anti-PD-1 targeted tumor therapy.

Methods/Case Report
Twenty cases of p53 abnormal endometrial cancers were obtained. All cases were PDL-1 +ve by immunohistochemistry. Two dual stains were performed - PD-1/CD4 and PD-1/CD8 antibodies.
Six high-power fields (40x objective) with the greatest concentration of lymphocytes were counted. The total number of CD4 or CD8-only cells was recorded for each of the two stained slides for each case. The total number of PD- 1/CD4 and PD-1/CD8 positive cells were counted and recorded.
The results were tabulated, and a paired t-test statistical analysis was performed to compare the total number of CD4 and CD8 cells and the percentage of PD-1/CD4 cells with the percentage of PD-1/CD8 positive cells.

Results (if a Case Study enter NA)
A statistically significant increase in the number of CD8 (Mean = 383) compared to CD4 cells (Mean = 317) was seen in the tumor microenvironment (p-value=0.0023). Evaluating PD-1 expression, the converse was true, and the percentage of PD-1/CD4 cells (Mean = 13.035%) was increased compared to the percentage of PD-1/CD8 cells (Mean = 9.205%), achieving statistical significance (p-value=0.0116).

Conclusion
The statistically significant increase in CD8 cells in the tumor and its stroma suggests that a robust cytotoxic response is being mounted to this high-risk molecular variant. The concurrent increase in CD4/PD-1 positive lymphocytes provides an appropriate microenvironment for the use of anti-PD-1 immunotherapy, since blockade of PD-1 on CD4 helper T cells may augment the tumor ablative cytotoxic properties of the CD8 positive lymphocytes.
This includes reinvigoration of exhausted CD8+ T cells. Anti-PD-1 may also prevent the inhibition of PD-1 positive CD8 cells.
Relocating a highly complex 5 million test per year hospital based laboratory - what you should know and what you should avoid
Authors: ZURETTI A 
Published: October 2024

Abstract

Introduction/Objective
A highly complex hospital based laboratory performing 5 million test per year in New York City was commanded to relocate due to a clinical department need to expand. This presented a challenge regarding the obtention of a suitable new space within the existing facility, the architectural design to optimize the performance of both Anatomic and Clinical Pathology, the choice between acquirring brand new instrumentation versus relocation of the existing instruments. At the same time, we had to interact with hospital wide Facilities Management and Information Services/ Electronic Medical records. In addtion, for quality improvement and to alleviate the shortage of licensed technologist in our state, it was decided that a robotic line was to be implemented in the new facility.

Methods/Case Report
Several space options were assessed. Once the most suitable space was found a decision was made to move in two phases, Anatomic Pathology first, and subsequently Clinical Pathology. New work stations were purchased for Anatomic Pathology. New instruments were obtained for Chemistry, Immunology and Hematology. All instruments were validated.. Our laboratory information system had to be upgraded in order to support the robotic line, which is to be implemented after the Clinical Laboratory move. This will facilitate the expansion of in house provision of laboratory services to outpatient facilities / clinics expandin our outreach. The new space includes room to expand as well as abundant swing space. Our next phase includes the relocation of our Blood Bank and expansion of our Microbiology Services

Results (if a Case Study enter NA)
Due to delays in the obtention of the State Occupational permit the move was postponed several times.
It was decided to move in two phases, once the permit was received.
The Laboratory successfully moved in a two week period, and was fully operational overnight.

Conclusion
The Laboratory successfully moved in a two week period, and one week later we underwent a routine State inspection, in which the rigourous inspectos encountered very few deficiencies. The Laboratory is fully operational to the satisfaction of our clinical departmenst and preparing to the next phase including Blood bank and expanding our outreach program
Enhancing Laboratory Outcomes Through “Stacked” Professional Credentials: A Study of ASCP BOC Trends
Authors: Baker J B , Spiczka A 
Published: October 2024

Abstract

Introduction/Objective
Laboratory medicine and pathology are rapidly evolving, requiring laboratory professionals to continuously adapt and enhance their skills to ensure high standards of patient care. The American Society for Clinical Pathology (ASCP), Board of Certification (BOC) has observed a notable increase in the number of credential holders obtaining multiple, or stacked, BOC credentials. This phenomenon is not limited to the U.S. but is also evident in various countries globally. This study aims to explore the trends of stacking credentials among BOC credential holders, examining its implications for professional development, career progression, and the overall impact on laboratory outcomes.

Methods/Case Report
This study utilized a comprehensive analysis of ASCP BOC’s credentialing data, focusing on individuals with multiple credentials. Data were segmented by degree (Bachelor’s, MBA, PhD, etc.), credential count (ranging from 2 to 10), and geographical distribution across the U.S. and internationally. The analysis sought to identify patterns, growth trends, and the professional demographics most inclined towards obtaining stacked credentials.

Results (if a Case Study enter NA)
The study revealed that approximately 11% of BOC credential holders possess two or more credentials, indicating a significant trend towards continuous professional development and specialization. The breakdown of stacked credentials by degree shows a higher percentage propensity among individuals with MBAs (as one degree type). Geographical analyses highlighted hotspots for professionals seeking multiple credentials both at the domestic U.S. level and internationally.

Conclusion
This suggests the BOC, and by extension the laboratory medicine and pathology community, can greatly benefit from promoting and facilitating the acquisition of multiple credentials. By doing so, the field can ensure a workforce that is not only highly qualified but also adaptable to the changing dynamics of healthcare, thereby reinforcing the indispensable role of laboratory professionals in the broader healthcare ecosystem.
Optimizing RT-qPCR Detection of Enveloped and Non-enveloped Viruses in Wastewater: A Comparative Study in Grenada
Authors: Farmer-Diaz K , Matthew-Bernard M , Macpherson C , Ramos-Nino M , Cheetham S , Mitchell K 
Published: October 2024

Abstract

Introduction/Objective
Wastewater-based epidemiology (WBE) is an effective methodology to monitor the community spread of pathogens and has successfully been used to identify potential outbreaks. Most standardized methodologies used in WBE for the detection of viruses have been validated for non-enveloped viruses; therefore, there is a need for the development of a standardized protocol for the detection of both enveloped (such as SARS- CoV-2) and non-enveloped viruses (such as Hepatitis A). Wastewater seeded with Pseudomonas syringae bacteriophage (Φ6), an enveloped virus surrogate, and coliphage MS2, a non-enveloped virus surrogate, were used to evaluate the efficiency of four different aluminium flocculation methods. Untreated wastewater spiked with known amounts of surrogates was used as a control for viral recovery.

Methods/Case Report
Four different viral concentration methods were used.
Method 1: AlCl3 flocculation at pH 3.5 followed by centrifugation, resuspension with 10% beef extract and filtered with a 0.22 μm filter.
Method 2: AlCl3 flocculation at pH 6.0 followed by room temperature agitation, centrifugation, and resuspension with 3% beef extract.
Method 3: Mixed method protocol-AlCl3 flocculation at pH 3.5 followed by room temperature agitation, centrifugation, resuspension with 3% beef extract.
Method 4: Mixed method protocol-AlCl3 flocculation at pH 6.0 followed by centrifugation, resuspension with 10% beef extract filtered with a 0.22 μm filter.
Viral RNA was extracted after concentration, and reverse-transcription quantitative polymerase chain reaction (RT- qPCR) was performed.

Results (if a Case Study enter NA)
The average Ct reduction of untreated wastewater compared to spiked was calculated for each method. The highest recovery of both Φ6 and MS2 was obtained using Method 3 (mixed protocol) with a significant difference at 95% confidence in the recovery of Φ6 (p= 0.0029) and MS2 (p= 0.0225).

Conclusion
Previous results from our lab demonstrate the importance of pH during the flocculation step of viral concentration using different methods of concentration. Here, the results suggest that the increased contact time between virus and the flocs is also critical. This can facilitate the implementation of WBE in Grenada to monitor and track potential viral outbreaks of both enveloped and non-enveloped viruses such as SARS-CoV-2 and Hepatitis A.
Molecular epidemiology of diabetic foot ulcers
Authors: Mensah S 
Published: October 2024

Abstract

Introduction/Objective
The study accessed the prevalence of Escherichia coli in diabetic diabetic foot infection(DFI) and diabetic foot osteomyelitis(DFOM).A single retrospective single centre was conducted on patients diagnosed with E.coli isolated from deep DFI and DFOM at Komfo Anokye Teaching Hospital over 2 year period.

Methods/Case Report
Phylogenetic backgrounds,virulence factors(VFs) and antibiotic resistance profiles were determined.Whole genome analysis of E.coli strains isolated from same periods were performed.
From two years study period,35 E.coli strains isolated from 33 patients were analysed,73% were isolated from DFOM

Results (if a Case Study enter NA)
The majority of the strains belonged to the virulent B2 and D phylogenetic groups(82%).These isolates exhibited a significant higher average of VFs number greater than strains belonging to the other groups (p&lt;0.0001).papG2 gene was significantly more detected in strains belonging to B2 phylogeny isolated from DFI compared to DFOM(p=0.003)
The most prevalent antibiotic resistance pattern was observed for ampicillin(82%)cotrimoxazole(45%) and ciprofloxacin (33%).The genome analysis of strains isolated at two periods in DFOM showed a decrease of the genome size and this decrease was more important for the strains isolated at 9 months(versus 4 months)

Conclusion
Shared mutation on the putative acy-CoA dehydrogenase-encoding gene aidB was observed on both strains. E.coli isolated from DFOM werA shared highly genetically diverse with different pathogenicity traits.Their adaptation on the bone structure could require genome reduction and some important modifications in the balance virulence and resistance of the bacteria