bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applying The Best Practice For Internal Quality Control (IQC) Management, Consolidation And Review Process In Sidra Medicine Clinical Chemistry Division
Authors: Asinas J M 
Published: October 2020

Abstract

Introduction/Objective
The management of internal quality control (IQC) in Sidra Medicine Clinical Chemistry Division has been evaluated in order to promote a more consolidated and efficient process of IQC management. The statistical data produced from Cerner QC Module are transferred to IQC review templates consisting of formulas to auto- calculate parameters such as multiple of expected QC failure frequency and desirable comparison limit between analyzers. The IQC review and documentation process using the in-house excel template requires several hours to complete, hence a faster and more efficient IQC management module is required. The main objective of this study is to improve the initial IQC management set up, work flow and review procedures and to implement Biorad Unity Real Time (URT) program to develop a more efficient IQC management system.

Methods
The URT software has been recently configured and implemented to consolidate and streamline IQC management. URT is built through Sidra Medicine IT Enterprise level which allows multiple users to login. IQC data are downloaded using scripts from Cerner which are filtered through Biorad Unity Connect (UC) software. Additional quality tools are also explored such as various user defined statistical reports, IQC analysis using peer reviewed total allowable error (TeA) and assignment of the most appropriate Westgard rules. Determination of sigma metrics and uncertainty of measurement is also performed using the URT application.

Results
The generation of any IQC report is less cumbersome and time consuming as compared with the previous process. However, some user defined formulas in the IQC templates are not found on the URT reports. The URT Levey Jennings chart are also more user friendly and directly compares the daily IQC data with Unity inter-laboratory peers enabling the production of instant and monthly reports through QCNet site when assay investigation is required and for IQC report documentation.

Conclusion
The combination of Cerner IQC, Unity Real-time, QCNet Inter-laboratory reports and in house IQC templates produce a high level and very detailed IQC review which effectively evaluate assay performance to assist on IQC troubleshooting and root cause analysis to be able to apply the most appropriate corrective actions.
Vendor-Recommended Protocol Is Not Adequate To Verify Analyzer Performance After Probe Replacement
Authors: Fathima S , Gallegos A F , Kumar V 
Published: October 2020

Abstract

Introduction/Objective
To verify performance after probe replacement on Siemens ADVIA® 1800 analyzer, the vendor recommends running 2 levels of quality control (QC) for each analyte; however, this approach provides only a snapshot of analyzer performance. Additional experiments were conducted to determine if the vendor-recommended protocol adequately verifies analyzer performance.

Methods
Serum from 20 random patients was mixed, centrifuged at 1000 g for 10 min, and supernatant prepared (PPS). Intra-assay precision was assessed by analyzing 20 replicates of 2 levels of QC, and PPS for the following indicator assays (total allowable error [TEa] in parentheses): alanine aminotransferase (20%), calcium (6%), creatinine (15%), immunoglobulin G (25%), and sodium (5 mEq/L). Inter-assay precision over past 30 days was calculated from the values (90 – 114) of 2 levels of QC. Violation of 13s QC rule is most commonly used for detecting critical error (error &gt; TEa). We used TEa/4 and TEa/3 as the acceptability criteria for intra- and inter-assay precision. Inter-assay precision was also compared to the precision claim by the vendor. Bias between the mean of QC values from intra- and inter- assay precision was calculated and TEa/4 used as the acceptability criterion.

Results
Intra-assay precision for both levels of QC for all analytes was acceptable. Intra-assay precision (5.48%) for only alanine aminotransferase in the PPS was unacceptable, indicating that patient matrix may impact precision for certain analytes. Inter-assay precision (2.24%) for level 1 QC for calcium was unacceptable. For all analytes, inter- assay precision compared to vendor’s claim was found to be significantly higher (32% - 405%). The bias was unacceptable for level 3 QC for sodium (-2.11).

Conclusion
Increased imprecision and/or bias may be observed if either probe replacement or alignment was not appropriate; or the verification protocol was not adequate. This study demonstrates the need to conduct experiments beyond vendor-recommended protocol to ensure production of clinically acceptable results.
Paris System Has A Higher Cytohistologic Correlation And Reproducibility Than Traditional Urine Cytology Method
Authors: Mendoza R P , Haidary T , Gupta R 
Published: October 2020

Abstract

Introduction/Objective
The major limitation of urine cytology is the lack of consensus regarding the terminology and diagnostic criteria that should be used for urothelial atypia. The main goal of the newly proposed Paris System for Reporting Urine Cytology is to concentrate primarily on the detection of high grade urothelial carcinoma while minimizing the detection of low grade lesions. This study aimed to apply the criteria and categories of the Paris system in retrospectively collected urine cytology specimens and assess histologic correlation and reproducibility.

Methods
Two senior pathologists independently reviewed retrospectively collected urine cytology specimens strictly following the Paris system criteria for categorization. Cytologic diagnosis were compared with previous cytology result and histologic diagnosis.

Results
A total of 67 patients were included in the study. The mean age is 65.8 years (36-89 years), majority were males (73.1%) and African American (89.6%). Urine cytology using traditional method showed mostly atypical results (58.2%), followed by reactive (26.9%), high-grade urothelial carcinoma (11.9%) and suspicious (3.0%). On the other hand, the Paris system had more negative results (62.7%), followed by atypical (19.4%), high-grade urothelial carcinoma (11.9%) and lastly suspicious (6.0%). All of negative cases (18 out of 18) and majority of HGUC cases (7 out of 8) were concordant between the two cytology methods. Traditional urine cytology method only yielded 71.4% histologic concordance, while 100% Paris system results were concordant with bladder histology. Majority of the atypical cases using traditional method were converted to negative, and a few atypical cases were converted to suspicious and high-grade. All results using Paris system were concordant between two general pathologists.

Conclusion
Using the Paris system in analyzing urine cytology resulted to higher cytohistologic concordance than traditional method. Majority of atypical cases from traditional method were converted to more definitive categories. The cytopathologic analyses from two general pathologists applying the criteria of Paris system had superior reproducibility. Applying the Paris system, therefore, can significantly improve the performance of urine cytopathology.
Case Series: Seventeen Year Institutional Review of Placental Chorangiomas
Authors: Kousar A , Takeda K , Rizvi A , Sutton A , Geisinger K 
Published: October 2020

Abstract

Introduction/Objective
Chorangioma is a rare tumor occurring in less than 0.5 - 1% of all pregnancies. Small chorangiomas (&lt; 4cm) are mostly asymptomatic and incidental. Large chorangiomas (&gt; 4 cm) may be associated with various fetal complications and complicated pregnancies. The aim of our study is to assess the ultrasound detection rate of these lesions.

Methods
A retrospective study of chorangioma cases seen at Vidant Medical Center between 2003 to 2019 was conducted. Size of the lesion, detection on prenatal imaging, gestational weeks at delivery, maternal age and pregnancy related fetal and maternal complications were analyzed.

Results
A total of 25761 placentas were examined from 2003 to 2019 in Vidant Medical Center. Out of these only thirty-nine cases (0.15%) of chorangioma were found. 41% of these women were above 30 years of age. 36 patients were non-Hispanic. 92.3 % (36 cases) of these lesions were less than 4cm and 7.6 %(3 cases) were above 4 cm, with only one recent case of 7.0 cm in greatest dimension. 92% of the total patients presented with complicated pregnancies. Preeclampsia, preterm delivery, gestational hypertension and intrauterine growth retardation were among the most common complications observed. 3 patients presented with oligohydramnios. Interestingly, none of the lesions were detected on prenatal ultrasound.

Conclusion
Large chorangiomas(&gt;4 cm) are rare but are known to be associated with adverse fetal outcomes. Our seventeen year institutional review shows the largest chorangioma to be 7 cm in greatest dimension. Regular ultrasound monitoring is required to pick up these benign lesions early and prevent adverse outcomes. A retrospective review is needed to determine why the lesions in our study were not detected radiographically.
Alterations of Hemoglobin Fractionation in a Sickle Cell Disease Patient on Voxelotor Therapy
Authors: Karimi S S , Ni H , Hsu L L 
Published: October 2020

Abstract

Introduction/Objective
Voxelotor is a molecule that allosterically binds to the alpha-chain of hemoglobin, resulting in increased oxygen affinity. This allosteric inhibition leads to prevention of hemoglobin polymerization and sickling of red blood cells in response to low oxygen tension. Voxelotor has been used to treat patients with Sickle Cell Disease (SCD) and recent literature indicates it may contribute to complex hemoglobin fractionation (HF) elution patterns. We report a novel case of a SCD patient on concurrent Hydroxyurea, Voxelotor and chronic RBC exchange transfusion treatment and discuss the implications of these three treatment modalities on HF and monitoring of SCD.

Methods
A 17-year-old female with SCD complicated by frequent vaso-occlusive crisis, and avascular necrosis managed with chronic RBC exchange and Hydroxyurea. Her HF prior to initiation of Voxelotor treatment showed 3.2% HbA2, 51% HbA, 6.0% HbF, and 41% HbS. Voxelotor therapy was initiated at 1500mg/day and HF was performed 10 days later. Whole blood was collected and subjected to High Performance Liquid Chromatography (HPLC) with reflex to RBC solubility and Capillary Electrophoresis.

Results
HF performed post-Voxelotor therapy revealed positive sickle solubility with a complex pattern of 2.7% HbA2, 49.2% HbA, 5.3% HbF, 15.7% HbS, 0% HbC, and two additional peaks of a 6.3% peak in the window-D region (retention time of 4.34) and 20.8% of an atypical Hb peak pattern (at the retentuin time of 4.18). The results reflected a complex HF of a HbSS patient on concurrent chronic RBC exchange transfusion, hydroxyurea therapy, and Voxelotor treatment. Post Voxelotor-therapy HF revealed a reduction in HbS from 41% to 15.7% with the emergence of two additional peaks. Chronic RBC exchange transfusion and Hydroxyurea treatment account for the observed fractionation of HbA and HbF, respectively. Based on recent literature, we attribute the emergence of the two additional peaks to Voxelotor therapy. All three therapies led to reduction in HbS.

Conclusion
Routine HF serves as an essential modality in diagnosis and monitoring of SCD. Voxelotor treatment alters the HF profile and may cause difficulty for interpretation. With the emergence of novel therapies, it is imperative for clinicians to provide medication information to clinical laboratories and pathologists to be fully aware of the effects of current treatments to correctly interpret and monitor SCD.
Leukemia Cutis in a Patient with Rare Indolent T-Prolymphocytic Leukemia - A Case Report and Review of the Literature
Authors: Da Silva Lameira F , Wang K , Rinker E , Jetly R 
Published: October 2020

Abstract

Introduction/Objective
T-cell prolymphocytic leukemia (T-PLL) is rare, comprising 2% of mature lymphocytic leukemias in adults. Clinical course is usually aggressive, however, 20-30% patients can have an indolent early phase. Most patients present with extensive disease with peripheral blood lymphocytosis, hepatosplenomegaly, and lymphadenopathy. T-PLL has a higher incidence in patients with ataxia-telangiectasia.

Methods
We present a case of a 67-year old man with history of somatic mutation of ataxia-telangiectasia gene (ATM) and multiple malignancies, including melanoma, skin and laryngeal squamous cell carcinomas, adrenal adenoma and spindle cell lung tumor (diagnosed on biopsy), who developed leukemia cutis during an indolent phase of T-PLL.

Results
Initial diagnosis of T-PLL was on routine complete blood count when patient had mild atypical lymphocytosis (5.5 x 109/L). Flow-cytometry immunophenotyping detected CD4 + 8 positive mature T-cells with no aberrant loss of T- cell antigens, and molecular studies confirmed clonal T-cell receptor beta and gamma gene rearrangements. T-PLL associated leukemia cutis was diagnosed on a leg skin nodule biopsy 10 months later. Subsequent bone marrow biopsy demonstrated low level involvement by T-PLL. The patient’s T-PLL followed an indolent trajectory for three years and treatment was withheld until symptomatic presentation. Rapid disease progression was heralded with emergence of widespread T-PLL leukemia cutis, rapidly increasing lymphocytosis, extensive lymphadenopathy, splenomegaly and increasing LDH levels.

Conclusion
Skin involvement is reportedly identified in 20% to 50% of T-PLL cases in some series. Skin manifestations can be heterogenous with a broad clinical differential. T-PLL associated leukemia cutis may not be recognized owing to the overall low incidence and in skin lesions appearing during an undiagnosed indolent early phase of T-PLL.We highlight the importance of accurate evaluation of non-specific skin lesions in early detection of T- PLL. Being aware of this diagnosis and early engagement in an interdisciplinary approach may allow for better outcomes of this aggressive malignancy.
Nodular Lymphocyte Predominant Hodgkin Lymphoma: A Rare Case with Fan Pattern E
Authors: Ozluk E , Wei E 
Published: October 2020

Abstract

Introduction/Objective
Growth patterns of nodular lymphocyte predominant Hogdkin lymphoma (NLPHL) has been further described by Fan et all. Pattern E is T cell/histiocyte rich large B-cell lymphoma-like and is quite rare. The treatment usually may follow large B cell lymphoma protocol instead of Hodgkin lymphoma regimen.

Methods
Here we report a patient with NLPHL pattern E. Patient was a 25 years-old African American man who initially presented with generalized lymphadenopathy.

Results
Biopsy of the axillary lymph node revealed effaced lymph node architecture by a malignant neoplasm in a diffuse and vaguely nodular pattern. In the background of a diffuse infiltrate, there were small to medium sized lymphocytes, numerous atypical large cells with irregular, basophilic nucleoli, and variable cytoplasm. The large cells focally sheeted out. Many histiocytes were also seen in the background. The large atypical cells were positive for CD20, BOB-1, OCT2, BCL-2 (focally), BCL-6, PAX5, and MUM-1, and IgD, whereas negative for BCL-1, CD10, CD15, CD30. CD2, CD3, CD4, CD5, CD7, CD8 highlighted numerous T cells with mild cytological atypia, forming rosettes around the large atypical cells. T cells were negative for ALK-1, CD1a, TdT with increased Ki-67 proliferation index around 35%. Although the surrounding T cells appear atypical in morphology, flow cytometric analysis showed predominantly reactive T-cells with no loss of T-cell associated antigens. PCR analysis showed a producible peak in a single IgH reaction. However, the fragment size of the peak observed did not meet the criteria. T-cell gene rearrangement by TCR gamma and TCR beta PCR was negative for monoclonal T-cells. BCL-1, BCL-2, and BCL-6 FISH panel were negative for gene rearrangements. Based on these findings the diagnosis was made at stage IV. Patient started treatment with R-CHOP therapy with subsequent relapse. Patient has been placed on RICE chemotherapy with partial response.

Conclusion
NLPHL Pattern E type should be differentiated from classical Hodgkin lymphoma, diffuse large B-cell lymphoma and peripheral T cell lymphoma because the treatment greatly differs from those with higher stage and tendency for recurrence. It is the pathologist role to lead the clinician and render a correct histopathologic diagnosis.
A Challenging Diagnosis of Acute Myeloid Leukemia with Myelodysplasia Related Changes in the Setting of Ayurvedic Supplements and B12 Deficiency
Authors: Goff R , Levyq R 
Published: October 2020

Abstract

Introduction/Objective
Bone marrow findings of myelodysplastic changes can be associated with vitamin or mineral deficiencies (B12, folic acid or copper), infections, inflammatory disorders, exposure to toxins, heavy metals, zinc excess, recent radio- or chemotherapy, or myeloid neoplasms including myelodysplasia (MDS) and acute myeloid leukemia (AML). We present a case of a 32 year old Indian woman who presented with fatigue and weakness. She has a history of vitamin B12 deficiency and has been taking Ayurvedic supplements. This clinical history is very important because studies have shown that vitamin B12 deficiency has led to incorrect diagnoses of AML and/or MDS. Additionally, Ayurvedic supplements can contain a variety of heavy metals which can contribute to myelodysplastic changes.

Results
A complete blood count and peripheral smear analysis showed pancytopenia with rare blasts. A bone marrow core biopsy with ancillary testing was performed to evaluate for a hematologic malignancy. Vitamin B12 testing and heavy metal analysis was necessary to reach a final diagnosis. Flow cytometric analysis of the marrow identified 19.5% CD34 positive myeloblasts. The aspirate and core are hypercellular with increased blasts (17% on aspirate and 20-25% on core biopsy) with trilineage dyspoiesis. AML panel by fluorescence in situ hybridization showed no abnormalities. Heavy metal analysis shows no increase in lead, cadmium, mercury and arsenic levels. Recent vitamin B12 tests show results within normal range secondary to successful replacement. Ultimately, chromosome analysis identifies t(3;12)(q26,p13) involving ETV6/MECOM characteristic of a very poor prognosis in MDS or AML. Molecular AML panel identified BCOR and PTPN11 gene mutations which are associated with more aggressive disease and a poor prognosis in myeloid neoplasms.

Conclusion
This case had multiple possible causes of myelodysplastic changes and it was necessary to exclude these factors before yielding the final diagnosis of Acute Myeloid Leukemia with myelodysplastic related changes which demonstrated a rare translocation t(3;12) ETV6/MECOM which has a poor prognosis.
Pediatric Patient With Neurological And Leukemic Peripheral Blood Involvement By Small Cell Variant Of ALK- Positive Anaplastic Large Cell Lymphoma (ALCL): Case Study
Authors: Reddy A C , Reddy K S 
Published: October 2020

Abstract

Casestudy
Anaplastic large cell lymphoma (ALCL), is a T-cell lymphoma typically consisting of large lymphoid cells including characteristic horseshoe- shaped hallmark cells. The rare small cell morphological variant of ALCL may pose a challenge in diagnosis, especially when the initial presentation is unusual.

Results
Our patient, a 7-year-old girl presented with a headache. A complete blood count showed leukocytosis and anemia. The smear was reported to have segmented neutrophils, reactive lymphocytes, and monocytes. A spinal tap was performed and flow analysis identified a minute aberrant T cell population (0.3% of total), positive for CD3, CD4, bright CD7; negative CD5, CD8 in the CSF sample. The peripheral blood sample was reviewed again; some small- medium atypical lymphocytes, with irregular nuclear contours and cytoplasmic azurophilic granules were noted. Flow immunophenotyping displayed an aberrant T cell population positive for CD45, CD2, CD3, bright CD7, CD4, CD13; negative CD30, TdT CD5, CD8, CD117, CD34; consistent with T cell lymphoma/leukemia. A cell block prepared from peripheral blood sample showed blood with numerous atypical cells with irregular nuclei positive for ALK, CD30, CD3, CD4, CD7; negative CD5 and CD8. A diagnosis of leukemic ALK(+) ALCL was rendered, though classic hallmark cells were difficult to see. A marrow biopsy showed interstitial and sinusoidal pattern of mainly small to medium-sized cells with irregular nuclei. Molecular study revealed ALK gene alteration showing characteristic NPM1-ALK fusion. The patient underwent a bone bone marrow transplantation but recently relapsed with a submandibular lymph hode biopsy showing the presence of many larger ALCL cells.

Conclusion
Correct clinical diagnosis of the small-cell variant of ALCL is often challenging as the scarce “hallmark cells” are scattered and difficult to recognize. While leukemic peripheral blood involvement is rare in ALCL, an association has been reported with small-cell variants, which may be a potential explanation for the poor prognosis and aggressive nature of small-cell variant ALCL. A meticulous examination of peripheral blood smears, comprehensive immunophenotypic studies, and early bone marrow and lymph node/tissue biopsy are needed to facilitate diagnosis.
Immune Modulation and CMV Reactivation In Sepsis-Induced Immunosuppression
Authors: Lambe G R , Kapadia F N , Khodaiji S , Rodrigues C 
Published: October 2020

Abstract

Introduction/Objective
Sepsis is a global health priority and is often accompanied by a transient immune paralysis, associated with impairment in innate and adaptive immunity leading to progressive immunosuppression and higher susceptibility to secondary infections. Reactivation of Cytomegalovirus (CMV) occurs frequently and has been associated with adverse outcomes even in immunocompetent patients, with sepsis. Study objective was to evaluate the association between incidence of CMV reactivation and immune alteration in sepsis-induced immunosuppression in patients with prolonged sepsis.

Methods
Prospective observational study, which included consecutive patients admitted to hospital ICU, with severe sepsis and length of stay &gt; 48 hours. Patients with other causes of immune-suppression and anti-CMV treatment were excluded. Blood samples were collected on enrolment and further weekly until 21 days or death/discharge.
Quantification of CMV viremia was done using RT-PCR (qPCR). Markers used to evaluate immune suppression using Flow Cytometry were i) lymphocyte subsets (CD3+,CD19+,CD16+CD56+,CD4+,CD8+ and regulatory T cells - CD25+ CD127-), ii) surface receptor expression of HLA-DR on monocytes, and Programmed Death marker expression (PD-1) on T lymphocyte, iii) Measurement of pro-inflammatory(IL-6,TNF-a,IFN-g) and anti-inflammatory cytokines(IL-4,IL-10) by Cytometric Bead Array (CBA) assay.

Results
A total of 25 CMV IgG positive patients and 11 healthy controls were analyzed. CMV reactivation occurred in 20 patients. Median time for reactivation was 7 days. Patients with CMV reactivation had significant T-cell lymphopenia (p&lt;0.01). PD-1 expression on both CD4+ and CD8+ T cells in these patients was markedly elevated as compared to non-reactive group. HLA-DR expression was significantly low on monocytes in all sepsis patients (p&lt;0.01) vs healthy controls; however it did not show any significant correlation. Levels of IL-6 showed marked elevation from day 7 while, IL-10 was observed to be significantly higher from day 0 in CMV reactivated group as compared to the CMV non-reactive group of patients.

Conclusion
Our study evidence suggests that monitoring lymphocyte subsets, PD-1expression on T lymphocyte, and levels of IL-6/IL-10 using flow cytometry, may serve as indicators for reactivation of CMV. Individualized immune therapy such as PD-1 receptor blockade drugs can be used to optimize treatment of patients with severe sepsis.