bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advantages of the Use of Alcor iSED Automated Sed Rate Analyzer vs Manual Sed Rate in Evaluation and/or Monitoring the Treatment in Patients, CMCVAMC Experience
Authors: Patel Sahilkumar , Jhala Darshana 
Published: September 2019

Abstract

Objectives
The automated Alcor iSED automated instrument has a major impact on the proper management of the patients in a timely manner with use of a minimal amount of the blood (100 µL). The Alcor iSED analyzer has introduced a new technology that forgoes sample preparation by using a Load and Go technology. We were previously using the Westergren tube method, which required special preparation of the tube to load into a special provided sealed cup. The entire procedure was tedious and time-consuming. To overcome, we acquired and implemented the Alcor iSED analyzer for an efficient and prompt reporting of sedimentation rate.

Methods
A sample was aspirated and dispensed from a closed tube, then dispensed into a capillary, and quantitative capillary photometry (aggregation) was used to measure ESR faster than traditional methods by capturing the kinetics of red blood cell aggregation in a controlled testing environment during the most critical phase of sedimentation, commonly referred to as the lag or Rouleaux formation phase. As a part of quality assurance monitoring, retrospective split analysis was performed for 75 samples. Analysis was performed using a Passing-Bablok regression analysis with the MedCalc program.

Results
Our results demonstrated significant differences between the two methods for the TAT. The TAT was significantly decreased with Alcor iSED (3 minutes for the first specimen and then 15-20 seconds for each sequential specimen) as compared to the manual Westergren method (1 hour), which significantly improved the reporting of results to the providers to monitor the treatment.

Conclusion
The Alcor iSED analyzer has provided truly shortened TAT erythrocyte sedimentation rate, allowing for better patient care and treatment.
Impact of the Opioid/Fentanyl Epidemic on the Toxicology Laboratory’s Workload: The CMCVAMC Experience
Authors: Petersen Jeffrey , George Thomas , Jhala Darshana 
Published: September 2019

Abstract

Introduction
Opiates have long been used by both the population at large and the veteran population as a drug of abuse. However, recently, fentanyl—a synthetic opioid—has risen in prominence in this opioid drug abuse epidemic as a drug used by suppliers to “cut” heroin, to masquerade for another opiate, or for direct usage. As this is a recent phenomenon, the new increasing need to test for fentanyl for clinical reasons has a major impact on the toxicology laboratory’s workload.

Method
Quality assurance/improvement data were obtained to determine the number of fentanyl tests by gas chromatography/mass spectroscopy (GC/MS) performed by the toxicology laboratory since quarter 1 of 2011 (October-December 2010) to quarter 1 of 2018 (October-December 2017). The numbers of tests required for clinical care in each quarter were tabulated and compared in a graph. Quarters for each year begin and end in October.

Results
The total number of GC/MS tests for fentanyl needed for clinical care has been drastically increasing recently. From 2011 to 2015, the yearly number of tests clinically needed has ranged from 83 to 92. In 2016, the total number of clinically needed tests for fentanyl spiked to 167 and by fiscal year 2017 included 1,108 fentanyl GC/MS tests. The last examined quarter (quarter 1 of fiscal year 2018) included 527 tests, which is more than the highest number from 2017 (377 in quarter 4 of 2017).

Conclusion
The increasing use of fentanyl in the opioid epidemic appears to have played a role in significantly increasing the clinical need to test for fentanyl by GC/MS, increasing the volume by over 10 to 15 times. The role of fentanyl in the opioid epidemic remains a significant public health concern.
PD-L1 Immunohistochemistry on Cell Block Preparations From Different Fixatives: A Pilot Study
Authors: Costa Victoria , Kim David , Goyal Abha , He Bing , Liu Yifang , Rao Rema 
Published: September 2019

Abstract

Objectives
Immunohistochemistry especially for biomarkers such as PD-L1 in personalized medicine is increasingly being performed on cell blocks from cytopathology samples. We evaluated the effects of staining cell blocks (CBs) from different cytologic fixatives using four different commercially available PD-L1 antibody clones.

Methods
PD-L1 immunohistochemistry (IHC) using four different commercially available clones was performed on eight cell blocks processed from two different fixatives and also on eight formalin-fixed tissues. The clones used were 22C3 at 1:50 dilution and 1:100 dilution, SP263, SP142, and E1L3N. The cell block (CB) samples contained cells that strongly express PD-L1 and either fixed in CytoLyt (methanol-based fixative, n = 4) or CytoRich (ethanol-formalin-based fixative, n = 4). Formalin-fixed control tissues (tonsillar tissue, n = 4; stomach, n = 4) were also included.

Results
Expression for PD-L1 was noted on all the CytoRich fixed cell blocks (n = 4) for all four antibody clones, with the intensity and distribution of expression comparable to the formalin fixed tissues (n = 8). However, consistent absence of expression for PD-L1 was noted on all the CytoLyt fixed cell blocks (n = 4) for all four antibody clones.

Conclusion
The results of this pilot study demonstrate that PD-L1 IHC on cell blocks is feasible. However, there is a need to validate IHC protocols according to specific fixation methods.
IL-15 as an Immune Modulator in Schistosomiasis
Authors: Reust Mary 
Published: September 2019

Abstract

Introduction
Schistosomiasis affects approximately 200,000,000 people globally, with 93% of these cases in sub-Saharan Africa. Women who have been infected with Schistosoma haematobium have four times the risk of contracting HIV due to a change in their cervical mucosal immunity. The mechanism for this altered cervical mucosal immunity was not understood until a recent study published by Downs et al, which showed IL-15 levels were significantly lower in cervicovaginal lavage fluid samples of women with Schistosoma haematobium. Schistosoma mansoni, known to cause intestinal schistosomiasis, has also shown the potential to increase the risk of contracting HIV. The objective for this study is to see if IL-15 levels in peripheral blood are significantly different between patients positive for S mansoni and negative controls.

Methods
Enzyme-linked immunosorbent assays (BD Biosciences, San Jose, CA) for IL-15 were performed on plasma collected from 84 patients in villages in sub-Saharan Africa. These samples were collected at screening, 3-month follow-up, 6-month follow-up, and 9-month follow-up appointments.

Results
Of 249 plasma samples tested, 20 had detectable IL-15 levels ranging from 8.329 pg/mL to above the upper limit of detection of 500 pg/mL. While the patients that had detectable IL-15 in the peripheral blood were half S mansoni negative and half S mansoni positive, when an S mansoni–positive patient was positive for IL-15, it was across all timepoints.

Conclusion
The role of IL-15 as an immune modulator can explain the elevated levels in S mansoni–positive patients. All patients in the study were tested for significant comorbidities, with no correlation seen within the negative controls. Further testing is needed to investigate the role of IL-15 in the alteration of localized areas of infection with both Schistosoma mansoni and Schistosoma haematobium. More samples are currently being collected from the patient population in Tanzania, and future studies are planned.
Immunohistochemical Expression of BCL10 and Three Markers in Extranodal Marginal Zone Lymphoma and Other Small B-Cell Lymphomas
Authors: Zhang Xiaohong 
Published: September 2019

Abstract
Extranodal marginal zone lymphoma (EMZL) is a low-grade B-cell lymphoma representing about the third most common non-Hodgkin lymphoma in the Western world. EMZL shows heterogeneous morphological features and expresses no specific immunohistochemical markers except B-cell markers. BCL10 and MALT mutations causing NF-kB pathway activation play an important role in oncogenesis of EMZL. Aberrant nuclear expression of BCL10 is reported in some EMZLs. Nuclear expression of BCL10 has not been well compared between EMZL and other small B-cell lymphomas. The aim of this study is to evaluate the expression of BCL10 and three markers in different small B-cell lymphomas. Tissue microarray blocks and selected tissue blocks, formalin fixed and paraffin embedded, were selected for immunohistochemical (IHC) studies. More than 100 cases of different small B-cell lymphomas include EMZL, small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), and hairy cell leukemia (HCL) in the bone marrow biopsy. Commercially available antibodies from DAKO for BCL-10, IRTA-1, LEF-1, and SOX-11 were used according to the protocol. Immunoreactivity in greater than 20% of the tumor cells was considered positive. BCL-10 nuclear expression occurred mostly in EMZL but also in other small B-cell lymphomas except LPL and HCL. Cytoplasmic expression of IRTA-1 was detected in all cases of EMZL and also in SLL, MCL, and FL cases; it was negative in LPL and HCL. Nuclear expression of LEF-1 was detected mostly in SLL cases, a few cases of MZL, and none of the cases of MCL, FL, LPL, and HCL. Nuclear staining of SOX11 was found in most MCL cases; it was negative in all cases of SLL, EMZL, FL, LPL, and HCL. The IHC markers of BCL-10, IRTA-1, LEF-1, and SOX11 increase our ability to make accurate diagnosis of small B-cell lymphomas.
A Case of Langerhans Cell Histocytosis Masquerading as a Colon Polyp
Authors: Bishop Bradie , Lynch David , Brady Robert 
Published: September 2019

Abstract
Langerhans cell histocytosis, otherwise known as eosinophilic granuloma, is a rare neoplastic process composed of Langerhans cells and eosinophils. Most cases present during childhood, with the bones and skin being the most common organs involved. Other organs are occasionally involved, with some systemic cases involving the gastrointestinal tract. Presentations of Langerhans cell histocytosis range from single-organ involvement to systemic involvement. Fewer than five cases of isolated Langerhans cell histocytosis in the gastrointestinal system in adults have been reported.
We present a case of Langerhans cell histocytosis incidentally discovered during routine colonoscopy in a 67-year-old otherwise healthy woman. Initial colonoscopy performed 7 years prior demonstrated a sessile serrated adenoma, fragments of tubular adenomas, and hyperplastic polyps. Repeat colonoscopy 3 years later demonstrated a sessile serrated adenoma and hyperplastic polyp. Upon repeat colonoscopy 4 years later, the patient had nine subcentimeter polyps. One of the ascending colon polyp fragments demonstrated a well-circumscribed, submucosal nodule of granular pink histocytes with folded to clefted and reniform nuclei. Numerous eosinophils were present in the background. These findings were consistent with Langerhans cell histocytosis. The remaining polyps were a tubular adenoma and hyperplastic polyps. A CT chest/abdomen/pelvis did not demonstrate any evidence of systemic disease. One year postdiagnosis, the patient had not had recurrence of symptoms.
Unifocal Langerhans cell histocytosis rarely presents in the gastrointestinal tract of an adult and is believed to have a good prognosis with limited recurrence. The patient is being closely followed for development of systemic disease.
Waldenstrom Macroglobulinemia/Lymphoplasmacytic Lymphoma Concomitant With Non-IgM Plasma Cell Neoplasm: Report of 5 Cases With Laboratory Evidence of Biclonal B-Cell Neoplasms in Single Individuals
Authors: McCracken Jenna , Neff Jadee , Zhao Yue , Wang Endi 
Published: September 2019

Abstract

Introduction
Plasma cell neoplasm (PCN) is rarely associated with Waldenstrom macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL), and its clonal relationship to WM/LPL is unclear.

Methods
We retrospectively analyzed five cases of PCN concomitant with WM/LPL for clinicopathologic features.

Results
Of five patients, three were female and two were male with a median age of 75 years at diagnosis of concurrent PCN-WM/LPL. Three cases presented with serum paraprotein of IgM type and had a diagnosis of WM/LPL before identifying concurrent PCN, with an interval of 1 to 10 years. In the remaining two cases, PCN and WM/LPL were concurrently diagnosed. All patients demonstrated biclonal M-spikes with distinct heavy chain isotypes but concordant light chain isotype (kappa or lambda) by immunofixation electrophoresis. In all four cases, two neoplastic populations were highlighted with immunohistochemistry, including expression of CD56/cyclin D1 (1), cyclin D1 (2), and IgA (1) in neoplastic plasma cells and negativity of CD56/cyclin D1 in LPL. Of three patients with clinical information available, two were treated with chemotherapy, and the other was treated with autologous stem cell transplant. At follow-up, one patient died of PCN progression at 24 months, one had recurrent WM/LPL at 144 months, and the other was alive with disease 5 months after the diagnosis of concurrent neoplasms.

Conclusion
Discordant heavy chain isotype restrictions between PCN and WM/LPL suggest biclonal B-cell neoplasms, which is supported by PCN’s phenotypic distinction, such as expression of cyclin D1 and/or CD56, from coexisting WM/LPL. However, our cases had WM/LPL either preceding or concurring with PCN, and all exhibited concordant light chain restrictions, raising a possibility that PCN may be evolved from WM/LPL with class switching. This issue of clonal relationship between the two B-cell neoplasm and underlying pathogenesis remains to be investigated with sequencing analysis on sorted PCN or WM/LPL and comparison of mutation profiles between them.
Evaluation of a 42-Gene Next-Generation Sequencing Panel for Detection of Acute Myeloid Leukemia Mutations for Clinical Use
Authors: Rosenthal Sun Hee , Gerasimova Anna , Ma Charles , Sugganth Daniel , Racke Frederick , Lacbawan Felicitas 
Published: September 2019

Abstract

Objectives
Identification of genetic alterations by molecular and cytogenetic testing has an important role in the classification, risk stratification, and management of acute myeloid leukemia (AML). We evaluated a next-generation sequencing (NGS) panel that assesses IDH2, FLT3, NPM1, and TP3 and 38 other genes associated with diagnostic, prognostic, and/or therapeutic utility in AML, with a turnaround time of 8 to 14 days, using a DNA input of 50 ng.

Methods
In total, 110 patients, 65 males and 45 females, at a median age of 58 years (range: 2-68 years) with clinical diagnosis of AML were included in this study. Targeted regions were captured by hybridization with complementary biotinylated DNA baits, and NGS was performed on an Illumina NextSeq500 instrument. Sequence reads were analyzed using a bioinformatics pipeline that was developed in house. Analytical sensitivity of the assay is ~5% mutated alleles with 100% specificity.

Results
A total of 296 pathogenic mutations in 38 genes were detected in 95 of 110 samples (86%). On average, three mutations (range 1-10) were detected per positive sample. Variant frequency ranged from 3.0% to 96.1%. Most frequently mutated genes were TET2 (18.2%), FLT3 (18.2%), TP53 (17.3%), RUNX1 (15.5%), NPM1 (14.5%), ASXL1 (12.7%), NRAS (11.8%), and CEBPA (10.9%). In total, 166 of 296 (56%) mutations from 13 genes had prognostic significance, 42 of 296 (14%) mutations from three genes (CEBPA, NPM1, RUNX1) had diagnostic significance, and 40 of 296 (14%) mutations from three genes (IDH1, IDH2, FLT3) had therapeutic significance.

Conclusion
This focused 42-gene targeted panel identifies mutations of clinical significance in over 85% of patients with a clinical diagnosis of AML.
Clear Cell Odontogenic Carcinoma of the Maxilla: A Case Report With Emphasis on Differential Diagnoses
Authors: Taherian Mehran , Alhazmi Yaser , Baqai Saad 
Published: September 2019

Abstract

Objectives
Clear cell odontogenic carcinoma (CCOC) is a rare malignant odontogenic epithelial neoplasm composed mainly of clear cells. It was first described in early 1980s with great uncertainty of its behavior. Nearly 100 well-characterized cases have been reported to date with mean age at presentation of 54 years and female-to-male ratio of 1.6:1. It shows greater predilection for mandible compared to maxilla. Herein, we present a case of CCOC arising in maxilla and discuss the clinicopathologic presentation with emphasis on the potential differential diagnoses of other head and neck clear cell tumors (HNCCTs).

Case Presentation
A 68-year-old male presented with facial swelling and hard palate bleeding. CT scan revealed large destructive mass at the floor of right maxillary antrum with involvement of hard palate. Biopsy showed invasive carcinoma with squamous differentiation and focal keratinization. No evidence of lymph node metastasis was noted radiographically. The patient subsequently underwent total maxillectomy with complete resection of the tumor.

Results
Histologic sections revealed tumor arranged in lobular islands showing biphasic morphology including peripheral palisaded hyperchromatic basaloid cells and central clear to faintly eosinophilic cells with well-demarcated cell membranes. The intervening stroma was fibrous and showed hyalinization. The diagnosis of CCOC was made on the basis of tumor morphology in conjunction with EWSR1 gene rearrangement, which was detected by fluorescence in situ hybridization (FISH).

Conclusion
CCOC, although rare, should be considered in the differential diagnosis of tumors with a clear cell component. It can mimic a variety of HNCCTs, particularly clear cell variant of squamous cell carcinoma, clear cell tumors from minor salivary glands, or metastases from other sites. These tumors can be locally aggressive with a relatively high recurrence rate. Pathologists should be cognizant of this entity with other HNCCTs and the use of proper ancillary testing to avoid potential pitfalls.
The Use of One Normal Hydrochloric Acid as a Background Cleaner for Periodic Acid–Schiff Staining Technique
Authors: Iyiola Sina , Adegoke Aremu , Adeleke Samuel 
Published: September 2019

Abstract

Objectives
Sulfurous rinsing was considered nonessential as contained in the published periodic acid–Schiff technique because it did not clear the background better than tap water washing. The objective of this work is to elucidate the use of 1N HCl as a better background cleaner in the periodic acid–Schiff staining technique.

Methods
This is an experimental research. Normal samples of antrium, kidney, spleen, muscle, liver, and appendix, as well as histopathologically diagnosed samples of glycogen storage disease of the liver, alpha-1-antitrypsin deficient liver, aspergillosis nasal cavity sample, and glomerulosclerosis samples were obtained from the pathological archive. These samples were stained with a newly purchased commercially prepared Schiff reagent and overstained commercially prepared Schiff’s solution causing nonspecific background staining and laboratory-prepared Schiff reagent. Oxidation was done with 1% periodic acid for 5 minutes, washed for 5 minutes with distilled water, and stained for 10 minutes in Schiff’s reagent, but 20-minute staining was observed for the overstained Schiff reagent, oxidized in running tap water for 15 minutes. It was then rinsed in 1N HCl for 20 seconds, washed in tap water for 2 minutes, and counterstained with hematoxylin for 2 minutes. The same procedure was done for another set of slides as standards without 1N HCl rinsing done. The slides were examined under the microscope and compared for specificity.

Results
Slides rinsed in 1N HCl showed a clear differentiation of strong, weak, and non-PAS-positive substances. The overall effect of these staining characteristics was more pronounced in the use of laboratory-prepared Schiff.

Conclusion
The use of 1N HCl as a differentiator made the PAS technique more specific in its staining characteristics, especially with the use of laboratory-prepared Schiff’s reagent, which is commonly used in developing countries owing to a high cost of commercially prepared Schiff’s solution.
Umbrella Cells Mimicking Focal High-Grade Urothelial Carcinoma in Low-Grade Papillary Urothelial Carcinoma
Authors: Hassan Muhammad Masood , Naab Tammey , Afsari Ali 
Published: September 2019

Abstract

Objectives
Low-grade papillary urothelial carcinoma (LGUC) has overall a preserved orderly appearance, minimal variability in architecture, and lack of significant cytologic atypia and mitotic activity without pleomorphism. A total of 53.8% of LGUC cases recur with 18.3% progression to high-grade UC. Even focal HGUC in LGUC can be a harbinger of progression. Accurate pathological interpretation is paramount in predicting recurrence and determining treatment.

Methods
A 63-year-old male with a past medical history of coronary artery disease, benign prostate hyperplasia, and obesity was referred to urology with a chief complaint of chronic hematuria. Cystoscopy with transurethral resection of bladder tumor was performed, which revealed mainly LGUC with focal high-grade-appearing UC.

Results
Histologic sections revealed papillary architecture with fused fronds, low-grade nuclear atypia, and scattered mitoses comprising 95% of the tissue submitted. No muscular wall invasion by carcinoma was seen. However, in one section, collections of large cells with well-defined cytoplasmic borders, multinucleation, and rare nuclear grooves were identified. The morphology raised the suspicion of a focal HGUC. Diffuse expression of CK20 and low Ki-67 proliferation index (1%) favored umbrella cells.

Conclusion
Our case reinforces the fact that sectioning can reveal foci, suspicious for HGUC, especially in urothelium. However, proper interpretation of morphology combined with the help of immunohistochemistry aids in accurate diagnosis, which is critical in determining proper clinical management of the patient.
HIT: Anti-Platelet Factor 4-Heparin (PF4-H) Assay Validation and Comparison Study
Authors: De Luna Mark 
Published: September 2019

Abstract

Objectives
The aims of the study were to perform an instrument validation of the HemosIL HIT-Ab (PF4-H) Assay and to compare the sensitivities and specificities of the three HIT tests (HemosIL HIT-Ab [PF4-H] Assay, PIFA Heparin/PF4 Assay, and Immucor PF4 ELISA) versus the gold standard Serotonin Release Assay performed in ARUP Laboratories and versus each other.

Methods
The HemosIL HIT-Ab (PF4-H) Assay was validated on the ACL TOP 750 using calibrators, controls, and samples from UF Pathology Laboratories and ARUP Laboratories that were previously tested for the HIT-Ab IgG via an ELISA method. EP Evaluator was used to calculate statistical data.

Results
A total of 116 samples were assayed using the HemosIL HIT-Ab (PF4-H) Assay and the PIFA Heparin/PF4 Rapid Assay. Overall, there were 125 positive tests and 255 negative tests for anti-PF4-H (ACL

TOP
39 positive, 77 negative;

PIFA
11 positive, 105 negative;

ELISA
60 positive, 56 negative). There were 15 positive and 17 negative for the SRA. The comparison between the ACL TOP and SRA had a sensitivity of 80.0% and specificity of 35.3%. ELISA vs SRA had a sensitivity of 100.0% but had a 0.0% specificity. The PIFA vs SRA correlation had a sensitivity of 0.0% and specificity of 88.2%. The ACL TOP versus UF Health’s current HIT ELISA method had a good comparison as well, with a sensitivity of 61.7% and a specificity of 96.4%.

Conclusion
The three HIT methods (ACL TOP, ELISA, and PIFA) compared to the SRA showed that the ACL TOP had a good positive agreement, but poor negative agreement; however, the ACL TOP had a very good negative agreement with the ELISA method. The PIFA cartridge test had an overall poor performance with no positive agreement with the SRA and poor sensitivity versus the ACL TOP and ELISA methods.