bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic Concordance of Histologic Lung Cancer Type Between Bronchial Biopsy and Cytology Specimens Taken During the Same Bronchoscopic Procedure
Authors: Sackett Melanie K. , Salomão Diva R. , Donovan Janis L. , Yi Eunhee S. , Aubry Marie Christine 
Published: February 2021

Abstract
Context.—The diagnosis of lung cancer is often confirmed by cytology and biopsy specimens obtained during a bronchoscopic procedure. At our institution, these specimens are read by different pathologists, and the rate of concordance was not known.
Objectives.—To evaluate the concordance rate in the diagnosis of lung cancer types between cytology and biopsy specimens and to correlate discordance with patient outcome.
Design.—Specimens obtained during the same procedure, between January 1, 2000, and December 31, 2005, were identified. Cases with cytology and biopsy specimens positive for cancer were evaluated for concordance of histologic type, small cell versus non–small cell lung carcinoma. Cases with different types were considered discordant, and slides were reviewed.
Results.—Of 231 cases, 225 (97.4%) had concordant diagnoses. Discordance was the result of misinterpretation of undifferentiated carcinoma, overinterpretation of squamous dysplasia, interpretation of suboptimal specimens with necrosis and crush artifact, and sampling error.
Conclusions.—Even though the cytology and biopsy specimens were reviewed by different pathologists, the concordance rate for histologic type at our institution was high, emphasizing that this is a safe practice. The few discordant cases did not affect the patient's outcome.
PAX-2 Is a Helpful Marker for Diagnosing Metastatic Renal Cell Carcinoma: Comparison With the Renal Cell Carcinoma Marker Antigen and Kidney-Specific Cadherin
Authors: Ozcan Ayhan , Zhai Qihui , Javed Rehana , Shen Steven S. , Coffey Donna , Krishnan Bhuvaneswari , Truong Luan D. 
Published: February 2021

AbstractContext.—The diagnosis of metastatic renal cell carcinoma (RCC) remains problematic.Objective.—To evaluate the role of PAX-2, a renal tubular cell transcription factor, in the diagnosis of metastatic RCC. PAX-2 expression in metastatic RCC was compared with that of the renal cell carcinoma marker antigen (RCCM) and kidney-specific cadherin (KSC), which are 2 known markers for RCC.Design.—Immunostaining for PAX-2, RCCM, and KSC was performed on consecutive tissue sections of 95 metastatic RCCs (77 clear cell, 8 papillary, 5 sarcomatoid, and 5 collecting duct) and 183 metastatic tumors other than RCC.Results.—For PAX-2, positive immunoreactivity was detected in 77% clear cell, 75% papillary, 100% collecting duct, and 0% sarcomatoid metastatic RCCs. For RCCM, positive immunoreactivity was detected in 49% clear cell, 75% papillary, 0% collecting duct, and 0% sarcomatoid metastatic RCCs. For KSC, only 2 metastatic clear cell RCCs (3%) were positive. In combination, all markers were positive in 0% of cases; all markers were negative in 23% of cases (17 clear cell, 1 papillary, and for all 5 sarcomatoid); and at least 1 marker was positive in 76% of cases (PAX-2 only in 28% of cases [21 clear cell, 1 papillary, and 5 collecting duct] and RCCM only in 3% of cases [2 clear, 1 papillary]). Of 183 metastatic tumors other than RCC, 14 were positive for PAX-2 (nodal metastasis of carcinoma of colon [1], breast [1], endometrium [1], and ovary [1]; and omental metastasis of carcinoma of uterus or ovary [10]).Conclusions.—PAX-2 is a sensitive and specific marker for metastatic RCC. The diagnostic yield would be marginally increased by adding RCCM, but not KSC, as an immunomarker.
International Normalized Ratio Versus Plasma Levels of Coagulation Factors in Patients on Vitamin K Antagonist Therapy
Authors: Gulati Gene , Hevelow Megan , George Melissa , Behling Eric , Siegel Jamie 
Published: February 2021

Abstract
Context.—The key question when managing patients on warfarin therapy who present with life-threatening bleeding is how to use the international normalized ratio (INR) to best direct corrective therapy. The corollary question for the clinical laboratory is at what level will the INR reflect a critical value that requires notifying the clinician.
Objective.—To determine the levels of vitamin K–dependent factors over a range of INR values.
Design.—Evaluation of the vitamin K–dependent coagulation factor levels on plasma remnants from patients in whom a prothrombin time and INR was ordered to monitor warfarin therapy. There were a total of 83 specimens evaluated with an INR range from 1.0 to 8.26.
Results.—The mean activity levels of all 4 factors remained near or above 50% when the INR was less than 1.5. The average factor X level was 23% when the INR range was 1.6 to 2.5, but levels of factors II, VII, and IX did not drop below the hemostatic range until the INR was greater than 2.5. At an INR of 3.6 or more, the activity levels of all 4 factors were less than 30% in more than 90% of the specimens.
Conclusion.—Levels of factors II, VII, IX, and X declined with increasing INR but not at the same rate and not to the same level at a given INR. However, most of the values were below the hemostatic value once the INR was 3.6 or more, the level that was also considered critical for physician notification.
Granulomatous Inflammation—An Underestimated Cause of False-Positive Diagnoses in Lung Fine-Needle Aspirates: Observations From the College of American Pathologists Nongynecologic Cytopathology Interlaboratory Comparison Program
Authors: Auger Manon , Moriarty Ann T. , Laucirica Rodolfo , Souers Rhona , Chmara Beth Anne , Fatheree Lisa A. , Wilbur David C. 
Published: February 2021

Abstract
Context—The false-positive rate for fine-needle aspirates of the lung has been cited as less than 1% for granulomatous inflammation, comprising one of the known causes of false-positive diagnoses.
Objective—To determine the rate of false-positive diagnoses of granulomatous inflammation for lung fine-needle aspirates by assessing the false-positive response rate in the context of the College of American Pathologists Nongynecologic Cytopathology Interlaboratory Comparison Program.
Design—We performed a retrospective review of 1092 participant responses for lung fine-needle aspirate challenges with the reference diagnosis of specific infections/granulomatous inflammation from 1998 to 2008 from the College of American Pathologists Nongynecologic Cytopathology Interlaboratory Comparison Program. False-positive rates by participant type (pathologist versus cytotechnologist), general diagnosis category, reference diagnosis, and preparation type were analyzed for the pathologists' responses.
Results—Of the 502 general category responses for pathologists, 428 (85.3%) were benign, 55 (11%) were malignant, and 19 (3.8%) were suspicious. There was no difference in the false-positive rate between preparations (P  =  .76) or participants (P  =  .39). Of those responses by pathologists that were benign, only 68.7% (292 of 425) were an exact match to granulomatous inflammation. Non–small cell carcinoma, adenocarcinoma, and squamous carcinoma represented 64% of false-positive/suspicious responses, while small cell carcinoma and carcinoid comprised 13%.
Conclusion—In an interlaboratory comparison program, granulomatous inflammation represents an important cause of false-positive/suspicious responses in lung fine-needle aspirates (14.8%) and is much higher than false-positive rates reported historically in clinical studies. These results highlight the importance of granulomatous inflammation as a mimic of carcinoma.
Reliability and Reproducibility of the Edmondson Grading of Hepatocellular Carcinoma Using Paired Core Biopsy and Surgical Resection Specimens
Authors: Pirisi Mario , Leutner Monica , Pinato David J. , Avellini Claudio , Carsana Luca , Toniutto Pierluigi , Fabris Carlo , Boldorini Renzo 
Published: February 2021

Abstract
Context—It has been claimed that the Edmondson and Steiner grading system (EGS) values should be obtained preoperatively to select patients with hepatocellular carcinoma for liver transplantation. However, EGS reliability in biopsy specimens has been questioned.
Objective—To verify the reliability of the EGS using core biopsy specimens and its reproducibility among pathologists.
Design—Paired biopsy and surgical specimens obtained from 40 patients (subset 1) were retrieved by means of computer-aided search of the pathology records and blindly and independently reviewed. The EGS interrater agreement was measured using κ statistics. After having held a consensus meeting, pathologists graded an additional 21 paired hepatocellular carcinoma specimens (subset 2).
Results—Analyzing subset 1, pathologists gave significantly lower EGS grades to the biopsy specimens (P &lt; .001), for which the observed agreement was 32.5% (κ  =  0.021), which increased to 82.5% (κ  =  0.186) if only 2 categories were considered (low grade, EGS I–II; high grade, EGS III–IV). The observed agreement in the case of the surgical specimens was 52.5% (κ  =  0.199), which increased to 62.5% (κ  =  0.275) when the low- and high-grade scores were merged. The observed agreement between the assessments of paired biopsy and surgical specimens was 50.0% for pathologist 1 (κ  =  0.057) and 35.0% for pathologist 2 (κ  =  0.078). Merging the EGS grades did not improve the strength of the agreement. Analyzing subset 2 (after the consensus meeting), the observed agreement between pathologists improved more on biopsies (76.2%, κ  =  0.614) than on surgical specimens (61.9%, κ  =  0.434).
Conclusions—The EGS is easily underestimated in core biopsy specimens, and interrater disagreement between pathologists can be significant unless consensus meetings are held.
Sarcomatoid Carcinoma of Esophagus
Authors: Raza Muhammad Adeel , Mazzara Paul F. 
Published: February 2021

Abstract
Sarcomatoid carcinoma of the esophagus is an uncommon malignancy, representing approximately 2% of esophageal carcinomas. It has also been referred to as carcinosarcoma, pseudosarcoma, pseudosarcomatous squamous cell carcinoma, spindle cell carcinoma, and polypoid carcinoma, reflecting the uncertainty of its pathogenesis. Histologically, carcinomatous and sarcomatous components coexist. The clinical and radiologic findings resemble other esophageal neoplasms. Sarcomatoid carcinoma often presents as a large, intraluminal, polypoid mass on barium esophagram. Despite its size, however, sarcomatoid carcinoma has a more favorable prognosis than other malignant esophageal neoplasms, likely because of its exophytic growth into the lumen, rather than deep invasion. This article provides a brief overview of the clinicopathologic features and possible pathogenesis of this uncommon tumor.
Evaluation of First-Draw Whole Blood, Point-of-Care Cardiac Markers in the Context of the Universal Definition of Myocardial Infarction: A Comparison of a Multimarker Panel to Troponin Alone and to Testing in the Central Laboratory
Authors: Lee-Lewandrowski Elizabeth , Januzzi James L , Grisson Ricky , Mohammed Asim A , Lewandrowski Grant , Lewandrowski Kent 
Published: February 2021

Abstract
Context.—Previous studies evaluating point-of-care testing (POCT) for cardiac biomarkers did not use current recommendations for troponin cutoff values or recognize the recent universal definition of acute myocardial infarction. Traditionally, achieving optimal sensitivity for the detection of myocardial injury on initial presentation required combining cardiac troponin and/or creatine kinase isoenzyme MB with an early marker, usually myoglobin. In recent years, the performance of central laboratory combining cardiac troponin assays has improved significantly, potentially obviating the need for a multimarker panel to achieve optimum sensitivity.
Objective.—To compare 2 commonly used POCT strategies to a fourth generation, central laboratory cardiac troponin T assay on first-draw specimens from patients being evaluated for acute myocardial infarction in the emergency department. The 2 strategies included a traditional POCT multimarker panel and a newer POCT method using cardiac troponin I alone.
Design.—Blood specimens from 204 patients presenting to the emergency department with signs and/or symptoms of myocardial ischemia were measured on the 2 POCT systems and by a central laboratory method. The diagnosis for each patient was determined by retrospective chart review.
Results.—The cardiac troponin T assasy alone was more sensitive for acute myocardial infarction than the multimarker POCT panel with equal or better specificity. When compared with a POCT troponin I, the cardiac troponin T was also more sensitive, but this difference was not significant. The POCT troponin I alone also had the same sensitivity as the multimarker panel.
Conclusions.—Testing for combining cardiac troponin alone using newer, commercially available, central laboratory or POCT assays performed with equal or greater sensitivity to acute myocardial infarction as the older, traditional, multimarker panel. In the near future, high-sensitivity, central laboratory troponins will be available for routine clinical use. As a result, the quality gap between central laboratories and older POCT methods will continue to widen, unless the performance of the POCT methods is improved.
CD34+ Cell Enumeration by Flow Cytometry: A Comparison of Systems and Methodologies
Authors: Ngoma Alain , Saito Shunnichi , Ohto Hitoshi , Ikeda Kazuhiko , Yasuda Hiroyasu , Kawabata Kinuyo , Kanno Takahiro , Kikuta Atsushi , Mochizuki Kazuhiro , Nollet Kenneth E. 
Published: February 2021

Abstract
Context.—An increasing number of medical centers can collect bone marrow, peripheral blood, or umbilical cord stem cells. Pathology laboratories should accommodate this trend, but investment in additional equipment may be impractical.
Objectives.—To compare CD34+ cell counting results by using 2 widely available flow cytometry systems, with and without the use of a separate hematology analyzer (ie, single-platform versus dual-platform methodologies).
Design.—Whole blood and peripheral blood stem cell (PBSC) samples were analyzed from 13 healthy allogeneic PBSC donors and 46 autologous PBSC donors with various malignancies. The Cytomics FC500 (Beckman Coulter, Fullerton, California) was compared with the FACSCalibur (BD Biosciences, San Jose, California). Dual-platform CD34+ cell counting incorporated data from a KX-21 hematology analyzer (Sysmex, Kobe, Japan).
Results.—Subtle differences in CD34+ cell counting between 2 systems and 2 methods did not achieve statistical significance.
Conclusion.—Different systems and methods for CD34+ cell enumeration, properly validated, can support care for patients undergoing transplants and provide meaningful data for multicenter studies or meta-analyses.
Mucolipidosis Type III α/β: The First Characterization of This Rare Disease by Autopsy
Authors: Kerr Darcy A , Memoli Vincent A , Cathey Sara S , Harris Brent T 
Published: February 2021

Abstract
We report findings from an autopsy of a 45-year-old woman with the rare lysosomal storage disease mucolipidosis type III α/β. Her disease manifested most notably as multiple bone and cartilage problems with tracheal and bronchial malacia. Principal autopsy findings included gross abnormalities in bone and cartilage with corresponding microscopic cytoplasmic lysosomal granules. These cytoplasmic granules were also seen in histologic preparations of the brain, myocardium, heart valves, and fibroblasts of the liver and skin by light and electron microscopy. By electron microscopy there were scattered, diffuse vesicular cytoplasmic granules in neurons and glia and an increase in lysosomal structures with fine electron lucent granularity in the above tissue types. Our findings help elaborate current understanding of this disease and differentiate it from the mucopolysaccharidoses and related disorders. To our knowledge, this is the first report to document pathologic findings in a patient with mucolipidosis type III α/β by autopsy.
Four Molecular Subtypes of Colorectal Cancer and Their Precursor Lesions
Authors: Kang Gyeong Hoon 
Published: February 2021

Abstract
Context.—In addition to chromosomal instability and microsatellite instability (MSI), a third pathway, epigenetic instability, has been implicated in progression to colorectal carcinogenesis. CpG island methylator phenotype (CIMP) refers to a subset of colorectal cancers (CRCs) that occur through the epigenetic instability pathway and that are characterized by widespread hypermethylation of promoter CpG island loci, resulting in the inactivation of several tumor suppressor genes or tumor-related genes. Colorectal cancers can be classified into 4 molecular subtypes according to their CIMP and MSI statuses: CIMP+/MSI+, CIMP+/MSI−, CIMP−/MSI+, and CIMP−/MSI−. There are differences between Western (United States and European Union) and Eastern (Korea and China) populations in the number of CRCs that are MSI+, and in the number of MSI+ CRCs that are CIMP+.
Objective.—To review the clinicopathologic and molecular features of the 4 molecular subtypes of CRCs and their precursor lesions, and to emphasize geographic differences in CRCs between Eastern and Western populations.
Data Sources.—This article is based on the author's own experimental data and a literature review of relevant articles indexed in PubMed (US National Library of Medicine).
Conclusion.—The 4 molecular subtypes of CRC that are defined by their CIMP and MSI statuses are characterized by their own distinct clinicopathologic and molecular features and precursor lesions. In particular, the clinicopathologic features of MSI+ CRCs differ depending on the CIMP status. Further understanding of the heterogeneity in CRC molecular pathways may help to explain the diverse morphologic features of CRCs.
Molecular Diagnostics of Gliomas
Authors: Nikiforova Marina N. , Hamilton Ronald L. 
Published: February 2021

AbstractContext.—Gliomas are the most common primary brain tumors of adults and include a variety of histologic types and morphologies. Histologic evaluation remains the gold standard for glioma diagnosis; however, diagnostic difficulty may arise from tumor heterogeneity, overlapping morphologic features, and tumor sampling. Recently, our knowledge about the genetics of these tumors has expanded, and new molecular markers have been developed. Some of these markers have shown diagnostic value, whereas others are useful prognosticators for patient survival and therapeutic response.Objective.—To review the most clinically useful molecular markers and their detection techniques in gliomas.Data Sources.—Review of the pertinent literature and personal experience with the molecular testing in gliomas.Conclusions.—This article provides an overview of the most common molecular markers in neurooncology, including 1p/19q codeletion in oligodendroglial tumors, mutations in the isocitrate dehydrogenase 1 and 2 genes in diffuse gliomas, hypermethylation of the O6-methylguanine-DNA methyltransferase gene promoter in glioblastomas and anaplastic gliomas, alterations in the epidermal growth factor receptor and phosphatase and tensin homolog genes in high-grade gliomas, as well as BRAF alterations in pilocytic astrocytomas. Molecular testing of gliomas is increasingly used in routine clinical practice and requires that neuropathologists be familiar with these genetic markers and the molecular diagnostic techniques for their detection.
Knowledge Management Practices towards Competitive Advantage: Study on SMEs in Sri Lanka
Authors: Erandi Himasha , Sachitra Vilani 
Published: February 2021

Purpose: Knowledge Management (KM) can be defined as capturing, distributing, and effectively using knowledge. Organizations become more knowledge intensive and they are hiring “minds” more than “hands”. The organization practice has shown that knowledge, when properly used and leveraged, could drive it to become more innovative and thus, more competitive. The investments on intangible resources and the creation of capabilities made by the SMEs are quite problematic. The main reason of conducting this study is to examine the effects of Knowledge Management Practices (KMP) to gain competitive advantage (CA) of SMEs in Sri Lanka.
Methods: Explanatory research approach was utilized followed with quantitative research method. Knowledge Creation, Knowledge Validation, Knowledge Presentation, Knowledge Distribution and Knowledge Application were considered as Knowledge Management Practices. The study was conducted with 32 SMEs in Colombo District.
Findings: According to the overall assessment of Knowledge Management Practices in SMEs, 12.5 percent of respondents were never heard about Knowledge Management while 6.3 percent were thinking that it is just a management activity that organizations are already engaging with. Further, 34.4 percent opined that Knowledge Management is a strategic part of the business while 15.6 percent stated Knowledge Management is not existence at their organizations. Fortunately, 40.6 percent believed that Knowledge Management Practices could be beneficial for the organizations. Correlation analysis result indicated moderate positive correlation among knowledge creation, validation, presentation, distribution, application and competitive advantage of SMEs. Regression analysis results revealed that of knowledge distribution was the only significant determinant of competitive advantage of SMEs.
Research Implications: The findings could be beneficial to SMEs to share and manage tacit and explicit knowledge and information effectively within their entity to achieve competitive advantage. Organizational learning will help them to enhance their decision-making process more effectively. The smooth and accelerate access to information and knowledge and manages to engage in work will be bonuses of having a good Knowledge Management Practices in the society.
Limitations: The study was conducted based on the sample of SMEs in Colombo District, as in Colombo area population is relatively high and it is the business hub of Sri Lanka. Generalizability of the findings might be restricted.
Pharmacy, Medicine and Nursing Students’ Perceptions about Learning Pharmacology
Authors: Ahmed Nehad J. , Alrawili Abdulrahman S. , Alkhawaja Faisal Z. 
Published: February 2021

Aim: This study aims to evaluate health students' perceptions toward pharmacology.
Methodology: This study included a self-administered questionnaire that inquired concerning their perceptions about learning pharmacology. The survey was translated to Arabic language and after that it was validated and converted to online Google Form and then the link was sent to the students.
Results: Most of the students was less than 22 years old (67.90%) in addition to that most of them were females (81.48%). About 38.27% of the respondents were pharmacy students. More than 90% of the respondents said that pharmacology is an interesting subject in the university courses. Most of the students agreed that there should be more emphasis on studying case studies not only theoretical teaching (88.89%).
Conclusion: The study found that the perceptions of students regarding pharmacology were positive. It is important to add a practical training for pharmacology in the hospital not only teaching it theoretically. Moreover, it is important to integrate pharmacology horizontally with other related course such as pathophysiology and pharmacotherapy.