bluuebunny/crossref_metadata_2025_split huggingface dataset:
Importance of the Second Opinion in Surgical Breast Pathology and Its Therapeutic Implications
Authors: Ibarra A , Baksai K , Vial M 
Published: October 2020

Abstract

Introduction/Objective
Histopathological diagnosis determines surgical management and complementary therapies in patients with breast cancer. There has been reported significant diagnostic divergences, between 7.8 and 26%, and in tumor markers between 3.4 and 41%. We evaluate the agreement between diagnoses of general pathologists and specialists of our center, in which serious discrepancies could have therapeutic repercussions.

Methods
Method: A retrospective study from 2012 to 2019. The cases were classified in benign and malignant. The atypical lesions were included with benign. Major disagreements were considered when there was a change in diagnosis from benign to malignant or vice versa, variation from intraepithelial to microinvasive carcinomas, infiltrating to intraductal carcinomas or vice versa. When necessary, we repeat routine stains and/or immunostains, or add new immunostains.
Material: 295 cases. 294 women and 1 man. 228 biopsies and 67 immunostains of prognostic-predictive factors.

Results
We found diagnostic differences in 46/295 cases (15.6%). Major discrepancies in 32 cases (10.8%). In morphological diagnoses 11/228 (4.8%) and in immunodeterminations 20/67 (29.9%). In diagnostic changes, they highlighted 3 cases of ductal carcinoma in situ (DCIS) to benign, 2 cases of benign lesions to DCIS, 1 benign to invasive ductal carcinoma (IDC), 1 DCIS to IDC and 1 IDC to DCIS.

Conclusion
We found serious diagnostic divergences in 32 of 295 cases, 10.8%, which could have varied the therapeutic approach. In morphological interpretation 4.8% and in immunohistochemical results 29.9%. This should motivate multidisciplinary teams to routinely use the second opinion in surgical breast disease
Increased Fecal Calprotectin Levels in Crohn’s Disease Correlate with Elevated Serum Th1- and Th17-Associated Cytokines
Authors: Kamel Y S 
Published: October 2020

Abstract

Introduction/Objective
Patient-reported symptoms and endoscopic disease activity do not correlate well in Crohn’s disease (CD). This warrants the need for reliable biomarkers to early detect active intestinal inflammation. Currently, the fecal calprotectin level is the most commonly used biomarker for inflammatory activity in CD. However, the diagnostic accuracy of the fecal calprotectin level is not fully efficacious and diagnosis may be further improved by the identification of other biomarkers for active CD. Here, we studied the association of a variety of serum disease markers with fecal calprotectin levels in CD patients.

Methods
39 CD patients were included and subdivided into ‘normal’ (defined as &lt; 200 mg/kg feces) and ‘increased’ (defined as &gt; 200 mg/kg feces) fecal calprotectin level groups. Serum levels of 37 different cytokines, chemokines and markers for angiogenesis and vascular injury were quantified by an electrochemiluminescence multiplex assay (V- PLEX Human Biomarker 40-Plex Kit of Meso Scale Discovery ®). Correlations between individual biomarkers and the fecal calprotectin level were assessed using Spearman’s correlation coefficient (ρ).

Results
A highly significant positive correlation was observed between the pro-inflammatory serum cytokines IFN-γ and CRP and fecal calprotectin levels (P &lt; 0.01). Moreover, fecal calprotectin levels showed a significant positive correlation with IL-6, TNF-β, SAA and IL-17A (P &lt; 0.05).

Conclusion
We show that a positive correlation exists between multiple serum Th1- and Th17-associated cytokines and the fecal calprotectin level. These cytokines and CRP may serve as additional biomarkers for determining disease activity and evaluating treatment response in CD. Ultimately, this may result in more efficient treatment of active disease in CD patients and prevention of complications.
Diagnostic Accuracy & Pathology Revised Reports: Evidence-Based Guideline Development
Authors: Spiczka A , Waibel L , Garcia E , Kundu I , Garris R , Jacobs J , Brown A 
Published: October 2020

Abstract

Introduction/Objective
Diagnostic errors in pathology may have adverse impact on patient outcomes and are often rectified through revised reports (RR). Improving patient outcomes with accurate RR is a tangible yet challenging benefit to assuring continuous quality improvement (CQI). Assessment and elevation of RR optimization requires counterbalance of workflow complexity in the diagnostic reporting domain. Implications inform best-practice guidelines for pathology RR and exemplify improved patient outcomes by driving down negative impacts from diagnostic errors.

Methods
A “Survey for RR in Pathology: Reality & Best Practices” was sent via email to relevant stakeholders. The 8-item survey was designed by the National Pathology Quality Registry team & ASCP’s Institute for Science, Technology & Policy. The model included quantitative and qualitative feedback to probe current experiences with RR. The survey was open April 1-30, 2019, via Key Survey and used snowball sampling.

Results
Key results illuminate necessity for RR standardization. Survey findings represent 172 respondents. Ninety- two percent of respondents indicated report accuracy as a major indication for optimizing RR practices & positively impacting patient care. Pathology practices assure appropriate RR by notifying a care provider when a change in diagnosis necessitates RR (89%) & 86% of respondents indicate delineation of RR types (e.g. addenda, amendment). Still 54% of respondents see inappropriate RR use with lack of notification to care providers and 48% indicate no delineation of RR types. This balance-counterbalance highlights deviations from optimized RR and a need for guidelines. Effects on patient care or impact to a patient’s treatment plan was indicated by 43% who affirmed stratification of diagnostic discrepancies as major vs. minor. Solely focusing on changes in diagnosis (benign vs. malignant) was heralded by 19% of respondents as a reason to categorize diagnostic discrepancies. Forty-two percent of respondents indicate data-driven CQI in the RR domain.

Conclusion
Identified RR practice gaps decrease diagnostic accuracy, confirming the need for optimal RR guidelines. RR guidelines should focus on standardized nomenclature; active dialogue between laboratory team & clinical care partners; streamlined workflows to assure accuracy; & valuing transparency to derive improved patient outcomes based on high-quality diagnostic pathology RR.
Comparison of Manual and Digital Assessment of KI-67 in Neuroendocrine Tumors
Authors: Raju B S , Quinton M , Hassell L 
Published: October 2020

Abstract

Introduction/Objective
Proliferative activity is an essential prognostic and treatment indicator for neuroendocrine tumors (NET). Ki-67 proliferation index, if reported by unaided microscopic estimation on hot-spot locations could lead to variability and inconsistencies. This study aims to compare the Ki-67 assessment of NETs by visual estimation versus automated digital image analysis (Roche iCoreo/Virtuoso).

Methods
212 patients with Ki-67-graded GI NETs (117 G1; 61 G2; 34 G3) from 2010 to 2019 were reassessed using digital image analysis quantification of hot spot areas of at least 500 cells (average 800 cells). Revised tumor grades were assigned according to the European Neuroendocrine Tumor Society guidelines and the 2010 World Health Organization classification and compared to initially reported grade.

Results
We found 75% concordance for G1, with 22% of cases upgraded to G2 and 3% of cases upgraded to G3. For G2, there was 70.5% agreement, with 13.1% of cases downgraded to G1 and 16.4% upgraded to G3. For G3, there was 100% agreement, (kappa=0.64, overall). Retrospective review of discordant G3 cases revealed cases with known metastasis, small fragments of tissue, or polyps. Scanning and scoring required approximately 10 minutes per case.

Conclusion
Our data shows the time/effort difference of visually estimating versus automated digital analysis may lead to significant classification errors in these tumors. Although digital analysis has limitations, including tumor heterogeneity, misidentification of tumor cells, and poor immunostaining which could require manual counting by a pathologist, this rigor should be reinforced and explicitly stated to increase accuracy and reproducibility of grading.
Monitoring Of IGF-1 Levels In Type 2 Diabetic Patients With Macro And Microvascular Complications
Authors: Wasim H , Abdelmonem M , Samir S , Salah A 
Published: October 2020

Abstract

Introduction/Objective
Introduction: Type-2 diabetes have a risk factor of multiple complications such as coronary artery diseases (CAD), premature atheroscalerosis and diabetic retinopathy. IGF-1 is regulated by a balance of hormones such as growth hormone and insulin. It is important that circulating IGF1 in serum has normal levels to maintain glucose metabolism.
Objectives: Monitoring of IGF-1levels in T2DM with macrovascular complications (CVD) and microvascular complications (retinopathy).

Methods
Subjects and methods: The collection of samples started in June 2018 and ended in December 2018. A total of 114 subjects were enrolled in this study; 98 clinically diagnosed T2D patients who were recruited from the outpatient clinic of the National Institute for Diabetes and Endocrinology “NIDE”, in addition to 16 healthy comparable control subjects (without diabetes). The subjects divided into 3 groups. Group 1; a population of 44 T2D patients with macrovascular complications (28 females and 16 males), the mean age was 57.4 years. Group 2; a population of 54 T2D patients with microvascular complicatios (34 females and 20 males), the mean age was 59.1 years. Group 3; a population of 16 healthy subjects (12 female and 4 males), the mean age was 59.2 years. Levels of FBS, C-peptide, HbA1c, Lipid profile, lipoprotein(a), hs-CRP and microalbuminurea were measured in all subjects. Seum concentration of IGF-1 was measured by commercially immunoenzymatic ELIZA method.

Results
It was found that serum concentration of IGF-1 decreased in diabetic patients groups compared to the control one. The mean±SD of group 1, group 2 and group 3 were (332.2±152.2), (316.9 ±142.2) and (625.4 ± 257.7) respectively.

Conclusion
It was observed that there was a negative correlation between serum IGF-1 levels in T2D patients compared to the control group. Also, it was found that T2D patients with microvascular complications had lower IGF-1 levels than patients with macrovascular ones. It seems that IGF-1 strongly involved in the incidence and pathogenesis of T2DM complications.
Performance Assessment on Buffy Coat Examination for Human Granulocytic Anaplasmosis Diagnosis
Authors: Ye Q , Li H , Wang G 
Published: October 2020

Abstract

Introduction/Objective
Anaplasma phagocytophilum is an obligate gram-negative intracellular bacterium that causes human granulocytic anaplasmosis (HGA). The diagnostic tests for HGA include buffy coat examination, culture, PCR, and serology. In our lab, suspected patient will be subjected to buffy coat examination, and the result will be further confirmed with PCR. The aim of the study is to assess the epidemiology of HGA diagnosed at WMC during 06/2014- 08/2019, and as well as the performance accuracy of buffy coat examination as compared to PCR.

Methods
The results of buffy coat examination and in house HGA PCR from 06/2014 to 08/2019 were collected from SoftLAB and SoftMOL, respectively.

Results
A total of 1,057 blood specimens were tested by buffy coat examination from 06/2014-08/2019; among them, 658 specimens were also analyzed by HGA PCR assay (Fig. 1). Positivity for buffy coat examination and PCR was 2.6% and 6.1%, respectively. Overall, using PCR as reference diagnostic method, 42 new HGA cases were identified.
The number of new HGA cases varied among years from 2 to 15, with year of 2017 having the greatest number of total cases (Fig. 2). Further analyzing new HGA cases by months reveal HGA starts in April and ends in December, and peaks at June and July (Fig. 3).
When comparing buffy coat result to PCR, 17 positive buffy coat tests were confirmed positive in PCR test, and 619 negative buffy coat tests were also consistent with negative PCR test result. However, 21 cases which were initially negative in buffy coat examination were positive in PCR tests. On the other hand, 1 positive buffy coat examination case was negative in PCR (table 1). Overall, using PCR as a reference test, the sensitivity and specificity of buffy coat examination are 44.7% and 99.8%, respectively.

Conclusion
Buffy coat examination has high specificity but low sensitivity in detecting HGAcompared to PCR. Low sensitivity is most likely due to variable presence of intracytoplasmic aggregates of HGA in peripheral blood neutrophils and technically incompetency of testing personnel. Overall, it is a good test for laboratory confirmation of clinically suspected HGA cases. We suggest clinicians to add HGA PCR to all the buffy coat examination to avoid missing potential HGA diagnosis. Moreover, more training and competency on testing personnel may improve the sensitivity of buffy coat exam for diagnosis of HGA.
Legionella Test Reporting at a Regional Veteran Affairs Medical Center
Authors: Petersen J M , Jhala D 
Published: October 2020

Abstract

Introduction/Objective
The appropriate reporting and monitoring of legionella antigen and culture test volumes and results is a veteran affairs quality assurance regulatory requirement. Legionnaires disease incidence has been noted to be increasing in the United States, and it has also been documented that health care facilities are especially high- risk settings for the transmission of Legionella bacteria from the building water systems to the occupants. However, studies of Legionella test epidemiology for non-veteran hospitals is sparse in the literature. To provide perspective, here we report the total legionella antigen and culture tests from quarter 1 2016 to quarter 4 2019 to provide a regional perspective.

Methods
Quality assurance data on both the total number of Legionella antigen and culture tests and the recorded number of positive cases were reviewed from quarter 1 2016 to quarter 4 2019 and tabulated. This data is collected routinely as per veteran affairs regulatory directives.

Results
There were a total of 1613 legionella antigen tests and 1287 legionella cultures. None of the Legionella cultures were positive during the study period. Nonetheless, there were 3 positive urinary antigen tests for a total calculated percentage of 0.00002%.

Conclusion
The presence of positive Legionella antigen tests at a regional veteran affairs medical center indicates that a robust quality assurance program is tremendous benefit to monitoring Legionella at a major medical institution in order to prompt action to prevent hospital-based spread.
An Emerging Infection: Streptococcal Toxic Shock-Like Syndrome Caused By Group B Streptococcus (GBS), Streptococcus Agalactiae
Authors: Rajack F , Afsari A , Ramadan A M , Naab T J 
Published: October 2020

Abstract

Introduction/Objective
Streptococcus agalactiae, Group B Streptococcus (GBS), is a major cause of neonatal sepsis and infections in pregnant women. However, incidence of invasive GBS infections has more than doubled in the last two decades with highest risk in adults 65 years or older. Other risk factors are diabetes, malignancy, and immunocompromised state. Bacteremia and skin soft tissue infections are the most common invasive infections in nonpregnant adults. Rarely GBS infection has a fulminating pyrogenic exotoxin-mediated course characterized by acute onset, multiorgan failure, shock, and sometimes death, referred to as toxic shock-like syndrome.

Methods
A 77-year-old hypertensive female with uncontrolled type 2 diabetes mellitus and a history of bilateral foot ulcers presented to the hospital in probable septic shock. Clinical diagnosis of necrotizing fasciitis was made and she underwent bilateral lower limb amputations.

Results
Grossly soft tissue appeared gray. Microscopically fascia was necrotic without neutrophils present and Gram stain revealed sheets of Gram positive cocci. These findings reflected histopathologic Stage III necrotizing fasciitis, which is associated with 47% mortality. Autopsy showed a similar histology of Stage III necrotizing fasciitis involving the surgical stump. Erythema and desquamation of the upper limbs bilaterally and multi-organ failure met the clinical picture of Streptococcal Toxic Shock Syndrome (STSS) and fulfilled the criteria for TSS due to Group A Streptococcus (GAS), defined by The Working Group on Severe Streptococcal Infections.

Conclusion
Group B Streptococcal Toxic Shock-Like Syndrome may have a similar outcome to STSS caused by GAS and other pathogens and, in limited studies, mortality has been 30% or greater.
Assessment of Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF- MS) for Accurate Bacterial Identification in Clinical Labs
Authors: Abdel-Rahman M , Azab M S , Meibed M , El-Kholy A , Elmetwalli A W 
Published: October 2020

Abstract

Introduction/Objective
On behalf of the diagnostic Medical Laboratory rapid, and accurate identification of bacteria with their one-to-one anti-microbial susceptibility outlines is of ultimate importance for the management of infected patients. Contemporary microbial identification methods employed in routine clinical diagnostic laboratories relies on the use of conventional phenotypic methods. Phenotypic methods are time consuming with minimum turn-around times of at least 24 hrs and in many occurrences of 48hrs. With the intention of accelerate laboratory processes the MALDI-TOF MS was familiarized. MALDI-TOF MS is established on proteomic profiling and permits for rapid identification of bacteria. This technology has not been widely used in Egypt, but has been regularly used in Europe for the past few years.

Methods
Two hundred forty three positive non duplicate blood cultures were accrued over a period of six months. Experimental aliquots were taken from excess sample material that was collected as part of routine clinical care. 105 were positive for Gram negative bacilli, 123 were positive for Gram positive cocci, 3 positive for Gram positive bacilli, and 7 were positive for yeast. MALDI-TOF identification was compared to conventional identification. Conventional identification consisted of a combination of MALDI-TOF identification of a subcultures colony by direct smear, biochemical reactions, Vitek 2, and molecular identification.

Results
Ninety seven of the one hundred and five blood cultures positive for Gram negative bacilli were monomicrobial. The majority of these were identified as Escherichia coli by conventional methods, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa. Eighty-four of these monomicrobial cultures were identified by MALDI-TOF to the species level. Eighty-one of the eighty-four were concordant with the conventional identification (96.4%).

Conclusion
The MALDI-TOF proved to be useful for the rapid and reliable identification of g-ve bacteria from the clinical specimens. The difference in turnaround time for bacterial identification was significant between MALDI-TOF MS and VITEK 2 with minimal preparation for the blood cultures.
A Rare Case of Chronic Myeloid Leukemia with t(3;9;22) 3-way Translocation
Authors: Elzamly S , Padilla O , McAlice M , Gohar M , Gaur S , Tonk S , Chavali S 
Published: October 2020

Abstract

Introduction/Objective
Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm originating from malignant clonal proliferation of a pluripotent hematopoietic stem cell. CML is characterized by a reciprocal translocation between chromosomes 9 and 22, t(9;22)(q34;q11), that gives rise to an abnormal chromosome 22 called the Philadelphia (Ph) chromosome. The translocation results in the formation of a chimeric BCR-ABL1 fusion gene, which is the molecular hallmark of the disease. However, 5-10% of CML patients present with additional chromosomal abnormalities which is often considered a sign of clonal evolution, genetic instability, and is generally thought to portend a poor prognosis.

Methods
We present a case of CML with a rare 3- way translocation, t(3;9;22)(q21;q34;q11.2), who achieved a major molecular response on imatinib for 18 months. A review of the literature and Mitelman database search is presented focusing on the prognostic implications of this 3 way translocation in the era of tyrosine kinase inhibitors starting in 2001 till now.

Results
Twenty seven cases were reported, but the patient therapeutic response to imatinib and clinical outcome were only reported in 11 cases. Nine cases achieved a cytogenetic remission while the remaining two cases had an adverse outcome.

Conclusion
Taken in conjunction with the favorable outcome in our patient, we suggest that t(3;9;22) is not an adverse prognostic factor in the era of tyrosine kinase inhibitors.
Features of Failed Genomic Testing in Advanced NSCLC Specimens
Authors: Gardner E M , Li W , Cohen M B , Topaloglu U , Ramkissoon S 
Published: October 2020

Abstract

Introduction/Objective
Lung cancer continues to be the leading cause of cancer death in the United States. For individuals with advanced lung cancer, genomic testing has the potential to direct patients and their care teams toward a targeted therapy or a specific clinical trial. In some instances, however, submitted specimens fail to meet test standards or do not survive the analytic process. The implications of a failed genomic test for patients can be grave. In this study, we aim to identify common features among non-small cell lung cancer (NSCLC) samples submitted from our medical center that failed FoundationOne testing (Foundation Medicine Inc. Cambridge, MA).

Methods
From all 366 NSCLC samples listed in the FoundationOne database, we identified 31 (8.5%) unique and accessible accession numbers submitted from our institution that failed processing between 2013-2018. These 31 samples were compared for common features, including NSCLC subtype, tumor location, sampling method, tumor size, submitting team, and reported error type.

Results
From all of our samples, 45% (14/31) were adenocarcinoma, 29% (9/31) were squamous cell carcinoma (SCC), 22% (7/31) were NSCLC otherwise unspecified, and 3% (1/31) was adenoid cystic carcinoma. The majority of samples (20/31) were sampled from primary sites including core biopsies (n=9), FNA (n=5), lobectomy specimens (n=4), and bronchial washings (n=2). The remaining metastatic samples came from sites including lymph node, bone, brain, and adrenal gland. Per FoundationOne: the majority of samples (27, 87%) failed following sequencing, while the remaining four (4, 13%) samples failed in the analytic phase.

Conclusion
At this time, it remains unclear why many of these samples failed sequencing. Our next steps include comparing the degree of necrosis from samples and comparing our failed sample pool to a successful sample pool of equal size to remove potential confounding factors.