bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of Soluble Fms-Like Tyrosine Kinase-1 (sFlt-1) and Placental Growth Factor (PlGF) Assays on Cobas e602 System
Authors: Tang Nga Yeung , Rana Sarosh , Yeo Kiang-Teck J 
Published: October 2020

Abstract

Background
Preeclampsia is a leading hypertensive disorder in pregnant women. The angiogenic biomarkers, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio, have been shown to be associated with diagnosis and prediction of preeclampsia. The objective of this study is to validate the analytical performance of sFlt-1 and PlGF on the Cobas e602 system (Roche Diagnostics Corporation).

Method
Intra-day and inter-day precisions for both sFlt-1 and PlGF assays were assessed using quality control materials provided from Roche Diagnostics. The accuracies for both assays were assessed by running 60 patient samples, which have been previously analyzed on the Elecsys 411 analyzer (Roche Diagnostics Corporation) at the Beth Israel Deaconess Medical Center. Linearity studies for both assays were performed using patient plasma spiked with recombinant sFlt-1 and PlGF proteins (R&D systems). Hemolysis, icterus, lipemia and biotin interference studies were performed by spiking hemolysate, bilirubin, intralipid or biotin into either pooled patient plasma with detectable levels of sFlt-1 and PlGF or otherwise, patient plasma spiked with recombinant sFlt-1 and PlGF proteins.

Results
Total precisions for both assays demonstrated CVs of &lt;5.0%. The sFlt-1 and PlGF assays demonstrated analytical measuring ranges of 3060,000 pg/mL and 79,000 pg/mL, respectively (r2 &gt; 0.98). Lower limit of quantitation (10% CV) was 30 pg/mL for sFlt-1 and 7 pg/mL for PlGF, respectively. Interference studies showed sFlt-1 and PlGF were not significantly affected by hemolysis up to H-indices of 500 and 1000 respectively; both assays were not affected by bilirubin up to an I-index of 60, and lipemia up to an L-index of 2800. Biotin at concentrations &gt;30 ng/mL caused significant negative bias for both sFlt-1 and PlGF assays. Comparison studies showed the following: Cobas e602 sFLT-1 = 1.09 [Elecsys 411 sFLT-1] +203 (r2=0.97, Sy/x=1234, n=58); Cobas e602 PlGF = 1.10 [Elecsys 411 PlGF] +47 (r2=0.99, Sy/x=22.1, n=58); Cobas e602 sFLT-1/PlGF ratio = 0.94 [Elecsys 411 sFLT-1/PlGF ratio] +3.5 (r2=0.91, Sy/x=50, n=58).

Conclusion
sFlt-1 and PlGF measured on Roche Diagnostics Cobas e602 system demonstrated excellent analytical performance and are acceptable for clinical use once approved in the US.
Co-Culture of Acinetobacter calcoaceticus-baumannii complex and Staphylococcus saprophyticus Supports Simple Point Contamination Model in Recent Cases of Transfusion-Related Sepsis
Authors: Kerantzas Christopher , Merwede Jacob , Snyder Edward , Hendrickson Jeanne , Tormey Christopher , Kazmierczak Barbara , Peaper David 
Published: October 2020

Abstract
The CDC recently reported a series of four septic transfusion reactions across three states resulting from contamination of apheresis platelet products. The apheresis platelets were contaminated with strains of both Acinetobacter calcoaceticus-baumannii complex (ACBC) and Staphylococcus saprophyticus (Ss). Two of the reported septic transfusion reactions occurred at our institution. The CDC investigation showed that isolates of each species were genetically related and suggested a point source of contamination. However, the contamination of blood products with ACBC is rare and the co-occurrence of these two species in all four cases was unusual. We hypothesized that there was an augmentative interaction between the clinical isolates of ACBC and Ss from these cases that contributed to their repeated co-occurrence. To test this hypothesis, we compared the growth characteristics of ACBC and Ss when cultured together versus independently. We used isolates from the contaminated platelets for our studies and performed experiments using both solid and liquid growth media. Experiments on solid media assessed density of growth and macroscopic morphology after cross-streaking on Columbia Blood Agar (CBA) and Luria-Bertani (LB) agar. Experiments in liquid media assessed growth by CFU counts in LB broth, platelet-poor plasma, and apheresis platelets. Growth in apheresis platelets was performed using standard, room temperature blood bank platelet storage conditions. Results of these experiments showed a higher CFU concentration of Ss when co-cultured with ACBC in LB broth only after several days, as compared to Ss alone under the same conditions. Otherwise, there was no evidence of augmented growth by either CFU concentration or growth rate in LB broth, plasma, or platelets at other time points. Similarly, there was no evidence of augmented growth by colony density or morphology when cross-streaking strains on either CBA or LB agar. As a result, we conclude that the co-occurrence of these two species in platelets is likely a coincidence of the point contamination suggested by the CDC investigation and not the result of growth augmentation between the two species.
Utilization and Laboratory Monitoring of Andexanet Alfa Reversal of Factor Xa Inhibitors in Bleeding Patients
Authors: Alipour Zahra , Jackups Ronald 
Published: October 2020

Abstract

Introduction
Andexanet alfa, a reversal agent for factor Xa inhibitors rivaroxaban and apixaban, was approved by the Food and Drug Administration in May 2018 for patients with life-threatening bleeding. It acts by competing with endogenous factor Xa to block anticoagulant activity. Intravenous administration rapidly reduces anti-factor Xa activity. Because andexanet became available only recently, there is high potential for inappropriate use. Our objective was to investigate utilization and laboratory monitoring of andexanet in our hospital system in order to improve utilization.

Methods
This is a retrospective study with review of charts in the electronic medical record from April 2019 to February 2020. Charts were reviewed for the time of andexanet administration, anti-factor Xa testing before and after administration, turnaround time (TAT) for anti-factor Xa testing, and patient’s status after treatment.

Results
We identified 33 patients who received andexanet in our hospital system. Intracranial hemorrhage was the most common clinical symptom. Of 33 patients, 12 patients (36%) expired, one transferred to hospice, 18 (55%) were discharged alive, and two recent cases are alive awaiting disposition. Only 12 patients (36%) had anti-factor Xa testing performed prior to administration of andexanet, with one additional patient receiving testing only after administration. Factor Xa activity was misordered for anti-factor Xa in one patient. TAT for anti-factor Xa in these patients ranged from 25–112 minutes, with median 35.5 minutes. Of the 12 patients who had anti-factor Xa testing prior to administration, 4 expired and 8 survived. Pre-administration anti-factor Xa activity was significantly lower in patients who expired than in patients who survived (0.3 vs. 1.8 IU/ml, P value = 0.02).

Conclusion
Currently, anti-factor Xa testing is not ordered for most patients receiving andexanet alfa in our hospital system. Although not necessary for dosing decisions, anti-factor Xa testing may be useful prior to administration to identify patients unlikely to benefit from anticoagulant reversal. Despite a small sample size, there was a statistically significant difference in anti-factor Xa activity by patient outcome, suggesting that andexanet may be unhelpful in patients with low anti-factor Xa activity. Based on these findings, we are building an electronic order set to facilitate proper administration of this medication.
Utilization of P16 in Head and Neck Cytology and Surgical Specimens After the Release of CAP Guidelines
Authors: Laharwani H , Manucha V , Jefferson G , Jackson L 
Published: October 2020

Abstract

Introduction/Objective
HPV-positive oropharyngeal squamous cell carcinoma is biologically and clinically unique and has a survival advantage over other head and neck squamous cell carcinomas. In December 2017 College of American Pathologist published guidelines for testing HPV status in head and neck cancer. It was recommended that pathologists perform HR-HPV testing on head and neck squamous cell carcinomas from all patients with known oropharyngeal SCC not previously tested for HR-HPV, with suspected oropharyngeal SCC, or with metastatic SCC of unknown primary. The aim of this study was to determine the compliance of pathologists following the CAP guidelines.

Methods
Cases that underwent HPV testing using p16 immunohistochemistry for the years 2017 and 2019 were retrieved. Based on the guidelines, p16 testing was designated as “indicated” or “not indicated”.

Results
There were 196 cases in which p16 testing was performed in a period of 3 consecutive years. Of these, 175 were FNA/ biopsies and 21 were surgical resections. In 69 cases (56 FNAs and 13 biopsies) the biopsy was performed on neck masses with unknown primary. The compliance for p16 testing in OPC and Lymph nodes with metastatic SCC of unknown primary was 100%. In 34 (17.3%) cases p16 testing was not indicated, the most common reason being wrong site (85%) including the larynx, oral tongue, the floor of the mouth, buccal mucosa, and nasal mass. Of the unindicated p16s, 20 (58%) were received in consultation for continuity of care.

Conclusion
Not being clear about the site of the tumor is the most common reason for unindicated p16 testing. A clear designation of biopsy site and proper communication between pathologist and surgeon can improve utilization of p16 testing in head and neck carcinomas.
Pathological Study of Stillbirths Placentas at Muhimbili National Hospital, Tanzania
Authors: Malango A E 
Published: October 2020

Abstract

Introduction/Objective
Stillbirth is defined as fetal death that occurs at gestational age of ≥28 weeks. In our setting clinical assessment is the only method used to determine cause of stillbirths, with no reported proportion of unknown clinical diagnosis. Studies showed that unknown cause of stillbirths can be reduced by examination of placenta.
Causal identification aids in the mourning process and identifying recurrence risks. The study aimed to describe pathological changes in the placentas of stillbirths which have risk to cause fetal death

Methods
A descriptive cross-sectional study done for the period of 6 months, it involved examination of 80 placentas of stillbirths born at gestational age of ≥ 28 weeks, placentas were fixed in 10% neutral buffered formalin for 8–12 hours. Grossing and interpretation of placenta pathology was according to Amsterdam Placental Workshop Group Consensus Statement.

Results
Out of 80 stillbirths, 32(40%) had unknown clinical diagnosis. Majority of stillbirth placentas 71(91%) found with either one or combined pathologies with the risk to cause stillbirth. Maternal vascular malperfusion was the commonest pathology and was significantly associated with preterm stillbirths. Maternal floor infarction, a placenta pathology with risk to cause fetal death and high risk of recurrence was among the pathologies found, was seen in 4(5%) of stillbirth placentas.

Conclusion
Findings in this study clearly indicated the importance of pathological examination of placenta in determining cause of stillbirth. Placenta examination in stillbirths can identify more pathology related to stillbirths than clinical assessment alone.
Omphaloceles Associated with Chromosomal Segmental Alterations Carry a Poor Prognosis
Authors: Zhou H 
Published: October 2020

Abstract

Introduction/Objective
Omphaloceles are frequently associated with chromosomal abnormalities, including aneuploidy and segmental alterations. High resolution chromosomal microarray analysis (CMA) can detect segmental alterations &lt; 5 Mb, which is not detectable by G-banding. However, the prognostic significance of the segmental alteration in infant with omphalocele is not elucidated.

Methods
To identify omphalocele cases with genetic studies, a CoPath database search (1/2000 - 7/2017) was performed with key words “omphalocele” and “genetic”. From 1/2000 to 12/2008, only G-banding was performed. From 1/2009 to 7/2017, omphalocele cases were screened with karyotyping. Cases with normal karyotype were reflexed to CMA. Copy number gains/losses and corresponding genes were analyzed by the Affymetrix Chromosome Analysis Suite.

Results
Follow-up data are available in 75% (67/89) cases. There is no significant difference of the overall survival rate of male and female patients (80.5% vs 76.9%; χ 2, p = 0.7645). There are 16.9% (15/89) omphaloceles with aneuploidy, 10.1% (9/89) cases with segmental alterations by CMA, and 73.0% (65/89) cases with normal CMA and/or normal karyotype. Although patients with segmental alterations have a significantly higher survival rate than those with aneuploidy (44.4% vs 0%, χ2, p = 0.0119), their overall survival rate is significantly lower than infant with normal CMA and/or normal karyotype (44.4% vs 82.8%; χ2, p &lt; 0.0001). Infants with segmental alterations carry a significantly worse prognosis than infants with normal genetic study.

Conclusion
To date, this is the first study of the prognostic significance of segmental alteration in infants with omphalocele. Our data demonstrated that omphaloceles with segmental alterations carry a significantly worse prognosis than those with normal CMA and/or karyotype. It is crucial to convey the prognosis to the parents with a fetus carrying segmental alterations; so the family could make an informed decision and get ready for an infant with special needs.
Carcinosarcomas of Ovary/Fallopian Tube: A Rare Entity
Authors: Vo D M , Verma K , Khullar P , Vintzileos W , Jimenez E 
Published: October 2020

Abstract

Introduction/Objective
Adnexal carcinosarcomas (MMMTs) are rare tumors (1–4% ovarian carcinomas) with worse prognosis than high grade serous carcinomas (HGS) at similar stage. They typically present at age 64–66, often with peritoneal involvement. They are biphasic tumors with stem cells undergoing divergent epithelial and sarcomatous differentiation. The epithelial component is usually HGS and drives progression of the tumor. The mesenchymal component can be homologous with high-grade spindled cells or heterologous with malignant cartilage, bone, muscle or fat. Metastases are mostly epithelial; metastatic sarcomatous components are unusual. We reviewed our single- institutional experience of adnexal MMMTs.

Methods
We reviewed our pathology database (2001–2019) to find all cases of adnexal MMMTs. We reviewed their histological features, histology of metastases and clinical outcomes.

Results
Our series consisted of 12 cases. Patients aged 41–82 years. The primary tumor sites were ovary (6 cases, 50%), fallopian tube (4, 33%), 1 each (8%) in paratubal region and infundibular ligament. Fallopian tube was involved in 8/12 cases (4 cases as primary MMMT, 4 cases with STIC or HGS). Epithelial component was serous (75%), endometrioid (17%) and mucinous (8%). Sarcomatous component was homologous in 5 cases (41%), heterologous in 7 cases: cartilage (33%), cartilage/muscle (8%), muscle (8%), cartilage/muscle/fat (8%). 3 cases were FIGO stage I, 9 had peritoneal metastases (8 stage III, 1 stage IV). Six cases had metastatic HGS; 3 had metastatic HGS with sarcomatous component, 2 with heterologous elements. Aberrant p53 pattern was seen in 7/12 and TP53 mutation was noted in 6/12. Ten patients received cytoreductive surgery and chemotherapy. 7 patients are alive with progression free survival ranging 6–59 months, 2 survived for 25 and 29 months, 3 are lost to follow-up.

Conclusion
Metastatic sarcomatous heterologous elements are rare in uterine carcinosarcomas and may suggest adnexal origin. They may correlate with worse outcome; in our series, 1/2 died after 29 months, the other was lost to follow-up. Fallopian tube involvement (75% of our cases) is of significance as identical TP53 mutation has been identified in a case report of ovarian carcinosarcoma with fallopian tube STIC. Also, our 2 cases of infundibular ligament and paratubal region may indicate seeding from fallopian tube. Further studies are needed to confirm the correlation.
Retinal Ependymoma: A Rare Extra-Axial Presentation
Authors: Abou Shaar R , Arora K , Keller C 
Published: October 2020

Abstract

Introduction/Objective
Ependymomas are well-demarcated and slow-growing neuroepithelial neoplasms that comprise 3–9% of primary CNS tumors. The vast majority of ependymomas arise either intracranially, mostly in children, or in the spinal cord and are associated with ependymal lining. Histologic hallmarks are perivascular pseudorosettes, ependymal rosettes and alternating zones of nuclear crowding and nuclear free zones composed of coarse cell processes. In high grade ependymomas increased mitoses, necrosis and nuclear pleomorphism may be seen.

Methods
We present the case of a 63-year-old woman in with a past medical history of retinopathy of prematurity, glaucoma and right eye enucleation. She presented with a painful blind left eye refractory to medical treatment and subsequently underwent left eye enucleation.

Results
On histologic examination, an incidental retinal ependymoma was identified. The neoplastic cells were fusiform and had long coarsely fibrillar cell processes. Characteristic periodicity of nuclear crowding and scarcity was observed. In places, neoplastic cell processes extended radially to delicate and sometimes hyalinized blood vessels, forming so-called perivascular pseudorosettes. Definite ependymal rosettes were not recognized in the examined sections. Stigmata of chronicity were found, such as ischemic type necrosis, blood vessels with dystrophic calcifications and foci of ossification replete with fibroadipose tissue in the marrow spaces.
The neoplastic cells labeled with antibodies against glial fibrillary acidic protein (GFAP), thus confirming glial lineage in the neoplastic cell. Additionally, there was scattered intracytoplasmic expression of epithelial membrane antigen (EMA) in a dot-like or circular pattern. The latter is well described in ependymomas and often used to support the diagnosis.

Conclusion
Ependymomas rarely occur at extracranial sites, such as the chest, abdomen and pelvis. We are presenting the fourth case of retinal ependymoma reported in literature. The tumor had classical immunomorphologic findings.
Ciliated Carcinoma Associated With Human Papiloma Virus: Presentation As Cervical Metastasis Of Unknown Primary
Authors: Ibarra A , Las Heras F , Antonio L , Montero P , Besa P , Henriquez J , Labra Y 
Published: October 2020

Abstract

Introduction/Objective
There is a significant increase in high-risk human papilloma virus (HPV) -related carcinomas of the head and neck. Half of them debut with metastases in cervical nodes, of expansive growth, usually cystic-necrotic. Most are oropharyngeal primaries. They are non-keratinizing squamous carcinomas with mild atypia, sometimes with exceptional characteristics, such as glandular differentiation and inclusion of ciliated cells

Methods
Clinical Case: 39-year-old male patient, operated two years ago, in another institution, for cervical metastasis from HPV-related Ciliated Carcinoma (HPV-RCC), 4.5 x 2 cm. No primary cancer was found in his study. Two months ago, a new 4.3 x 2.7 cm metastasis was resected, performing a right cervical dissection, with another 36 lymph nodes without tumor. Palatine tonsils, adenoids are removed and a biopsy of the oral mucosa is taken, and no malignancy was found. In our center, biopsies of the tongue and right glosso-tonsillar fold are taken, without objectify malignancy.

Results
The metastases had macroscopic cystic-necrotic appearance. Histology corresponded to nonkeratinizing squamous carcinoma with microcystic spaces and the presence of ciliated columnar cells. The immunohistochemical study gave strong and diffuse positivity for p16. The real-time multiple PCR study detected HPV genotype 16.

Conclusion
We present an exceptional case of Ciliated Carcinoma Related to HPV, a recently described entity. These are nonkeratinizing squamous neoplasms, which include cystic spaces and ciliated columnar cells. Both components reveal HPV positivity, with p16 expression and high-risk viral typing. HPV-RCC should be considered in the differential diagnosis of well-differentiated squamous lesions of the oropharyngeal cavity and at the cervical level, with non-neoplastic cysts. Our patient will undergo radiotherapy protocol, for unknown primary
Malignant Proliferating Pilar Tumor: A Rare Mimic of Squamous Cell Carcinoma
Authors: Beversdorf W , Rinker E 
Published: October 2020

Abstract

Introduction/Objective
Proliferating pilar tumor is a rare cutaneous adnexal neoplasm, closely resembling and potentially misdiagnosed as conventional squamous cell carcinoma. Malignant forms are recognized; however, differentiating criteria have not been firmly established due to their exceptional rarity. Prognosis is variable, with recurrence or metastasis reported in up to 25% of patients within a very small data set.

Methods
We present a case of a 31 year old male who underwent excision of a posterior neck mass clinically presumed to be a recurrent benign cyst in 2018. Initial excision was performed at an outside institution approximately 10 years prior, and a pathology report was not included in his record.

Results
Our resection specimen contained a 5.5 cm lobulated, cystic and solid mass involving the dermis and subcutis with superficial ulceration. Tumor histology was consistent with malignant proliferating pilar tumor as described in other reported cases, showing a proliferation of pleomorphic squamous cells infiltrating the dermis and associated desmoplasia. The tumor featured abundant pilar keratinization with focal necrosis and increased mitotic activity. Numerous smaller pilar cysts exhibiting varying degrees of squamous atypia studded the periphery of the dominant mass. The immunohistochemical profile of this case also exhibited similarities to other reports, with focal positivity for calretinin and CD34 as well as an increased Ki-67 proliferative index (up to 70–80%). While other reports document diffuse expression of p53, our case demonstrated complete absence of p53 staining.

Conclusion
We present this case to highlight the importance of recognizing pilar differentiation within squamous lesions, examine pathologic features associated with malignant behavior, and discuss the relationship between histologic characteristics and clinical outcomes in this exceedingly rare tumor group.