bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality Improvement Project Demonstrate that Prolonged Pre-Analytical Time Does Not Lead to False Negative Blood Cultures
Authors: Abada E , Khan M Y , Yerrapotu N , Pardeshi V , Zaiem F , Nguyen H , Raval K , Mitchel R , Fairfax M 
Published: October 2020

Abstract

Introduction/Objective
Bacterial infection is a significant cause of morbidity and mortality. Prompt identification of microorganisms and their susceptibilities to antimicrobial therapies is critical in the management of patients with bloodstream infections. Blood cultures are collected in paired aerobic and anaerobic bottles. However, transport delays might allow some organisms to grow extensively prior to incubation in the blood culture instruments, leading to false-negative culture results. The Detroit Medical Center utilizes the BD Bactec™ instruments for blood culture incubation and the Verigene DNA-based molecular assay for the identification of bacteria and major resistance genes. It has a core microbiology lab that serves 6 hospitals, however, 2 of the hospitals are remotely located.
The aim of this project was to determine if transportation delays led to significant false-negative culture results. If significant false negativity occurred, additional Bactec™ instruments would need to be purchased.

Methods
For one month, we tracked the collection of blood cultures to incubation time at one of the remote hospitals. All blood cultures that remain negative after 164 hours of incubation are routinely discarded. However, in this case, they were subcultured to a Petri plate containing chocolate agar for 30 days. Any organisms that grew were identified by standard lab techniques.

Results
Of the 547 negative culture bottles that were subcultured for possible false-negative results, only 3 (0.5%) bottles grew bacteria. All three were isolated from different patients. The mean time from blood collection to incubation in the instrument was 4-8 hours. The isolates either met criteria for contaminated cultures, or they grew the same pathogen that had previously been identified in the paired bottle from the same culture. The organisms isolated include coagulase negative Staphylococcus species, Staphylococcus pettenkoferi, and Pseudomonas aeruginosa. No unexpected pathogenic organisms were detected.

Conclusion
Our results demonstrate that prolonged pre-analytical time does not lead to false-negative blood culture results. The patients’ diagnoses were not changed, therefore, the purchase of additional blood culture instruments was not necessary. However, transportation time from the patient floors to the main microbiology lab needs to be improved to meet the recommended 2 hours pre-analytical time.
Risk of Urban Zoonosis from Geese Colonized with Antimicrobial Resistant Bacteria
Authors: Leu-Burke G M , Mendoza G , Rue I 
Published: October 2020

Abstract

Introduction/Objective
Zoonotic disease occurs through direct fecal contact with increased exposure resulting in higher infection rates. Antimicrobial resistant colonization occurs in wild birds, however the spread of microbial resistance correlates with increased human activity. Anchorage actively develops urban park environments with pastoral lawns and abundant water sources creating an inviting habitat for human and geese populations. By 2018, Alaska Fish and Game reported a 10-fold increase in migrating Canadian Geese resulting in significant environmental damage, including fecal contamination. At the same time, Anchorage experienced an uptake use of their parks and costal trails for both recreation and homeless camps. To determine potential exposure, sixty-eight geese fecal samples were collected in fourteen urban park locations.

Methods
Fecal samples were incubated in thioglycolate broth at 37oC for 24 hours then cultured to chromogenic screening agar for vancomycin resistant enterococcus (VRE), methicillin resistant Staphylococcus aureus (MRSA), and extended spectrum beta-lactamase (ESBL) enterobacteriaceae. Potential MRSA, VRE or ESBL colonies were further identified using standard biochemical testing with confirmation of antimicrobial resistance by disk diffusion.

Results
Forty percent of all fecal samples collected were colonized with VRE or ESBL producing Escherichia coli with eighty-six percent of collection sites positive for one or more antimicrobial resistant bacterium. Seven percent of fecal samples were positive for both organisms. MRSA was not identified. The highest concentration of antimicrobial resistant bacteria was discovered on the Campbell Creek Trail (83%), which winds alongside Providence Hospital.

Conclusion
Transmission of infectious agents can occur due to environmental exposure, which increases in individuals who are either housing insecure or chronically homeless. Urban green spaces are often sites for unregulated camping by individuals who lack consistent residential housing. Discovery of antimicrobial resistant colonization in geese populating nearly ninety percent of Anchorage’s parks and trails creates a significant public health issue, with the homeless population targeted for poor outcome due to their immunocompromised status.
Continued evaluation is essential to predict infection risk and impact on healthcare delivery, especially in vulnerable populations.
Novel Autoantibodies Biomarkers Panel to Prognosticate the Clinical Outcomes in Advanced-stage NSCLC Patients Receiving Anti PD-1/PD-L1 Immunotherapy
Authors: Tarhoni I , Fhied C , Borgia J A , Fidler M J , Batus M , Bonomi P 
Published: October 2020

Abstract

Introduction/Objective
Lung cancer is the leading cause of cancer-related deaths worldwide, with a majority of cases detected at a non-resectable advanced stage. Current anti PD-1/-L1 therapy has reformed cancer treatment strategies with remarkable clinical outcomes in non-small cell lung cancer (NSCLC). However, the overall response rate is still marginal, demonstrating the need for biomarkers predictive of response. The objective of this study is to develop a serum based panel to prognosticate clinical response in advanced NSCLC patients receiving anti PD-1/-L1 therapy.

Methods
Pooled sera from two response groups (Poor response, n=20, overall survival &lt; 12 months; Good response, n=20, overall survival &gt; 12 months) were evaluated via the HuProt™ Human Proteome Microarray (CDI laboratories, Baltimore, MD) to identify expressed neoantigens. Recombinant proteins representative to identified neoantigens along with their corresponding antibodies, were commercially acquired to develop a robust 13-plex bead- based immunoassay to evaluate the autoantibodies in pretreatment sera from 125 advanced-stage NSCLC patients. Finally, levels of autoantibodies were correlated to clinical outcome, including progression free survival (PFS), overall survival (OS) and grade III adverse events.

Results
Low baseline levels of ZNF695, MCM4, PRMT2, FGD3, GTF2A1, GLUL, CDCA3, ZNF277, GARS, GBP2, UBL7, and ASNA1 autoantibodies were found to be associated with a longer PFS (all p-values &lt; 0.01), whereas increased levels were associated with a poor PFS outcome (0.06, HR=0.66, 95% CI). Low levels of ZNF695, MCM4, PRMT2, FGD3, GARS, GBP2, and UBL7 autoantibodies were associated with favorable OS (all p-values &lt; 0.01).

Conclusion
In this study we demonstrated that serum autoantibodies have great promise to serve as a prognostic tool for immunotherapy response. We successfully developed a high performance multiplexed serum based assay to evaluate autoantibodies in an advanced NSCLC patients receiving anti PD-1/-L1 therapy.
Liquid Biopsy In Stage Iv Non-Small Cell Lung And Prostate Cancers And Prevalence Of Ethnicity And Risk Factors: A Va Medcial Center Experience
Authors: Dalal S , Jhala D 
Published: October 2020

Abstract

Introduction/Objective
The advent of Liquid biopsy (LB) is a milestone in precision oncology. This minimally invasive revolutionary technique analyses circulating tumor DNA and detects signature genomic alterations. Advanced-stage prostate cancers are more common in African Americans both in general and veteran patient population, while general cohort Caucasians are more prone to advanced/metastatic NSCLC. Risk factor for these cancers is smoking; agent orange exposure and its relationship with aggressiveness/ethnicity for veterans is sparse in the literature. We performed a QA study for advanced lung/prostate cancers of veteran patients on LB.

Methods
QA documentation from Foundation One (Cambridge MA, NGS) on LB performed for the regional Veteran Affairs Medical Center (VAMC) from May 2019 to April 2020 were reviewed. The testing was performed on advanced NSCLC/prostate cancer cases with evidence of advanced tumor progression. Data for ethnicity, risk factors, post therapy PSA, Gleason score and genetic mutations noted.

Results
A total of 30 LBs were performed over this time period. Of 30 LBs, 23 were prostate and 7 were lung cancers. 2/30 had unknown ethnic background. 19/28 (67.8%) were of African American origin, 18 of which had advanced prostate cancers. 11/28 were white, of which 3/30 were advanced NSCLC. One patient declined to reveal risk factor exposure, hence 17/29 (58.6%) had smoking, 15/29 (51.7%) had a risk of herbicide, agent orange exposure; and, 10/29 (34.4%) had both risk factor exposures. 6/29 (20.6%) African American veterans had combined risk factors. 9/10 (90%) veterans which had dual exposure presented with either Gleason score of 9 or as metastasis. Post therapy PSA ranged from 0.5 to 1870 ng/ml and did not corelate with the aggressiveness of the cancer or therapy response.

Conclusion
Veteran patient population has slightly higher incidence of ethnic African Americans presenting with advanced NSCLC/prostate cancers compared to general patient cohort. Although incidence of smoking is similar, combined exposure with agent orange, increases the aggressiveness of the disease three-fold. Real-time monitoring of the therapy response and multimodal benefits by LB is of immense help in morbidly ill veterans, compared to post- therapy PSA monitoring or invasive tissue biopsy. Role of LB should also be explored for early screening/triaging the veterans.
Tumor budding (TB) in Colorectal Cancer (CRC), The Best Slide To Count On!
Authors: Aldyab M , Najjar S , Rand J V , Lee H 
Published: October 2020

Abstract

Introduction/Objective
TB is a strong prognosticator in CRC. The international TB consensus conference (ITBCC, 2016) proposed a “hot spot” approach for TB grading. We aimed to identify the characteristics of sections with the highest TB grade utilizing ITBCC’s method.

Methods
Resected CRC cases, excluding treated cases, were retrieved. All tumor sections were examined. Section TB grade(sTB) was noted. The highest sTB was deemed the final TB grade(fTB) of each case. The following categories were assessed: 1) maximum T stage; 2) presence of benign mucosa; 3) presence of a precursor lesion; 4) highest tumor volume; 5) presence of lymphovascular invasion(LVI). In cases where a given category was demonstrated in &gt;1 section, the section with the highest sTB was used. High risk features (HFR) included T4, &lt;12 lymph nodes, positive margin, high grade tumor, perineural invasion and LVI. Pearson’s correlation was performed to compare two groups using a p-value of &lt;0.05.

Results
147 cases were examined. fTB was 1=25.2%, 2=40.8% and 3=34%. 63 tumors involved the left colon and 62 had nodal disease. Of 119 cases with known MMR status 44 were MMR deficient. sTB was uniform across the categories in 101(68.7%) and uneven in 46(32.3%) cases. 12(24.5%) of 49 stage II CRC without HRF showed uneven sTB, with 2 showing 2-tier discrepancy (sTB1, fTB3). sTB was highest for category 3 (94.1%, P&lt;.001), followed by category 2 (91.8%, P&lt;.001), and lowest for category 1 (82.3%, P&lt;.001), which remained true after subgrouping by MMR status and tumor location.

Conclusion
While about 70% of cases showed uniform TB grading across categories, choosing the slide(s) with a precursor lesion or benign mucosa increases the probability of correctly grading TB. Given the management implication, it may be prudent to scan all tumor slides in stage II CRC without HRF to avoid under-grading of TB.
Microarray Findings of Intraplacental Choriocarcinoma: A Report of Four Cases
Authors: Emanuel A , Schandl C , Bruner E 
Published: October 2020

Abstract

Introduction/Objective
Gestational trophoblastic neoplasia (GTN) is a group of poorly understood diseases characterized by an abnormal and overtly malignant proliferation of trophoblastic tissue. Choriocarcinoma, which may also be nongestational in origin, is a particularly invasive and aggressive variant of GTN that is composed of a dimorphic trophoblast population. Many studies have attempted to define choriocarcinoma via various cytogenetic, molecular, and epigenetic means; however, the exact etiology and pathogenesis of this tumor remain unclear, in large part due to its rarity. Estimates of the incidence of choriocarcinoma range from 1 in 24,000 to 1 in 40,000 pregnancies. Intraplacental tumors are even less common with 62 reported cases and an estimated incidence of 1 in 160,000 placentas. In an effort to better understand the pathogenesis of this rare entity, four cases of choriocarcinoma (of which three are intraplacental and one is intrauterine occurring one year following an unremarkable pregnancy) diagnosed at our institution since 2010 were identified for chromosomal microarray.

Methods
DNA was extracted from formalin-fixed, paraffin-embedded blocks of four matched cases: tumor and normal placenta. Single nucleotide polymorphism (SNP) microarray analysis was performed to assess genomic copy number differences between the tumor and the placenta from which it arose (Infinium Global Diversity Array-8 v1.0 BeadChip with an I Scan System; Illumina, San Diego, CA). Analysis of a placenta not affected by tumor was also performed.

Results
Early partial data review demonstrates copy number aberrations in choriocarcinoma arising in placental tissue. Additional interpretation of the data is ongoing.

Conclusion
DNA chromosomal microarray analysis was performed to search for genomic copy number differences in between the tumor and the placenta from which it arose. Recent studies suggest gestational choriocarcinoma oncogenesis may differ from that of other malignancies, but this conclusion is based on a low number of recurrent DNA mutations. SNP microarray analysis may further refine the current understanding of the oncogenesis of gestational choriocarcinoma.
Large B-Cell Lymphoma With IRF4 Rearrangement Involving Lung
Authors: Li C , Teruya B , Bhavana D , Althof P 
Published: October 2020

Abstract

Introduction/Objective
Large B-cell lymphoma (LBCL) with IRF4 rearrangement is a new entity described in the 2017 WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. It is characterized by monotonous proliferation of medium to large sized cells with strong expression of IRF4/MUM1 and IRF4 rearrangement. It accounts for only 0.05% of all diffuse LBCLs and affects predominantly children and young adults with a median age of 12 years. The reported sites of disease include lymph nodes of head and neck, Waldeyer ring and gastrointestinal tract. Here, we report a case of LBCL in a 74-year-old female patient that presented with a lung nodule.

Methods
H&E staining, Immunohistochemistry and Fluorescence in-situ hybridization (FISH) were used to characterize this lesion.

Results
H&E stained sections of lung nodule biopsy showed diffuse proliferation of medium- to large-sized tumor cells. Immunohistochemistry showed tumor cells are positive for CD10, BCL6 and IRF4/MUM1. FISH showed rearrangement of IRF4, but is negative for MYC, BCL2 and BCL6 translocations.

Conclusion
To the best of our knowledge, this is the first case of LBCL with IRF4 rearrangement reported involving the lung in an old patient. Cases that show coexpression of CD10, BCL6 and IRF4/MUM1 should be tested for IRF4 rearrangement despite patient’s age and the site of disease. Generally, prognosis of this disease is favorable following chemotherapy with or without radiation. However, data are lacking regarding older patients and diseases involving atypical sites due to very limited number of cases reported earlier.
Epstein - Barr Virus (EBV) Associated B-Cell Lymphoma: An Unusual Involvement Of The Heart And Kidney In An HIV Positive Patient With Concurrent Cytomegalovirus (CMV) Pneumonia And Pneumocystis Jirovecii Pneumonia (PCP)
Authors: Dehghani A , Alshal M , Alawad M , Zuretti A , Shao C 
Published: October 2020

Abstract

Introduction/Objective
We report a 68-year-old man with Human immunodeficiency virus (HIV) infection and significant weight loss during the past two years who presented with dyspnea. He was not receiving any treatment for HIV infection, and his viral load and CD4 count were 178000 copies/ml and 8 cells/mm3, respectively. The radiologic examination was concerning for Pneumocystis jirovecii pneumonia. The Bronchoalveolar lavage was positive for Pneumocystis jirovecii. The patient expired despite the comprehensive treatment, and the autopsy was requested.

Methods
The autopsy showed heavy lungs with diffuse consolidation and white discoloration involving all lobes. The left ventricular wall and right kidney cortex showed foci of white discoloration measuring 1 and 0.8 cm, respectively.

Results
The microscopic examination of lungs showed concurrent CMV pneumonia, and PCP confirmed by immunohistochemical staining for CMV and GMS special stain. The histologic evaluation of the heart and the right kidney and immunohistochemical staining for CD20 and CD3 in addition to in situ hybridization (ISH) for EBER revealed infiltrative malignant cells, which were positive for CD20 and EBER and negative for CD3. The EBV associated B-cell lymphoma involving the heart, and the right kidney was diagnosed

Conclusion
EBV is involved in human lymphomagenesis, particularly in HIV patients. There is a tendency for the lymphoma to involve the extranodal sites, including the CNS, gastrointestinal tract, liver, and bone marrow. However, the involvement of the heart and kidneys occurs very rarely. The autopsy findings of Lung co-infection with PCP and CMV and EBV associated lymphoma involving atypical locations is a rare and unique combination of AIDS-defining illnesses in this patient.
Exophiala Dermatitidis Isolated From Blood In Patient With Steroid Use
Authors: Yurtsever N , Dougherty P , Condon S , Orsini R , Berman M , Berry G J , Duong S 
Published: October 2020

Abstract

Casestudy
Exophiala dermatitidis is a dematiaceous mold that is associated with subcutaneous, central nervous system and pulmonary infections; osteomyelitis; and disseminated disease. Isolation of E. dermatitidis from patients with mild symptoms may be difficult to interpret whether is a contaminant or asymptomatic patient with serious infection. However, it is important to diagnose asymptomatic patients early in the stage because of up to 25% mortality rate.

Results
77-year-old male with history of chronic obstructive pulmonary disease presented to his pulmonologist with cough. He was started on azithromycin and steroids. His cough worsened and he was transitioned to levofloxacin with continuation of steroid treatment. In addition, he developed fatigue, weakness, poor appetite, chills and nights sweat along with some urinary complaints. His chest X-ray showed infiltrates and he was diagnosed with left lower lung pneumonia and urinary tract infection and was treated with doxycycline and ciprofloxacin. Blood cultures were drawn. Additional past medical history was not significant.
Blood culture became positive on day 4 of incubation. Gram stain showed yeast-like cells, but the blood culture multiplex PCR was negative. Serum cryptococcus antigen was negative. Three days later, a dark shiny olive-colored colony with dark obverse side was isolated. It grew at 42 C. Microscopic examination revealed hyaline and pigmented hyphae with brown conidia. It was identified as Exophiala dermatitidis and confirmed by the state public health laboratory. Blood cultures drawn after hospital admission remained negative. Patient’s symptoms improved with antibiotic treatment. Therefore the clinicians believed that the E. dermatitidis was a probable contaminant and patient was discharged with follow-up. During the follow-up process he developed respiratory infection with Coronavirus (HKU1, NL63, 229E, OC43). Follow-up continues.

Conclusion
Blood cultures are not sensitive for mold infection especially for an uncommon contaminant like E. dermatitidis, it may be difficult to decide whether a positive culture is a real result or not. Fungal antigen tests such as beta-D-glucan test may be helpful in distinguishing between invasive infection and contaminant. Additionally, we believe that in our case, steroid use could have caused a temporary immunosuppression and led to Exophiala dermatitidis infection.
Discontinuous Involvement of Spermatic Cord Soft Tissue in Testicular Germ Cell Tumors: A Multi-Institution Experience
Authors: Ali A , So J , Khani F , Kvetoslava M , Miyamoto H , Osunkoya A , Rodriguez Pena M , Magi-Galluzzi C , Raspollini M R , Scarfo F , Zynger D L 
Published: October 2020

Abstract

Introduction/Objective
In the 8th Edition AJCC Cancer Staging Manual, discontinuous involvement of spermatic cord soft tissue (DISC) by testicular germ cell tumors (GCT) is regarded as metastatic deposit (pM1), placing the patient in clinical prognostic stage group (CPSG) III. We conducted a multi-institution study to corroborate or refute the current recommendations. Methods: Thirty-eight cases of GCT with spermatic cord involvement were collected from 13 institutions in Europe, Phillipines and America. Clinical and pathologic data was obtained.

Results
Tumors included 28 (73%) non-seminomatous and 10 (26%) seminomatous GCTs. Mean testicular tumor size was 6.6 cm (range 1.3-18). After review by an uropathologist, cases were classified as cord LVI [T2] (n=3), continuous cord involvement (CCI) [T3] (n=13), and DISC (n=22). Mean cord tumor size for DISC was 0.9 cm (range 0.1-4.5).
CPSG was available for 33 and follow-up (FU) for22 patients with a mean length of FU of 38 months (range 2-144). Seven (39%) DISC patients were CPSG II (regional LN metastases), and 11 (61%) CPSG III (distant metastases). On FU, 5 (45%) DISC patients had no evidence of disease (NED); 6 (55%) were alive with disease (AWD). Three (25%)
CCI patients were CPSG I (local disease), 6 (50%) CPSG II, and 3 (25%) CPSG III. On FU, 6 (60%) CCI patients were NED, 4 (40%) AWD. Cord LVI patients were one in each CPSG. One cord LVI patient was NED, the others were lost at FU. All DISC (100%) patients with available CPSG had advanced disease (CPSG II or III), compared to 75% of CCI, and 67% of cord LVI patients.

Conclusion
Although it did not reach statistical significance (p=0.054; Fisher’s exact test), DISC patients were more likely to have CPSG II and III compared to CCI patients. Our findings suggest a worse behavior in patients with DISC, supporting a higher pathologic stage than CCI.