bluuebunny/crossref_metadata_2025_split huggingface dataset:
Usefulness of Liquid Biopsy for Veteran Patients with Metastatic Lung Cancer
Authors: Dalal S , Petersen J M , Jhala D , Allbee A 
Published: November 2023

Abstract

Introduction/Objective
The National Comprehensive Cancer Network (NCCN) non-small cell lung cancer (NSCLC) Guidelines Panel strongly advises the use of broad molecular tumor profiling to identify rare driver mutations in patients with advanced or metastatic disease. This testing could either be performed on the tumor sample itself or from liquid biopsy with next generation sequencing. Liquid biopsy presents a minimally invasive opportunity to obtain molecular information from circulating tumor cells (CTC) that may impact treatment. However, the literature of metastatic lung cancers targeted by liquid biopsies and the mutations found is sparse, particularly for the veteran population.

Methods/Case Report
A retrospective review was performed of all patients with a submitted liquid biopsy specimen at a Veteran Affairs Medical Center (VAMC) from November 26th, 2019, to March 3rd, 2023, to exa mine those
patients with metastatic lung cancer. Information on mutations detected was collected.

Results (if a Case Study enter NA)
There were a total of 35 patient specimens with a history of metastatic lung cancer, from which 34 cases had an available liquid biopsy report. The first liquid biopsy for a patient with metastatic lung cancer was sent on November 26th, 2019. Some of the more common mutations identified through the liquid biopsy included KRAS (7/34), TP53 (15/34), and TERT promoter (3/34). 5 of these 34 cases had no reportable genomic alterations detected.

Conclusion
Liquid biopsies are a non-invasive, powerful diagnostic tool that is highly useful for broad molecular tumor profiling for precise management and for appropriate counseling of patients on treatment as per the standard of care clinical practice guidelines (such as from the NCCN).
Malignant Melanoma with Atypical Phenotype and RAC1 Mutation
Authors: Vail E , Gayhart M , Azimpouran M 
Published: November 2023

Abstract

Introduction/Objective
Melanoma, a highly invasive form of skin cancer associated with high mortality rates, poses significant challenges in diagnosis and treatment. RAC1, a member of the RHO family of GTPases, plays a crucial role as a molecular switch in cellular processes. A specific mutation in RAC1, caused by C &gt; T transition induced by UV radiation, leads to P29S alteration, activating the SRF/MRTF pathway and triggering a phenotypic switch towards a mesenchymal phenotype.

Methods/Case Report
We present a case of a 74-year-old male patient who presented with a six-week history of right neck swelling. Ultrasonography revealed an enlarged lymph node in the right posterior triangle of the neck. PET scan showed a well- defined, moderately metabolically active lesion measuring 1.4x1.7cm. Initial biopsy indicated a diagnosis of malignant metastatic sarcomatous neoplasm. To establish a definitive diagnosis and determine the appropriate treatment plan, excision of the lymph node was performed. Histological examination revealed lymph node involvement by large, highly atypical cells exhibiting prominent nucleoli and frequent mitotic figures. Immunohistochemical analysis demonstrated positive staining for SOX10 and S100, while Melan-A and HMB45 were negative. Epithelial markers were also negative, although focal keratin positivity was observed. Further investigations were conducted to identify a primary or extranodal site. Routine dermatology visits had previously shown no evidence of primary cutaneous melanoma.

Results (if a Case Study enter NA)
Genomic profiling through next-generation sequencing (NGS) identified multiple alterations, including BRAF (G469R- exon 11, missense alteration), TP53 (R248W, missense alteration in TP53), RAC1 (P29S, missense alteration), TERT (Promoter Site Variant; chr5:g.1295228G&gt;A c.-124C&gt;T), and NF1 (Q1815, nonsense alteration). The tumor exhibited a high tumor mutational burden (TMB) and an ultraviolet (UV) signature characterized by C &gt; T transitions.

Conclusion
Diagnosing melanoma with RAC1 mutation poses significant challenges due to its potential to induce phenotypic switching. Understanding the role of RAC1 mutations in driving melanoma progression can help improve diagnostic accuracy and guide targeted therapeutic strategies.
Disseminating Education about HER2-Low Breast Cancer through Twitter Chats and Tweetorials
Authors: Kim J , Chivukula M , Feldman M , Wei S , Baskota S , Bui M , Khoury T , Akhtar I , Beumer K , Kelly M , O'Regan R , Krystel-Whittemore M 
Published: November 2023

Abstract

Introduction/Objective
Social media is often used to disseminate new information and as a teaching tool that reaches a broad audience. When practice-changing data about HER2-Low metastatic breast cancer (MBC) emerged in 2022, ASCP developed CME/CMLE Twitter chats and Tweetorials to educate pathologists and laboratory professionals about how these updates will impact the diagnosis and care of patients with HER2-Low MBC. These activities were funded by educational grants from AstraZeneca and Daiichi Sankyo, Inc.

Methods/Case Report
Working with faculty who were active on Twitter, ASCP organized Twitter chats and Tweetorials to increase awareness about HER2-Low MBC and address how these changes will impact clinical care. A Twitter chat is a live, interactive Tweet-based discussion held on Twitter. Also called Tweet chats, these events run for 1 hr and use hashtags to keep the discussion organized. A Tweetorial is a combination of threaded Tweets that teach about a specific topic. Activities were certified for continuing education credit and were designed to be short, practical, and relevant for pathologists and laboratory professionals.

Results (if a Case Study enter NA)
In 2022 and 2023, ASCP used the hashtag #HER2Low to organize Twitter chats and Tweetorials. Each chat had four faculty members responding to 6-8 questions and averaged 2.2 million impressions (an impression is the # of times a Tweet is served in a timeline or search result). Faculty covered the challenges differentiating an IHC score of 0 vs 1+, the emerging use of digital pathology, ways to improve reporting, and other challenges with IHC scoring. Tweets may be amplified by Retweets (a re-posting of a Tweet), so a Tweet sent by a faculty member often reached over 1,000 views. Tweetorials had polling questions, text, images, videos, and links to journal articles. Each Tweetorial achieved over 1,400 views and over 535,000 impressions during its first week. Collectively, the Twitter Chats and Tweetorials led to over 1,050 CME/CMLE certificates.

Conclusion
Twitter is an evolving platform that is actively used by pathologists (see #PathTwitter) and laboratory professionals to share knowledge to a broad audience and foster a community of learning. Since content posted on Twitter remains enduring and searchable, people may find old Tweets and see which topics achieved high impressions. When spreading education on new practice-changing topics like HER2-Low breast cancer, Twitter can be an effective platform for broad content dissemination.
Orthogonal biomarkers of Inflammation due to Aging Identified in Saliva and Serum
Authors: Jensen M M , Vu D , Vigerust D , Gupta R , Maecker H T , Nguyen T T 
Published: November 2023

Abstract

Introduction/Objective
The relationship between age and inflammation is well established, but little is known about the contribution of different biological fluids to this relationship. This study aims to compare inflammatory markers in young and old subjects using human saliva and serum samples.

Methods/Case Report
Saliva and serum were collected from young (18-27 years, n=15) and old (53-68 years, n=15) subjects without any reported pathologies and analyzed for inflammatory markers using an Olink® Target 96 Inflammation panel. Each group consisted of individuals with no known pathologies and in good health with 8 female and 7 male patients per group. Salvia samples were using a spectrum solutions Saliva Mulitiomic Device with associated preservation solution. Matched serum samples were taken within 15 minutes of saliva collection. Results from the link were analyzed using a two-way ANOVA with a Sidak correction for multiple comparisons.

Results (if a Case Study enter NA)
Results showed that there were significant differences in inflammatory marker levels between young and old subjects in both saliva and serum samples. However, some specific changes were only found in saliva such as changes to CD8A, IL7, CXCL11, TRAIL, IL20RA, NFG-β, CXCL10, CCL28, DNER CD40, and CXCL1. Other distinct changes were identified only serum samples for CDCP1, OPG, MCP4, FDG23, FDF5, LIFR, FLT3L, IL-33, CCL25, NT3, and TWEAK. Interestingly, only MCP1, CXCL9, CST5, showed statistically significant changes in both saliva and serum, indicating 89% orthogonality for the inflammatory markers analyzed. Only CXCL5 showed variation based on the subject’s sex assigned at birth in both serum and saliva.

Conclusion
These findings suggest that saliva and serum are both useful biological fluids for the assessment of age- related changes in inflammation and provide distinct sets of information. This data provides valuable information for understanding the mechanisms of aging and disease could benefit from the analysis of multiple biological fluid samples.
A novel GLCC1::BRAF fusion with independent MYCN and MYC amplifications in primary tumor and metastasis in pediatric pancreatic acinar carcinoma
Authors: Miller L J , Heider A , Shao L 
Published: November 2023

Abstract

Introduction/Objective
Pediatric pancreatic acinar cell carcinoma (PACC) is a rare malignancy, comprising 5-15% of pediatric pancreatic tumors. BRAF rearrangement is found in 20-30% of PACC cases, most commonly an inversion in chromosome 7. We report a case of PACC with GLCC1::BRAF fusion.

Methods/Case Report
A 10-year-old male presented with six months of weight loss, back pain, and loose stools. Imaging demonstrated concentric soft tissue thickening around the celiac axis and superior mesenteric artery, clinically interpreted as vasculitis. Follow-up imaging showed extension of the soft tissue thickening, prompting biopsy of a periaortic lymph node showing metastatic PACC. Pancreaticduodenectomy revealed a 3.8 cm pancreatic neck mass with perineural invasion and metastatic deposits in multiple lymph nodes and retroperitoneal soft tissue.
Fluorescence in situ hybridization of both specimens demonstrated BRAF gene rearrangement, with the partner identified as GLCC1 by next generation sequencing and fusion assays. Microarray on the lymph node demonstrated amplification of MYC on chromosome 8, but not in the resection specimen, which showed gain of chromosome 2 and amplification of MYCN.

Results (if a Case Study enter NA)
NA

Conclusion
The GLCC1::BRAF fusion has previously been reported once in a case of pheochromocytoma with peritoneal seeding. The MYC gene family members, c-MYC and MYCN, are involved many cancer types; amplifications are often associated with unfavorable prognosis in tumors such as neuroblastoma. However, the amplification of both genes in the same tumor at different loci has not been reported. The combination of the primary GLCC1::BRAF fusion with secondary amplification of MYC and MYCN is likely to drive the aggressive behavior and metastasis in this case of PACC. Treatment for PACC includes chemoradiation and BRAF inhibition. However, BRAF rearrangements without the V600E mutation show variable response to BRAF inhibitors. Potential alternatives include inhibitors to other targets within the BRAF signaling pathway. Further investigation is needed to determine the clinicopathologic impact of these novel genetic aberrancies.
Evaluating Genetic Alterations in Metastatic Pancreatic Neuroendocrine Tumors with Potential Therapeutic and Prognostic Applications: A Comparative In Silico Study with Metastatic Neuroendocrine Tumors Originating from the Small Intestine and Rectum
Authors: Mousavi S , Mirzaei Baboli K , Arabi M , Bereimipour A 
Published: November 2023

Abstract

Introduction/Objective
Pancreatic neuroendocrine tumors (P-NET) are diverse tumors with slow growth and varying levels of potential malignant behavior. The overall 5-year survival rates for P-NET are approximately 95%, 72%, and 23% if localized, and in cases of regional and distant metastasis respectively. These tumors exhibit a low rate of mutations but show varied genomic abnormalities, contributing to their unpredictable nature. In this study, we aimed to find the genetic alterations observed in metastatic P-NET for their potential therapeutic and prognostic applications and compared these tumors to metastatic neuroendocrine tumors originating from the small intestine (SI-NET) and rectum (R-NET).

Methods/Case Report
We initially extracted RNA-seq datasets from the GEO database. Next, we analyzed the datasets in six defined groups and differentially expressed genes were obtained by comparison to controls. Either of the groups of P-NET, SI-NET, or R-NET cases were evaluated individually and altogether (primary vs metastatic; 4 groups) and in 2 groups comparing primary/metastatic P-NET cases to primary/metastatic cases of SI-NET plus R- NET. Using a Venn diagram, we isolated the commonality between gene expression profiles. Afterward, we obtained the ontology of genes and signaling pathways from KEGG and Enrichr. Finally, we drew the protein network and evaluated the proteins in GEPIA and TCGA clinical databases.

Results (if a Case Study enter NA)
A total of 212 cases including 113 P-NET (83 primary and 30 metastatic), 81 SI- NET (44 primary and 37 metastatic), and 18 R-NET (3 primary and 15 metastatic) were selected. We found 8 genes (ORM1, HP, APOA2, HRG, KNG1, ALB, SERPINC1, and AHSG) are mutually markedly upregulated in cases of metastatic P-NET and SI-NET but were not identified in metastatic R-NET. The products of these genes were predominantly involved in complement cascades. CABYR, MYCN, and CALU genes were among the most upregulated genes specifically isolated in the metastatic P-NET that played roles in activating intracellular signaling pathways, transcription, and protein folding.

Conclusion
The shared upregulated genes in metastatic P-NET and SI-NET may support the relatively better prognosis of these tumors in comparison to the metastatic R-NET due to the activation of the complement cascade (immune system). Furthermore, the identified genetic alterations in the metastatic P-NET cases may have potential therapeutic and prognostic applications for future use.
Qualitopix: Artificial intelligence-based quantitative quality assurance of immunohistochemistry staining-The Henry Ford Health experience
Authors: Baba O 
Published: November 2023

Abstract

Introduction/Objective
Immunohistochemistry (IHC) offers crucial patient data for diagnosis, prognosis, and treatment. Pathologists currently assess stain quality subjectively, comparing control sections to patient tissue. Qualitopix (Visiopharm, Denmark) is a cloud-based platform that enables objective, quantitative analysis of staining consistency through external cell line controls.

Methods/Case Report
Over six months, we tested 1121 slides from five cell-line blocks with epitopes of different intensities for ER, PR, Ki-67, Her-2 Neu, and PD-L1. Slides were stained using Ventana Benchmark Ultra (Roche, Basel, Switzerland) for ER, PR, and Her-2 and Dako Omnis (Agilent, Santa Clara, California, United states) for Ki-67 and PD-L1. They were scanned with DP 200 scanner (Roche) and uploaded to Qualitopix for image analysis. Cells were detected using artificial intelligence and classified based on diaminobenzidine (DAB) staining intensity, reported as H-scores (0-100). Outliers were determined at 1 standard deviation. a selection of outliers was rescanned. Inter- scanner comparisons and repeatability studies were performed for ER and 50 within and between the DP 200 and HT scanners (Roche).

Results (if a Case Study enter NA)
Our analysis revealed a 26-34% rate of outliers at 1 SD for the five stains, 10 times higher than the currently reported number from our lab. Most outliers (70-100%) remained out of range at rescanning, suggesting pre-analytical technical issues. 5-33% of slides failed analysis due to technical errors. Poor discrimination between sequential cores of varying intensity for ER and Ki-67 was noted. Inter-scanner comparison and repeatability studies demonstrated precise and consistent H-scores within and across both scanning platforms for ER and PR.

Conclusion
Qualitopix offers automated, objective, and quantitative quality assurance for IHC stain quality assessment, a hitherto manual, subjective and qualitative-driven process. Our findings emphasize the need for continuous IHC quality monitoring. The origin of outliers, technical failures, and their correlation with pathologist's subjective findings require further investigation.
Use of Plasmapheresis in Heparin Induced Thrombocytopenia in Patients Undergoing Urgent Cardiac Surgery
Authors: Bava Ejas Palathingal , Epelman Mathew , Yeldo Nicholas , Uribe-Marquez Santiago , Lopez-Plaza Ileana 
Published: November 2023

Abstract
Heparin Induced Thrombocytopenia (HIT) is a potentially life-threatening but uncommon disease process characterized by IgG antibodies that recognize platelet factor 4/heparin immune complexes causing thrombocytopenia and thrombosis. Although therapeutic plasmapheresis (PLEX) appears to be effective, protocols regarding how and when to institute PLEX remain elusive. At our institution, we put together a standardized approach to assess the interventional success across patients that included 1 plasmapheresis procedure per day over 4 days, processing one plasma volume and using thawed plasma as the replacement fluid. Treatment effectiveness was evaluated by pre- and post-interventional HIPA OD levels and platelet count. Treatment aim was to decrease the HIPA OD to less than 0.6 and obtain a normal platelet count.
The aim of this study was to design a protocol for PLEX to address urgent need for patients with HIT for which heparin is planned for intraoperative cardiac surgery requiring cardiopulmonary bypass (CPB) anticoagulation.
We retrospectively examined the medical records of 2 HIT-positive patients who underwent PLEX prior to cardiac surgery at our large quaternary care hospital. Both patients had a 4Ts score of 5, with a medium probability of disease. One patient's HIT was confirmed by a positive serotonin release assay (SRA). The second patient had persistently negative confirmatory test but was deemed clinical HIT.
The first patient is a 53-year-old female, who was admitted for mitral valve replacement, aortic valve replacement, and tricuspid valve repair. She was confirmed HIT by positive SRA. Three sessions of PLEX were performed on consecutive days. Her HIPA (heparin induced platelet antibody) O.D. value decreased from 1.925 to 0.534 and platelet counts normalized. The second patient is a 73-year-old male, who was admitted for LVAD implantation and LV thrombus resection. Two sessions of PLEX were performed on consecutive days. His HIPA O.D. value deceased from 1.261 to &lt; 0.4 (negative) and platelet counts normalized. For both patients, the last PLEX procedure was performed the day of surgery, and the cardiac surgical procedure was completed successfully.
Based on these 2 patients, we have proposed a protocol for PLEX in HIT patients as follows: daily plasmapheresis x 4 days will be performed until the OD has decreased to less than 0.6 and platelet count has normalized. Each plasmapheresis will consist of the processing of one plasma volume, using thawed plasma as the replacement fluid. The last plasmapheresis will occur on the day of surgery prior to surgery. Further assessment will be performed if the targeted parameters have not been met by the 4th plasmapheresis procedure.
In conclusion, we present 2 patients with HIT who benefitted from PLEX prior to cardiac surgery under CPB. We will adopt the protocol used for these 2 patients as our standard of practice moving forward.
Evaluating the utility and challenges associated with "anonymous" patients in the electronic medical record
Authors: Rogers Kai , Krasowski Matthew 
Published: November 2023

Abstract
Electronic medical records (EMRs) allow for the creation of "test" patients that can be used for training new users, testing changes before they go "live", simulating the placement of orders, or for a range of similar applications. Test patients are commonly utilized in EMR validation, support, or “playground” environments that might use a copy of the production EMR database but do not connect to the official medical record to prevent billing errors or patient harm. However, there are a variety of cases where it is useful to have test or anonymous patients within the EMR production environment as well. One example of this is infectious disease testing for employee blood-borne pathogen exposure (e.g., needlestick injury) that may need to be stored in a de-identified or restricted manner to comply with workplace privacy regulations. There are also instances, generally in emergency situations, where a medical record is created for a patient about whom little identifying information is known. In this example, these so-called "anonymous" patients are assigned random or arbitrarily pre-determined birthdates (e.g., 1/1/1900) and on occasion have no sex assigned in their chart. This poses a variety of challenges from a laboratory standpoint as it can be difficult to provide accurate normal ranges for laboratory results that are age and/or gender specific. Additionally, this has on occasion resulted in an inability to identify appropriate blood products as these recommendations are similarly based on age and gender. Another layer of complexity comes as additional information regarding the patient is made available, and health care information services merges data from a previously anonymous account to a specific patient record. Such mergers can result in cancellation of pending orders, errors in reporting laboratory results, or other complications depending on the specific process utilized. Surprisingly, there is little to no literature regarding the use cases for these “test” and “anonymous” patients or the challenges associated with their existence in the EMR. To explore this topic, we identified three classes of patients in our institutional EMR: true virtual “test” patients, “anonymous” patients that were subsequently identified, and “anonymous” patients that were never identified. Basic characteristics of these patients (sex and date of birth) and available laboratory results were compiled. Along with this, we present a series of instructional cases adapted from actual patient safety events at our institution involving anonymous patient records. These illustrative cases highlight the utility of these “test” and “anonymous” patients, as well as the challenges these pose on an institutional and individual level. Lastly, we provide recommendations on how best to manage similar scenarios that may arise.