Digital Commons Network^™

Liquid Biopsy: From Concept To Clinical Application, Catherine Alix-Panabières, Dario Marchetti, Julie E. Lang

Pathology Research and Scholarship

The diagnosis and treatment of cancer presents a physical and mental burden to the patient, often involving diagnostic biopsies and surgeries or chemotherapeutic approaches with severe side-effects. Advances which enable early detection of cancer and close monitoring of the disease course without invasive procedures, and which can underpin a tailored approach to treatment, can therefore make a big difference to the quality of life of patients. Liquid biopsies can be used to access tumor cells and tumor DNA circulating in the blood. Monitoring these species can provide a minimally invasive and repeatable means to detect cancer, or gain information about …

Iron Promotes Glycolysis To Drive Colon Tumorigenesis., Zhaoli Liu, Luke Villareal, Lavanya Goodla, Hyeoncheol Kim, Daniel M. Falcon, Mohammad Haneef, David R. Martin, Li Zhang, Ho-Joon Lee, Daniel Kremer, Costas A. Lyssiotis, Yatrik M. Shah, Henry C. Lin, Hui-Kuan Lin, Xiang Xue

Pathology Research and Scholarship

Colorectal cancer (CRC) is the third most common cancer and is also the third leading cause of cancer-related death in the USA. Understanding the mechanisms of growth and progression of CRC is essential to improve treatment. Macronutrients such as glucose are energy source for a cell. Many tumor cells exhibit increased aerobic glycolysis. Increased tissue micronutrient iron levels in both mice and humans are also associated with increased colon tumorigenesis. However, if iron drives colon carcinogenesis via affecting glucose metabolism is still not clear. Here we found the intracellular glucose levels in tumor colonoids were significantly increased after iron treatment.

Salivary Duct Carcinoma Arising In A Warthin Tumor Of The Parotid Gland: A Rare Case Report With Review Of Literature And Pd-L1 Expression, Kaitlyn J. Nielson, Gamaliel Lorenzo, Shweta Agarwal

Pathology Research and Scholarship

Warthin's tumor is the second most common neoplasm of the parotid gland and consists of 2 components, including lymphoid stroma and glandular epithelium. Malignant transformation in this tumor is mostly seen in the lymphoid component; however, the carcinomatous transformation of the epithelial component is extremely rare. Cases of latter reported in the literature include squamous cell carcinoma, adenocarcinoma, mucoepidermoid carcinoma, oncocytic carcinoma, Merkel cell carcinoma, and undifferentiated carcinoma. We describe an extremely rare case of salivary duct carcinoma arising in a Warthin tumor in a 64-year-old male. Patient presented with an enlarging left parotid mass, biopsy of which showed salivary …

Deep Neural Network Based Tissue Deconvolution Of Circulating Tumor Cell Rna, Fengyao Yan, Limin Jiang, Fei Ye, Jie Ping, Tetiana Y. Bowley, Scott A. Ness, Chung-I Li, Dario Marchetti, Jijun Tang, Yan Guo

Pathology Research and Scholarship

Prior research has shown that the deconvolution of cell-free RNA can uncover the tissue origin. The conventional deconvolution approaches rely on constructing a reference tissue-specific gene panel, which cannot capture the inherent variation present in actual data. To address this, we have developed a novel method that utilizes a neural network framework to leverage the entire training dataset. Our approach involved training a model that incorporated 15 distinct tissue types. Through one semi-independent and two complete independent validations, including deconvolution using a semi in silico dataset, deconvolution with a custom normal tissue mixture RNA-seq data, and deconvolution of longitudinal circulating …

Early Antibody Treatment, Inflammation, And Risk Of Post-Covid Conditions, Kelly A. Gebo, Sonya L. Heath, Yuriko Fukuta, Xianming Zhu, Sheriza Baksh, Allison G. Abraham, Feben Habtehyimer, David Shade, Jessica Ruff, Malathi Ram, Oliver Laeyendecker, Reinaldo E. Fernandez, Eshan U. Patel, Owen R. Baker, Shmuel Shoham, Edward R. Cachay, Judith S. Currier, Jonathan M. Gerber, Barry Meisenberg, Donald N. Forthal, Laura L. Hammitt, Moises A. Huaman, Adam Levine, Giselle S. Mosnaim, Bela Patel, James H. Paxton, Jay S. Raval, Catherine G. Sutcliffe, Shweta Anjan, Thomas Gniadek, Seble Kassaye, Janis E. Blair, Karen Lane, Nichol A. Mcbee, Amy L. Gawad, Piyali Das, Sabra L. Klein, Andrew Pekosz, Evan M. Bloch, Daniel Hanley, Arturo Casadevall, Aaron A R Tobian, David J. Sullivan

Pathology Research and Scholarship

Approximately 20% of individuals infected with SARS-CoV-2 experienced long-term health effects, as defined PCC. However, it is unknown if there are any early biomarkers associated with PCC or whether early intervention treatments may decrease the risk of PCC. In a secondary analysis of a randomized clinical trial, this study demonstrates that among outpatients with SARS-CoV-2, increased IL-6 at time of infection is associated with increased odds of PCC. In addition, among individuals treated early, within 5 days of symptom onset, with COVID-19 convalescent plasma, there was a trend for decreased odds of PCC after adjusting for other demographic and clinical …

The Fda-Approved Compound, Pramipexole And The Clinical-Stage Investigational Drug, Dexpramipexole, Reverse Chronic Allodynia From Sciatic Nerve Damage In Mice, And Alter Il-1Β And Il-10 Expression From Immune Cell Culture, J E Sanchez, S Noor, M S Sun, J Zimmerly, A Pasmay, J J Sanchez, A G Vanderwall, M K Haynes, L A Sklar, P R Escalona, E D Milligan

Pathology Research and Scholarship

During the onset of neuropathic pain from a variety of etiologies, nociceptors become hypersensitized, releasing neurotransmitters and other factors from centrally-projecting nerve terminals within the dorsal spinal cord. Consequently, glial cells (astrocytes and microglia) in the spinal cord are activated and mediate the release of proinflammatory cytokines that act to enhance pain transmission and sensitize mechanical non-nociceptive fibers which ultimately results in light touch hypersensitivity, clinically observed as allodynia. Pramipexole, a D2/D3 preferring agonist, is FDA-approved for the treatment of Parkinson's disease and demonstrates efficacy in animal models of inflammatory pain. The clinical-stage investigational drug, R(+) enantiomer of pramipexole, dexpramipexole, …

Transfusion Reactions Associated With Covid-19 Convalescent Plasma In Outpatient Clinical Trials, Moises A. Huaman, Jay S. Raval, James H. Paxton, Giselle S. Mosnaim, Bela Patel, Shweta Anjan, Barry R. Meisenberg, Adam C. Levine, Christi E. Marshall, Anusha Yarava, Aarthi G. Shenoy, Sonya L. Heath, Judith S. Currier, Yuriko Fukuta, Janis E. Blair, Emily S. Spivak, Joann R. Petrini, Patrick B Broderick, William Rausch, Marieelena Cordisco, Jean Hammel, Benjamin Greenblatt, Valerie C Cluzet, Daniel Cruser, Kevin Oei, Matthew Abinante, Laura L. Hammitt, Catherine G. Sutcliffe, Donald N. Forthal, Martin S Zand, Edward R. Cachay, Seble G. Kassaye, Malathi Ram, Ying Wang, Piyali Das, Karen Lane, Nichol A Mcbee, Amy L Gawad, Nicky Karlen, Daniel E Ford, Oliver Laeyendecker, Andrew Pekosz, Sabra L. Klein, Stephan Ehrhardt, Bryan Lau, Sheriza N. Baksh, David M. Shade, Arturo Casadevall, Daniel F. Hanley, Jiangda Ou, Thomas J. Gniadek, Alyssa Ziman, Shmuel Shoham, Kelly A. Gebo, Evan M. Bloch, Aaron A R Tobian, David J. Sullivan, Jonathan M. Gerber

Pathology Research and Scholarship

BACKGROUND: COVID-19 convalescent plasma (CCP) is an important therapeutic option for outpatients at high risk of hospitalization from SARS-CoV-2 infection. We assessed the safety of outpatient CCP transfusions administered during clinical trials.

STUDY DESIGN AND METHODS: We analyzed data pertaining to transfusion-related reactions from two randomized controlled trials in the U.S. that evaluated the efficacy of CCP versus control plasma in various ambulatory settings. Multivariable logistic regression was used to assess whether CCP was associated with transfusion reactions, after adjusting for potential confounders.

RESULTS: The combined study reported 79/1351 (5.9%) adverse events during the transfusion visit, with the majority 62/1351 …

Atypical Squamous Verrucous Lesions Of The Oral Cavity: Challenges In Interpretation Of Small Incisional Biopsies, Ryland Richards, Shweta Agarwal

Pathology Research and Scholarship

BACKGROUND: Squamous verrucous proliferative lesions of oral cavity can pose a diagnostic challenge for the general pathologist, especially on small biopsies. The superficial nature of incisional biopsies and inconsistent histologic terminologies used for these lesions contribute to often-discrepant clinical diagnosis, resulting in delayed treatment. This study aims to explore the proliferative squamous lesions of oral cavity, correlate biopsy & resection diagnoses, and evaluate possible reasons for discrepant diagnosis (if any).

DESIGN: A retrospective review of oral verrucous squamous lesions was undertaken. Pathology database was searched for oral cavity biopsies from January2018 through August2022 with the keywords: atypical, verrucous, squamous, and …

The Antiviral Effects Of A Mek1/2 Inhibitor Promote Tumor Regression In A Preclinical Model Of Human Papillomavirus Infection-Induced Tumorigenesis, Adrian J. Luna, Jesse M. Young, Rosa T. Sterk, Virginie Bondu, Fred A. Schultz, Donna F. Kusewitt, Huining Kang, Michelle A. Ozbun

Pathology Research and Scholarship

Human papillomaviruses (HPVs) are a significant public health concern due to their widespread transmission, morbidity, and oncogenic potential. Despite efficacious vaccines, millions of unvaccinated individuals and those with existing infections will develop HPV-related diseases for the next two decades and beyond. The continuing burden of HPV-related diseases is exacerbated by the lack of effective therapies or cures for infections, highlighting the need to identify and develop antivirals. The experimental murine papillomavirus type 1 (MmuPV1) model provides opportunities to study papillomavirus pathogenesis in cutaneous epithelium, the oral cavity, and the anogenital tract. However, to date the MmuPV1 infection model has not …

High Extracellular Glucose Promotes Cell Motility By Modulating Cell Deformability And Contractility Via The Camp-Rhoa-Rock Axis In Human Breast Cancer Cells, Mijung Oh, Skylar Batty, Nayan Banerjee, Tae-Hyung Kim

Pathology Research and Scholarship

The mechanical properties, or mechanotypes, of cells are largely determined by their deformability and contractility. The ability of cancer cells to deform and generate contractile force is critical in multiple steps of metastasis. Identifying soluble cues that regulate cancer cell mechanotypes and understanding the underlying molecular mechanisms regulating these cellular mechanotypes could provide novel therapeutic targets to prevent metastasis. Although a strong correlation between high glucose level and cancer metastasis has been demonstrated, the causality has not been elucidated, and the underlying molecular mechanisms remain largely unknown. In this study, using novel high-throughput mechanotyping assays, we show that human breast …

Preliminary Incidence And Trends Of Infections Caused By Pathogens Transmitted Commonly Through Food - Foodborne Diseases Active Surveillance Network, 10 U.S. Sites, 2022, Miranda J. Delahoy, Hazel J. Shah, Daniel Lowell Weller, Logan C. Ray, Kirk Smith, Suzanne Mcguire, Rosalie T. Trevejo, Elaine Scallan Walter, Katie Wymore, Tamara Rissman, Marcy Mcmillian, Sarah Lathrop, Bethany Laclair, Michelle M. Boyle, Stic Harris, Joanna Zablotsky-Kufel, Kennedy Houck, Carey J. Devine, Carey E. Lau, Robert V. Tauxe, Beau B. Bruce, Patricia M. Griffin, Daniel C. Payne

Pathology Research and Scholarship

Each year, infections from major foodborne pathogens are responsible for an estimated 9.4 million illnesses, 56,000 hospitalizations, and 1,350 deaths in the United States (1). To evaluate progress toward prevention of enteric infections in the United States, the Foodborne Diseases Active Surveillance Network (FoodNet) conducts surveillance for laboratory-diagnosed infections caused by eight pathogens transmitted commonly through food at 10 U.S. sites. During 2020-2021, FoodNet detected decreases in many infections that were due to behavioral modifications, public health interventions, and changes in health care-seeking and testing practices during the COVID-19 pandemic. This report presents preliminary estimates of pathogen-specific annual incidences during …

Symptom Duration And Resolution With Early Outpatient Treatment Of Convalescent Plasma For Coronavirus Disease 2019: A Randomized Trial, Sheriza N. Baksh, Sonya L. Heath, Yuriko Fukuta, David Shade, Barry Meisenberg, Evan M. Bloch, Aaron A R Tobian, Emily S. Spivak, Bela Patel, Jonathan Gerber, Jay S. Raval, Donald Forthal, James Paxton, Giselle Mosnaim, Shweta Anjan, Janis Blair, Edward Cachay, Judith Currier, Piyali Das, Moises Huaman, Catherine Sutcliffe, Anusha Yarava, Arturo Casadevall, David Sullivan, Daniel Hanley, Kelly A Gebo

Pathology Research and Scholarship

BACKGROUND: Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) reduces hospitalizations among outpatients treated early after symptom onset. It is unknown whether CCP reduces time to symptom resolution among outpatients.

METHODS: We evaluated symptom resolution at day 14 by trial arm using an adjusted subdistribution hazard model, with hospitalization as a competing risk. We also assessed the prevalence of symptom clusters at day 14 between treatments. Clusters were defined based on biologic clustering, impact on ability to work, and an algorithm.

RESULTS: Among 1070 outpatients followed up after transfusion, 381 of 538 (70.8%) receiving CCP and 381 of 532 (71.6%) receiving …

Key Takeaways For Knowledge Expansion Of Early-Career Scientists Conducting Transdisciplinary Research In Energetics And Cancer (Trec): A Report From The Trec Training Workshop 2022, Che-Pei Kung, Meghan B. Skiba, Erika J. Crosby, Jessica Gorzelitz, Mary A. Kennedy, Bethany A. Kerr, Yun Rose Li, Sarah Nash, Melanie Potiaumpai, Amber S. Kleckner, Dara L. James, Michael F. Coleman, Ciaran M. Fairman, Gloria C. Galván, David O. Garcia, Max J. Gordon, Mathilde His, Lyndsey M. Hornbuckle, So-Youn Kim, Tae-Hyung Kim, Amanika Kumar, Mélanie Mahé, Karen K. Mcdonnell, Jade Moore, Sangphil Oh, Xinghui Sun, Melinda L. Irwin

Pathology Research and Scholarship

The overall goal of the annual Transdisciplinary Research in Energetics and Cancer (TREC) Training Workshop is to provide transdisciplinary training for scientists in energetics and cancer and clinical care. The 2022 Workshop included 27 early-to-mid career investigators (trainees) pursuing diverse TREC research areas in basic, clinical, and population sciences. The 2022 trainees participated in a gallery walk, an interactive qualitative program evaluation method, to summarize key takeaways related to program objectives. Writing groups were formed and collaborated on this summary of the 5 key takeaways from the TREC Workshop. The 2022 TREC Workshop provided a targeted and unique networking opportunity …

Transferrin Receptor-Mediated Iron Uptake Promotes Colon Tumorigenesis, Hyeoncheol Kim, Luke B. Villareal, Zhaoli Liu, Mohammad Haneef, Daniel M. Falcon, David R. Martin, Ho-Joon Lee, Michael K. Dame, Durga Attili, Ying Chen, James Varani, Jason R. Spence, Olga Kovbasnjuk, Justin A. Colacino, Costas A. Lyssiotis, Henry C. Lin, Yatrik M. Shah, Xiang Xue

Pathology Research and Scholarship

Transferrin receptor (TFRC) is the major mediator for iron entry into a cell. Under excessive iron conditions, TFRC is expected to be reduced to lower iron uptake and toxicity. However, the mechanism whereby TFRC expression is maintained at high levels in iron-enriched cancer cells and the contribution of TFRC to cancer development are enigmatic. Here the work shows TFRC is induced by adenomatous polyposis coli (APC) gene loss-driven β-catenin activation in colorectal cancer, whereas TFRC-mediated intratumoral iron accumulation potentiates β-catenin signaling by directly enhancing the activity of tankyrase. Disruption of TFRC leads to a reduction of colonic iron levels and …

Pathology Education Powered By Virtual And Digital Transformation: Now And The Future, Lewis A. Hassell, Syeda Fatima Absar, Chhavi Chauhan, Suzanne Dintzis, Carol Farver, Samreen Fathima, Eric F. Glassy, Jeffery F. Goldstein, Rama Gullapalli, Jonhan Ho, Lisa K. Koch, James E. Madory, Kamran M. Mirza, Phuong Nhat Nguyen, Liron Pantanowitz, Anil Parwani, Rebecca Rojansky, Robert P. Seifert, Rajendra Singh, Ehab A. Elgabry, Marilyn Bui

Pathology Research and Scholarship

CONTEXT.—: Myriad forces are changing teaching and learning strategies throughout all stages and types of pathology education. Pathology educators and learners face the challenge of adapting to and adopting new methods and tools. The digital pathology transformation and the associated educational ecosystem are major factors in this setting of change.

OBJECTIVE.—: To identify and collect resources, tools, and examples of educational innovations involving digital pathology that are valuable to pathology learners and teachers at each phase of professional development.

DATA SOURCES.—: Sources were a literature review and the personal experience of authors and educators.

CONCLUSIONS.—: High-quality digital pathology tools and …

The Onset Of Rare Earth Metallosis Begins With Renal Gadolinium-Rich Nanoparticles From Magnetic Resonance Imaging Contrast Agent Exposure, Joshua Deaguero, Tamara Howard, Donna Kusewitt, Adrian Brearley, Abdul-Mehdi Ali, James H. Degnan, Stephen Jett, John Watt, G Patricia Escobar, Karol Dokladny, Brent Wagner

Pathology Research and Scholarship

The leitmotifs of magnetic resonance imaging (MRI) contrast agent-induced complications range from acute kidney injury, symptoms associated with gadolinium exposure (SAGE)/gadolinium deposition disease, potentially fatal gadolinium encephalopathy, and irreversible systemic fibrosis. Gadolinium is the active ingredient of these contrast agents, a non-physiologic lanthanide metal. The mechanisms of MRI contrast agent-induced diseases are unknown. Mice were treated with a MRI contrast agent. Human kidney tissues from contrast-naïve and MRI contrast agent-treated patients were obtained and analyzed. Kidneys (human and mouse) were assessed with transmission electron microscopy and scanning transmission electron microscopy with X-ray energy-dispersive spectroscopy. MRI contrast agent treatment resulted in …

Gaps In The Screening Process For Women Diagnosed With Cervical Cancer In Four Diverse Us Health Care Settings, Chun R. Chao, Jessica Chubak, Elisabeth F. Beaber, Aruna Kamineni, Connie Mao, Michael J. Silverberg, Jasmin A. Tiro, Celette Skinner, Michael Garcia, Douglas A. Corley, Rachel L. Winer, Tina Raine-Bennett, Sarah Feldman, Cosette M. Wheeler

Pathology Research and Scholarship

BACKGROUND: Potential care gaps in the cervical cancer screening process among women diagnosed with cervical cancer in an era with increased human papillomavirus (HPV) testing have not been extensively evaluated.

METHODS: Women diagnosed with cervical cancer between ages 21 and 65 at four study sites between 2010 and 2014 were included. Screening histories were ascertained from 0.5 to 4 years prior to cervical cancer diagnosis. We identified potential care gaps in the screening history for each woman and classified them into one of three mutually exclusive types: lack of a screening test, screening test failure, and diagnostic/treatment care gap. Distributions …

Humanized Patient-Derived Xenograft Models Of Disseminated Ovarian Cancer Recapitulate Key Aspects Of The Tumor Immune Environment Within The Peritoneal Cavity, Mara P. Steinkamp, Irina Lagutina, Kathryn J. Brayer, Fred Schultz, Danielle Burke, Vernon S. Pankratz, Sarah F. Adams, Laurie G. Hudson, Scott A. Ness, Angela Wandinger-Ness

Pathology Research and Scholarship

UNLABELLED: The importance of the immune microenvironment in ovarian cancer progression, metastasis, and response to therapies has become increasingly clear, especially with the new emphasis on immunotherapies. To leverage the power of patient-derived xenograft (PDX) models within a humanized immune microenvironment, three ovarian cancer PDXs were grown in humanized NBSGW (huNBSGW) mice engrafted with human CD34

SIGNIFICANCE: huPDX models are ideal preclinical models for testing novel therapies. They reflect the genetic heterogeneity of the patient population, enhance human myeloid differentiation, and recruit immune cells to the tumor microenvironment.

Humanized Patient-Derived Xenograft Models Of Disseminated Ovarian Cancer Recapitulate Key Aspects Of The Tumor Immune Environment Within The Peritoneal Cavity, Mara P. Steinkamp, Irina Lagutina, Kathryn J. Brayer, Fred Schultz, Danielle Burke, Vernon S. Pankratz, Sarah F. Adams, Laurie G. Hudson, Scott A. Ness, Angela Wandinger-Ness

Pathology Research and Scholarship

UNLABELLED: The importance of the immune microenvironment in ovarian cancer progression, metastasis, and response to therapies has become increasingly clear, especially with the new emphasis on immunotherapies. To leverage the power of patient-derived xenograft (PDX) models within a humanized immune microenvironment, three ovarian cancer PDXs were grown in humanized NBSGW (huNBSGW) mice engrafted with human CD34

SIGNIFICANCE: huPDX models are ideal preclinical models for testing novel therapies. They reflect the genetic heterogeneity of the patient population, enhance human myeloid differentiation, and recruit immune cells to the tumor microenvironment.

Dysregulation Of The Prune2/Pca3 Genetic Axis In Human Prostate Cancer: From Experimental Discovery To Validation In Two Independent Patient Cohorts, Richard C. Lauer, Marc Barry, Tracey L. Smith, Andrew Maltez Thomas, Jin Wu, Ruofei Du, Ji-Hyun Lee, Arpit Rao, Andrey S. Dobroff, Marco A. Arap, Diana N. Nunes, Israel T. Silva, Emmanuel Dias-Neto, Isan Chen, Dennis J. Mccance, Webster K. Cavenee, Renata Pasqualini, Wadih Arap

Pathology Research and Scholarship

BACKGROUND: We have previously shown that the long non-coding (lnc)RNA

METHODS: The reciprocal

RESULTS: We consistently observed increased expression of

CONCLUSIONS: We concluded that upregulation of the lncRNA

FUNDING: We received support from the Human Tissue Repository and Tissue Analysis Shared Resource from the Department of Pathology of the University of New Mexico School of Medicine and a pilot award from the University of New Mexico Comprehensive Cancer Center. RP and WA were supported by awards from the Levy-Longenbaugh Donor-Advised Fund and the Prostate Cancer Foundation. EDN reports research fellowship support from the Brazilian National Council for Scientific and Technological …

The Next Phase In Patient Safety Education: Towards A Standardized, Tools-Based Pathology Patient Safety Curriculum: A Call To Action From The Association Of Pathology Chairs' Residency Program Directors Section Training Residents In Patient Safety Workgroup, Cynthia K. Harris, Yigu Chen, Erin L. Alston, Ali Brown, Devon Chabot-Richards, Suzanne M. Dintzis, Mark L. Graber, Ronald Jackups Jr, Lesley C. Lomo, Jennifer Laudadio, Priscilla S. Markwood, Kaitlyn J. Nielson, Von Samedi, Barbara Sampson, Richard L. Haspel, Nadeem Zafar, Kathleen T. Montone, John Childs, Kristie L. White, Yael K. Heher

Pathology Research and Scholarship

Patient safety education is a mandated Common Program Requirement of the Accreditation Council for Graduate Medical Education and for the Royal College of Physicians and Surgeons of Canada in all medical residency and fellowship programs. Although many hospitals and healthcare environments have general patient safety education tools for trainees, few to none focus on the unique training milieu of pathologists, including a mix of highly automated and manual error-prone processes, frequent multiplicity of events, and lack of direct patient relationships for error disclosure. We established a national Association of Pathology Chairs-Program Directors Section Workgroup focused on patient safety education for …

Combined Neuroendocrine And Squamous Cell Carcinoma Of The Sinonasal Tract: A Morphologic And Immunohistochemical Analysis And Review Of Literature, Shweta Agarwal, Annemieke Van Zante, Michaela L. Granados

Pathology Research and Scholarship

Sinonasal malignancies constitute 3% of head and neck cancers, with squamous cell carcinoma (SCC) the most common histology. Neuroendocrine carcinomas (NEC) are rare, with a subset showing neuroendocrine carcinoma and a non-neuroendocrine component. The pathogenesis of these combined tumors is largely unknown, and TP53 driver mutations may play a role. A database search for combined NEC was performed across two institutions (UNM and UCSF) spanning 15 years. Excluding NUT midline carcinoma, 3 cases met inclusion criteria. All were morphologically NEC + SCC and underwent a comprehensive immunohistochemical evaluation. Tumors demonstrated two components histologically: moderately to poorly differentiated SCC and high-grade …

Assessing Knowledge And Perceptions About Cancer Among American Indians Of The Zuni Pueblo, Nm, Safia Safi, Donica Ghahate, Jeanette Bobelu, Andrew L. Sussman, Joseph Rodman, Angela Wandinger-Ness, Shiraz I. Mishra, Thomas Faber, Cheryl Willman, Vallabh Shah

Pathology Research and Scholarship

American Indians (AIs) in New Mexico have lower cancer screening rates compared to other populations and are more likely to be diagnosed with cancer at an advanced stage of the disease as reported by Li et al. (Archives of Internal Medicine 163(1):49-56, 2003). AIs also have the lowest 5-year cancer survival rates compared to any ethnic/racial group in the USA as reported by Clegg et al. (Arch Intern Med 162:1985-1993, 2002) and Edwards et al. (Cancer 97:1407-1427, 2005). Numerous barriers such as cultural beliefs, fear, fatalism, mistrust, stigma, and lack of culturally appropriate interventions could contribute to low cancer screening …

Agent-Based Modeling Predicts Rac1 Is Critical For Ovarian Cancer Metastasis, Melanie Rivera, Leslie Toledo-Jacobo, Elsa Romero, Tudor I. Oprea, Melanie E. Moses, Laurie G. Hudson, Angela Wandinger-Ness, Martha M. Grimes

Pathology Research and Scholarship

Experimental and computational studies pinpoint rate-limiting step(s) in metastasis governed by Rac1. Using ovarian cancer cell and animal models, Rac1 expression was manipulated, and quantitative measurements of cell-cell and cell-substrate adhesion, cell invasion, mesothelial clearance, and peritoneal tumor growth discriminated the tumor behaviors most highly influenced by Rac1. The experimental data were used to parameterize an agent-based computational model simulating peritoneal niche colonization, intravasation, and hematogenous metastasis to distant organs. Increased ovarian cancer cell survival afforded by the more rapid adhesion and intravasation upon Rac1 overexpression is predicted to increase the numbers of and the rates at which tumor cells …

Neutralizing Covid-19 Convalescent Plasma In Adults Hospitalized With Covid-19: A Blinded, Randomized, Placebo-Controlled Trial, Wesley H. Self, Allison P. Wheeler, Thomas G. Stewart, Harry Schrager, Jason Mallada, Christopher B. Thomas, Vince D. Cataldo, Hollis R. O'Neal, Nathan I. Shapiro, Conor Higgins, Adit A. Ginde, Lakshmi Chauhan, Nicholas J. Johnson, Daniel J. Henning, Stuti J. Jaiswal, Manoj J. Mammen, Estelle S. Harris, Sonal R. Pannu, Maryrose Laguio-Vila, Wissam El Atrouni, Marjolein De Wit, Daanish Hoda, Claudia S. Cohn, Carla Mcwilliams, Carl Shanholtz, Alan E. Jones, Simon Mucha, Tina S. Ipe, Xian Qiao, Stephen J. Schrantz, Aarthi Shenoy, Richard D Fremont, Eric J. Brady, Robert H. Carnahan, James D. Chappell, James E. Crowe, Mark R. Denison, Pavlo Gilchuk, Laura J. Stevens, Rachel E. Sutton, Isaac Thomsen, Sandra M. Yoder, Amanda J. Bistran-Hall, Jonathan D. Casey, Christopher J. Lindsell, Li Wang, Jill M. Pulley, Jillian P. Rhoads, Gordon R. Bernard, Todd W. Rice, Jay S. Raval

Pathology Research and Scholarship

BACKGROUND: Convalescent plasma has been one of the most common treatments for COVID-19, but most clinical trial data to date have not supported its efficacy.

RESEARCH QUESTION: Is rigorously selected COVID-19 convalescent plasma with neutralizing anti-SARS-CoV-2 antibodies an efficacious treatment for adults hospitalized with COVID-19?

STUDY DESIGN AND METHODS: This was a multicenter, blinded, placebo-controlled randomized clinical trial among adults hospitalized with SARS-CoV-2 infection and acute respiratory symptoms for < 14 days. Enrolled patients were randomly assigned to receive one unit of COVID-19 convalescent plasma (n = 487) or placebo (n = 473). The primary outcome was clinical status (disease severity) 14 days following study infusion measured with a seven-category ordinal scale ranging from discharged from the hospital with resumption of normal activities (lowest score) to death (highest score). The primary outcome was analyzed with a multivariable ordinal regression model, with an adjusted odds ratio (aOR) < 1.0 indicating more favorable outcomes with convalescent plasma than with placebo. In secondary analyses, trial participants were stratified according to the presence of endogenous anti-SARS-CoV-2 antibodies ("serostatus") at randomization. The trial included 13 secondary efficacy outcomes, including 28-day mortality.

RESULTS: Among 974 randomized patients, 960 were included in the primary analysis. Clinical status on the ordinal outcome scale at 14 days did not differ between the convalescent plasma and placebo …

Accuracy Of Forensic Pathologists In Incorporating Post-Mortem Ct (Pmct) In Forensic Death Investigation, Yohsuke Makino, Kana Unuma, Kurt B. Nolte, Natalie L. Adolphi

Pathology Research and Scholarship

Post-mortem computed tomography (PMCT) is now performed routinely in some medical examiner's offices, and the images are typically interpreted by forensic pathologists. In this study, the question of whether pathologists appropriately identify significant PMCT findings and incorporate them into the death investigation report and the cause and manner of death (COD and MOD) statements was addressed. We retrospectively reviewed 200 cases where PMCT was performed. The cases were divided into four categories: (1) full autopsy without radiology consultation (n = 77), (2) external exam without radiology consultation (n = 79), (3) full autopsy with radiology consultation (n = 26), (4) …

Dna Methylation Testing With S5 For Triage Of High-Risk Hpv Positive Women, Rachael Adcock, Belinda Nedjai, Attila T. Lorincz, Dorota Scibior-Bentkowska, Rawinder Banwait, Norah Torrez-Martinez, Michael Robertson, Jack Cuzick, Cosette M. Wheeler

Pathology Research and Scholarship

Methylation of host and viral genes is promising for triage of women with high-risk human papillomavirus infections (hrHPV). Using a population-based sample of hrHPV positive women with cervical biopsies within 12 months after cervical screening, the clinical value of the S5 methylation classifier (S5), HPV genotyping and cytology were compared as potential triage tests, for outcomes of cervical intraepithelial neoplasia (CIN) grade 3 or greater (CIN3+), CIN2+ and CIN2, and the area under the curve (AUC) calculated. S5 scores increased with histopathology severity (P

International Consensus Classification Of Myeloid Neoplasms And Acute Leukemias: Integrating Morphologic, Clinical, And Genomic Data., Daniel A. Arber, Attilio Orazi, Robert P. Hasserjian, Michael J. Borowitz, Katherine R. Calvo, Hans-Michael Kvasnicka, Sa A. Wang, Adam Bagg, Tiziano Barbui, Susan Branford, Carlos E. Bueso-Ramos, Jorge E. Cortes, Paola Dal Cin, Courtney E. Dinardo, Hervé Dombret, Eric J. Duncavage, Benjamin L. Ebert, Elihu H. Estey, Fabio Facchetti, Kathryn Foucar, Naseema Gangat, Umberto Gianelli, Lucy A. Godley, Nicola Gökbuget, Jason Gotlib, Eva Hellström-Lindberg, Gabriela S. Hobbs, Ronald Hoffman, Elias J. Jabbour, Jean-Jacques Kiladjian, Richard A. Larson, Michelle M Le Beau, Mignon L-C Loh, Bob Löwenberg, Elizabeth Macintyre, Luca Malcovati, Charles G. Mullighan, Charlotte Niemeyer, Olatoyosi M. Odenike, Seishi Ogawa, Alberto Orfao, Elli Papaemmanuil, Francesco Passamonti, Kimmo Porkka, Ching-Hon Pui, Jerald P. Radich, Andreas Reiter, Maria Rozman, Martina Rudelius, Michael R. Savona, Annette Schmitt-Graeff, Akiko Shimamura, Jorge Sierra, Wendy A. Stock, Richard M. Stone, Martin S. Tallman, Jürgen Thiele, Hwei-Fang Tien, Alexandar Tzankov, Alessandro M. Vannucchi, Paresh Vyas, Andrew H. Wei, Olga K. Weinberg, Mario Cazzola, Hartmut Döhner, Ayalew Tefferi, Agnieszka Wierzbowska

Pathology Research and Scholarship

The classification of myeloid neoplasms and acute leukemias was last updated in 2016 within a collaboration between the World Health Organization (WHO), the Society for Hematopathology, and the European Association for Haematopathology. This collaboration was primarily based on input from a clinical advisory committees (CACs) composed of pathologists, hematologists, oncologists, geneticists, and bioinformaticians from around the world. The recent advances in our understanding of the biology of hematologic malignancies, the experience with the use of the 2016 WHO classification in clinical practice, and the results of clinical trials have indicated the need for further revising and updating the classification. As …

The Genomic Landscape Of Pediatric Acute Lymphoblastic Leukemia, Samuel W. Brady, Kathryn G. Roberts, Zhaohui Gu, Lei Shi, Stanley Pounds, Deqing Pei, Cheng Cheng, Yunfeng Dai, Meenakshi Devidas, Chunxu Qu, Ashley N. Hill, Debbie Payne-Turner, Xiaotu Ma, Ilaria Iacobucci, Pradyuamna Baviskar, Lei Wei, Sasi Arunachalam, Kohei Hagiwara, Yanling Liu, Diane A Flasch, Yu Liu, Matthew Parker, Xiaolong Chen, Abdelrahman H. Elsayed, Omkar Pathak, Yongjin Li, Yiping Fan, J Robert Michael, Michael Rusch, Mark R. Wilkinson, Scott Foy, Dale J. Hedges, Scott Newman, Xin Zhou, Jian Wang, Colleen Reilly, Edgar Sioson, Stephen V. Rice, Victor Pastor Loyola, Gang Wu, Evadnie Rampersaud, Shalini C. Reshmi, Julie Gastier-Foster, Jaime M. Guidry Auvil, Patee Gesuwan, Malcolm A. Smith, Naomi Winick, Andrew J. Carroll, Nyla A. Heerema, Richard C. Harvey, Cheryl L. Willman, Eric Larsen, Elizabeth A. Raetz, Michael J. Borowitz, Brent L. Wood, William L. Carroll, Patrick A. Zweidler-Mckay, Karen R. Rabin, Leonard A. Mattano, Kelly W. Maloney, Stuart S. Winter, Michael J. Burke, Wanda Salzer, Kimberly P. Dunsmore, Anne L. Angiolillo, Kristine R. Crews, James R. Downing, Sima Jeha, Ching-Hon Pui, William E. Evans, Jun Yang, Mary V. Relling, Daniela S. Gerhard, Mignon L. Loh, Stephen P. Hunger, Jinghui Zhang, Charles G. Mullighan

Pathology Research and Scholarship

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Here, using whole-genome, exome and transcriptome sequencing of 2,754 childhood patients with ALL, we find that, despite a generally low mutation burden, ALL cases harbor a median of four putative somatic driver alterations per sample, with 376 putative driver genes identified varying in prevalence across ALL subtypes. Most samples harbor at least one rare gene alteration, including 70 putative cancer driver genes associated with ubiquitination, SUMOylation, noncoding transcripts and other functions. In hyperdiploid B-ALL, chromosomal gains are acquired early and synchronously before ultraviolet-induced mutation. By contrast, ultraviolet-induced mutations precede chromosomal …

The Validity Of Mcat Scores In Predicting Students' Performance And Progress In Medical School: Results From A Multisite Study, Joshua T. Hanson, Kevin Busche, Martha L. Elks, Loretta E. Jackson-Williams, Robert A. Liotta, Chad Miller, Cindy A. Morris, Barton Thiessen, Kun Yuan

Pathology Research and Scholarship

PURPOSE: This is the first multisite investigation of the validity of scores from the current version of the Medical College Admission Test (MCAT) in clerkship and licensure contexts. It examined the predictive validity of MCAT scores and undergraduate grade point averages (UGPAs) for performance in preclerkship and clerkship courses and on the United States Medical Licensing Examination Step 1 and Step 2 Clinical Knowledge examinations. It also studied students' progress in medical school.

METHOD: Researchers examined data from 17 U.S. and Canadian MD-granting medical schools for 2016 and 2017 entrants who volunteered for the research and applied with scores from …