Digital Commons Network^™

Spatially Distributed Infection Increases Viral Load In A Computational Model Of Sars-Cov-2 Lung Infection, Melanie E. Moses, Steven Hofmeyr, Judy L. Cannon, Akil Andrews, Rebekah Gridley, Monica Hinga, Kirtus Leyba, Abigail Pribisova, Vanessa Surjadidjaja, Humayra Tasnim, Stephanie Forrest

Pathology Research and Scholarship

A key question in SARS-CoV-2 infection is why viral loads and patient outcomes vary dramatically across individuals. Because spatial-temporal dynamics of viral spread and immune response are challenging to study in vivo, we developed Spatial Immune Model of Coronavirus (SIMCoV), a scalable computational model that simulates hundreds of millions of lung cells, including respiratory epithelial cells and T cells. SIMCoV replicates viral growth dynamics observed in patients and shows how spatially dispersed infections can lead to increased viral loads. The model also shows how the timing and strength of the T cell response can affect viral persistence, oscillations, and control. …

Burden Of Mycoplasma Genitalium And Bacterial Coinfections In A Population-Based Sample In New Mexico, Anne Hammer, Patti E. Gravitt, Rachael Adcock, Nicole Patterson, Jack Cuzick, Cosette M. Wheeler

Pathology Research and Scholarship

In this population-based US study, the overall prevalence of Mycoplasma genitalium was 1.95% (95% confidence interval [CI], 1.62%-2.34%), declining from 6.12% (95% CI, 4.72%-7.92%) in women aged 21 to 24 years to 0.48% (95% CI, 0.25%-0.94%) in women aged 40 to 64 years. The prevalence of coinfections with Chlamydia trachomatis and Trichomonas vaginalis was low.

The Report From Asfa Covid-19 Taskforce: Considerations And Prioritization On Apheresis Procedures During The Sars-Cov-2 Coronavirus Disease (Covid-19) Pandemic, Chisa Yamada, Jan C. Hofmann, Volker Witt, Gaurav K. Gupta, Jeffrey L. Winters

Pathology Research and Scholarship

Since vaccination for SARS-CoV-2 coronavirus started, the trajectory of patient numbers infected with the virus has improved once; however, variants of SARS-CoV-2 have emerged and more people have been infected; therefore, pandemic status is still far from resolution. Government and social efforts to prevent coronavirus infection continue in most states in the US and globally even after the Centers for Disease Control and Prevention declared some restriction relief for fully vaccinated people in March 2021. Healthcare institutions and various professional organizations have developed guidelines or policies to prevent the spread of these coronaviruses in the setting of apheresis. In this …

Microrna Analysis Of Human Stroke Brain Tissue Resected During Decompressive Craniectomy/Stroke-Ectomy Surgery, Andrew P. Carlson, William Mckay, Jeremy S. Edwards, Radha Swaminathan, Karen S. Santacruz, Ron L. Mims, Howard Yonas, Tamara Roitbak

Pathology Research and Scholarship

BACKGROUND: Signaling pathways mediated by microRNAs (miRNAs) have been identified as one of the mechanisms that regulate stroke progression and recovery. Recent investigations using stroke patient blood and cerebrospinal fluid (CSF) demonstrated disease-specific alterations in miRNA expression. In this study, for the first time, we investigated miRNA expression signatures in freshly removed human stroke brain tissue.

METHODS: Human brain samples were obtained during craniectomy and brain tissue resection in severe stroke patients with life-threatening brain swelling. The tissue samples were subjected to histopathological and immunofluorescence microscopy evaluation, next generation miRNA sequencing (NGS), and bioinformatic analysis.

RESULTS: miRNA NGS analysis detected …

Bioengineered Models To Study Microenvironmental Regulation Of Glioblastoma Metabolism, Joseph Chen, Hyunchul Lee, Philipp Schmitt, Caleb J. Choy, Donald M. Miller, Brian J. Williams, Elaine L. Bearer, Hermann B. Frieboes

Pathology Research and Scholarship

Despite extensive research and aggressive therapies, glioblastoma (GBM) remains a central nervous system malignancy with poor prognosis. The varied histopathology of GBM suggests a landscape of differing microenvironments and clonal expansions, which may influence metabolism, driving tumor progression. Indeed, GBM metabolic plasticity in response to differing nutrient supply within these microenvironments has emerged as a key driver of aggressiveness. Additionally, emergent biophysical and biochemical interactions in the tumor microenvironment (TME) are offering new perspectives on GBM metabolism. Perivascular and hypoxic niches exert crucial roles in tumor maintenance and progression, facilitating metabolic relationships between stromal and tumor cells. Alterations in extracellular …

Integrin Activation Is An Essential Component Of Sars-Cov-2 Infection, Peter Simons, Derek A. Rinaldi, Virginie Bondu, Alison M. Kell, Steven Bradfute, Diane S. Lidke, Tione Buranda

Pathology Research and Scholarship

SARS-CoV-2 infection depends on binding its spike (S) protein to angiotensin-converting enzyme 2 (ACE2). The S protein expresses an RGD motif, suggesting that integrins may be co-receptors. Here, we UV-inactivated SARS-CoV-2 and fluorescently labeled the envelope membrane with octadecyl rhodamine B (R18) to explore the role of integrin activation in mediating cell entry and productive infection. We used flow cytometry and confocal microscopy to show that SARS-CoV-2^R18 particles engage basal-state integrins. Furthermore, we demonstrate that Mn2+, which induces integrin extension, enhances cell entry of SARS-CoV-2^R18. We also show that one class of integrin antagonist, which binds to …

Tetraspanin Cd82 Regulates S1pr, Chelsea A. Saito-Reis, Victoria D. Balise, Erica M. Pascetti, Magdalena Jiminez, Jennifer M. Gillette

Pathology Research and Scholarship

Hematopoietic stem and progenitor cell (HSPC) mobilization into the blood occurs under normal physiological conditions and is stimulated in the clinic to enable the isolation of HSPCs for transplantation therapies. In the present study, we identify the tetraspanin CD82 as a novel regulator of HSPC mobilization. Using a global CD82 knockout (CD82KO) mouse, we measure enhanced HSPC mobilization after granulocyte-colony stimulating factor (G-CSF) or AMD3100 treatment, which we find is promoted by increased surface expression of the sphingosine 1-phosphate receptor 1 (S1PR

Ethics Of Ai In Pathology: Current Paradigms And Emerging Issues, Chhavi Chauhan, Rama R. Gullapalli

Pathology Research and Scholarship

Deep learning has rapidly advanced artificial intelligence (AI) and algorithmic decision-making (ADM) paradigms, affecting many traditional fields of medicine, including pathology, which is a heavily data-centric specialty of medicine. The structured nature of pathology data repositories makes it highly attractive to AI researchers to train deep learning models to improve health care delivery. Additionally, there are enormous financial incentives driving adoption of AI and ADM due to promise of increased efficiency of the health care delivery process. AI, if used unethically, may exacerbate existing inequities of health care, especially if not implemented correctly. There is an urgent need to harness …

Molecular Classification Improves Risk Assessment In Adult Bcr-Abl1-Negative B-All, Elisabeth Paietta, Kathryn G. Roberts, Victoria Wang, Zhaohui Gu, Georgina A N Buck, Deqing Pei, Cheng Cheng, Ross L. Levine, Omar Abdel-Wahab, Zhongshan Cheng, Gang Wu, Chunxu Qu, Lei Shi, Stanley Pounds, Cheryl L. Willman, Richard Harvey, Janis Racevskis, Jan Barinka, Yanming Zhang, Gordon W. Dewald, Rhett P. Ketterling, David Alejos, Hillard M. Lazarus, Selina M. Luger, Letizia Foroni, Bela Patel, Adele K. Fielding, Ari Melnick, David I. Marks, Anthony V. Moorman, Peter H. Wiernik, Jacob M. Rowe, Martin S. Tallman, Anthony H. Goldstone, Charles G. Mullighan, Mark R. Litzow

Pathology Research and Scholarship

Genomic classification has improved risk assignment of pediatric, but not adult B-lineage acute lymphoblastic leukemia (B-ALL). The international UKALLXII/ECOG-ACRIN E2993 (#NCT00002514) trial accrued 1229 adolescent/adult patients with BCR-ABL1- B-ALL (aged 14 to 65 years). Although 93% of patients achieved remission, 41% relapsed at a median of 13 months (range, 28 days to 12 years). Five-year overall survival (OS) was 42% (95% confidence interval, 39, 44). Transcriptome sequencing, gene expression profiling, cytogenetics, and fusion polymerase chain reaction enabled genomic subtyping of 282 patient samples, of which 264 were eligible for trial, accounting for 64.5% of E2993 patients. Among patients with outcome …

Uptake Of Co-Testing With Hpv And Cytology For Cervical Screening: A Population-Based Evaluation In The United States, Jack Cuzick, Ruofei Du, Rachael Adcock, Walter Kinney, Nancy Joste, Ruth M. Mcdonald, Kevin English, Salina M. Torres, Debbie Saslow, Cosette M. Wheeler

Pathology Research and Scholarship

OBJECTIVES: Human papillomavirus (HPV) testing for cervical screening has been shown to increase the yield of precancerous disease and reduce the incidence of cervical cancer more than cytology alone. Here we document the state-wide uptake of co-testing with HPV and cytology in women aged 30-64 years as recommended by national and international bodies.

METHODS: Registry-based study of all screening cytology and HPV tests in New Mexico from 2008 to 2019 among women aged 21-64 years, with a focus on cytology negative tests to distinguish co-testing from reflex HPV testing to triage equivocal or mildly abnormal cytology.

RESULTS: A total of …

Myeloid/Lymphoid Neoplasms With Flt3 Rearrangement, Guilin Tang, Wayne Tam, Nicholas J. Short, Prithviraj Bose, David Wu, Stephanie N. Hurwitz, Adam Bagg, Heesun J. Rogers, Eric D. Hsi, Andres E. Quesada, Wei Wang, Roberto N. Miranda, Carlos E. Bueso-Ramos, L Jeffrey Medeiros, Valentina Nardi, Robert P. Hasserjian, Daniel A. Arber, Attilio Orazi, Kathryn Foucar, Sa A. Wang

Pathology Research and Scholarship

Myeloid/lymphoid neoplasms (M/LN) with 13q12/FLT3 rearrangement have been suggested as candidates for possible inclusion in the World Health Organization classification group of M/LN with eosinophilia (M/LN-eo). We report 12 patients with confirmed FLT3 rearrangement, six with t(12;13)/ETV6-FLT3; one with ins(13;22)/BCR-FLT3; and five with an unconfirmed partner gene located on chromosome bands 2p16, 3q27, 5q15, 5q35, and 7q36. Disease presentations were heterogeneous, including lymphoblastic leukemia/lymphoma, myeloid sarcoma, chronic eosinophilic leukemia, chronic myelomonocytic leukemia, and myelodysplastic syndrome. However, some common features were observed, such as extramedullary involvement (n = 7, 58%), associated eosinophilia in blood, bone marrow, or tissue (n = 8, …

Current Advances In Transfusion Medicine 2020: A Critical Review Of Selected Topics By The Aabb Clinical Transfusion Medicine Committee, Elizabeth S. Allen, Claudia S. Cohn, Sara Bakhtary, Nancy M. Dunbar, Thomas Gniadek, Courtney K. Hopkins, Jessica Jacobson, Parvez M. Lokhandwala, Ryan A. Metcalf, Colin Murphy, Micah T. Prochaska, Jay S. Raval, Hua Shan, Emily K. Storch, Monica B. Pagano

Pathology Research and Scholarship

BACKGROUND: The AABB Clinical Transfusion Medicine Committee (CTMC) compiles an annual synopsis of the published literature covering important developments in the field of transfusion medicine (TM), which has been made available as a manuscript published in Transfusion since 2018.

METHODS: CTMC committee members reviewed original manuscripts including TM-related topics published electronically (ahead) or in print from December 2019 to December 2020. The selection of topics and manuscripts was discussed at committee meetings and chosen based on relevance and originality. Next, committee members worked in pairs to create a synopsis of each topic, which was then reviewed by two additional committee …

Longitudinal Assessment Of Cytokine Expression And Plasminogen Activation In Hantavirus Cardiopulmonary Syndrome Reveals Immune Regulatory Dysfunction In End-Stage Disease, Peter Simons, Yan Guo, Virginie Bondu, Susan L. Tigert, Michelle Harkins, Samuel Goodfellow, Cana Tompkins, Devon Chabot-Richards, Xuexian O. Yang, Laura Gonzalez Bosc, Steven Bradfute, Daniel A. Lawrence, Tione Buranda

Pathology Research and Scholarship

Pathogenic New World orthohantaviruses cause hantavirus cardiopulmonary syndrome (HCPS), a severe immunopathogenic disease in humans manifested by pulmonary edema and respiratory distress, with case fatality rates approaching 40%. High levels of inflammatory mediators are present in the lungs and systemic circulation of HCPS patients. Previous studies have provided insights into the pathophysiology of HCPS. However, the longitudinal correlations of innate and adaptive immune responses and disease outcomes remain unresolved. This study analyzed serial immune responses in 13 HCPS cases due to Sin Nombre orthohantavirus (SNV), with 11 severe cases requiring extracorporeal membrane oxygenation (ECMO) treatment and two mild cases. We …

Cd44 Engagement Enhances Acute Myeloid Leukemia Cell Adhesion To The Bone Marrow Microenvironment By Increasing Vla-4 Avidity, Julia C. Gutjahr, Elisabeth Bayer, Xiaobing Yu, Julia M. Laufer, Jan P. Höpner, Suzana Tesanovic, Andrea Härzschel, Georg Auer, Tanja Rieß, Astrid Salmhofer, Eva Szenes, Theresa Haslauer, Valerie Durand-Onayli, Andrea Ramspacher, Sandra P. Pennisi, Marc Artinger, Nadja Zaborsky, Alexandre Chigaev, Fritz Aberger, Daniel Neureiter, Lisa Pleyer, Daniel F. Legler, Veronique Orian-Rousseau, Richard Greil, Tanja N. Hartmann

Pathology Research and Scholarship

Adhesive properties of leukemia cells shape the degree of organ infiltration and the extent of leukocytosis. CD44 and the integrin VLA-4, a CD49d/CD29 heterodimer, are important factors of progenitor cell adhesion in bone marrow (BM). Here, we report their cooperation in acute myeloid leukemia (AML) by a novel non-classical CD44-mediated way of inside-out VLA-4 activation. In primary AML BM samples from patients and the OCI-AML3 cell line, CD44 engagement by hyaluronan induced inside-out activation of VLA-4 resulting in enhanced leukemia cell adhesion on VCAM-1. This was independent from VLA-4 affinity regulation but based on ligand-induced integrin clustering on the cell …

Depressed Right Ventricular Systolic Function In Heart Failure Due To Constrictive Pericarditis, Veena Raizada, Kimi Sato, Alaa Alashi, Arnav Kumar, Deborah Kwon, Jay Ramchand, Amy Dillenbeck, Ross E. Zumwalt, Adarsh S. Vangala, Tyler D. Earley, Allan Klein

Pathology Research and Scholarship

AIMS: Heart failure in constrictive pericarditis (CP) is attributed to impaired biventricular diastolic filling. However, diseases that cause CP due to myocardial infiltration and fibrosis can also impair biventricular systolic function (sf) and contribute to heart failure. This study of patients with CP examined biventricular sf and the effect of myocardial infiltration by pericardial diseases and the resulting fibrosis on ventricular sf.

METHODS AND RESULTS: Histopathologic examinations of right ventricular (RV) and left ventricular (LV) myocardia and pericardia were performed on three autopsied hearts of patients with pericardial diseases. Additionally, in 40 adults with clinical heart failure and 40 healthy …

Mitophagy Protein Pink1 Suppresses Colon Tumor Growth By Metabolic Reprogramming Via P53 Activation And Reducing Acetyl-Coa Production, Kunlun Yin, Jordan Lee, Zhaoli Liu, Hyeoncheol Kim, David R Martin, Dandan Wu, Meilian Liu, Xiang Xue

Pathology Research and Scholarship

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the US. Understanding the mechanisms of CRC progression is essential to improve treatment. Mitochondria is the powerhouse for healthy cells. However, in tumor cells, less energy is produced by the mitochondria and metabolic reprogramming is an early hallmark of cancer. The metabolic differences between normal and cancer cells are being interrogated to uncover new therapeutic approaches. Mitochondria targeting PTEN-induced kinase 1 (PINK1) is a key regulator of mitophagy, the selective elimination of damaged mitochondria by autophagy. Defective mitophagy is increasingly associated with various diseases including CRC. However, a …

Overcoming The Limitations Of 'Accident' As A Manner Of Death For Drug Overdose Mortality: Case For A Death Certificate Checkbox, Ian R H Rockett, Eric D. Caine, Hilary S. Connery, Kurt B. Nolte

Pathology Research and Scholarship

Collectively, the epidemic increases in the United States of opioid-related deaths and suicides during the first two decades of the 21st century have exposed shortcomings in current forensic and epidemiological approaches for determining and codifying manner of death-a vital function fulfilled by medical examiners, coroners and nosologists-the foundation for the National Violent Death Reporting System (NVDRS), an incident-based surveillance system providing individual-level information on decedent characteristics, manner, cause and circumstances of suicide, homicide and other violent injury deaths. Drug intoxication deaths are generally classified as 'accidents' or unintentional, a fundamental mischaracterisation; most arose from repetitive self-harm behaviours related to substance …

Acute Myeloid Leukemia: Therapy Resistance And A Potential Role For Tetraspanin Membrane Scaffolds, Muskan Floren, Jennifer M. Gillette

Pathology Research and Scholarship

Acute myeloid leukemia (AML) is characterized by the disruption of myeloid differentiation and accumulation of blast cells in the bone marrow. While AML patients respond favorably to induction chemotherapy, long-term outcomes remain poor due to a high rate of chemoresistance. Advances with targeted therapies, which can be used in combination with conventional chemotherapy, have expanded therapeutic options for patients. However, remission is often short-lived and followed by disease relapse and drug resistance. Therefore, there is a substantial need to improve treatment options by identifying novel molecular and cellular targets that regulate AML chemosensitivity. Membrane scaffolds such as the tetraspanin family …

Lysmd3: A Mammalian Pattern Recognition Receptor For Chitin, Xin He, Brad A. Howard, Yang Liu, Aaron K. Neumann, Liwu Li, Nidhi Menon, Tiffany Roach, Shiv D. Kale, David C. Samuels, Hongyan Li, Trenton Kite, Hirohito Kita, Tony Y. Hu, Mengyao Luo, Caroline N. Jones, Uju Joy Okaa, Diane L. Squillace, Bruce S. Klein, Christopher B. Lawrence

Pathology Research and Scholarship

Chitin, a major component of fungal cell walls, has been associated with allergic disorders such as asthma. However, it is unclear how mammals recognize chitin and the principal receptor(s) on epithelial cells that sense chitin remain to be determined. In this study, we show that LYSMD3 is expressed on the surface of human airway epithelial cells and demonstrate that LYSMD3 is able to bind chitin, as well as β-glucan, on the cell walls of fungi. Knockdown or knockout of LYSMD3 also sharply blunts the production of inflammatory cytokines by epithelial cells in response to chitin and fungal spores. Competitive inhibition …

Clinical, Immunophenotypic And Genomic Findings Of Nk Lymphoblastic Leukemia: A Study From The Bone Marrow Pathology Group, Olga K. Weinberg, Karen M. Chisholm, Chi Young Ok, Yuri Fedoriw, Bartosz Grzywacz, Jason H. Kurzer, Emily F. Mason, Karen A. Moser, Siddharth Bhattacharya, Mina Xu, Daniel Babu, Kathryn Foucar, Wayne Tam, Adam Bagg, Attilio Orazi, Tracy I. George, Wei Wang, Sa A. Wang, Daniel A. Arber, Robert P. Hasserjian

Pathology Research and Scholarship

Natural killer (NK) cells are lymphocytes of the native immune system that play a pivotal role in host defense and immune surveillance. While the conceptual view of NK-neoplasms is evolving, little is known about the rare NK lymphoblastic leukemia (NK-LL), which remains as a provisional entity in the 2016 WHO Classification. The goal of this study is to characterize NK-LL cases and compare with other CD56 co-expressing acute leukemias. We identified 105 cases, diagnosed as NK-LL (6), CD56+ acute undifferentiated leukemia (AUL) (6), CD56+ T-lymphoblastic leukemia (T-LL) (51), and CD56+ acute myeloid leukemia (AML) (42). Compared to AUL patients, NK-LL …

Secondary Cytogenetic Abnormalities In Core-Binding Factor Aml Harboring Inv(16) Vs T(8;21), Se Young Han, Krzysztof Mrózek, Jenna Voutsinas, Qian Wu, Elizabeth A. Morgan, Hanne Vestergaard, Robert Ohgami, Philip M. Kluin, Thomas Kielsgaard Kristensen, Sheeja Pullarkat, Michael Boe Møller, Ana-Iris Schiefer, Linda B. Baughn, Young Kim, David Czuchlewski, Jacobien R. Hilberink, Hans-Peter Horny, Tracy I. George, Michelle Dolan, Nam K. Ku, Cecilia Arana Yi, Vinod Pullarkat, Jessica Kohlschmidt, Amandeep Salhotra, Lori Soma, Clara D. Bloomfield, Dong Chen, Wolfgang R. Sperr, Guido Marcucci, Christina Cho, Cem Akin, Jason Gotlib, Sigurd Broesby-Olsen, Melissa Larson, Michael A. Linden, H Joachim Deeg, Gregor Hoermann, Miguel-Angel Perales, Jason L. Hornick, Mark R. Litzow, Ryotaro Nakamura, Daniel Weisdorf, Gautam Borthakur, Gerwin Huls, Peter Valent, Celalettin Ustun, Cecilia C S Yeung

Pathology Research and Scholarship

Patients with core-binding factor (CBF) acute myeloid leukemia (AML), caused by either t(8;21)(q22;q22) or inv(16)(p13q22)/t(16;16)(p13;q22), have higher complete remission rates and longer survival than patients with other subtypes of AML. However, ∼40% of patients relapse, and the literature suggests that patients with inv(16) fare differently from those with t(8;21). We retrospectively analyzed 537 patients with CBF-AML, focusing on additional cytogenetic aberrations to examine their impact on clinical outcomes. Trisomies of chromosomes 8, 21, or 22 were significantly more common in patients with inv(16)/t(16;16): 16% vs 7%, 6% vs 0%, and 17% vs 0%, respectively. In contrast, del(9q) and loss of …

Efficacy Of As04-Adjuvanted Vaccine Against Human Papillomavirus (Hpv) Types 16 And 18 In Clearing Incident Hpv Infections: Pooled Analysis Of Data From The Costa Rica Vaccine Trial And The Patricia Study, Joseph E. Tota, Frank Struyf, Allan Hildesheim, Paula Gonzalez, Martin Ryser, Rolando Herrero, John Schussler, Naveen Karkada, Ana Cecilia Rodriguez, Nicolas Folschweiller, Carolina Porras, Mark Schiffman, John T. Schiller, Wim Quint, Aimée R. Kreimer, Matti Lehtinen, Cosette M. Wheeler, Joshua N Sampson

Pathology Research and Scholarship

Clinical trial data and real-world evidence suggest that the AS04-adjuvanted vaccine targeting human papillomavirus types 16 and 18 (AS04-HPV-16/18) vaccine provides nearly 90% protection against cervical intraepithelial neoplasia grade 3 or higher irrespective of type, among women vaccinated before sexual debut. This high efficacy is not fully explained by cross-protection. Although AS04-HPV-16/18 vaccination does not affect clearance of prevalent infections, it may accelerate clearance of newly acquired infections. We pooled data from 2 large-scale randomized controlled trials to evaluate efficacy of the AS04-HPV-16/18 vaccine against clearance of nontargeted incident infections. Results of our analysis do not suggest an effect in …

Hbme1 And Ck19 Expression In Non-Invasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (Niftp) Vs Other Follicular Patterned Thyroid Lesions, Qandeel Sadiq, Radhika Sekhri, Daniel T Dibaba, Qi Zhao, Shweta Agarwal

Pathology Research and Scholarship

BACKGROUND: Thyroid neoplasms with follicular architecture can have overlapping morphologic features and pose diagnostic confusion among pathologists. Various immunohistochemical stains have been investigated as potential diagnostic markers for PTC, among which HBME1 and CK19 have gained popularity. Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) poses similar diagnostic challenges with interobserver variability and is often misdiagnosed as adenomatoid nodule or follicular adenoma. This study aims to evaluate expression of HBME1 and CK19 in NIFTPs in comparison to other well-differentiated thyroid neoplasms and benign mimickers.

METHOD: Seventy-three thyroid cases diagnosed over a period of 3 years at Methodist University Hospital, …

Covid-19 Convalescent Plasma: Interim Recommendations From The Aabb, Claudia S. Cohn, Lise Estcourt, Brenda J. Grossman, Monica B. Pagano, Elizabeth S. Allen, Evan M. Bloch, Arturo Casadevall, Dana V. Devine, Nancy M. Dunbar, Farid Foroutan, Thomas J. Gniadek, Ruchika Goel, Jed Gorlin, Michael J. Joyner, Ryan A. Metcalf, Jay S. Raval, Todd W. Rice, Beth H. Shaz, Ralph R. Vassallo, Jeffrey L. Winters, Gregory Beaudoin, Aaron A R Tobian

Pathology Research and Scholarship

No abstract provided.

Passive Immunity Trial For Our Nation (Passiton): Study Protocol For A Randomized Placebo-Control Clinical Trial Evaluating Covid-19 Convalescent Plasma In Hospitalized Adults, Wesley H. Self, Thomas G. Stewart, Allison P. Wheeler, Wissam El Atrouni, Amanda J. Bistran-Hall, Jonathan D. Casey, Vince D. Cataldo, James D. Chappell, Claudia S. Cohn, Jessica B. Collins, Mark R. Denison, Marjolein De Wit, Sheri L. Dixon, Abhijit Duggal, Terri L. Edwards, Magali J. Fontaine, Adit A. Ginde, Michelle S. Harkins, Thelma Harrington, Estelle S. Harris, Daanish Hoda, Tina S. Ipe, Stuti J. Jaiswal, Nicholas J. Johnson, Alan E. Jones, Maryrose Laguio-Vila, Christopher J. Lindsell, Jason Mallada, Manoj J. Mammen, Ryan A. Metcalf, Elizabeth A. Middleton, Simon Mucha, Hollis R. O'Neal, Sonal R. Pannu, Jill M. Pulley, Xian Qiao, Jay S. Raval, Jillian P. Rhoads, Harry Schrager, Carl Shanholtz, Nathan I. Shapiro, Stephen J. Schrantz, Isaac Thomsen, Krista K. Vermillion, Gordon R. Bernard, Todd W. Rice

Pathology Research and Scholarship

BACKGROUND: Convalescent plasma is being used widely as a treatment for coronavirus disease 2019 (COVID-19). However, the clinical efficacy of COVID-19 convalescent plasma is unclear.

METHODS: The Passive Immunity Trial for Our Nation (PassITON) is a multicenter, placebo-controlled, blinded, randomized clinical trial being conducted in the USA to provide high-quality evidence on the efficacy of COVID-19 convalescent plasma as a treatment for adults hospitalized with symptomatic disease. Adults hospitalized with COVID-19 with respiratory symptoms for less than 14 days are eligible. Enrolled patients are randomized in a 1:1 ratio to 1 unit (200-399 mL) of COVID-19 convalescent plasma that has …

Runx2 Regulates Leukemic Cell Metabolism And Chemotaxis In High-Risk T Cell Acute Lymphoblastic Leukemia, Filip Matthijssens, Nitesh D. Sharma, Monique Nysus, Christian K. Nickl, Huining Kang, Dominique R. Perez, Beatrice Lintermans, Wouter Van Loocke, Juliette Roels, Sofie Peirs, Lisa Demoen, Tim Pieters, Lindy Reunes, Tim Lammens, Barbara De Moerloose, Filip Van Nieuwerburgh, Dieter L. Deforce, Laurence C. Cheung, Rishi S. Kotecha, Martijn Dp Risseeuw, Serge Van Calenbergh, Takeshi Takarada, Yukio Yoneda, Frederik W. Van Delft, Richard B. Lock, Seth D. Merkley, Alexandre Chigaev, Larry A. Sklar, Charles G. Mullighan, Mignon L. Loh, Stuart S. Winter, Stephen P. Hunger, Steven Goossens, Eliseo F. Castillo, Wojciech Ornatowski, Pieter Van Vlierberghe, Ksenia Matlawska-Wasowska

Pathology Research and Scholarship

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with inferior outcome compared with that of B cell ALL. Here, we show that Runt-related transcription factor 2 (RUNX2) was upregulated in high-risk T-ALL with KMT2A rearrangements (KMT2A-R) or an immature immunophenotype. In KMT2A-R cells, we identified RUNX2 as a direct target of the KMT2A chimeras, where it reciprocally bound the KMT2A promoter, establishing a regulatory feed-forward mechanism. Notably, RUNX2 was required for survival of immature and KMT2A-R T-ALL cells in vitro and in vivo. We report direct transcriptional regulation of CXCR4 signaling by RUNX2, thereby promoting chemotaxis, adhesion, …

Surveillance Systems For Monitoring Cervical Cancer Elimination Efforts: Focus On Hpv Infection, Cervical Dysplasia, Cervical Screening And Treatment., Julia M L Brotherton, Cosette Wheeler, Gary M. Clifford, Miriam Elfström, Marion Saville, John Kaldor, Dorothy A. Machalek

Pathology Research and Scholarship

In order to achieve the global elimination of cervical cancer as a public health problem, close surveillance of progress in public health and clinical activities and outcomes across the three pillars of vaccination, screening and treatment will be required. Surveillance should ideally occur within an integrated system that is planned, funded, and regularly evaluated to ensure it is providing timely, accurate and relevant feedback for action. In this paper, we conceptualise the main public health surveillance objectives as process and outcome measures in each of the three pillars. Process measures include coverage/participation measures for vaccination, screening and treatment alongside the …

Optimizing The Use Of Telemedicine In Oncology Care: Postpandemic Opportunities, Karen E. Knudsen, Cheryl Willman, Robert Winn

Pathology Research and Scholarship

Utilization of telehealth as part of the cancer care delivery continuum dramatically escalated in response to the COVID-19 pandemic at major cancer centers across the globe. The rapid shift toward telehealth visits for nontreatment cancer care provided immediate benefit through reducing unnecessary risk of exposure, overcoming transportation barriers faced by both patients and caregivers, and fast-tracking care transformation. As such, delineating the impact of telehealth on access, health equity, quality, and outcomes will be essential for refining the use of digital strategies and telehealth toward optimizing cancer care. Herein, experiences to date with telehealth usage for oncology care are reviewed, …

Mathematical Modeling Of The Impact Of Recirculation On Exchange Kinetics In Tandem Extracorporeal Membrane Oxygenation And Therapeutic Plasma Exchange, Charles Puelz, Jonathan L. Marinaro, Yara A. Park, Boyce E. Griffith, Charles S. Peskin, Jay S. Raval

Pathology Research and Scholarship

Vascular access connection configurations during tandem extracorporeal membrane oxygenation (ECMO) and therapeutic plasma exchange (TPE) may impact exchange kinetics. In these tandem procedures, typically the TPE inlet line is proximal to the TPE return line with respect to blood flow in the ECMO device, maximizing the opportunity for replacement fluid homogenization within the ECMO circuit. However, if TPE inlet and return line connections are switched, recirculation-a phenomenon in which replacement fluid leaving the TPE return line is prematurely drawn into the TPE inlet line prior to satisfactory homogenization within the ECMO circuit-will occur. Such recirculation could diminish TPE efficacy in …

A Randomized Control Trial To Test A Peer Support Group Approach For Reducing Social Isolation And Depression Among Female Mexican Immigrants, Janet Page-Reeves, Cristina Murray-Krezan, Lidia Regino, Jackie Perez, Molly Bleecker, Daniel Perez, Bill Wagner, Susan Tigert, Elaine L. Bearer, Cathleen E. Willging

Pathology Research and Scholarship

BACKGROUND: Female Mexican Immigrants (FMIs) experience high rates of depression compared with other populations. For this population, depression is often exacerbated by social isolation associated with the experience of immigration. Aim 1. To measure whether a culturally situated peer group intervention will reduce depression and stress associated with the experience of immigration. Aim 2. To test whether an intervention using a "women's funds of knowledge" approach results in improved resilience, knowledge and empowerment. Aim 3. To investigate whether a culturally situated peer group intervention using a women's funds of knowledge approach can give participants a sense and experience of social …