Digital Commons Network^™

Digital Image Analysis For The Detection Of Group B Streptococcus From Chromid Strepto B Medium Using Phenomatrix Algorithms, Justin Baker, Karen Timm, Matthew Faron, Nathan Ledeboer, Karissa Culbreath

Pathology Research and Scholarship

Group B Streptococcus (GBS) can be found to colonize about 25% of all healthy, adult women and is the leading infectious cause of early neonatal morbidity and mortality in the United States. This study evaluated the clinical performance of PhenoMatrix (PM) chromogenic detection module (CDM) digital imaging software in detection of GBS from LIM broth plated on ChromID Strepto B chromogenic medium (ChromID) using the WASP automated processor. The performance of the PM CDM was compared to manual culture review of the digital images and molecular detection of GBS. ChromID alone had a sensitivity and specificity of 84.5% and 94.7%, …

Analytical And Clinical Sample Performance Characteristics Of The Onclarity Assay For The Detection Of Human Papillomavirus, Stephen Young, Laurence Vaughan, Karen Yanson, Karen Eckert, Aojun Li, James Harris, Aaron Ermel, James A. Williams, Mohammad Al-Ghoul, Catherine L. Cammarata, Stephanie N. Taylor, Ronald Luff, Charles K. Cooper, Barbara Van Der Pol

Pathology Research and Scholarship

The objective of this study was to determine the result reproducibility and performance of the BD Onclarity human papillomavirus (HPV) assay (Onclarity) on the BD Viper LT platform using both contrived and clinical specimens. Reproducibility was assessed in BD SurePath liquid-based cytology (LBC) medium (SurePath) using contrived panels (HPV genotype 16 [HPV16] positive, HPV18 positive, or HPV45 positive) or clinical specimens (HPV16, -18, -31, -33/58, -45, or -52 positive or HPV negative). In addition, specimens from 3,879 individuals from the Onclarity trial were aliquoted prior to or following cytology processing and tested for HPV. Finally, specimens were collected using either …

Evolution Of The Epigenetic Landscape In Childhood B Acute Lymphoblastic Leukemia And Its Role In Drug Resistance, Shella Saint Fleur-Lominy, Nikki A. Evensen, Teena Bhatla, Gunjan Sethia, Sonali Narang, Jun H. Choi, Xiaotu Ma, Jun J. Yang, Stephen Kelly, Elizabeth Raetz, Richard C. Harvey, Cheryl Willman, Mignon L. Loh, Stephen P. Hunger, Patrick A. Brown, Kylie M. Getz, Cem Meydan, Christopher E. Mason, Aristotelis Tsirigos, William Carroll

Pathology Research and Scholarship

Although B-cell acute lymphoblastic leukemia (B-ALL) is the most common malignancy in children and while highly curable, it remains a leading cause of cancer-related mortality. The outgrowth of tumor subclones carrying mutations in genes responsible for resistance to therapy has led to a Darwinian model of clonal selection. Previous work has indicated that alterations in the epigenome might contribute to clonal selection, yet the extent to which the chromatin state is altered under the selective pressures of therapy is unknown. To address this, we performed chromatin immunoprecipitation, gene expression analysis, and enhanced reduced representation bisulfite sequencing on a cohort of …

A State-Wide Population-Based Evaluation Of Cervical Cancers Arising During Opportunistic Screening In The United States, Christopher Mathews, Michael Robertson, Charles L. Wiggins, Yolanda J. Mcdonald, Daniel W. Goldberg, Isabel C. Scarinci, Jack Cuzick, Cosette M Wheeler, Rebecca Landy, Peter D. Sasieni

Pathology Research and Scholarship

OBJECTIVE: Despite widespread cervical screening, an estimated 13,800 women will be diagnosed with cervical cancer in the United States in 2020. To inform improvements, the screening histories of women diagnosed with cervical cancer in New Mexico were assessed.

METHODS: Data were collected on all cervical screening, diagnostic tests and treatment procedures for all women diagnosed with cervical cancer aged 25-64 yrs. in New Mexico from 2006 to 2016. Women were categorized by their screening attendance in the 5-40 months (screening interval) and 1-4 months (peri-diagnostic interval) prior to cancer diagnosis.

RESULTS: Of the 504 women diagnosed between May 2009-December 2016, …

Transfusion Of Blood Components Containing Abo-Incompatible Plasma Does Not Lead To Higher Mortality In Civilian Trauma Patients, Jansen N. Seheult, Nancy M. Dunbar, John R. Hess, Erin E. Tuott, Mohammad Bahmanyar, Jessica Campbell, Magali Fontaine, Jenna Khan, Ara Ko, Jian Mi, Michael F. Murphy, Tara Nykoluk, Jessica Poisson, Jay S. Raval, Andrew Shih, Jason L. Sperry, Julie Staves, Michelle Wong, Matthew T S Yan, Alyssa Ziman, Mark H. Yazer

Pathology Research and Scholarship

BACKGROUND: This study investigated the effect on mortality of transfusing ABO-incompatible plasma from all sources during trauma resuscitation.

METHODS: Demographic, transfusion, and survival data were retrospectively extracted on civilian trauma patients. Patients were divided by receipt of any quantity of ABO-incompatible plasma from any blood product (incompatible group) or receipt of solely ABO-compatible plasma (compatible group). The primary outcome was 30-day mortality, while other outcomes included 6- and 24-hour mortality. Mixed-effects logistic regression was used to model the effect of various predictor variables, including receipt of incompatible plasma, on mortality outcomes.

RESULTS: Nine hospitals contributed data on a total of …

Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Antibody Titers In Convalescent Plasma And Recipients In New Mexico: An Open Treatment Study In Patients With Coronavirus Disease 2019, Steven B. Bradfute, Ivy Hurwitz, Alexandra V. Yingling, Chunyan Ye, Qiuying Cheng, Timothy P Noonan, Jay S. Raval, Nestor R. Sosa, Gregory J. Mertz, Douglas J. Perkins, Michelle S. Harkins

Pathology Research and Scholarship

BACKGROUND: Convalescent plasma (CP) is a potentially important therapy for coronavirus disease 2019 (COVID-19). However, knowledge regarding neutralizing antibody (NAb) titers in donor plasma and their impact in patients with acute COVID-19 remains largely undetermined. We measured NAb titers in CP and in patients with acute COVID-19 before and after transfusion through the traditional Food and Drug Administration investigational new drug pathway.

METHODS: We performed a single-arm interventional trial measuring NAb and total antibody titers before and after CP transfusion over a 14-day period in hospitalized patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection.

RESULTS: NAb titers in …

Unrecognised Self-Injury Mortality (Sim) Trends Among Racial/Ethnic Minorities And Women In The Usa, Ian R H Rockett, Eric D. Caine, Hilary S. Connery, Kurt B. Nolte, Paul S. Nestadt, Lewis S. Nelson, Haomiao Jia

Pathology Research and Scholarship

AIM: To assess whether an enhanced category combining suicides with non-suicide drug self-intoxication fatalities more effectively captures the burden of self-injury mortality (SIM) in the USA among US non-Hispanic black and Hispanic populations and women irrespective of race/ethnicity.

METHODS: This observational study used deidentified national mortality data for 2008-2017 from the CDC's

RESULTS: While the suicide rate increased by 29% for blacks, 36% for Hispanics and 25% for non-Hispanic whites between 2008 and 2017, corresponding SIM rate increases were larger at 109%, 69% and 55% (p

CONCLUSION: Application of SIM exposed substantial excess burdens from substance poisoning relative to suicide …

At Three Years, Patients With Acute Lymphoblastic Leukaemia Are Still At Risk For Relapse. Results Of The International Mrc Ukallxii/Ecog E2993 Trial, Chezi Ganzel, Xin V. Wang, Jacob M. Rowe, Susan M. Richards, Georgina Buck, David I. Marks, Mark R. Litzow, Elisabeth M. Paietta, Letizia Foroni, Selina M. Luger, Cheryl L. Willman, Charles G. Mullighan, Kathryn G. Roberts, Peter H. Wiernik, Dan Douer, Hillard M. Lazarus, Martin S. Tallman, Anthony H. Goldstone

Pathology Research and Scholarship

Late relapse [>3 years from complete remission (CR)] in acute lymphoblastic leukaemia (ALL), is unusual. Data from the MRC UKALLXII/ECOG E2993 trial are presented to evaluate the incidence and characteristics of late relapse in adult ALL. Of 1,909 patients, 1,752 (92%) achieved CR and among these 757 (43·2%) relapsed; 691 (91·3%) within three years and 66 (8·7%) beyond. Among these 66 patients, median time to relapse was 47 (37-144) months. Relapse beyond three years occurred in 3·8% of all who achieved CR. The cumulative risk of relapse was 40%, 43% and 45% at three, five and ten years respectively. …

Antibodies To Variable Domain 4 Linear Epitopes Of The Chlamydia Trachomatis Major Outer Membrane Protein Are Not Associated With Chlamydia Resolution Or Reinfection In Women, Amanda L. Collar, Alexandria C. Linville, Susan B. Core, Cosette M. Wheeler, William M. Geisler, David S. Peabody, Bryce Chackerian, Kathryn M. Frietze

Pathology Research and Scholarship

Chlamydia trachomatis is an obligate intracellular bacterium. C. trachomatis infection is the most prevalent bacterial sexually transmitted infection and can lead to pelvic inflammatory disease and infertility in women. There is no licensed vaccine for C. trachomatis prevention, in part due to gaps in our knowledge of C. trachomatis-specific immune responses elicited during human infections. Previous investigations of the antibody response to C. trachomatis have identified immunodominant antigens and antibodies that can neutralize infection in cell culture. However, epitope-specific responses to C. trachomatis are not well characterized, and the impact of these antibodies on infection outcome is unknown. We …

Minimizing Surgical Blood Loss At Cesarean Hysterectomy For Placenta Previa With Evidence Of Placenta Increta Or Placenta Percreta: The State Of Play In 2020, John C. Kingdom, Sebastian R. Hobson, Ally Murji, Lisa Allen, Rory C. Windrim, Evelyn Lockhart, Sally L. Collins, Hooman Soleymani Majd, Moiad Alazzam, Feras Naaisa, Alireza A. Shamshirsaz, Michael A. Belfort, Karin A. Fox

Pathology Research and Scholarship

The evolution of multidisciplinary team-based care for women with placenta accreta spectrum disorder has delivered stepwise improvements in clinical outcomes. Central to this overall goal is the ability to limit blood loss at surgery. Placement of inflatable balloons within the pelvic arteries, most commonly in the anterior divisions of the internal iliac arteries, became popular in many centers, at the expense of prolonging surgical care and with attendant risks of vascular injury. In tandem, the need to expose pelvic sidewall anatomy to safely identify the course of the ureters re-popularized the alternative strategy of ligating the same anterior divisions of …

Ascites In The "Tafro" Syndrome: Does The Squeeze Make The Juice, Aamer Abbass, Sameen Khalid, Laura Toth, Steven Eberhardt, Denis Mccarthy

Pathology Research and Scholarship

A 41-year-old healthy female underwent cholecystectomy due to symptomatic gallstone related acute cholecystitis. A week later she was readmitted with fatigue, low grade fever, worsening pallor, generalized edema including bilateral leg swelling and abdominal distension with pain. Laboratory evaluation showed mild normocytic anemia (Hgb 7 g/dL [12–16 g/dL]), mean corpuscular volume 92 fL (80–100 fL), mild leukocytosis with WBC count 12,000/µL (4000–11,000/µL), thrombocytopenia (platelet count 55,000/µL [150,000–400,000/µL]). Comprehensive metabolic panel showed normal serum electrolytes, blood urea nitrogen, creatinine, and liver profile, except for low serum total protein of 5.1 g/dL (6.1–8.2 g/dL) and hypoalbuminemia (albumin 2.4 g/dL [3.4–4.7 g/dL]). Urinalysis …

Covid-19: Postmortem Diagnostic And Biosafety Considerations, J Matthew Lacy, Erin G. Brooks, Joshua Akers, Danielle Armstrong, Lauren Decker, Adam Gonzalez, William Humphrey, Romana Mayer, Matthew Miller, Catherine Perez, Jose Antonio Ruiz Arango, Lakshmanan Sathyavagiswaran, Wendy Stroh, Suzanne Utley

Pathology Research and Scholarship

As a result of the 2019 novel human coronavirus (COVID-19) global spread, medical examiner/coroner offices will inevitably encounter increased numbers of COVID-19-infected decedents at autopsy. While in some cases a history of fever and/or respiratory distress (eg, cough or shortness of breath) may suggest the diagnosis, epidemiologic studies indicate that the majority of individuals infected with COVID-19 develop mild to no symptoms. Those dying with-but not of-COVID-19 may still be infectious, however. While multiple guidelines have been issued regarding autopsy protocol in cases of suspected COVID-19 deaths, there is some variability in the recommendations. Additionally, limited recommendations to date have …

Postmortem Computed Tomography In Firearm Homicides: A Retrospective Case Series, Marloes E M Vester, Kurt B Nolte, Gary M. Hatch, Chandra Y. Gerrard, Reinoud D. Stoel, Rick R. Van Rijn

Pathology Research and Scholarship

Postmortem computed tomography (PMCT) is integrated into the evaluation of decedents in several American medical examiner offices and medicolegal death investigative centers in many other countries. We retrospectively investigated the value of PMCT in a series of firearm homicide cases from a statewide centralized medical examiner's office that occurred during 2016. Autopsies were performed or supervised by board-certified forensic pathologists who reviewed the PMCT scans prior to autopsy. PMCT scans were re-evaluated by a forensic radiologist blinded to the autopsy findings and scored by body region (head-neck, thoracoabdominal, and extremities). Injury discrepancies were scored using a modified Goldman classification and …

Adjunctive Testing By Cytology, P16/Ki-67 Dual-Stained Cytology Or Hpv16/18 E6 Oncoprotein For The Management Of Hpv16/18 Screen-Positive Women, Leticia Torres-Ibarra, Attila T. Lorincz, Cosette M. Wheeler, Jack Cuzick, Rubí Hernández-López, Donna Spiegelman, Leith León-Maldonado, Berenice Rivera-Paredez, Pablo Méndez-Hernández, Eduardo Lazcano-Ponce, Jorge Salmerón

Pathology Research and Scholarship

High-risk human papillomavirus type 16/18 (HPV16/18) genotyping is unable to accurately discriminate nonprogressive infections from those that will progress to cervical cancer. Our study aimed to assesses if additional testing either with liquid-based cytology (LBC) or the putative progression markers p16/Ki-67 and HPV16/18 E6 oncoprotein (E6) can improve the efficiency of HPV16/18 genotyping for triaging high-risk HPV (hrHPV)-positive women through better cancer risk stratification. Women attending colposcopy after positive HPV16/18 genotyping results within the Forwarding Research for Improved Detection and Access for Cervical Cancer Screening and Triage (FRIDA) hrHPV-based screening study in Tlaxcala, Mexico, underwent further testing with LBC, p16/Ki-67 …

Therapeutic Plasma Exchange Taper Does Not Decrease Exacerbations In Immune Thrombotic Thrombocytopenic Purpura Patients, Jay S. Raval, Marshall A. Mazepa, Marian A. Rollins-Raval, Raj S. Kasthuri, Yara A. Park

Pathology Research and Scholarship

BACKGROUND: Despite rapid and intensive treatments with therapeutic plasma exchange (TPE) and immunosuppression, immune thrombotic thrombocytopenic purpura (TTP) patients are at risk of disease exacerbation, i.e., early recurrence of TTP within 30 days of achieving treatment response. TPE taper, a practice of performing additional TPE procedures after achieving treatment response, is commonly performed for decreasing exacerbations, although no evidence supports this practice.

STUDY DESIGN AND METHODS: In this prospective observational investigation over four years, our center switched its standard of care for treating all TTP patients from not performing TPE taper after achieving treatment response (i.e., no-taper cohort) to performance …

Sars-Cov-2 Reverse Genetics Reveals A Variable Infection Gradient In The Respiratory Tract, Yixuan J. Hou, Kenichi Okuda, Caitlin E. Edwards, David R. Martinez, Takanori Asakura, Kenneth H. Dinnon, Takafumi Kato, Rhianna E. Lee, Boyd L. Yount, Teresa M. Mascenik, Gang Chen, Kenneth N. Olivier, Andrew Ghio, Longping V. Tse, Sarah R. Leist, Lisa E. Gralinski, Alexandra Schäfer, Hong Dang, Rodney Gilmore, Satoko Nakano, Ling Sun, M Leslie Fulcher, Alessandra Livraghi-Butrico, Nathan I. Nicely, Mark Cameron, Cheryl Cameron, David J. Kelvin, Aravinda De Silva, David M. Margolis, Alena Markmann, Luther Bartelt, Ross Zumwalt, Fernando J. Martinez, Steven P. Salvatore, Alain Borczuk, Purushothama R. Tata, Vishwaraj Sontake, Adam Kimple, Ilona Jaspers, Wanda K. O'Neal, Scott H. Randell, Richard C. Boucher, Ralph S. Baric

Pathology Research and Scholarship

The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 …

Clinicopathologic Implications Of Myb And Beta-Catenin Expression In Adenoid Cystic Carcinoma, Susan Park, Manali Vora, Annemieke Van Zante, Joseph Humtsoe, Hyun-Su Kim, Sue Yom, Shweta Agarwal, Patrick Ha

Pathology Research and Scholarship

BACKGROUND: Adenoid cystic carcinoma (ACC) is the second most common malignancy of the salivary glands, accounting for ~ 1% of malignant tumors of the head and neck region and 10% of salivary gland neoplasms. Predicting the long-term outcomes of patients with ACC is still challenging, as reliable prognostic biomarkers are not available. Among salivary gland tumors, Myb overexpression is highly specific for ACC. In addition, the MYB-NF1B fusion translocation is a hallmark of ACC, and although the detection of this translocation does not appear to impact prognosis, the MYB-NF1B fusion is also implicated in MYB upregulation. Myb has recently been …

Comparison Of Tissue Molecular Biomarker Testing Turnaround Times And Concordance Between Standard Of Care And The Biocartis Idylla Platform In Patients With Colorectal Cancer, Gregory J. Tsongalis, M Rabie Al Turkmani, Michael Suriawinata, Michael J. Babcock, Kristi Mitchell, Yi Ding, Lisa Scicchitano, Adrian Tira, Lela Buckingham, Sara Atkinson, Amy Lax, Dara L. Aisner, Kurtis D. Davies, Holly N. Wood, Stacey S. O'Neill, Edward A. Levine, Judy Sequeira, Shuko Harada, Gina Defrank, Ravikumar Paluri, Bradford A. Tan, Heather Colabella, Christopher Snead, Marcia Cruz-Correa, Virginia Ramirez, Arnaldo Rojas, Huiya Huang, Alexander C. Mackinnon, Fernando U. Garcia, Sharon M. Cavone, Mutasim Elfahal, Gyorgy Abel, Mohammad A. Vasef, Andrew Judd, Mark W. Linder, Khaled Alkhateeb, William L. Skinner, Ralph Boccia, Kashyap Patel

Pathology Research and Scholarship

OBJECTIVES: Management of colorectal cancer warrants mutational analysis of KRAS/NRAS when considering anti-epidermal growth factor receptor therapy and BRAF testing for prognostic stratification. In this multicenter study, we compared a fully integrated, cartridge-based system to standard-of-care assays used by participating laboratories.

METHODS: Twenty laboratories enrolled 874 colorectal cancer cases between November 2017 and December 2018. Testing was performed on the Idylla automated system (Biocartis) using the KRAS and NRAS-BRAF cartridges (research use only) and results compared with in-house standard-of-care testing methods.

RESULTS: There were sufficient data on 780 cases to measure turnaround time compared with standard assays. In-house polymerase chain …

Age-Adjusted D-Dimer Cutoffs: A Warning From The Laboratory, Marian A. Rollins-Raval, Richard A. Marlar, Andrew J. Goodwin

Pathology Research and Scholarship

D-dimer assays have been Food and Drug Administration (FDA)–approved or cleared for results below a manufacturer-defined cutoff in conjunction with low or intermediate pretest clinical probability to rule out venous thromboembolism.¹ Given apparent overall increase of D-dimer level with age, clinical guidelines have recommended application of an age-adjusted D-dimer–level cutoff to exclude suspected pulmonary embolus specifically in patients with low or intermediate pretest clinical probability.^2,3 Despite additional studies and literature availble, these guidelines themselves rest solely on the Age-Adjusted D-Dimer Cutoff Levels to Rule Out Pulmonary Embolism: The ADJUST-PE Study,⁴ applying an age-adjusted D-dimer–level …

Relationships Of P16 Immunohistochemistry And Other Biomarkers With Diagnoses Of Cervical Abnormalities: Implications For Last Terminology, Philip E. Castle, Rachael Adcock, Jack Cuzick, Nicolas Wentzensen, Norah E. Torrez-Martinez, Salina M. Torres, Mark H. Stoler, Brigitte M. Ronnett, Nancy E. Joste, Teresa M. Darragh, Patti E. Gravitt, Mark Schiffman, William C. Hunt, Walter K. Kinney, Cosette M. Wheeler

Pathology Research and Scholarship

CONTEXT.—: Lower Anogenital Squamous Terminology (LAST) standardization recommended p16

OBJECTIVE.—: To describe the relationships of p16 IHC and other biomarkers associated with cervical cancer risk with biopsy diagnoses.

DESIGN.—: A statewide, stratified sample of cervical biopsies diagnosed by community pathologists (CPs), including 1512 CIN2, underwent a consensus, expert pathologist panel (EP) review (without p16 IHC results), p16 IHC interpretation by a third pathology group, and human papillomavirus (HPV) genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytologic interpretations were also available.

RESULTS.—: Biopsies were more likely to test p16 IHC positive with increasing severity of CP …

Traumatic Injury Results In Prolonged Circulation Of Ultralarge Von Willebrand Factor And A Reduction In Adamts13 Activity, Mitchell R. Dyer, William E. Plautz, Margaret V. Ragni, Wyeth Alexander, Shannon Haldeman, Jason L. Sperry, Francis X. Guyette, Brian S. Zuckerbraun, Marian A. Rollins-Raval, Jay S. Raval, Matthew D. Neal

Pathology Research and Scholarship

BACKGROUND: Increases in plasma von Willebrand Factor (VWF) levels, accompanied by decreases in the metalloprotease ADAMTS13, have been demonstrated soon after traumatic injury while downstream effects remain unclear.

STUDY DESIGN AND METHODS: A cohort of 37 injured trauma patients from a randomized control trial investigating the use of prehospital plasma transfusion were analyzed for activity and antigen levels of ADAMTS13 and VWF at 0 and 24 hours after admission. Relevant clinical data were abstracted from the medical records. Trauma patient plasma was analyzed via agarose gel electrophoresis to evaluate the effects of injury on VWF multimer composition compared to healthy …

Tetraspanin Cd82 Drives Acute Myeloid Leukemia Chemoresistance By Modulating Protein Kinase C Alpha And Β1 Integrin Activation, Muskan Floren, Sebastian Restrepo Cruz, Christina M. Termini, Kristopher D. Marjon, Keith A. Lidke, Jennifer M. Gillette

Pathology Research and Scholarship

A principal challenge in treating acute myeloid leukemia (AML) is chemotherapy refractory disease. As such, there remains a critical need to identify key regulators of chemotherapy resistance in AML. In this study, we demonstrate that the membrane scaffold, CD82, contributes to the chemoresistant phenotype of AML. Using an RNA-seq approach, we identified the increased expression of the tetraspanin family member, CD82, in response to the chemotherapeutic, daunorubicin. Analysis of the TARGET and BEAT AML databases identifies a correlation between CD82 expression and overall survival of AML patients. Moreover, using a combination of cell lines and patient samples, we find that …

Total Plasma Volume Determinations For Patients With Potentially Challenging Conditions Requiring Therapeutic Plasma Exchange: Dealer's Choice, Lizabeth Rosenbaum, Mindi Johnson, Marissa Li, Jay S. Raval

Pathology Research and Scholarship

LETTER TO THE EDITORTotal plasma volume determinations for patients withpotentially challenging conditions requiring therapeuticplasma exchange: Dealer's choiceTo the Editor:Determination of total blood volume (TBV) and totalplasma volume (TPV) are essential steps in the process ofinitiating therapeutic plasma exchange (TPE).1Regardlessof the specific disease for which a procedure is to be per-formed, apheresis instruments typically require height,weight, sex, and hematocrit data to calculate TPV. For rou-tine patients, these calculations are generally straightfor-ward to perform and are accurate. However, certainconditions raise the concern of possibly inaccurate TPVdeterminations. These potentially challenging conditionsinclude obesity, pregnancy, and limb amputation. Despitenumerous modifications available to typical TBV and …

Association Of Immunophenotype With Expression Of Topoisomerase Ii Α And Β In Adult Acute Myeloid Leukemia, Andrew P. Michelson, Shannon Mcdonough, Cheryl L. Willman, Eric R. Koegle, John E. Godwin, Stephen H. Petersdorf, Alan F. List, Megan Othus, Frederick R. Appelbaum, Jerald P. Radich, Mahrukh K. Ganapathi, Anjali S. Advani, Ram N. Ganapathi

Pathology Research and Scholarship

Anthracyclines used in the treatment of acute myelogenous leukemia (AML) inhibit the activity of the mammalian topoisomerase II (topo II) isoforms, topo II α and topo IIβ. In 230 patients with non-M3 AML who received frontline ara-C/daunorubicin we determined expression of topo IIα and topo IIβ by RT-PCR and its relationship to immunophenotype (IP) and outcomes. Treatment outcomes were analyzed by logistic or Cox regression. In 211 patients, available for analysis, topo IIα expression was significantly lower than topo IIβ (P < 0.0001). In contrast to topo IIα, topo IIβ was significantly associated with blast percentage in marrow or blood (P = 0.0001), CD7 (P = 0.01), CD14 (P < 0.0001) and CD54 (P < 0.0001). Event free survival was worse for CD56-negative compared to CD56-high (HR = 1.9, 95% CI [1.0-3.5], p = 0.04), and overall survival was worse for CD-15 low as compared to CD15-high (HR = 2.2, 95% CI [1.1-4.2], p = 0.02). Ingenuity pathway analysis indicated topo IIβ and immunophenotype markers in a network associated with cell-to-cell signaling, hematological system development/function and inflammatory response. Topo IIβ expression reflects disease biology of highly proliferative disease and distinct IP but does not appear to be an independent variable influencing outcome in adult AML patients treated with anthracycline-based therapy.

Drug Resistance Of Previously Treated Tuberculosis Patients With Diabetes Mellitus In Shandong, China, Wan-Mei Song, Yi-Fan Li, Jin-Yue Liu, Ning-Ning Tao, Yao Liu, Qian-Yun Zhang, Ting-Ting Xu, Shi-Jin Li, Qi-Qi An, Si-Qi Liu, Chun-Bao Yu, Lei Gao, Cui-Xiang Yu, Min Zhang, Huai-Chen Li

Pathology Research and Scholarship

BACKGROUND: Although the association between diabetes mellitus (DM) and tuberculosis (TB) has been well-documented for centuries, evidence of the link between diabetes and drug resistance among previously treated TB patients remains limited and inconsistent.

METHODS: An observational study was performed that involved 1791 retreated TB-no DM patients (refers to TB cases without diabetes) and 93 retreated TB-DM patients (refers to TB cases with diabetes) in Shandong, China from 2004 to 2017. Baseline data including demographic and clinical characteristics, drug susceptibility test (DST) results, and diabetes status were collected. Categorical baseline characteristics were compared by Fisher's exact or Pearson Chi-square test. …

Evaluating Screening Participation, Follow-Up, And Outcomes For Breast, Cervical, And Colorectal Cancer In The Prospr Consortium, William E. Barlow, Elisabeth F. Beaber, Berta M. Geller, Aruna Kamineni, Yingye Zheng, Jennifer S. Haas, Chun R. Chao, Carolyn M. Rutter, Ann G. Zauber, Brian L. Sprague, Ethan A. Halm, Donald L. Weaver, Jessica Chubak, V Paul Doria-Rose, Sarah Kobrin, Tracy Onega, Virginia P. Quinn, Marilyn M. Schapira, Anna N A Tosteson, Douglas A. Corley, Celette Sugg Skinner, Mitchell D. Schnall, Katrina Armstrong, Cosette M. Wheeler, Michael J. Silverberg, Bijal A. Balasubramanian, Chyke A. Doubeni, Dale Mclerran, Jasmin A. Tiro

Pathology Research and Scholarship

BACKGROUND: Cancer screening is a complex process encompassing risk assessment, the initial screening examination, diagnostic evaluation, and treatment of cancer precursors or early cancers. Metrics that enable comparisons across different screening targets are needed. We present population-based screening metrics for breast, cervical, and colorectal cancers for nine sites participating in the Population-based Research Optimizing Screening through Personalized Regimens consortium.

METHODS: We describe how selected metrics map to a trans-organ conceptual model of the screening process. For each cancer type, we calculated calendar year 2013 metrics for the screen-eligible target population (breast: ages 40-74 years; cervical: ages 21-64 years; colorectal: ages …

Sclerosing Epithelioid Mesenchymal Neoplasm Of The Pancreas - A Proposed New Entity, Olca Basturk, Britta Weigelt, Volkan Adsay, Jamal K Benhamida, Gokce Askan, Lu Wang, Maria E. Arcila, Giuseppe Zamboni, Noriyoshi Fukushima, Rodrigo Gularte-Mérida, Arnaud Da Cruz Paula, Pier Selenica, Rahul Kumar, Fresia Pareja, Christopher A. Maher, John Scholes, Yoshinao Oda, Donatella Santini, Leona A. Doyle, Iver Petersen, Uta Flucke, Christian Koelsche, Samuel J. Reynolds, Aslihan Yavas, Andreas Von Deimling, Jorge S. Reis-Filho, David S. Klimstra

Pathology Research and Scholarship

We have encountered pancreatic tumors with unique histologic features, which do not conform to any of the known tumors of the pancreas or other anatomical sites. We aimed to define their clinicopathologic features and whether they are characterized by recurrent molecular signatures. Eight cases were identified; studied histologically and by immunohistochemistry. Selected cases were also subjected to whole-exome sequencing (WES; n = 4), RNA-sequencing (n = 6), Archer FusionPlex assay (n = 5), methylation profiling using the Illumina MethylationEPIC (850k) array platform (n = 6), and TERT promoter sequencing (n = 5). Six neoplasms occurred in females. The mean age …

Hobnail Cells In Encapsulated Papillary Thyroid Carcinoma: Report Of 2 Cases With Immunohistochemical And Molecular Findings And Literature Analysis, Shweta Agarwal, Qandeel Sadiq, Ibrahim Ortanca

Pathology Research and Scholarship

Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland with most tumors behaving in an indolent fashion. However, morphologic variants have been described, such as tall cell, diffuse sclerosing, columnar cell etc. which are biologically more aggressive. One of these variants includes the more recently described hobnail variant (HVPTC) which shows micropapillae and presence of large cells with apically placed hyperchromatic nuclei, reverse polarity, and eosinophilic cytoplasm, akin to hobnail cells. The presence of >30% hobnail cells in a PTC deserves categorization as a hobnail variant. This variant is usually associated with extra thyroidal extension, …

The Impact Of An Undergraduate Biology Class On Donor Recruitment At A Hospital-Based Blood Donor Center, Alexis R. Peedin, Yara A. Park, Marshall A. Mazepa, Thomas Neish, Jay S. Raval, R Chad Siniard

Pathology Research and Scholarship

OBJECTIVES: A biology class, BIOL 294H, taught undergraduates about platelet donation while partnering with the University of North Carolina's (UNC's) hospital-based Blood Donation Center to recruit apheresis platelet donors. We identified our platelet donors' demographics and learned how BIOL 294H affected recruitment.

METHODS: Every platelet donor presenting to the UNC Blood Donation Center from February 7, 2017, to March 10, 2017, was asked to complete an electronic 10-question survey.

RESULTS: A total of 159 unique donors completed the survey; 64% were female and 75% were between ages 18 and 25 years. Overall, 70% were UNC undergraduate students. Over half (56%) …

Heparin-Induced Thrombocytopenia Associated With Collection Of Hematopoietic Progenitor Cells By Apheresis, Jay S. Raval, Yara A. Park, Irina Perjar, Marshall A. Mazepa, Benjamin G. Vincent, Alice D. Ma, Marian A. Rollins-Raval

Pathology Research and Scholarship

Heparin-induced thrombocytopenia (HIT) can occur following exposure to heparin and is characterized by thrombocytopenia with increased risk for thrombosis. This condition is mediated by formation of immunoglobulin G antibodies against platelet factor 4/heparin complexes that can subsequently lead to platelet activation. Herein, we detail the clinical and laboratory findings, treatments, and outcomes of two patients who developed HIT and thrombosis after undergoing collection of hematopoietic progenitor cells by apheresis (HPC-A) for autologous HPC transplant. Given that heparin may be used during HPC-A collections, these cases emphasize the importance of prompt consideration of HIT in patients that develop thrombocytopenia and thrombosis …