Pathology Commons^™

Urine Alcam, Pf4 And Vcam-1 Surpass Conventional Metrics In Identifying Nephritis Disease Activity In Childhood-Onset Systemic Lupus Erythematosus, Samar A Soliman, Anam Haque, Kamala Vanarsa, Ting Zhang, Faten Ismail, Kyung Hyun Lee, Claudia Pedroza, Larry A Greenbaum, Sherene Mason, M John Hicks, Scott E Wenderfer, Chandra Mohan

Faculty, Staff and Students Publications

OBJECTIVES: Serial kidney biopsy for repeat evaluation and monitoring of lupus nephritis (LN) in childhood-onset Systemic Lupus Erythematosus (cSLE) remains challenging, thus non-invasive biomarkers are needed. Here, we evaluate the performance of ten urine protein markers of diverse nature including cytokines, chemokines, and adhesion molecules in distinguishing disease activity in cSLE.

METHODS: Eighty-four pediatric patients meeting ≥4 ACR criteria for SLE were prospectively enrolled for urine assay of 10 protein markers normalized to urine creatinine, namely ALCAM, cystatin-C, hemopexin, KIM-1, MCP-1, NGAL, PF-4, Timp-1, TWEAK, and VCAM-1 by ELISA. Samples from active renal (LN) and active non-renal SLE patients were …

Loss Of H2r Signaling Disrupts Neutrophil Homeostasis And Promotes Inflammation-Associated Colonic Tumorigenesis In Mice, Zhongcheng Shi, Yuko Mori-Akiyama, Wa Du, Robert Fultz, Yanling Zhao, Wenly Ruan, Susan Venable, Melinda A Engevik, James Versalovic

Faculty, Staff and Students Publications

BACKGROUND & AIMS: We previously showed that histamine suppressed inflammation-associated colonic tumorigenesis through histamine type 2 receptor (H2R) signaling in mice. This study aimed to precisely elucidate the downstream effects of H2R activation in innate immune cells.

METHODS: Analyses using online databases of single-cell RNA sequencing of intestinal epithelial cells in mice and RNA sequencing of mouse immune cells were performed to determine the relative abundances of 4 histamine receptors among different cell types. Mouse neutrophils, which expressed greater amounts of H2R, were collected from the peritoneum of wild-type and H2R-deficient mice, of which low-density and high-density neutrophils were extracted …

The Curious Case Of Hla-Dr-Positive Apl, Kanta Devi, Natasha Bahadur Ali

Section of Haematology/Oncology

The triad of weak/absent CD34, negative HLA-DR expression, and positivity to CD117 is pathognomonic for the diagnosis of acute promyelocytic leukemia. However, in rare cases, strong positivity to HLD-DR and CD34 may be noted.

Inhibition Of Nadph Oxidase Blocks Netosis And Reduces Thrombosis In Heparin-Induced Thrombocytopenia, Halina H L Leung, Jose Perdomo, Zohra Ahmadi, Feng Yan, Steven E. Mckenzie, Beng H Chong

Department of Medicine Faculty Papers

Heparin-induced thrombocytopenia (HIT) is associated with severe and potentially lethal thrombotic complications. NETosis was recently shown to be an important driver of thrombosis in HIT. We investigated the role of reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and their contributions to thrombus development in HIT. We showed that neutrophil activation by HIT immune complexes induced ROS-dependent NETosis. Analysis of thrombi formed in a microfluidics system showed ROS production in both platelets and neutrophils, and abundant neutrophil extracellular traps (NETs) and ROS distributed throughout the clot. Neutrophil-targeted ROS inhibition was sufficient to block HIT-induced NETosis …

Lipid A-Ara4n As An Alternate Pathway For (Colistin) Resistance In Klebsiella Pneumonia Isolates In Pakistan, Kiran I. Masood, Seema Umar, Zahra Hasan, Joveria Farooqi, Safina Abdul Razzak, Nazish Jabeen, Jason Rao Jason Rao, Sadia Shakoor, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objectives: This study aimed to explore mechanism of colistin resistance amongst Klebsiella pneumoniae isolates through plasmid mediated mcr-1 gene in Pakistan. Carbapenem and Colistin resistant K. pneumoniae isolates (n = 34) stored at - 80 °C as part of the Aga Khan University Clinical Laboratory strain bank were randomly selected and subjected to mcr-1 gene PCR. To investigate mechanisms of resistance, other than plasmid mediated mcr-1 gene, whole genome sequencing was performed on 8 clinical isolates, including 6 with colistin resistance (MIC > 4 μg/ml) and 2 with intermediate resistance to colistin (MIC > 2 μg/ml).
Results: RT-PCR conducted revealed absence of …

Primary Localized Amyloidosis Of The Ureter With Osseous Metaplasia Presenting As A Suspicious Ureteral Mass, Nada Shaker, Zofia Tynski, Madeline Hudlak, Roy R Brown, Shadi Qasem, Anil Parwani

Pathology and Laboratory Medicine Faculty Publications

Primary amyloidosis of the ureter is a rare disease that is difficult to distinguish from urothelial carcinoma. Only 50 cases of primary ureter amyloidosis have been reported since it was first described in 1937. Of these, only five cases of ureter amyloidosis with osseous metaplasia were reported. In this study, we report the clinical presentation of ureter primary amyloidosis that presented as a mass with osseous metaplasia. The aim of this study is to provide clinicians with knowledge about the clinical/radiologic manifestation that raise the suspicion of amyloidosis, bearing in mind the importance of differentiating it from other "malignant" processes.

Durable Response To Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, And Prednisone (Bv-Chp) In A Patient With Cd30-Positive Ptcl Arising As A Post-Transplant Lymphoproliferative Disorder (Ptld), Jennifer Hong, William T Johnson, Saritha Kartan, Anitha S Gonsalves, Jonathan M. Fenkel, Jerald Z. Gong, Pierluigi Porcu

Department of Medical Oncology Faculty Papers

T-cell PTLDs are lymphoid proliferations that develop in recipients of SOT or allogeneic HSCT. They carry an extremely poor prognosis with a reported median survival of only 6 months. The infrequency with which they are encountered makes treatment a challenge due to the lack of prospective trials to guide management. The significantly higher risk of morbidity and mortality in T-cell PTLD, compared to B-cell PTLD, underscores the challenge of treating these patients and the need for new therapeutic options. Brentuximab vedotin, an ADC targeting CD30, is FDA-approved in combination with CHP as front-line treatment for patients with CD30 expressing PTCL. …

Effect Of 3 Days Of Oral Azithromycin On Young Children With Acute Diarrhea In Low-Resource Settings: A Randomized Clinical Trial, Antibiotics For Children With Diarrhea (Abcd) Study Group, Tahmeed Ahmed, Farah Naz Qamar, Mohammad Tahir Yousafzai, Shahida Qureshi, Sadia Shakoor, Rozina Thobani, Aneeta Hotwani, Furqan Kabir, Jan Mohammed

Department of Paediatrics and Child Health

Importance: World Health Organization (WHO) guidelines do not recommend routine antibiotic use for children with acute watery diarrhea. However, recent studies suggest that a significant proportion of such episodes have a bacterial cause and are associated with mortality and growth impairment, especially among children at high risk of diarrhea-associated mortality. Expanding antibiotic use among dehydrated or undernourished children may reduce diarrhea-associated mortality and improve growth.
Objective: To determine whether the addition of azithromycin to standard case management of acute nonbloody watery diarrhea for children aged 2 to 23 months who are dehydrated or undernourished could reduce mortality and improve linear …

Multiplex Pcr Pathogen Detection In Acute Gastroenteritis Among Hospitalized Us Children Compared With Healthy Controls During 2011-2016 In The Post-Rotavirus Vaccine Era., Christopher J. Harrison, Ferdaus Hassan, Brian R. Lee, Julie Boom, Leila C. Sahni, Coreen Johnson, James Dunn, Daniel C. Payne, Mary E. Wikswo, Umesh Parashar, Rangaraj Selvarangan

Manuscripts, Articles, Book Chapters and Other Papers

Background: Despite vaccine-induced decreases in US rotavirus (RV) disease, acute gastroenteritis (AGE) remains relatively common. We evaluated AGE pathogen distribution in hospitalized US children in the post-RV vaccine era.

Methods: From December 2011 to June 2016, the New Vaccine Surveillance Network (NVSN) conducted prospective, active, population-based surveillance in hospitalized children with AGE. We tested stools from 2 NVSN sites (Kansas City, Houston) with Luminex x-TAG Gastrointestinal Pathogen Panels (Luminex GPP) and analyzed selected signs and symptoms.

Results: For 660 pediatric AGE inpatients and 624 age-matched healthy controls (HCs), overall organism detection was 51.2% and 20.6%, respectively (P < .001). Among AGE subjects, GPP polymerase chain reaction detected >1 virus …

The Role Of Decorin And Biglycan Signaling In Tumorigenesis, Valentina Diehl, Lisa Sophie Huber, Jonel Trebicka, Malgorzata Wygrecka, Renato V. Iozzo, Liliana Schaefer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The complex and adaptive nature of malignant neoplasm constitute a major challenge for the development of effective anti-oncogenic therapies. Emerging evidence has uncovered the pivotal functions exerted by the small leucine-rich proteoglycans, decorin and biglycan, in affecting tumor growth and progression. In their soluble forms, decorin and biglycan act as powerful signaling molecules. By receptor-mediated signal transduction, both proteoglycans modulate key processes vital for tumor initiation and progression, such as autophagy, inflammation, cell-cycle, apoptosis, and angiogenesis. Despite of their structural homology, these two proteoglycans interact with distinct cell surface receptors and thus modulate distinct signaling pathways that ultimately affect cancer …

Outcomes Of Patients With Double/Triple Expressor Diffuse Large B-Cell Lymphoma (Dlbcl) Treated With R-Da-Epoch/R-Chop: A Single-Center Experience, Kanta Devi, Mohammad Usman Shaikh, Natasha Bahadur Ali, Salman Adil, Maria Khan, Salman Muhammad Soomar

Section of Haematology/Oncology

In Pakistan 76.4% of all NHLs to be diagnosed as DLBCLs. The survival of R-CHOP is better compared to the DA-REPOCH treatment regimen. A prospective follow-up study was conducted with 113 patients to study the outcomes of treatment. Multivariable cox-proportional hazard model was used to estimate the hazard ratios in patients receiving these treatment regimens considering p-value ≤0.05 significant. The survival rate among double/triple expressor lymphoma patients received R-DA-EPOCH was 82.8%, and 83.3% received R-CHOP. For double/triple expressor lymphoma patients received R-DA-EPOCH. The findings of our study demonstrated that the survival rate in both R-CHOP and R-DA-EPOCH is mostly …

Rare Case Of Mediastinal Myeloid Sarcoma, Kanta Devi, Salman Adil, Natasha Bahadur Ali, Nasir Ali, Hammad Khan

Section of Haematology/Oncology

Myeloid sarcoma is a rare tumor mass with extra medullary growth pattern, composed of myeloblast or immature myeloid cells. Myeloid sarcoma (MS) is a distinct clinical presentation of acute myeloid leukemia (AML) where less than 1% of patients present with prominent extra medullary disease which most commonly involves the bone, skin, lymph node, soft tissues, gastrointestinal tract or testes. The recommended treatment regimen in isolated myeloid sarcoma or with bone marrow involvement is upfront systemic chemotherapy. We report a case of a young female with anterior mediastinal mass diagnosed as myeloid sarcoma which was refractory to chemotherapy.

Intracranial Mesenchymal Tumors With Fet-Creb Fusion Are Composed Of At Least Two Epigenetic Subgroups Distinct From Meningioma And Extracranial Sarcomas, Emily A. Sloan, Rohit Gupta, Christian Koelsche, Jason Chiang, Javier E. Villanueva-Meyer, Sanda Alexandrescu, Jennifer E. Eschbacher, Wesley Wang, Manuela Mafra, Nasir Ud Din

Department of Pathology and Laboratory Medicine

Intracranial mesenchymal tumor, FET-CREB fusion-positive' occurs primarily in children and young adults and has previously been termed intracranial angiomatoid fibrous histiocytoma (AFH) or intracranial myxoid mesenchymal tumor (IMMT). Here we performed genome-wide DNA methylation array profiling of 20 primary intracranial mesenchymal tumors with FET-CREB fusion to further study their ontology. These tumors resolved into two distinct epigenetic subgroups that were both divergent from all other analyzed intracranial neoplasms and soft tissue sarcomas, including meningioma, clear cell sarcoma of soft tissue (CCS), and AFH of extracranial soft tissue. The first subgroup (Group A, 16 tumors) clustered nearest to but independent of …

Upregulated Type I Interferon Responses In Asymptomatic Covid-19 Infection Are Associated With Improved Clinical Outcome, Kiran I. Masood, Maliha Yameen, Javeria Ashraf, Saba Shahid, Syed Faisal Mahmood, Asghar Nasir, Nosheen Nasir, Bushra Jamil, Najia Karim Ghanchi, Iffat Khanum, Safina Abdul Razzak, Akber Kanji, Rabia Hussain, Martin E. Rottenberg, Zahra Hasan

Department of Pathology and Laboratory Medicine

Understanding key host protective mechanisms against SARS-CoV-2 infection can help improve treatment modalities for COVID-19. We used a blood transcriptome approach to study biomarkers associated with differing severity of COVID-19, comparing severe and mild Symptomatic disease with Asymptomatic COVID-19 and uninfected Controls. There was suppression of antigen presentation but upregulation of inflammatory and viral mRNA translation associated pathways in Symptomatic as compared with Asymptomatic cases. In severe COVID-19, CD177 a neutrophil marker, was upregulated while interferon stimulated genes (ISGs) were downregulated. Asymptomatic COVID-19 cases displayed upregulation of ISGs and humoral response genes with downregulation of ICAM3 and TLR8. Compared across …

A Biocultural Analysis Of The Impacts Of Interactions Between West Africans And Europeans During The Trans-Atlantic Trade At Elmina, Ghana, Heidi Ellen Miller

USF Tampa Graduate Theses and Dissertations

This project utilizes a biocultural approach to assess the demographics and health of the West African population from Elmina, Ghana. Elmina, selected by the Portuguese in 1482 as the site of the first European trade fort in sub-Saharan Africa, grew from a small coastal fishing village to a large settlement over the course of more than 400 years of trade and cultural entanglement. Taken over by the Dutch and then ceded to the British, the people of Elmina navigated significant cultural changes, changes and experiences that can be detected in their skeletal remains. Bioarchaeological research concerned with the effects of …

Low-Grade Primary Splenic Cd10-Positive Small B-Cell Lymphoma/Follicular Lymphoma, Rami Abdulbaki, Parastou Tizro, Victor E. Nava, Maria Gomes Da Silva, Joao L. Ascensao

Pathology Faculty Publications

No abstract provided.

Metabolic Adaptation To The Chronic Loss Of Ca 2+ Signaling Induced By Ko Of Ip 3 Receptors Or The Mitochondrial Ca 2+ Uniporter, Michael P. Young, Zachary T Schug, David M. Booth, David I Yule, Katsuhiko Mikoshiba, György Hajnóczky, Suresh K Joseph

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Calcium signaling is essential for regulating many biological processes. Endoplasmic reticulum inositol trisphosphate receptors (IP3Rs) and the mitochondrial Ca2+ uniporter (MCU) are key proteins that regulate intracellular Ca2+ concentration. Mitochondrial Ca2+ accumulation activates Ca2+-sensitive dehydrogenases of the tricarboxylic acid (TCA) cycle that maintain the biosynthetic and bioenergetic needs of both normal and cancer cells. However, the interplay between calcium signaling and metabolism is not well understood. In this study, we used human cancer cell lines (HEK293 and HeLa) with stable KOs of all three IP3R isoforms (triple KO [TKO]) or MCU to examine metabolic and bioenergetic responses to the chronic …

Rotavirus Genotype Trends And Gastrointestinal Pathogen Detection In The United States, 2014-2016: Results From The New Vaccine Surveillance Network., Mathew D. Esona, M Leanne Ward, Mary E. Wikswo, Slavica M. Rustempasic, Rashi Gautam, Charity Perkins, Rangaraj Selvarangan, Christopher J. Harrison, Julie A. Boom, Janet A. Englund, Eileen J. Klein, Mary Allen Staat, Monica M. Mcneal, Natasha Halasa, James Chappell, Geoffrey A. Weinberg, Daniel C. Payne, Umesh D. Parashar, Michael D. Bowen

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Following the implementation of rotavirus vaccination in 2006, severe acute gastroenteritis (AGE) due to group A rotavirus (RVA) has substantially declined in US children. We report the RVA genotype prevalence as well as coinfection data from 7 US New Vaccine Surveillance Network sites during 3 consecutive RVA seasons, 2014-2016.

METHODS: A total of 1041 stool samples that tested positive for RVA by Rotaclone enzyme immunoassay were submitted to the Centers for Disease Control and Prevention (CDC) for RVA genotyping and multipathogen testing.

RESULTS: A total of 795 (76%) samples contained detectable RVA when tested at the CDC. Rotavirus disease …

Allergic Bronchopulmonary Aspergillosis Misdiagnosed As Smear Negative Pulmonary Tuberculosis; A Retrospective Study From Pakistan, Nousheen Iqbal, Muhammad Dawood Amir Sheikh, Kauser Jabeen, Safia Awan, Muhammad Irfan

Section of Pulmonary & Critical Care

Background: Undiagnosed allergic bronchopulmonary aspergillosis (ABPA) can lead to chronic persistent symptoms. In country like Pakistan where tuberculosis (TB) is endemic, a significant proportion of ABPA patients are misdiagnosed as smear negative TB before reaching a diagnosis of ABPA due to chronicity of symptoms.This lead to empiric use of ATT(Anti-tuberculous therapy) and delay in primary diagnosis. The aim of the study is to determine such proportion of ABPA patients.|
Material and methods: This retrospective study was conducted at the outpatient pulmonology clinic of a tertiary care hospital in Karachi, Pakistan from January 2017 to December 2018. Xpert MTB/Rif, TB smear …

Gender Differences In Urothelial Bladder Cancer: Effects Of Natural Killer Lymphocyte Immunity, Charles T. Lutz, Lydia Livas, Steven R. Presnell, Morgan Sexton, Peng Wang

Pathology and Laboratory Medicine Faculty Publications

Men are more likely to develop cancer than women. In fact, male predominance is one of the most consistent cancer epidemiology findings. Additionally, men have a poorer prognosis and an increased risk of secondary malignancies compared to women. These differences have been investigated in order to better understand cancer and to better treat both men and women. In this review, we discuss factors that may cause this gender difference, focusing on urothelial bladder cancer (UBC) pathogenesis. We consider physiological factors that may cause higher male cancer rates, including differences in X chromosome gene expression. We discuss how androgens may promote …