Pathology Commons^™

Myeloperoxidase (Mpo) Immunostaining Can Identify Endothelial Injury Of Peritubular Capillaries And Glomeruli In Renal Antibody Mediated Rejection, Olabisi Afolayan-Oloye, Megan Moore, Wei Li, Hassan Kanaan, Ping Zhang

Conference Presentation Abstracts

Background: C4d positive staining in peritubular capillaries (PTC) of renal grafts has been used as a marker to support antibody mediated rejection (AMR), if there are morphologic changes of AMR and the renal recipient has positive donor specific antibody. But it is not clear if the C4d staining is related to any peritubular and glomerular injury during AMR. As injured endothelial cells can uptake the MPO into the endothelial cells, we used MPO immunostaining to highlight glomerular endothelial injury in crescentic glomerulonephritis previously. The goal of this study was to determine if there was an endothelial injury of PTC and …

A Soft Tissue Tumor With Eml4-Alk Fusion, Granular Cell Changes, Metastasis, And Response To Kinase Inhibitor Therapy In A Young Girl, Zhenhong Qu, Chris Hysell, Ping Zhang, Mark Micale

Conference Presentation Abstracts

Background: An increasing number of soft tissue neoplasms with fusion of well-defined driver genes are being discovered. We report such a case in a 3-year-old girl with a 2-year follow-up. Design: The patient first presented at age of 3.5 years with a painless right axillary/chest wall mass without constitutional symptoms. MRI demonstrated a 4.5 x 3.5 x 3.5 cm T2 hyper- and T1 hypointense mass. The mass was excised and showed a well-demarcated solid lesion with a homogeneous pale-white fleshy cut surface. No necrosis, myxoid or cystic change, hemorrhage, or calcification was noted. Microscopically, it was a variably hypercellular lesion …

Molecular Epidemiology Of Mycobacterium Tuberculosis Complex Strains In Urban And Slum Settings Of Nairobi, Kenya, Glennah Kerubo, Perpetua Ndungu, Yassir Adam Shuaib, Evans Amukoye, Gunturu Revathi, Susanne Homolka, Samuel Kariuki, Matthias Merker, Stefan Niemann

Pathology, East Africa

Kenya is a country with a high tuberculosis (TB) burden. However, knowledge on the genetic diversity of Mycobacterium tuberculosis complex (MTBC) strains and their transmission dynamics is sparsely available. Hence, we used whole-genome sequencing (WGS) to depict the genetic diversity, molecular markers of drug resistance, and possible transmission clusters among MTBC strains in urban and slum settings of Nairobi. We analyzed 385 clinical MTBC isolates collected between 2010 and 2015 in combination with patients’ demographics. We showed that the MTBC population mainly comprises strains of four lineages (L1–L4). The two dominating lineages were L4 with 55.8% (n = 215) and …

Influenza Clinical Testing And Oseltamivir Treatment In Hospitalized Children With Acute Respiratory Illness, 2015-2016., Lubna Hamdan, Varvara Probst, Zaid Haddadin, Herdi Rahman, Andrew J. Spieker, Simon Vandekar, Laura S. Stewart, John V. Williams, Julie A. Boom, Flor Munoz, Janet A. Englund, Rangaraj Selvarangan, Mary A. Staat, Geoffrey A. Weinberg, Parvin H. Azimi, Eileen J. Klein, Monica Mcneal, Leila C. Sahni, Monica N. Singer, Peter G. Szilagyi, Christopher J. Harrison, Manish Patel, Angela P. Campbell, Natasha B. Halasa

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Antiviral treatment is recommended for all hospitalized children with suspected or confirmed influenza, regardless of their risk profile. Few data exist on adherence to these recommendations, so we sought to determine factors associated with influenza testing and antiviral treatment in children.

METHODS: Hospitalized children(ARI) were enrolled through active surveillance at pediatric medical centers in seven cities between 11/1/2015 and 6/30/2016; clinical information was obtained from parent interview and chart review. We used generalized linear mixed-effects models to identify factors associated with influenza testing and antiviral treatment.

RESULTS: Of the 2299 hospitalized children with ARI enrolled during one influenza season, …

Proteinuria In Thrombotic Microangiopathy (Tma) Can Be Associated With Adaptive Partial Podocytopathy With Focal Podocyte Hyperplasia, Megan Moore, Olabisi Afolayan-Oloye, Wei Li, Hassan Kanaan, Ping Zhang

Conference Presentation Abstracts

Background: TMA associated renal failure is easy to understand, but it has been difficult to explain the significant proteinuria in some cases of TMA. We recently confirmed that 100% of hyperplastic podocytes in collapsing glomerulopathy stained positively for CD133 (a stem cell/progenitor marker) as previously reported. The goal of this study was to determine if there was significant fusion of foot processes (FFP) and CD133-positive hyperplastic podocytes in TMA to correlate with the proteinuria. Design: The study included 12 negative controls (renal parenchyma away from renal cell carcinoma) and 25 TMA cases, either induced by drugs or due to other …

Proteinuria In Thrombotic Microangiopathy (Tma) Can Be Associated With Adaptive Partial Podocytopathy With Focal Podocyte Hyperplasia, Megan Moore, Olabisi Afaolayan-Oloye, Wei Li, Hassan Kanaan, Ping Zhang

Conference Presentation Abstracts

Background: TMA associated renal failure is easy to understand, but it has been difficult to explain the significant proteinuria in some cases of TMA. We recently confirmed that 100% of hyperplastic podocytes in collapsing glomerulopathy stained positively for CD133 (a stem cell/progenitor marker) as previously reported. The goal of this study was to determine if there was significant fusion of foot processes (FFP) and CD133-positive hyperplastic podocytes in TMA to correlate with the proteinuria. Design: The study included 12 negative controls (renal parenchyma away from renal cell carcinoma) and 25 TMA cases, either induced by drugs or due to other …

Variants Associated With Bedaquiline (Bdq) Resistance Identified In Rv0678 And Efflux Pump Genes In Mycobacterium Tuberculosis Isolates From Bdq Naïve Tb Patients In Pakistan, Dania Khalid Saeed, Sadia Shakoor, Safina Abdul Razzak, Zahra Hasan, Saba Faraz Sabzwari, Zahida Azizullah, Akber Kanji, Asghar Nasir, Samreen Shafiq, Najia Karim Ghanchi, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background: Mutations in the Rv0678, pepQ and atpE genes of Mycobacterium tuberculosis (MTB) have been reported to be associated with reduced antimycobacterial susceptibility to bedaquiline (BDQ). Resistance conferring mutations in treatment naïve MTB strains is likely to have implications for BDQ based new drug regimen that aim to shorten treatment duration. We therefore investigated the genetic basis of resistance to BDQ in MTB clinical isolates from BDQ naïve TB patients from Pakistan. In addition, mutations in genes associated with efflux pumps were investigated as an alternate mechanism of resistance.
Methods: Based on convenience sampling, we studied 48 MTB clinical isolates …

Repair-Assisted Damage Detection Reveals Biological Disparities In Prostate Cancer Between African Americans And European Americans, Kimiko L Krieger, Jie H Gohlke, Kevin J Lee, Danthasinghe Waduge Badrajee Piyarathna, Patricia D Castro, Jeffrey A Jones, Michael M Ittmann, Natalie R Gassman, Arun Sreekumar

Faculty, Staff and Students Publications

African Americans (AA) are two times more likely to be diagnosed with and succumb to prostate cancer (PCa) compared to European Americans (EA). There is mounting evidence that biological differences in these tumors contribute to disparities in patient outcomes. Our goal was to examine the differences in DNA damage in AA and EA prostate tissues. Tissue microarrays with matched tumor-benign adjacent pairs from 77 AA and EA PCa patients were analyzed for abasic sites, oxidative lesions, crosslinks, and uracil content using the Repair Assisted Damage Detection (RADD) assay. Our analysis revealed that AA PCa, overall, have more DNA damage than …

Novel Role Of Ghrelin Receptor In Gut Dysbiosis And Experimental Colitis In Aging, Ji Yeon Noh, Chia-Shan Wu, Jennifer A A Deluca, Sridevi Devaraj, Arul Jayaraman, Robert C Alaniz, Xiao-Di Tan, Clinton D Allred, Yuxiang Sun

Faculty, Staff and Students Publications

Chronic low-grade inflammation is a hallmark of aging, which is now coined as inflamm-aging. Inflamm-aging contributes to many age-associated diseases such as obesity, type 2 diabetes, cardiovascular disease, and inflammatory bowel disease (IBD). We have shown that gut hormone ghrelin, via its receptor growth hormone secretagogue receptor (GHS-R), regulates energy metabolism and inflammation in aging. Emerging evidence suggests that gut microbiome has a critical role in intestinal immunity of the host. To determine whether microbiome is an integral driving force of GHS-R mediated immune-metabolic homeostasis in aging, we assessed the gut microbiome profiles of young and old GHS-R global knockout …

A Review Of Coronaviruses Associated With Kawasaki Disease: Possible Implications For Pathogenesis Of The Multisystem Inflammatory Syndrome Associated With Covid-19, Fatima Farrukh Shahbaz, Russell Seth Martins, Abdullah Umair, Ronika Devi Ukrani, Kauser Jabeen, M Rizwan Sohail, Erum Khan

Medical College Documents

Multisystem Inflammatory Syndrome in Children (MIS-C), representing a new entity in the spectrum of manifestations of COVID-19, bears symptomatic resemblance with Kawasaki Disease (KD). This review explores the possible associations between KD and the human coronaviruses and discusses the pathophysiological similarities between KD and MIS-C and proposes implications for the pathogenesis of MIS-C in COVID-19. Since 2005, when a case-control study demonstrated the association of a strain of human coronavirus with KD, several studies have provided evidence regarding the association of different strains of the human coronaviruses with KD. Thus, the emergence of the KD-like disease MIS-C in COVID-19 may …

Response Of Eltrombopag In Immune Thrombocytopenia And Acquired Idiopathic Aplastic Anemia: A Single-Center Experience, Abdul Muqtadir Abbasi, Mohammad Usman Shaikh, Natasha Bahadur Ali, Maria Khan, Salman Muhammad Soomar

Section of Haematology/Oncology

Eltrombopag has been used in ITP and found its use in AA armamentarium recently. We retrospectively analyzed 61 patients at a tertiary care center in Pakistan from January 2015 to January 2021. They included patients with severe AA who were refractory to at least one course of immunosuppressive therapy and persistent/chronic ITP who have received at least one previous treatment for ITP. Responses to Eltrombopag in our population were comparable to real-world experiences while tolerable hepatotoxicity and GI issues were notable. We found Eltrombopag to be a safe and efficacious agent for treating patients with ITP and AA.

Noncoding-Rna-Based Therapeutics With An Emphasis On Prostatic Carcinoma-Progress And Challenges., Victor E. Nava, Pin-Yu Perera, Nirbhay Kumar, Maneesh Jain

Pathology Faculty Publications

Noncoding RNAs (ncRNAs) defy the central dogma by representing a family of RNA molecules that are not translated into protein but can convey information encoded in their DNA. Elucidating the exact function of ncRNA has been a focus of discovery in the last decade and remains challenging. Nevertheless, the importance of understanding ncRNA is apparent since these molecules regulate gene expression at the transcriptional and post-transcriptional level exerting pleiotropic effects critical in development, oncogenesis, and immunity. NcRNAs have been referred to as "the dark matter of the nucleus", and unraveling their role in physiologic and pathologic processes will provide vast …

Lymphoma With Tuberculous Granulomas, Jyoti Mohan Lal, Anila Rashid

Department of Pathology and Laboratory Medicine

Chronic granulomatous inflammation is a common finding in lymphoproliferative disorders (LPDs), but it is important to exclude coexisting mycobacterium tuberculosis (MTB) especially in patients from areas of high endemicity. This case emphasizes the relevance of performing MTB culture on bone marrow exhibiting LPD and concomitant granulomas

A Summary Of The Inaugural Who Classification Of Pediatric Tumors: Transitioning From The Optical Into The Molecular Era., Stefan M Pfister, Miguel Reyes-Múgica, John K C Chan, Henrik Hasle, Alexander J Lazar, Sabrina Rossi, Andrea Ferrari, Jason A Jarzembowski, Kathy Pritchard-Jones, D. Ashley Hill, Thomas S Jacques, Pieter Wesseling, Dolores H López Terrada, Andreas Von Deimling, Christian P Kratz, Ian A Cree, Rita Alaggio

Pathology Faculty Publications

Pediatric tumors are uncommon, yet are the leading cause of cancer-related death in childhood. Tumor types, molecular characteristics, and pathogenesis are unique, often originating from a single genetic driver event. The specific diagnostic challenges of childhood tumors led to the development of the first World Health Organization (WHO) Classification of Pediatric Tumors. The classification is rooted in a multilayered approach, incorporating morphology, IHC, and molecular characteristics. The volume is organized according to organ sites and provides a single, state-of-the-art compendium of pediatric tumor types. A special emphasis was placed on "blastomas," which variably recapitulate the morphologic maturation of organs from …

Maternal Lactobacillus Reuteri Supplementation Shifts The Intestinal Microbiome In Mice And Provides Protection From Experimental Colitis In Female Offspring, Mahesh Krishna, Melinda Engevik, Karen Queliza, Savini Britto, Rajesh Shah, Wenly Ruan, Hongtao Wang, James Versalovic, Richard Kellermayer

Faculty, Staff and Students Publications

The purpose of our experiment was to explore how stochastic (inter-individual variation) gut microbiome composition may link to inflammatory bowel disease (IBD) susceptibility and guide the development of a perinatal preventative probiotic. Dextran sodium sulfate (DSS) was introduced to C57BL/BJ mice to induce acute colitis as a model of IBD. Potentially protective bacteria were identified using a discovery-validation cohort approach toward stochastic DSS susceptibility.

Fecal Microbiota Transplantation Commonly Failed In Children With Co-Morbidities, Richard Kellermayer, Qinglong Wu, Dorottya Nagy-Szakal, Karen Queliza, Faith D Ihekweazu, Claire E Bocchini, Abria R Magee, Numan Oezguen, Jennifer K Spinler, Emily B Hollister, Robert J Shulman, James Versalovic, Ruth Ann Luna, Tor C Savidge

Faculty, Staff and Students Publications

OBJECTIVES: Fecal microbiota transplantation (FMT) is arguably the most effective treatment for recurrent Clostridioides difficile infection (rCDI). Clinical reports on pediatric FMT have not systematically evaluated microbiome restoration in patients with co-morbidities. Here, we determined whether FMT recipient age and underlying co-morbidity influenced clinical outcomes and microbiome restoration when treated from shared fecal donor sources.

METHODS: Eighteen rCDI patients participating in a single-center, open-label prospective cohort study received fecal preparation from a self-designated (single case) or two universal donors. Twelve age-matched healthy children and four pediatric ulcerative colitis (UC) cases from an independent serial FMT trial, but with a shared …

Sars-Cov-2 Anti-Spike Antibodies After Vaccination In Pediatric Heart Transplantation: A First Report, Joseph A Spinner, Christopher L Julien, Lily Olayinka, William J Dreyer, Claire E Bocchini, Flor M Munoz, Sridevi Devaraj

Faculty, Staff and Students Publications

BACKGROUND: BACKGROUND: There is a paucity of data regarding the antibody response to SARS-CoV-2 vaccination in children after solid organ transplant.

METHODS: We retrospectively reviewed the SARS-CoV-2 Anti-Spike IgG antibodies measured following SARS-CoV-2 vaccination at our pediatric heart transplant (HTx) center.

RESULTS: Among patients (median age 17.1 years) in whom antibody testing was performed (median 118 days post-vaccine completion), a SARS-CoV-2 Anti-Spike IgG antibody was detected in 28 of 40 (70%) post-HTx recipients (median antibody level 10.9 AU/ml). Neutropenia, diabetes mellitus, and previous use of rituximab were associated with absence of a detectable antibody. All 7 post-HTx patients with a …

Metabolism Of A Selective Serotonin And Norepinephrine Reuptake Inhibitor Duloxetine In Liver Microsomes And Mice, Xuan Qin, John M Hakenjos, Kevin R Mackenzie, Mercedes Barzi, Hemantkumar Chavan, Pranavanand Nyshadham, Jin Wang, Sung Yun Jung, Joie Z Guner, Si Chen, Lei Guo, Partha Krishnamurthy, Karl-Dimiter Bissig, Stephen Palmer, Martin M Matzuk, Feng Li

Faculty, Staff and Students Publications

Duloxetine (DLX) is a dual serotonin and norepinephrine reuptake inhibitor, widely used for the treatment of major depressive disorder. Although DLX has shown good efficacy and safety, serious adverse effects (e.g., liver injury) have been reported. The mechanisms associated with DLX-induced toxicity remain elusive. Drug metabolism plays critical roles in drug safety and efficacy. However, the metabolic profile of DLX in mice is not available, although mice serve as commonly used animal models for mechanistic studies of drug-induced adverse effects. Our study revealed 39 DLX metabolites in human/mouse liver microsomes and mice. Of note, 13 metabolites are novel, including five …

Clinical Influenza Testing Practices In Hospitalized Children At United States Medical Centers, 2015-2018., Mark W. Tenforde, Angela P. Campbell, Marian G. Michaels, Christopher J. Harrison, Eileen J. Klein, Janet A. Englund, Rangaraj Selvarangan, Natasha B. Halasa, Laura S. Stewart, Geoffrey A. Weinberg, John V. Williams, Peter G. Szilagyi, Mary A. Staat, Julie A. Boom, Leila C. Sahni, Monica N. Singer, Parvin H. Azimi, Richard K. Zimmerman, Monica M. Mcneal, H Keipp Talbot, Arnold S. Monto, Emily T. Martin, Manjusha Gaglani, Fernanda P. Silveira, Donald B. Middleton, Jill M. Ferdinands, Melissa A. Rolfes

Manuscripts, Articles, Book Chapters and Other Papers

At nine US hospitals that enrolled children hospitalized with acute respiratory illness (ARI) during 2015-2016 through 2017-2018 influenza seasons, 50% of children with ARI received clinician-initiated testing for influenza and 35% of cases went undiagnosed due to lack of clinician-initiated testing. Marked heterogeneity in testing practice was observed across sites.

Distribution Of Serotypes And Antibiotic Resistance Of Invasive Pseudomonas Aeruginosa In A Multi-Country Collection, Shamima Nasrin, Nicolas Hegerle, Shaichi Sen, Joseph Nkeze, Sunil Sen, Jasnehta Permala-Booth, Myeongjin Choi, James Sinclair, Milagritos D. Tapia, Sadia Shakoor

Department of Pathology and Laboratory Medicine

Background: Pseudomonas aeruginosa is an opportunistic pathogen that causes a wide range of acute and chronic infections and is frequently associated with healthcare-associated infections. Because of its ability to rapidly acquire resistance to antibiotics, P. aeruginosa infections are difficult to treat. Alternative strategies, such as a vaccine, are needed to prevent infections. We collected a total of 413 P. aeruginosa isolates from the blood and cerebrospinal fluid of patients from 10 countries located on 4 continents during 2005-2017 and characterized these isolates to inform vaccine development efforts. We determined the diversity and distribution of O antigen and flagellin types and …