Pathology Commons^™

Post Tuberculosis Treatment Infectious Complications, Desmond Hsu, Muhammad Irfan, Kauser Jabeen, Nousheen Iqbal, Rumina Hasan, Giovanni Battista Migliori, Alimuddin Zumla, Dina Visca, Rosella Centis, Simon Tiberi

Department of Pathology and Laboratory Medicine

Following greater attention and follow-up of patients with treated pulmonary tuberculosis (TB), it has emerged that infections are more likely to occur in this cohort of patients. This comes as no surprise, as pulmonary TB is a destructive process that leads to cicatrization, alteration of parenchyma, bronchiectasis, and scarring of the lung, with reduction of lung volumes and an impact on pulmonary function. In addition to relapse and re-infection with TB, other pathogens are increasingly recognized in post-TB patients. This paper serves as a summary and guide on how to approach the post-TB patient with new signs and symptoms of …

Non-Tuberculous Mycobacterial Infections-A Neglected And Emerging Problem, Imran Ahmed, Simon Tiberi, Joveria Farooqi, Kauser Jabeen, Dorothy Yeboah-Manu, Giovanni Battista Migliori, Rumina Hasan

Department of Pathology and Laboratory Medicine

Non-tuberculous mycobacteria (NTM) are ubiquitous dwellers of environmental niches and are an established cause of natural and nosocomial infections. The incidence of NTM infections is rising owing to a growing population of immunocompromised and vulnerable individuals, complex medical and surgical procedures, as well as increased awareness and diagnostic capabilities. The prevalence of different NTM varies between continents, regions, and countries. The true global burden of pulmonary and extrapulmonary disease is unknown and estimates are subject to under and/or over-estimation. Diagnosis requires confirmation by isolation of NTM along with clinical and radiological criteria, which may be suboptimal at all levels. Susceptibility …

Isolated Forefoot Juvenile Xanthogranuloma: Unique Case Study And Treatment In A Pediatric Patient, Brian Derner Dpm, Kristine Hoffman, Amy Storfa Md, Dustin Kruse Dpm, Paul A. Stone Dpm, Facfas

Podiatry

Juvenile xanthogranulomas (JXG) are a benign histiocytic cell proliferative disorder in early childhood. They most commonly present within the first two years of life with papular or nodular changes to the skin on the head, neck or upper trunk. Xanthogranulomas are mostly self-limiting, can be singular or multiple, and rarely can infer a systemic disease process1. The purpose of this study was to publish a unique finding of an extra-tendinous solitary mass in an otherwise healthy 17-year old, with surgical and medical treatment after diagnosis.

B Cells Migrate Into Remote Brain Areas And Support Neurogenesis And Functional Recovery After Focal Stroke In Mice, Sterling B. Ortega, Vanessa O. Torres, Sarah E. Latchney, Cody W. Whoolery, Ibrahim Z. Noorbhai, Katie Poinsatte, Uma M. Selvaraj, Monica A. Benson, Anouk J. M. Meeuwissen, Erik J. Plautz, Xiangmei Kong, Denise M. Ramirez, Apoorva D. Ajay, Julian P. Meeks, Mark P. Goldberg, Nancy L. Monson, Amelia J. Eisch, Ann M. Stowe

Neurology Faculty Publications

Lymphocytes infiltrate the stroke core and penumbra and often exacerbate cellular injury. B cells, however, are lymphocytes that do not contribute to acute pathology but can support recovery. B cell adoptive transfer to mice reduced infarct volumes 3 and 7 d after transient middle cerebral artery occlusion (tMCAo), independent of changing immune populations in recipient mice. Testing a direct neurotrophic effect, B cells cocultured with mixed cortical cells protected neurons and maintained dendritic arborization after oxygen-glucose deprivation. Whole-brain volumetric serial two-photon tomography (STPT) and a custom-developed image analysis pipeline visualized and quantified poststroke B cell diapedesis throughout the brain, including …

Hierarchical Clustering Analyses Of Plasma Proteins In Subjects With Cardiovascular Risk Factors Identify Informative Subsets Based On Differential Levels Of Angiogenic And Inflammatory Biomarkers, Zachary Winder, Tiffany L. Sudduth, David W. Fardo, Qiang Cheng, Larry B. Goldstein, Peter T. Nelson, Frederick A. Schmitt, Gregory A. Jicha, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Agglomerative hierarchical clustering analysis (HCA) is a commonly used unsupervised machine learning approach for identifying informative natural clusters of observations. HCA is performed by calculating a pairwise dissimilarity matrix and then clustering similar observations until all observations are grouped within a cluster. Verifying the empirical clusters produced by HCA is complex and not well studied in biomedical applications. Here, we demonstrate the comparability of a novel HCA technique with one that was used in previous biomedical applications while applying both techniques to plasma angiogenic (FGF, FLT, PIGF, Tie-2, VEGF, VEGF-D) and inflammatory (MMP1, MMP3, MMP9, IL8, TNFα) protein data to …

Urinary Bladder Metastasis From Breast Cancer: A Rare Cause Of Hematuria, Samuel Gitau, Allan Njau, Sitna Mwanzi

Imaging & Diagnostic Radiology, East Africa

Breast cancer is the most common cancer in women globally as well as in Kenya. The most common sites of metastases reported include the bones, liver and lung. Metastasis to the urinary bladder is relatively uncommon with only a few case reports in literature. It can therefore be easily overlooked as a cause of hematuria in these patients. We describe a rare case of a patient with breast cancer who presented with urinary bladder metastasis as a late complication of her illness.

Point-Of-Care Hpv Molecular Diagnostics For A Test-And-Treat Model In High-Risk Hiv Populations, Shahin Sayed, Michael Chung, Marleen Temmerman

Pathology, East Africa

Strategies for cervical cancer prevention and control in low-income and middle-income countries (LMICs) require concerted efforts to improve screening and access to treatment, especially in high-risk HIV populations. LMICs bear the largest burden of HIV infection, human papillomavirus (HPV) infection is common among HIV-infected women, risk of cervical cancer is increased in women with HIV/AIDS, and HIV clinics provide opportunities to screen and treat for cervical cancer in this population.

A Multicenter Case Control Study Of Association Of Vitamin D With Breast Cancer Among Women In Karachi, Pakistan, Uzma Shamsi, Shaista Khan, Syed Iqbal Azam, Aysha Habib, Amir Maqbool, Mohammad Hanif, Tiffany Gill, Romaina Iqbal, David Callen

Community Health Sciences

Background: The prevalence of vitamin D inadequacy and breast cancer are both high among women living in Karachi, Pakistan.
Methods: A matched case control study was conducted in two hospitals of Karachi, Pakistan to evaluate the association of vitamin D (serum 25-hydroxyvitamin D) concentrations, vitamin D supplementation and sun exposure with breast cancer among Pakistani women. A total of 411 newly diagnosed histologically confirmed primary breast cancer cases were enrolled and 784 controls, free of breast and any other cancers, were matched by age (year of birth ± 5 years), residence in the same geographic area and study site. Information …

Utility Of Ultrasound And Mammography In Detection Of Negative Axillary Nodal Metastasis In Breast Cancer, Anam Khan, Imrana Masroor, Kumail Khandwala, Summar Un-Nisa Abbasi, Muhammad Usman Tariq

Department of Radiology

Objective: The status of axillary lymph nodes is one of the most important prognostic factors in patients with breast cancer. A precise noninvasive evaluation of axillary lymph node status preoperatively, although challenging, is vital for optimization of the treatment plan for patients. The objective of our study was to assess the utility of ultrasound and mammography in detecting the absence of axillary lymph nodal metastasis in patients of breast cancer, taking histopathology as gold standard.
Methods: A cross-sectional study was conducted in the Department of Radiology, Aga Khan University Hospital, Karachi. All female patients between 20 and 95 years of …

Carcinoma In Situ Involving Sclerosing Adenosis On Core Biopsy: Diagnostic Pearls To Aid The Practicing Clinician And Avoid Overtreatment, Dana Richards, Alberto A. Ayala, Yun Wu, Lavinia P. Middleton

Pathology and Laboratory Medicine Faculty Publications

INTRODUCTION: Involvement of pre-existing benign lesions by ductal carcinoma in situ (DCIS) or lobular neoplasia (LN) can present difficult diagnostic challenges, and can easily cause misdiagnosis of invasive carcinoma and over-management of localized disease. Our objective was to gather the largest case series of DCIS and LN involving sclerosing adenosis (SA), and to report the characteristic features of these lesions, in order to provide histologic criteria for the diagnostician.

METHODS: Our database was searched for core biopsy material diagnosed as carcinoma in situ involving adenosis. Glass slides and pathology reports were reviewed. The cases were studied for salient features, and …

Ass1 Overexpression: A Hallmark Of Sonic Hedgehog Hepatocellular Adenomas; Recommendations For Clinical Practice., M. Sala, D. Gonzales, T. Leste-Lasserre, N. Dugot-Senant, V. Paradis, S. Di Tommaso, J. Dupuy, V. Pitard, C. Fan, F. Saltel, +26 Additional Authors

Journal Articles

Until recently, 10% of hepatocellular adenomas (HCAs) remained unclassified (UHCA). Among the UHCAs, the sonic hedgehog HCA (shHCA) was defined by focal deletions that fuse the promoter of Inhibin beta E chain with GLI1. Prostaglandin D2 synthase was proposed as immunomarker. In parallel, our previous work using proteomic analysis showed that most UHCAs constitute a homogeneous subtype associated with overexpression of argininosuccinate synthase (ASS1). To clarify the use of ASS1 in the HCA classification and avoid misinterpretations of the immunohistochemical staining, the aims of this work were to study (1) the link between shHCA and ASS1 overexpression and (2) the …

The Value Proposition For Pathologists: A Population Health Approach, B. S. Ducatman, A. M. Ducatman, J. M. Crawford, M. Laposata, F. Sanfilippo

Journal Articles

© The Author(s) 2020. The transition to a value-based payment system offers pathologists the opportunity to play an increased role in population health by improving outcomes and safety as well as reducing costs. Although laboratory testing itself accounts for a small portion of health-care spending, laboratory data have significant downstream effects in patient management as well as diagnosis. Pathologists currently are heavily engaged in precision medicine, use of laboratory and pathology test results (including autopsy data) to reduce diagnostic errors, and play leading roles in diagnostic management teams. Additionally, pathologists can use aggregate laboratory data to monitor the health of …

Molecular Pathology Economics 101: An Overview Of Molecular Diagnostics Coding, Coverage, And Reimbursement A Report Of The Association For Molecular Pathology, A. N. Sireci, J. L. Patel, L. Joseph, M. C. Hiemenz, O. C. Rosca, S. K. Caughron, S. A. Thibault-Sennett, T. L. Burke, D. L. Aisner

Journal Articles

No abstract provided.

Histopathologic Evaluation Of Placentas After Diagnosis Of Maternal Severe Acute Respiratory Syndrome Coronavirus 2 Infection., M. Gulersen, L. Prasannan, H. Tam Tam, C. N. Metz, B. Rochelson, N. Meirowitz, W. Shan, M. Edelman, K. A. Millington

Journal Articles

Background: The impact of maternal severe acute respiratory syndrome coronavirus 2 infection on placental histopathology is not well known.

Objective: To determine if any significant placental histopathologic changes occur after the diagnosis of severe acute respiratory syndrome coronavirus 2 infection during pregnancy and whether these changes are correlated with the presence or absence of symptoms associated with the infection.

Study Design: A retrospective cohort study of women diagnosed as having severe acute respiratory syndrome coronavirus 2 infection who delivered at a single center from April 9, 2020 to April 27, 2020, and had placental specimens reviewed by the Department of …

Analytical And Clinical Comparison Of Three Nucleic Acid Amplification Tests For Sars-Cov-2 Detection., E Smith, W Zhen, R Manji, D Schron, S Duong, Gj Berry

Journal Articles

No abstract provided.

Rapid Emergence Of Sars-Cov-2 In The Greater New York Metropolitan Area: Geolocation, Demographics, Positivity Rates, And Hospitalization For 46,793 Persons Tested By Northwell Health., S. B. Reichberg, P. P. Mitra, A. Haghamad, G. Ramrattan, J. M. Crawford, G. J. Berry, K. W. Davidson, A. Drach, S. Duong, S. Juretschko, N. I. Maria, Y. Yang, Y. C. Ziemba, Northwell Covid-19 Research Consortium

Journal Articles

BACKGROUND:In March 2020, the greater New York metropolitan area became an epicenter for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The initial evolution of case incidence has not been well characterized. METHODS:Northwell Health Laboratories tested 46,793 persons for SARS-CoV-2 from March 4 through April 10. The primary outcome measure was a positive reverse-transcription-polymerase-chain-reaction (RT-PCR) test for SARS-CoV-2. The secondary outcomes included patient age, sex, and race if stated; dates the specimen was obtained and the test result; clinical practice site sources; geo-location of patient residence; and hospitalization. RESULTS:From March 8 through April 10, a total of 26,735 of 46,793 …

Development Of A New Multiplex Real-Time Rt-Pcr Assay For Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Detection., W. Zhen, G. J. Berry

Journal Articles

This research describes the development of a new multiplex real-time RT-PCR test for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with primers designed to amplify a 108 bp target on the spike surface glycoprotein (S gene) and a hydrolysis TaqMan probe designed to specifically detect SARS-CoV-2. The limit of detection (LOD) and clinical performance of this new assay were evaluated. A LOD study with inactivated virus exhibited performance equal to the modified CDC assay, with a final LOD of 1301 ± 13 genome equivalents/mL for the Northwell Health Laboratories laboratory-developed test (NWHL LDT) versus 1249 ± 14 genome …

Clinical Evaluation Of Three Sample-To-Answer Platforms For The Detection Of Sars-Cov-2, W Zhen, E Smith, R Manji, D Schron, Gj Berry

Journal Articles

No abstract provided.

Histopathological Evaluation Of Placentas After Diagnosis Of Maternal Sars-Cov-2 Infection., M. Gulersen, L. Prasannan, H. T. Tam, C. N. Metz, B. Rochelson, N. Meirowitz, W. Shan, M. Edelman, K. A. Millington

Journal Articles

Background:The impact of maternal SARS-CoV-2 infection on placental histopathology is not well known. Objectives:To determine if significant placental histopathological changes occur after diagnosis of SARS-CoV-2 infection in pregnancy and whether these changes are correlated with the presence or absence of symptoms associated with infection. Study Design:Retrospective cohort study of women diagnosed with SARS-CoV-2 infection who delivered at a single center from April 9th to April 27th, 2020, and had placental specimens reviewed by pathology. Women with singleton gestations and laboratory-confirmed SARS-CoV-2 infection were eligible for inclusion. Historical controls selected from a cohort of women who delivered 6 months prior to …

Multiple Myeloma In A Young Female Presenting With Neurological Symptoms., M. Lee, X. Zhang, V. Nguyen, M. Hartley-Brown

Journal Articles

Background:Multiple myeloma is overall the 14th most common malignancy but is rarely seen in those younger than 35 years. Those in the younger age group have been shown to have a more aggressive course but reportedly have had similar responses to treatment compared to older cohorts. Extramedullary plasmacytomas are discrete soft tissue masses of neoplastic monoclonal plasma cells that often occur in patients with multiple myeloma. Case:This case entails a young female with new diagnosis of multiple myeloma and multiple extramedullary plasmacytomas presenting with neurological symptoms. She was treated with CyBorD regimen but was refractory and progressed. Treatment was changed …

Molecular Testing For Acute Respiratory Tract Infections: Clinical And Diagnostic Recommendations From The Idsa's Diagnostics Committee., K. E. Hanson, M. M. Azar, R. Banerjee, A. Chou, R. C. Colgrove, C. C. Ginocchio, M. K. Hayden, M. Holodiny, S. Jain, Diagnostics Committee Of The Infectious Diseases S, +4 Additional Authors

Journal Articles

The clinical signs and symptoms of acute respiratory tract infections (RTIs) are not pathogen specific. Highly sensitive and specific nucleic acid amplification tests have become the diagnostic reference standard for viruses and translation of bacterial assays from basic research to routine clinical practice represents an exciting advance in respiratory medicine. Most recently, molecular diagnostics have played an essential role in the global health response to the novel coronavirus pandemic. How best to use newer molecular tests for RTI in combination with clinical judNorthwell Healthnt and traditional methods can be bewildering given the plethora of available assays and rapidly evolving technologies. …

Reevaluation Of The Us Pathologist Workforce Size, S. J. Robboy, D. Gross, J. Y. Park, E. Kittrie, J. M. Crawford, R. L. Johnson, M. B. Cohen, D. S. Karcher, R. D. Hoffman, W. S. Black-Schaffer, +1 Additional Author

Journal Articles

No abstract provided.

3d Printed Alternative To The Standard Synthetic Flocked Nasopharyngeal Swabs Used For Covid-19 Testing., S. J. Decker, T. A. Goldstein, J. M. Ford, M. N. Teng, R. S. Pugliese, G. J. Berry, O. Bloom, D. A. Breining, J. Crawford, K. Kim, +12 Additional Authors

Journal Articles

BACKGROUND:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, can be detected in respiratory samples by Real-time Reverse Transcriptase (RT)-PCR or other molecular methods. Accessibility of diagnostic testing for COVID-19 has been limited by intermittent shortages of supplies required for testing, including flocked nasopharyngeal (FLNP) swabs. METHODS:We developed a 3D-printed nasopharyngeal (3DP) swab as a replacement of the FLNP swab. The performance of 3DP and FLNP swabs were compared in a clinical trial of symptomatic patients at three clinical sites (n=291) using three SARS-CoV-2 EUA tests: a modified version of the CDC Real-time Reverse Transcriptase (RT)-PCR Diagnostic …

Evaluation Of Concordance Between Original Death Certifications And An Expert Panel Process In The Determination Of Sudden Unexplained Death In Childhood, L. G. Crandall, J. H. Lee, D. Friedman, K. Lear, K. Maloney, J. K. Pinckard, P. Lin, T. Andrew, A. K. Williamson, O. Devinsky, +8 Additional Authors

Journal Articles

Importance: The true incidence of sudden unexplained death in childhood (SUDC), already the fifth leading category of death among toddlers by current US Centers for Disease Control and Prevention estimates, is potentially veiled by the varied certification processes by medicolegal investigative offices across the United States. Objective: To evaluate the frequency of SUDC incidence, understand its epidemiology, and assess the consistency of death certification among medical examiner and coroner offices in the US death investigation system. Design, Setting, and Participants: In this case series, 2 of 13 forensic pathologists (FPs) conducted masked reviews of 100 cases enrolled in the SUDC …

Neutrophils Are Mediators Of Metastatic Prostate Cancer Progression In Bone, Diane L. Costanzo-Garvey, Tyler Keeley, Adam J. Case, Gabrielle F. Watson, Massar Alsamraae, Yangsheng Yu, Kaihong Su, Cortney E. Heim, Tammy Kielian, Colm Morrissey, Jeremy S Frieling, Leah M. Cook

Journal Articles: Pathology and Microbiology

Bone metastatic prostate cancer (BM-PCa) significantly reduces overall patient survival and is currently incurable. Current standard immunotherapy showed promising results for PCa patients with metastatic, but less advanced, disease (i.e., fewer than 20 bone lesions) suggesting that PCa growth in bone contributes to response to immunotherapy. We found that: (1) PCa stimulates recruitment of neutrophils, the most abundant immune cell in bone, and (2) that neutrophils heavily infiltrate regions of prostate tumor in bone of BM-PCa patients. Based on these findings, we examined the impact of direct neutrophil-prostate cancer interactions on prostate cancer growth. Bone marrow neutrophils directly induced apoptosis …

Monocyte Metabolic Reprogramming Promotes Pro-Inflammatory Activity And Staphylococcus Aureus Biofilm Clearance, Kelsey J. Yamada, Cortney E. Heim, Xinyuan Xi, Kuldeep S. Attri, Dezhen Wang, Wenting Zhang, Pankaj K. Singh, Tatiana K. Bronich, Tammy Kielian

Journal Articles: Pathology and Microbiology

Biofilm-associated prosthetic joint infections (PJIs) cause significant morbidity due to their recalcitrance to immune-mediated clearance and antibiotics, with Staphylococcus aureus (S. aureus) among the most prevalent pathogens. We previously demonstrated that S. aureus biofilm-associated monocytes are polarized to an anti-inflammatory phenotype and the adoptive transfer of pro-inflammatory macrophages attenuated biofilm burden, highlighting the critical role of monocyte/macrophage inflammatory status in dictating biofilm persistence. The inflammatory properties of leukocytes are linked to their metabolic state, and here we demonstrate that biofilm-associated monocytes exhibit a metabolic bias favoring oxidative phosphorylation (OxPhos) and less aerobic glycolysis to facilitate their anti-inflammatory activity and biofilm …

Stochastic Expression Of Sae-Dependent Virulence Genes During Staphylococcus Aureus Biofilm Development Is Dependent On Saes, Elizabeth A. Delmain, Derek E. Moormeier, Jennifer L. Endres, Rebecca E. Hodges, Marat R. Sadykov, Alexander R. Horswill, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

The intricate process of biofilm formation in the human pathogen Staphylococcus aureus involves distinct stages during which a complex mixture of matrix molecules is produced and modified throughout the developmental cycle. Early in biofilm development, a subpopulation of cells detaches from its substrate in an event termed “exodus” that is mediated by SaePQRS-dependent stochastic expression of a secreted staphylococcal nuclease, which degrades extracellular DNA within the matrix, causing the release of cells and subsequently allowing for the formation of metabolically heterogenous microcolonies. Since the SaePQRS regulatory system is involved in the transcriptional control of multiple S. aureus virulence factors, the …

Fluorescent Sensor Arrays Can Predict And Quantify The Composition Of Multicomponent Bacterial Samples, Denis Svechkarev, Marat Sadykov, Lucas J. Houser, Kenneth W. Bayles, Aaron M. Mohs

Journal Articles: Pathology and Microbiology

Fast and reliable identification of infectious disease agents is among the most important challenges for the healthcare system. The discrimination of individual components of mixed infections represents a particularly difficult task. In the current study we further expand the functionality of a ratiometric sensor array technology based on small-molecule environmentally-sensitive organic dyes, which can be successfully applied for the analysis of mixed bacterial samples. Using pattern recognition methods and data from pure bacterial species, we demonstrate that this approach can be used to quantify the composition of mixtures, as well as to predict their components with the accuracy of ~80% …

An Integrated Computational And Experimental Study To Investigate Staphylococcus Aureus Metabolism, Mohammad Mazharul Islam, Vinai Chittezham Thomas, Matthew Van Beek, Jong-Sam Ahn, Abdulelah A. Alqarzaee, Chunyi Zhou, Paul D. Fey, Kenneth W. Bayles, Rajib Saha

Journal Articles: Pathology and Microbiology

Staphylococcus aureus is a metabolically versatile pathogen that colonizes nearly all organs of the human body. A detailed and comprehensive knowledge of staphylococcal metabolism is essential to understand its pathogenesis. To this end, we have reconstructed and experimentally validated an updated and enhanced genome-scale metabolic model of S. aureus USA300_FPR3757. The model combined genome annotation data, reaction stoichiometry, and regulation information from biochemical databases and previous strain-specific models. Reactions in the model were checked and fixed to ensure chemical balance and thermodynamic consistency. To further refine the model, growth assessment of 1920 nonessential mutants from the Nebraska Transposon Mutant Library …

Investigating The Effects Of Brainstem Neuronal Adaptation On Cardiovascular Homeostasis., James H Park, Jonathan Gorky, Babatunde Ogunnaike, Rajanikanth Vadigepalli, James S Schwaber

Articles, Abstracts, and Reports

Central coordination of cardiovascular function is accomplished, in part, by the baroreceptor reflex, a multi-input multi-output physiological control system that regulates the activity of the parasympathetic and sympathetic nervous systems via interactions among multiple brainstem nuclei. Recent single-cell analyses within the brain revealed that individual neurons within and across brain nuclei exhibit distinct transcriptional states contributing to neuronal function. Such transcriptional heterogeneity complicates the task of understanding how neurons within and across brain nuclei organize and function to process multiple inputs and coordinate cardiovascular functions within the larger context of the baroreceptor reflex. However, prior analysis of brainstem neurons revealed …