Medical Specialties Commons^™

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 …

Tlr2 And Caspase-1 Signaling Are Critical For Bacterial Containment But Not Clearance During Craniotomy-Associated Biofilm Infection, Amy L. Aldrich, Cortney E. Heim, Wen Shi, Rachel W. Fallet, Bin Duan, Tammy Kielian

Journal Articles: Pathology and Microbiology

BACKGROUND: A craniotomy is required to access the brain for tumor resection or epilepsy treatment, and despite precautionary measures, infectious complications occur at a frequency of 1-3%. Approximately half of craniotomy infections are caused by Staphylococcus aureus (S. aureus) that forms a biofilm on the bone flap, which is recalcitrant to antibiotics. Our prior work in a mouse model of S. aureus craniotomy infection revealed a critical role for myeloid differentiation factor 88 (MyD88) in bacterial containment and pro-inflammatory mediator production. Since numerous receptors utilize MyD88 as a signaling adaptor, the current study examined the importance of Toll-like receptor 2 …

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 …

Refractory Scleroderma Renal Crisis Precipitated After High-Dose Oral Corticosteroids And Concurrent Intravitreal Injection Of Bevacizumab., Ramy M Hanna, Lama Abdelnour, Jonathan E Zuckerman, Antoney J Ferrey, Alex Pai, Kambiz Vahabzadeh, James Wilson, Everado A Torres, Kamyar Kalantar-Zadeh, Ira B Kurtz

Articles, Abstracts, and Reports

Scleroderma renal crisis is a serious complication that can develop in certain patients with systemic sclerosis. Some risks have been identified as potential triggers of scleroderma renal crisis, including the high-dose oral corticosteroids. Here, we present a patient who developed clinically severe systemic sclerosis and scleroderma renal crisis after exposure to oral corticosteroids and intravitreal vascular endothelial growth factor blockade with bevacizumab for cotton wool spots. The patient's scleroderma renal crisis was severe, progressive, and refractory to the standard of care therapy: oral captopril. Biopsy showed a diffuse thrombotic microangiopathy and findings consistent with scleroderma renal crisis. We hypothesize that …

Social Media Engagement At Academic Conferences: Report Of The Association Of Pathology Chairs 2018 And 2019 Annual Meeting Social Media Committee, Yonah C. Ziemba, Dana Razzano, Timothy C. Allen, Adam L. Booth, Scott R. Anderson, Anne Champeaux, Michael D. Feldman, Valerie Fitzhugh, Simone Gittens, Marilea Grider, Mary Gupta, Christina Hanos, Karen Kelly, Tarush Kothari, Jennifer Laudadio, Amy Y. Lin, Kamran M. Mirza, Kathleen T. Montone, Priscilla S. Markwood

Pathology and Cell Biology Faculty Publications

The use of social media at academic conferences is expanding, and platforms such as Twitter are used to share meeting content with the world. Pathology conferences are no exception, and recently, pathology organizations have promoted social media as a way to enhance meeting exposure. A social media committee was formed ad hoc to implement strategies to enhance social media involvement and coverage at the 2018 and 2019 annual meetings of the Association of Pathology Chairs. This organized approach resulted in an 11-fold increase in social media engagement compared to the year prior to committee formation (2017). In this article, the …

Utilizing Social Media To Spread Knowledge: The Association Of Pathology Chairs Experience At The 2018 Annual Meeting, Dana Razzano, Yonah C. Ziemba, Adam L. Booth, Priscilla Markwood, Christina T. Hanos, Nicole Riddle

Pathology and Cell Biology Faculty Publications

No abstract provided.

Intravascular Lymphoma With Progressive Cns Hemorrhage And Multiple Dissections., Ricky Chen, Gurjeet Singh, J Scott Mcnally, Cheryl A Palmer, Adam De Havenon

Articles, Abstracts, and Reports

Introduction: Intravascular lymphoma (IVL) is an uncommon and often fatal disease characterized by intraluminal proliferation of lymphomatous cells within blood vessels. Because of a heterogeneous clinical presentation and lack of sensitive diagnostic protocols, diagnosis of IVL is most often made at autopsy. However, with early diagnosis and appropriate chemotherapy, the prognosis is greatly improved and complete remission is possible. In order to broaden the possible presentations of IVL, we present a patient with an atypical manifestation of biopsy-proven intravascular large B-cell lymphoma who suffered dissections of both intracranial and extracranial arteries in addition to progressive intracranial hemorrhages.

Conclusion: IVL is …

Analysis Of Terminal Duct Lobular Unit Involution In Luminal, Her-2enriched And Triple Negative Breast Cancer Subtypes, Joseph Nyaguti Kiwinga

Master of Medicine in Anatomic Pathology

Introduction: The terminal duct lobular unit (TDLU) of the breast is the most common origin of most breast cancers (BC). With increasing age and menopause, physiologic involution of TDLU occurs with a reduction in both the number and size of the lobules. Reduced TDLU involution is associated with a higher mammographic breast density (MBD) which by itself is a strong breast cancer risk factor. Recent studies have shown that TDLU involution is associated with a reduced risk of breast cancer and involution also differs with molecular subtypes of BC. Studies have shown that the etiology, pathogenesis and prognosis of the …

Determinants Of Pathological Response To Neoadjuvant Chemotherapy In Women With Breast Cancer In Kenya, Ngayu Munga Thairu

Master of Medicine in Anatomic Pathology

Background: Breast cancer (BC) is the most common cause of cancer deaths in Kenya. Standard treatment involves surgery followed by adjuvant chemo/radiotherapy as appropriate. Neoadjuvant chemotherapy (NACT) facilitates surgery in locally advanced breast cancer. The Residual Cancer Burden (RCB) is an objective, standardised measure of pathological response to NACT. Pathological complete response (pCR) (RCB Class 0) is a robust prognostic indicator, used in clinical trials. This study aimed to use RCB to improve understanding of current practice and effectiveness of NACT for breast cancer patients at Aga Khan University Hospital Nairobi (AKUH, N.).

Methods: 67 breast cancer patients …

Etiologies Of Lower Respiratory Tract Infections Among Adult Patients Presenting To A Tertiary Institution In Nairobi, Mary Achakolong

Master of Medicine in Anatomic Pathology

Background: Lower respiratory tract infections continue to contribute significantly to morbidity and mortality across all age groups globally. Viral pathogens in isolation or as co-infections are an important cause of pneumonia and associated with several life threatening syndromes that warrant appropriate and timely lifesaving diagnosis. Many viral respiratory infections demonstrate substantial regional and seasonal variations which are poorly understood. In addition, there are very few studies in sub-Saharan Africa that have examined the role of viruses as causes of community acquired pneumonia. The availability of molecular techniques such as multiplex PCR that are much more sensitive than traditional methods and …

Tick-Borne Infections In New Hampshire: An Evaluation Of The Diagnostic Process In A Local Patient Population, Katherine Anderson

Honors Theses and Capstones

Overall, approximately 95 percent of reported cases of vector-borne disease were associated with ticks, making these the most medically important group of arthropods in the United States.¹ Despite the prevalence of tick-borne infections, the process for the diagnosis of this condition is not well studied. This study aims to analyze data from a pool of 100 patients who underwent testing for tick-borne disease in the same institution in Dover, New Hampshire during the most recent peak tick season of 2019. Information utilized in this study included: patient age, sex, location of testing (inpatient versus outpatient), diagnostic testing methods used …

Hormonal Regulation Of Glycine Decarboxylase And Its Metabolic Outcomes, Ruta Milind Jog

Wayne State University Dissertations

The amino acid glycine is involved in generation of multiple critical metabolites including glutathione, heme, and creatinine. Interestingly, in both humans and rodents, circulating glycine levels are significantly reduced in obesity, glucose intolerance, type II diabetes and non-alcoholic fatty liver disease. The glycine cleavage system is the predominant glycine degradation pathway in humans. The rate-limiting enzyme of glycine cleavage system is glycine decarboxylase (GLDC), and loss-of-function mutations of GLDC cause hyperglycinemia. Here, we show that GLDC gene expression is upregulated in livers of mouse models of diabetes and diet-induced obesity as well as in the fasted state in normal animals. …

Von Willebrand Disease Among Women Of African Descent Attending The Aga Khan University Hospital Nairobi, With Menorrhagia, Angela Nabutilu Munoko

Master of Medicine in Clinical Pathology

Introduction: Von Willebrand Disease (VWD) is the most common heritable bleeding disorder with equal prevalence reported across the races. Women are more likely to present with excessive bleeding due to menstruation and child bearing. Studies have found that 5-24% of women presenting with menorrhagia have VWD. Women of African descent are under-represented in studies carried out on Von Willebrand disease and lower prevalence has been reported in this population. VWD has variable penetrance and racial differences in genetic mutations may influence presentation and disease severity. It was predicted that the standardization of the study conditions (case definition of menorrhagia, use …

Acute Mesenteric Thrombosis: A Hematologist Perspective, Bushra Moiz, Zaid Muslim, Zahraa Farrukh Siddiqui, Hasnain Zafar

Department of Pathology and Laboratory Medicine

No abstract provided.

Kidney Stone Analysis And Spiritual Guides (Pir Faqir): The Known-Unknowns, Lena Jafri, Aysha Habib Khan, Humaira Asif

Department of Pathology and Laboratory Medicine

No abstract provided.

Glycogen Storage Diseases-Time To Flip The Outdated Diagnostic Approach Centered On Liver Biopsy With The Molecular Testing, Sibtain Ahmed, Bushra Afroze

Department of Pathology and Laboratory Medicine

The glycogen storage diseases (GSDs) are a group of inherited metabolic disorders that result from a defect in any one of several enzymes required for either glycogen synthesis or glycogen degradation. The traditional diagnostic approach is based on the invasive hepatic or muscle biopsies, which are neither cost effective nor convenient. Molecular (gene testing) has emerged over the course of past few years as a robust alternative diagnostic tool, which not only confirms the diagnosis of GSDs but also clearly differentiates the types of GSDs allowing the initiation of the type-specific appropriate treatment for the particular type of GSDs. The …

Kidney Stone Analysis And Spiritual Guides (Pir Faqir): The Known-Unknowns, Lena Jafri, Aysha Habib Khan, Humaira Asif

Department of Pathology and Laboratory Medicine

No abstract provided.

Use Of Pefloxacin As A Surrogate Marker To Detect Ciprofloxacin Susceptibility In Salmonella Enterica Serotypes Typhi And Paratyphi A, Safia Moin, Mohammad Zeeshan, Sidra Laiq, Ahmed Raheem, Afia Zafar

Department of Pathology and Laboratory Medicine

Objective: To determine the use of pefloxacin as a surrogate marker to detect fluoroquinolone (ciprofloxacin) susceptibility against Salmonella enterica serotypes Typhi and Paratyphi A.
Methods: The prospective, descriptive cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, from September 2016 to March 2018, and comprised Salmonella Typhi and Paratyphi A isolates of blood cultures. Disk susceptibility tests and broth microdilution to test minimum inhibitory concentration were performed as per standard guidelines. Data was analysed using SPSS 21.
Results: Of the 138 isolates, 91(66%) were intermediate resistant to ciprofloxacin but were resistant to pefloxacin, 42(30%) were resistant to both …

Is It T3 Thyrotoxicosis? A Case Of Falsely Elevated Tri-Iodothyronine (T3) Levels Leading To A Diagnosis Of Multiple Myeloma, Nanik Ram, Saira Furqan, Sibtain Ahmed

Section of Diabetes, Endocrinology and Metabolism

We are presenting a case of falsely elevated T3 levels in a patient due to interference from monoclonal immunoglobulins. A 56-year-old, clinically euthyroid man referred to the endocrinology clinic of the Aga Khan university, Karachi Pakistan, for possible T3 thyrotoxicosis after thyroid function tests revealed total T3 >12.32 nmol/L (reference range 0.6-2.79), normal TSH, and total T4 level. There was a mismatch in clinical and laboratory parameters and preliminary laboratory results were suggestive of thyroid binding globulin abnormalities. Further evaluation in this context unmasked multiple myeloma. The presence of monoclonal immunoglobulins can lead to assay interference and spurious results. To …

Pbrm1 Acts As A P53 Lysine-Acetylation Reader To Suppress Renal Tumor Growth., Weijia Cai, Liya Su, Lili Liao, Zongzhi Z Liu, Lauren Langbein, Essel Dulaimi, Joseph R Testa, Robert G Uzzo, Zhijiu Zhong, Wei Jiang, Qin Yan, Qing Zhang, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

p53 acetylation is indispensable for its transcriptional activity and tumor suppressive function. However, the identity of reader protein(s) for p53 acetylation remains elusive. PBRM1, the second most highly mutated tumor suppressor gene in kidney cancer, encodes PBRM1. Here, we identify PBRM1 as a reader for p53 acetylation on lysine 382 (K382Ac) through its bromodomain 4 (BD4). Notably, mutations on key residues of BD4 disrupt recognition of p53 K382Ac. The mutation in BD4 also reduces p53 binding to promoters of target genes such as CDKN1A (p21). Consequently, the PBRM1 BD4 mutant fails to fully support p53 transcriptional activity and is defective …

A Community Of Care: Patterns Of Pathology And Trauma With A Focus On The Bioarchaeology Of Care At Carrier Mills, Il (10,000 – 1000 Bp), Alecia Schrenk

UNLV Theses, Dissertations, Professional Papers, and Capstones

Illness and injury are universal human experiences which are endowed with cultural meaning. Bioarchaeology has only recently begun to engage with the socioeconomic impacts of illness, injury, impairment, and healthcare provisioning in the past. This study examines how the Middle Archaic (6000 – 300 BC) and Early Woodland (1000 – 200 BC) hunter-gatherer community of Carrier Mills, Illinois was affected by and managed the socioeconomic burdens of poor health. The data presented in this study used bioarchaeological analyses to reveal patterns of poor health and healthcare provisioning within the Carrier Mills community. Bioarchaeology is ideally situated for such investigations since …

Sarcoidosis Of The Mandibular Condyle: A Rare Disease That Can Mimic Malignancy, Chad Sloan, Ben Lacrosse, Lei Yu, Alexander Braun, Scott Lauer, Timothy Donovan, John Baker, Jason Untrauer

Graduate Medical Education Research Journal

Sarcoidosis can involve any of the organs, however intraosseous involvement is rare and ranges from 5 to 15%, with lesions of the mandible being even rarer – currently with few known cases reported. Intraosseous lesions involving the mandible have been noted to be asymptomatic or associated with chronic jaw pain. Additionally, mandibular involvement can present as a lytic bone lesion mimicking osseous malignancy. Chronic polyarthritis is commonly associated with the progression of sarcoidosis and intraosseous involvement has been considered a late-stage sequelae. We report a case of biopsy-proven sarcoidosis within the mandibular condyle in an asymptomatic 56-year-old Caucasian female who …

Multiple Mitochondrial Thioesterases Have Distinct Tissue And Substrate Specificity And Coa Regulation, Suggesting Unique Functional Roles., Carmen Bekeova, Lauren Anderson-Pullinger, Kevin Boye, Felix Boos, Yana Sharpadskaya, Johannes M Herrmann, Erin L. Seifert

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Acyl-CoA thioesterases (Acots) hydrolyze fatty acyl-CoA esters. Acots in the mitochondrial matrix are poised to mitigate β-oxidation overload and maintain CoA availability. Several Acots associate with mitochondria, but whether they all localize to the matrix, are redundant, or have different roles is unresolved. Here, we compared the suborganellar localization, activity, expression, and regulation among mitochondrial Acots (Acot2, -7, -9, and -13) in mitochondria from multiple mouse tissues and from a model of Acot2 depletion. Acot7, -9, and -13 localized to the matrix, joining Acot2 that was previously shown to localize there. Mitochondria from heart, skeletal muscle, brown adipose tissue, and …