Population-Specific Mutation Patterns In Breast Tumors From African American, European American, And Kenyan Patients, Wei Tang, Jung S. Byun, Tiffany H. Dorsey, Harris G. Yfantis, Anuoluwapo Ajao, Huaitian Liu, Margaret S. Pichardo, Catherine M. Pichardo, Alexandra R. Harris, Shahin Sayed

Pathology, East Africa

Women of African descent have the highest breast cancer mortality in the United States and are more likely than women from other population groups to develop an aggressive disease. It remains uncertain to what extent breast cancer in Africa is reminiscent of breast cancer in African American or European American patients. Here, we performed whole-exome sequencing of genomic DNA from 191 breast tumor and non-cancerous adjacent tissue pairs obtained from 97 African American, 69 European American, 2 Asian American, and 23 Kenyan patients. Our analysis of the sequencing data revealed an elevated tumor mutational burden in both Kenyan and African …

P16 Expression And Recurrent Cervical Intraepithelial Neoplasia After Cryotherapy Among Women Living With Hiv, Daniel Maina, Michael H. Chung, Marleen Temmerman, Zahir Moloo, Jonathan Wawire, Sharon A. Greene, Elizabeth Unger, Shahin Sayed, Samah Sakr, Nelly Mugo

Pathology, East Africa

Background: The expression of p16 protein, a surrogate marker for high-risk human papillomavirus (hrHPV), is associated with cervical dysplasia. We evaluated correlates of p16 expression at treatment for high-grade cervical lesions and its utility in predicting the recurrence of cervical intraepithelial lesions grade 2 or higher (CIN2+) following cryotherapy among women with HIV.

Methods: This is a subgroup analysis of women with HIV in Kenya with baseline cervical biopsy-confirmed CIN2+ who were randomized to receive cryotherapy and followed every six-months for two-years for biopsy-confirmed recurrence of CIN2+. P16 immunohistochemistry was performed on the baseline cervical biopsy with a positive result …

Moans, Palpable Groin, And Entrapment Of Bone: A Case Of Malignant Peripheral Nerve Sheath Tumor In An Otherwise Healthy Hispanic Male, Nelson D. Gonzalez, Christine E. Loftis, Rosa Guedez-White

Research Symposium

Background: Malignant peripheral nerve sheath tumors (MPNTs) are rare malignant soft tissue sarcomas that have an incidence of about 0.001 %. MPNTs typically occur in individuals who have neurofibromatosis or secondary to radiation therapy and rarely occur sporadically. We present a case of a previously healthy 56-year-old gentleman who was diagnosed with MPNTs.

Case: A healthy 56-year-old gentleman presented with worsening LLQ abdominal pain for 6 months. Associated symptoms included bloating, LLE swelling, early satiety for the past 2 months, and a 5-10lb unintentional weight loss. Patient denied recent cough, night sweats, dyspnea, fever, chills, melena or hematochezia. Vitals were …

Unveiling The Potential Application Of Intraoperative Brain Smear For Brain Tumor Diagnosis In Low-Middle-Income Countries: A Comprehensive Systematic Review, Muhammad Shakir, Ahmed Altaf, Hawra Hussain, Syed Muhammad Aqeel Abidi, Zoey Petitt, Mahnoor Tariq, Ahmed Gilani, Syed Ather Enam

Section of Neurosurgery

Background: Immediate intraoperative histopathological examination of tumor tissue is indispensable for a neurosurgeon to track surgical resection. A brain smear is a simple, rapid, and cost-effective technique, particularly important in the diagnosis of brain tumors. The study aims to determine the effectiveness of intraoperative brain smear in the diagnosis of brain tumors in low- and middle-income countries (LMICs), while also evaluating its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy.
Methods: A comprehensive search of the literature was conducted using PubMed, Scopus, and Google Scholar. The retrieved articles were independently screened by two reviewers. The …

Hla-Ii-Dependent Neuroimmune Changes In Group A Streptococcal Necrotizing Fasciitis, Ganesh Ambigapathy, Santhosh Mukundan, Kumi Nagamoto-Combs, Colin Combs, Suba Nookala

Biomedical Sciences Faculty Publications

Streptococcus pyogenes (Group A Streptococcus, GAS) bacteria cause a spectrum of human diseases ranging from self-limiting pharyngitis and mild, uncomplicated skin infections (impetigo, erysipelas, and cellulitis) to highly morbid and rapidly invasive, life-threatening infections such as streptococcal toxic shock syndrome and necrotizing fasciitis (NF). HLA class II allelic polymorphisms are linked with differential outcomes and severity of GAS infections. The dysregulated immune response and peripheral cytokine storm elicited due to invasive GAS infections increase the risk for toxic shock and multiple organ failure in genetically susceptible individuals. We hypothesized that, while the host immune mediators regulate the immune responses against …

Outpatient Management Of Urinary Tract Infections By Medical Officers In Nairobi, Kenya: Lack Of Benefit From Audit And Feedback On Adherence To Treatment Guidelines, Florence Mbatia, James Orwa, Mary B. Adam, Gulnaz Mohamoud, Rodney Adam

Family Medicine, East Africa

Introduction: Acute uncomplicated urinary tract infections are common in outpatient settings but are not treated optimally. Few studies of the outpatient use of antibiotics for specifc diagnoses have been done in sub-Saharan Africa, so little is known about the prescribing patterns of medical ofcers in the region.

Methods: Aga Khan University has 16 outpatient clinics throughout the Nairobi metro area with a medical ofcer specifcally assigned to that clinic. A baseline assessment of evaluation and treatment of suspected UTI was performed from medical records in these clinics. Then the medical ofcer from each of the 16 clinics was recruited from …

September 2023: Region 10 Emerging Special Pathogen Treatment Center (Resptc) At Providence Sacred Heart Medical Center & Children’S Hospital, Providence - Special Pathogens Program

Special Pathogens Newsletters

REGION 10 SPECIAL PATHOGENS NEWSLETTER

The Combination Of Platelet Rich Plasma And Corticosteroids In Musculoskeletal And Musculotendinous Pathologies, Mikayla Stoudt

Master of Science in Physician Assistant Studies Capstone Presentations (Center City)

Background

- 126 million Americans reported to have a musculoskeletal or musculotendinous pathology in 2012¹

- Combined direct and indirect cost of these injuries in 2015 was $874 billion¹

- Corticosteroid injections have been the mainstay of invasive management after conservative methods fail
Long-term effects of corticosteroids

• Intra-articular injections for knee osteoarthritis resulted in cartilage volume loss¹⁰
• Harm to flexor tendons, neurovascular structures, and compromised integrity^{7, 11}

- Platelet Rich Plasma

• Sample patient blood --> Centrifuge --> Separate plasma and platelets from other blood products --> Reconcentrate the platelets into the plasma
• Platelets release growth factor …

Persistent Foci Of Infection: A Case Of Two Mycotic Aneurysms Separated In Time In A Patient With Infective E. Faecalis Endocarditis, Julia C. Stone, Joel Thompson, Joseph Hatem, Evan Basha

Advances in Clinical Medical Research and Healthcare Delivery

This is a case report of a patient who presented with mycotic aneurysms of two different blood vessels at separate hospital visits following a diagnosis of infective endocarditis.

The Role Of Dlc1Β In Attenuating Cardiac Ischemia-Reperfusion Injury During Heart Transplantation, Samantha L. Collings

Electronic Thesis and Dissertation Repository

Cardiac ischemia-reperfusion injury (IRI) occurs intra-operatively during heart transplantation (HTx), underpinning graft survival. Past research implicated the PI3K/Akt1 & RhoA/ROCK pathways in IRI. Rho-GTPase activity/Akt regulates Deleted-in-liver-cancer 1 protein’s beta-isoform (DLC1β). Therefore, we hypothesized that DLC1β overexpression (OE) had anti-apoptotic effects. In vitro, HL-1 cells (mouse cardiomyocytes) received chamber hypoxia-oxygenation reperfusion (H/R) for 24H4R with/without DLC1β plasmid, before collection for protein/mRNA analyses. DLC1β-OE resulted in downregulated pro-apoptotic mRNA expression (Bax/Cycs/Casp3), upregulated protective mRNA targets (BCl2/Akt1) and less late/early apoptosis via flow cytometry. Results were confirmed via H9C2 (rat cardiomyocyte) cell lines. In vivo, C57/BL6 mice received heterotopic HTx with/without DLC1β-OE …

Pitfalls In Machine Learning-Based Assessment Of Tumor-Infiltrating Lymphocytes In Breast Cancer: A Report Of The International Immuno-Oncology Biomarker Working Group On Breast Cancer, Jeppe Thagaard, Glenn Broeckx, Chowdhury Arif Jahangir, Sara Verbandt, Rajarsi Gupta, Reena Khiroya, Khalid Abduljabbar, Gabriela Acosta Haab, Balazs Acs, Shahin Sayed

Pathology, East Africa

Abstract: The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL …

Development, Roll-Out And Implementation Of An Antimicrobial Resistance Training Curriculum Harmonizes Delivery Of In-Service Training To Healthcare Workers In Kenya, Josiah Njeru, Joshua Odero, Sheilla Chebore, Mungai Ndung’U, Emmanuel Tanui, Evelyn Wesangula, Romona Ndanyi, Susan Githii, R Gunturu, Willy Mwangi

Pathology, East Africa

Background: Antimicrobial resistance (AMR) is an increasingly severe threat to global public health that requires action across different sectors. Selection of appropriate antimicrobials is an urgent challenge due to the emergence of drug resistance. In 2017, Kenya developed an AMR policy and National Action Plan to drive prevention and containment of AMR. A priority activity under AMR surveillance strategic objective was to develop a national AMR training curriculum for in-service healthcare workers. In this paper we discuss the development process, gains achieved through implementation across the country and lessons learned.

Methods: An initial stakeholders’ forum was convened to …

Spatial Analyses Of Immune Cell Infiltration In Cancer: Current Methods And Future Directions: A Report Of The International Immuno-Oncology Biomarker Working Group On Breast Cancer, David Page, Chowdhury Jahangir, Sara Verbandt, Rajarsi Gupta, Jeppe Thagaard, Reena Khiroya, Zuzana Kos, Khalid Abduljabbar, Sunil Badve, Shahin Sayed

Pathology, East Africa

Abstract: Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector-based). We then provide a compendium of spatial immune cell metrics that have been reported in the literature, summarizing prognostic associations in the context of a variety of cancers. We conclude by discussing two well-described …

Primary Adrenal Angiosarcoma: A Case Report And Review Of The Literature, Zunaira Naeem, Joon Yau Leong, Arianna Morton, Alaa Hrizat, Eric Shiffrin, Andrew Gomella, Peter Mccue, Mark Mann, Li Li

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Primary adrenal angiosarcoma is an extremely rare malignant tumor with challenging diagnosis. A 66-year-old woman had a 4.3 cm right adrenal mass suspicious for adrenal cortical carcinoma. Pathological examination demonstrated a hemorrhagic adrenal cyst with numerous irregularly shaped anastomosing vascular channels lined by atypical endothelial cells that had frequent atypical mitotic figures (12/10 HPF, Ki67 10%). The tumor cells were positive for CD31, ERG, and FLI-1, but negative for adrenal and other tumor lineage markers by immunohistochemistry. NGS fusion gene testing ruled out epithelioid hemangioendothelioma. Accurate diagnosis and differential inclusion are important for appropriate treatment of this rare tumor.

The Association Between Higher Expression Of Talin-1 And The Reduced Survival Rate In Ovarian Serous Carcinoma Patients, Mina Sharbatoghli, Leili Saeednejad Zanjani, Fahimeh Fattahi, Elham Kalantari, Zohre Habibi Shams, Mahshid Panahi, Medhi Totonchi, Mohsen Asadi-Lari, Zahra Madjd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background & Objective: Talin-1 is a constituent of the multiprotein adhesion complexes that play main role in the formation of tumors and migration in different types of malignancies. The present study aimed to assess expression and prognostic significance of the talin-1 protein in ovarian serous carcinoma (OSC) patients.

Methods: The expression of talin-1 in mRNA and its protein levels were investigated for ovarian cancer (OC) by using bioinformatics tools, including Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Gene Expression Database of Normal and Tumor Tissue 2 (GENT2), and The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) databases. …

Fibrosis-The Tale Of H3k27 Histone Methyltransferases And Demethylases, Morgan D. Basta, Svetlana Petruk, Alexander Mazo, Janice L. Walker

Department of Biochemistry and Molecular Biology Faculty Papers

Fibrosis, or excessive scarring, is characterized by the emergence of alpha-smooth muscle actin (αSMA)-expressing myofibroblasts and the excessive accumulation of fibrotic extracellular matrix (ECM). Currently, there is a lack of effective treatment options for fibrosis, highlighting an unmet need to identify new therapeutic targets. The acquisition of a fibrotic phenotype is associated with changes in chromatin structure, a key determinant of gene transcription activation and repression. The major repressive histone mark, H3K27me3, has been linked to dynamic changes in gene expression in fibrosis through alterations in chromatin structure. H3K27-specific homologous histone methylase (HMT) enzymes, Enhancer of zeste 1 and 2 …

Labrad : Vol 48, Issue 1 - July 2023, Aga Khan University Hospital, Karachi

LABRAD

• Editorial
• Articles
• Toxicology In Public Health: Mitigating Risk, Fostering Well-Being
• Predictive And Prognostic Biomarkers in Histopathology
• Cancer Registry and Public Health Surveillance - Role of Pathologists
• Diagnosis of Celiac Disease DQA1*02,05; DQB1*02,03:02 (DQ2&DQ8) in patients
• Magnifying The Clinical Value of Expert Review and Reassessment
• Urine Cytology: A Screening and Surveillance Test
• An Overview of Convalescent Plasma for The Treatment of COVID-19
• Role of Imaging in Public Health Care
• Microsatellite Instability (MSI) Testing
• MRI Liver with Hepatocyte-Specific Contrast Agent
• Basics and Role of Cytopathology
• Bone Tumors: From Timely Diagnosis to Improved Patient Outcome
• Differentiating Between Dengue Fever and Malaria Using The …

Oropharyngeal Teratoma: Five-Month-Old Presenting With Failure To Thrive And Severe Obstructive Sleep Apnea., Anna Lawrence, Melissa Gener, Shao Jiang, Jill M. Arganbright

Manuscripts, Articles, Book Chapters and Other Papers

Oropharyngeal teratomas are an extremely rare congenital tumor. They are often diagnosed prenatally and can cause significant airway obstruction and feeding difficulties at birth. We present a five-month-old female that was diagnosed with a palatal teratoma that presented with failure to thrive, difficulty feeding, and eventually with severe obstructive sleep apnea. We present a five-month-old term, otherwise healthy female who became stridulous after an episode of the respiratory syncytial virus at one month old. At three months old, an otolaryngologist diagnosed mild laryngomalacia with no mass identified, and no surgical intervention was recommended. Due to continued poor weight gain, at …

Resolved Peristomal Erosive Papulonodular Dermatitis Mimicking Nevoid Hyperkeratosis Of The Nipple And Areola, Christa M. Tomc, Daniel A. Nguyen, Joseph S. Susa, Stephen E. Weis

HCA Healthcare Journal of Medicine

Introduction

Nevoid hyperkeratosis of the nipple and areola (NHKNA) is a rare cutaneous entity with a distinct clinical and histological presentation. The type II form of this condition can result from various dermatoses, such as irritant contact dermatitis. Erosive papulonodular dermatitis is a chronic irritant dermatitis that often occurs in areas of occlusion and maceration, such as peristomal skin. Pseudoverrucous papules and nodules are a variant of erosive papulonodular dermatitis and have a non-specific histologic pattern of reactive hyperplasia.

Case Presentation

We present a case of a patient with resolved peristomal erosive papulonodular dermatitis who presented status-post ileostomy reversal with …

Immune Cells Localize To Sites Of Corneal Erosions In C57bl/6 Mice., Phuong M. Le, Sonali Pal-Ghosh, A. Menko, Mary Ann Stepp

Computational Medicine Center Faculty Papers

Recurrent epithelial erosions develop in the cornea due to prior injury or genetic predisposition. Studies of recurrent erosions in animal models allow us to gain insight into how erosions form and are resolved. While slowing corneal epithelial cell migration and reducing their proliferation following treatment with mitomycin C reduce erosion formation in mice after sterile debridement injury, additional factors have been identified related to cytokine expression and immune cell activation. The relationship between recruitment of immune cells to the region of the cornea where erosions form and their potential roles in erosion formation and/or erosion repair remains unexplored in the …