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 …

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 …

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 …

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 …

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 …

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 …

7-Ketocholesterol Promotes Retinal Pigment Epithelium Senescence And Fibrosis Of Choroidal Neovascularization Via Iqgap1 Phosphorylation-Dependent Signaling, Haibo Wang, Aniket Ramshekar, Thaonhi Cung, Chris Wallace-Carrete, Chandler Zaugg, Jasmine Nguyen, Gregory J. Stoddard, M. Elizabeth Hartnett

School of Medicine Faculty Publications

Accumulation of 7-ketocholesterol (7KC) occurs in age-related macular degeneration (AMD) and was found previously to promote fibrosis, an untreatable cause of vision loss, partly through induction of endothelial-mesenchymal transition. To address the hypothesis that 7KC causes mesenchymal transition of retinal pigment epithelial cells (RPE), we exposed human primary RPE (hRPE) to 7KC or a control. 7KC-treated hRPE did not manifest increased mesenchymal markers, but instead maintained RPE-specific proteins and exhibited signs of senescence with increased serine phosphorylation of histone H3, serine/threonine phosphorylation of mammalian target of rapamycin (p-mTOR), p16 and p21, β-galactosidase labeling, and reduced LaminB1, suggesting senescence. The cells …

Radiologic And Histologic Findings Of Locally Advanced Mucoepidermoid Carcinoma Managed With Total Surgical Excision, Christopher R. Huber, Don Truong, Joseph Hatem, Joel Thompson, Bryan Scott

Advances in Clinical Medical Research and Healthcare Delivery

The present case report provides images from computed tomography and histology of a patient with a salivary gland neoplasm consistent with mucoepidermoid carcinoma.

Gm1 Ganglioside As A Disease-Modifying Therapeutic For Parkinson’S Disease: A Multi-Functional Glycosphingolipid That Targets Multiple Parkinson’S Disease-Relevant Pathogenic Mechanisms, Jay S. Schneider

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting millions of patients worldwide. Many therapeutics are available for treating PD symptoms but there is no disease-modifying therapeutic that has been unequivocally shown to slow or stop the progression of the disease. There are several factors contributing to the failure of many putative disease-modifying agents in clinical trials and these include the choice of patients and clinical trial designs for disease modification trials. Perhaps more important, however, is the choice of therapeutic, which for the most part, has not taken into account the multiple and complex pathogenic mechanisms and processes involved …

A Cadaveric Case Study On Lung Cancer Pathology, Anna Beth Boyette, Sarah Kate Boyette, Haley Garrett, Janai Groves, Perry Chandler Mullis, Sofia Sirocchi, Shiv Dhiman, Savita Arya

Research Day

INTRODUCTION: Lung cancer is the most commonly diagnosed cancer amongst both genders, currently accounting for about 18% of all cancer deaths.

OBJECTIVES: The overall purpose of this study was to evaluate the pathology associated with the patient’s cause of death, cardiorespiratory failure and lung cancer. The secondary aims of this study were to confirm the presence of malignant neoplasms within a human cadaver, determine the type of cancer present, and take specimens for histological examination to evaluate the patient’s cause of death.

METHODS: This is a case report from one of the cadavers in the Gross Anatomy laboratory at the …

Immunophenotypic Expression Profile Of Multiple Myeloma Cases At A Tertiary Hospital In Nairobi Kenya, Isabella Mengich, Sheerien Rajput, Riyat Malkit, Zahir Moloo, Elizabeth Kagotho, El-Nasir Lalani, Anne Mwirigi

Pathology, East Africa

Introduction: Multiple myeloma (MM) is a plasma cell neoplasm that constitutes 10–15% of all hematopoietic neoplasms. Kenya is placed among the top five African countries for MM incidence and MM-related mortality. Prior studies have suggested that the aberrant expression of Cyclin D1, CD56, CD117 and Ki-67 on neoplastic plasma cells is useful in disease prognostication. The prevalence and significance of expression of these markers in a cohort of MM cases in Kenya has not been studied previously.

Methods: A retrospective cross-sectional study was carried out at the Aga Khan University Hospital, Nairobi. The study population included 83 MM …

Neonatal Reference Intervals For Thyroid Stimulating Hormone And Free Thyroxine Assayed On A Siemens Atellica® Im Analyzer: A Cross Sectional Study, Geoffrey Omuse, David Kawalya, Patrick Mugaine, Assumpta Chege, Daniel Maina

Pathology, East Africa

Background Deriving population specific reference intervals (RIs) or at the very least verifying any RI before adoption is good laboratory practice. Siemens has provided RIs for thyroid stimulating hormone (TSH) and free thyroxine (FT4) determined on their Atellica® IM analyzer for all age groups except the neonatal age group which provides a challenge for laboratories that intend to use it to screen for congenital hypothyroidism (CH) and other thyroid disorders in neonates. We set out to determine RIs for TSH and FT4 using data obtained from neonates undergoing routine screening for CH at the Aga Khan University Hospital, Nairobi, Kenya. …

Oral Manifestations Of Acute Lymphocytic Leukemia, Angela Yepes Dds, Ms, Mba, Juan Yepes Dds, Md, Mph, Ms, Drph, James E. Jones Dmd, Msd, Edd, Phd

The Journal of the Michigan Dental Association

Leukemia is the most prevalent malignancy of leukocytes and can occur in children and adults. Oral manifestations are part of the complexity of signs and symptoms in patients with leukemia and, in some patients, oral manifestations precede systemic manifestations. Oral signs of leukemia include spontaneous bleeding, gingival enlargement, and whiteness of the oral mucosa. Head and neck lymphadenopathy is common in patients with leukemia. Oral manifestations are the result of the direct invasion of immature cells in the oral cavity tissues or indirectly caused by the replacement of the normal blood cells for immature cells causing anemia, leucopenia, and thrombocytopenia. …