Pathology Commons^™

A New Pipeline For Clinico-Pathological And Molecular Placental Research Utilizing Ffpe Tissues., Jiaqi J O'Reilly, Stephanie Barak, Anna A Penn

Pathology Faculty Publications

The placenta is at the core of many pregnancy pathologies, but we have limited knowledge about placental function because of two key research barriers: 1) lack of guidelines for sample collection and pathologic diagnosis; and 2) limited tools are available for molecular analysis of stored placental samples. We aimed to create a searchable, population-based placental database of pathologic diagnoses, and to validate molecular methods for gene expression studies of matching formalin fixed paraffin embedded (FFPE) placental blocks. Our database has over 1000 pregnancies coded for clinical diagnosis with corresponding FFPE blocks that are available for gene expression studies. RNA harvested …

Segmental Absence Of Intestinal Musculature In A Child With Type Iv Ehlers-Danlos Syndrome, Nicole Zeky, Celia Short, Brent Keith, Randall Craver, Jessica A. Zagory

School of Medicine Faculty Publications

Patients with vascular Ehlers-Danlos syndrome (vEDS) have a defect in the formation of type III collagen. This defect puts patients at risk of vascular rupture, uterine rupture, and bowel perforations. The segmental absence of intestinal musculature is a rare histopathologic finding, wherein there is a lack of a muscularis propria layer in the intestinal wall. Although typically documented in the literature in neonates or adults, it can be seen in children of other ages. This is a case report of a patient who exhibits both rare entities, which has not been described in the literature to date.

Our Experience Of Treating Adult Bone Lymphoma, A Retrospective Cross-Sectional Study In A Tertiary Care Center, Aga Khan University Hospital, Karachi, Masood Umer, Muhammad Younus Khan Durrani, Javeria Saeed, Nasir Ud Din

Section of Orthopaedic Surgery

Objective: To determine the experience at the Aga Khan University Hospital in diagnosing and treating adult patients with primary lymphoma of bone.
Methodology: All patients with Primary lymphoma of bone (PLB) that were diagnosed and/or treated at Aga Khan University Hospital, Karachi from 2005 to 2019 were included as part of this study.
Results: There were 17 patients with PLB including 13 (76.5%) males and 4 (23.5%) females with a mean age of 44 ± 16.5 years. Nine patients were between 30-59 years of age at diagnosis. The mean follow-up time of patients was 80±46.7 months. Six patients had tumours …

Synchronous Primary Diffuse Large B-Cell Lymphoma And Papillary Thyroid Carcinoma: A Case Report Highlighting "Lymphoma First Approach", Rahim Dhanani, Ambreen Abdullah Unar, Muhammad Hassan Danish, Hamdan Ahmed Pasha, Ummiya Tahir, Mubasher Ikram

Section of Otolaryngology, Head & Neck Surgery

Papillary thyroid carcinoma (PTC) is the most common type of all thyroid carcinomas and accounts for up to 90% of all thyroid malignancies. It is the most indolent form of the disease and has an excellent prognosis. On the other hand, Primary thyroid lymphoma (PTL) is a rare entity accounting for only about 1% to 5% of all thyroid malignancies and only 2% of extranodal lymphomas. Synchronous PTC and PTL is a very rare condition and only a few cases have been reported in the literature up till now. We report one such case in a 52-year-old lady who was …

Prevalence And Determinants Of Inappropriate Antibiotic Dispensing At Private Drug Retail Outlets In Urban And Rural Areas Of Indonesia: A Mixed Methods Study, Luh Putu Lila Wulandari, Mishal Khan, Marco Liverani, Astri Ferdiana, Yusuf Ari Mashuri, Ari Probandari, Tri Wibawa, Neha Batura, Gill Schierhout, John Kaldor

Department of Pathology and Laboratory Medicine

Introduction: The aim of this mixed-method study was to determine the extent and determinants of inappropriate dispensing of antibiotics by licensed private drug retail outlets in Indonesia.
Methods: Standardised patients (SPs) made a total of 495 visits to 166 drug outlets (community pharmacies and drug stores) between July and August 2019. The SPs presented three clinical cases to drug outlet staff: parent of a child at home with diarrhoea; an adult with presumptive tuberculosis (TB); and an adult with upper respiratory tract infection (URTI). The primary outcome was the dispensing of an antibiotic without prescription, with or without the client …

Orofacial Manifestations Of Lyme Disease: A Systematic Review, Brenda Bradshaw, Kelsey M. Jones, Joleen M. Westerdale-Mcinnis, Holly Gaff

Dental Hygiene Faculty Publications

Purpose: Orofacial manifestations of Lyme disease can affect head and neck anatomical structures that are frequently examined by dental professionals. The purpose of this systematic review was to examine the literature for types and frequencies of orofacial manifestations documented in populations in the United States (US) with Lyme disease.

Methods: Four electronic databases (Dentistry and Oral Sciences, PubMed, Cinahl Plus, and Medline) were systematically searched during the summer of 2019 using keywords and MeSH terms to identify relevant studies. Search term alterations and synonyms were cross-checked using the US National Library of Medicine Unified Medical Language System Metathesaurus. Full-text, English …

Establishing Reference Interval For Thyroid-Stimulating Hormone In Children Below Two-Year Ages In Pakistani Population, Siraj Muneer, Imran Siddiqui, Hafsa Majid, Lena Jafri, Khadija N Humayun, Sibtain Ahmed, Aysha Habib Khan

Department of Pathology and Laboratory Medicine

Introduction: Reference intervals (RIs) of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are age, assay and population specific. Currently, the age and assay-specific RIs for TSH are not available for children under two years of age. This study aimed to establish reference intervals for serum concentrations of TSH and FT4 in healthy children aged 1-24 months as per CLSI C28-A3 guidelines.
Methods: This prospective cross-sectional study was conducted in children from 1 to 24 months visiting the clinical laboratory for serum vitamin D testing but without any recent illness, hospitalization, medication and history of maternal thyroid diseases from August 2018 …

Follicular Thyroid Carcinoma In A Developing Country: A 10-Year Retrospective Study, Abdul Aziz, Qamar Masood, Saadia Sattar, Saira Fatima, Najmul Islam

Section of Diabetes, Endocrinology and Metabolism

Background: The most common endocrine tumor is thyroid cancer. Follicular thyroid carcinoma (FTC) accounts for 5-10% of all thyroid cancers. Patients with FTC frequently present with more advanced diseases and a higher occurrence of distant metastases because of the propensity of vascular invasion. FTC is mainly treated with surgery while radioactive iodine (RAI) therapy is the main adjuvant therapy according to the American Thyroid Association guidelines.
Methodology: This was a retrospective observational study of FTC patients aged 18 and above conducted at a tertiary care hospital in Karachi from January 01, 2010 to December 31, 2019.
Results: A total of …

Diagnosis Of Classic Homocystinuria In Two Boys Presenting With Acute Cerebral Venous Thrombosis And Neurologic Dysfunction After Normal Newborn Screening, Alexander Asamoah, Sainan Wei, Kelly E. Jackson, Joseph H. Hersh, Harvey Levy

Pathology and Laboratory Medicine Faculty Publications

Homocystinuria, caused by cystathionine β-synthase deficiency, is a rare inherited disorder involving metabolism of methionine. Impaired synthesis of cystathionine leads to accumulation of homocysteine that affects several organ systems leading to abnormalities in the skeletal, cardiovascular, ophthalmic and central nervous systems. We report a 14-month-old and a 7-year-old boy who presented with neurologic dysfunction and were found to have cerebral venous sinus thromboses on brain magnetic resonance imaging (MRI)/magnetic resonance venogram (MRV) and metabolic and hypercoagulable work-up were consistent with classic homocystinuria. The 14-month-old boy had normal newborn screening. The 7-year-old boy initially had an abnormal newborn screen for homocystinuria …

Comparison Of Antimicrobial Efficacy Of Calcipex And Metapex In Endodontic Treatment Of Chronic Apical Periodontitis: A Randomised Controlled Trial Study Protocol, Momina Motiwala, Saqib Habib, Rabia Ghafoor, Seema Irfan

Section of Dental-Oral Maxillofacial Surgery

Introduction: Various intracanal medicaments have been used in cases of chronic apical periodontitis for appropriate disinfection of the root canal system to eliminate microbes especially from the inaccessible areas. Calcium hydroxide is the most common intracanal medicament available in various forms, but its effectiveness with or without iodoform using microbial culture is unknown. Therefore, our aim is to compare the antimicrobial efficacy of Calcipex and Metapex in endodontic treatment of teeth presenting with chronic apical periodontitis by assessing the bacterial load reduction.
Method and analysis: 60 single rooted teeth of patients with diagnosis of chronic apical periodontitis will be selected …

Sarcina Organism Of The Stomach: Report Of A Case, Andre Ene, Morgan H. Mccoy, Shadi Qasem

Pathology and Laboratory Medicine Faculty Publications

Sarcina Ventriculi is a gram-positive organism, rarely encountered as a human pathogen. It has been described in stomach specimens, often in patients with delayed gastric emptying. The exact role of this organism in human disease is not clear. In this case report, we describe a case of Sarcina organism associated with gastric ulceration. This organism is likely underreported and often overlooked, as it may not be obvious on routine staining. Awareness of this organism and further studies are needed to understand its role in human disease.

High-Density Blood Transcriptomics Reveals Precision Immune Signatures Of Sars-Cov-2 Infection In Hospitalized Individuals, Jeremy W. Prokop, Nicholas L. Hartog, Dave Chesla, William Faber

University Faculty Publications and Creative Works

The immune response to COVID-19 infection is variable. How COVID-19 influences clinical outcomes in hospitalized patients needs to be understood through readily obtainable biological materials, such as blood. We hypothesized that a high-density analysis of host (and pathogen) blood RNA in hospitalized patients with SARS-CoV-2 would provide mechanistic insights into the heterogeneity of response amongst COVID-19 patients when combined with advanced multidimensional bioinformatics for RNA. We enrolled 36 hospitalized COVID-19 patients (11 died) and 15 controls, collecting 74 blood PAXgene RNA tubes at multiple timepoints, one early and in 23 patients after treatment with various therapies. Total RNAseq was performed …

Gut Integrity And Duodenal Enteropathogen Burden In Undernourished Children With Environmental Enteric Dysfunction, Zehra Jamil, Najeeha Talat Iqbal, Romana Idress, Zubair Ahmad, Kamran Sadiq, Junaid Iqbal, Sana Syed, Aneeta Hotwani, Furqan Kabir, Kumail Ahmed, Sheraz Ahmed, Fayyaz Umrani, Fatima Aziz, Adil Kalam, Syed Asad Ali

Department of Biological & Biomedical Sciences

Environmental enteric dysfunction (EED) is a subclinical condition of intestinal inflammation, barrier dysfunction and malabsorption associated with growth faltering in children living in poverty. This study explores association of altered duodenal permeability (lactulose, rhamnose and their ratio) with higher burden of enteropathogen in the duodenal aspirate, altered histopathological findings and higher morbidity (diarrhea) that is collectively associated with linear growth faltering in children living in EED endemic setting. In a longitudinal birth cohort, 51 controls (WHZ > 0, HAZ > -1.0) and 63 cases (WHZ< -2.0, refractory to nutritional intervention) were recruited. Anthropometry and morbidity were recorded on monthly bases up to 24 months of age. Dual sugar assay of urine collected after oral administration of lactulose and rhamnose was assessed in 96 children from both the groups. Duodenal histopathology (n = 63) and enteropathogen analysis of aspirate via Taqman array card (n = 60) was assessed in only cases. Giardia was the most frequent pathogen and was associated with raised L:R ratio (p = 0.068). Gastric microscopy was more sensitive than duodenal aspirate in H. pylori detection. Microscopically confirmed H. pylori negatively correlated with HAZ at 24 months (r = -0.313, p = 0.013). Regarding histopathological parameters, goblet cell reduction significantly correlated with decline in dual sugar excretion (p< 0.05). Between cases and controls, there were no significant differences in the median (25th, 75th percentile) of urinary concentrations (μg/ml) of lactulose [27.0 (11.50, 59.50) for cases vs. 38.0 (12.0, 61.0) for controls], rhamnose [66.0 (28.0, 178.0) vs. 86.5 (29.5, 190.5)] and L:R ratio [0.47 (0.24, 0.90) vs. 0.51 (0.31, 0.71)] respectively. In multivariable regression model, 31% of variability in HAZ at 24 months of age among cases and controls was explained by final model including dual sugars. In conclusion, enteropathogen burden is associated with altered histopathological features and intestinal permeability. In cases and controls living in settings of endemic enteropathy, intestinal permeability test may predict linear growth. However, for adoption as a screening tool for EED, further validation is required due to its complex intestinal pathophysiology.

The Role Of Interspecies Recombination In The Evolution Of Antibiotic-Resistant Pneumococci, Joshua C. D'Aeth, Mark Pg Van Der Linden, Lesley Mcgee, Herminia De Lencastre, Paul Turner, Jae-Hoon Song, Stephanie W. Lo, Rebecca A. Gladstone, Gps Consortium, Sadia Shakoor

Department of Pathology and Laboratory Medicine

Multidrug-resistant Streptococcus pneumoniae emerge through the modification of core genome loci by interspecies homologous recombinations, and acquisition of gene cassettes. Both occurred in the otherwise contrasting histories of the antibiotic-resistant S. pneumoniae lineages PMEN3 and PMEN9. A single PMEN3 clade spread globally, evading vaccine-induced immunity through frequent serotype switching, whereas locally circulating PMEN9 clades independently gained resistance. Both lineages repeatedly integrated Tn916-type and Tn1207.1-type elements, conferring tetracycline and macrolide resistance, respectively, through homologous recombination importing sequences originating in other species. A species-wide dataset found over 100 instances of such interspecific acquisitions of resistance cassettes and flanking …

Indirect Determination Of Serum Creatinine Reference Intervals In A Pakistani Pediatric Population Using Big Data Analytics, Sibtain Ahmed, Jakob Zierk, Imran Siddiqui, Aysha Habib Khan

Department of Pathology and Laboratory Medicine

Background: The indirect methods of reference intervals (RI) establishment based on data mining are utilized to overcome the ethical, practical challenges and the cost associated with the conventional direct approach.
Aim: To generate RIs for serum creatinine in children and adolescents using an indirect statistical tool.
Methods: Data mining of the laboratory information system was performed for serum creatinine analyzed from birth to 17 years for both genders. The timeline was set at six years from January 2013 to December 2018. Microsoft Excel 2010 and an indirect algorithm developed by the German Society of Clinical Chemistry and Laboratory Medicine's Working …

Diagnostic Accuracy And Agreement Between Four Phenotypic Carbapenemase Detection Tests Among Enterobacterales, Fizza Farooqui, Seema Irfan, Sidra Laiq

Department of Pathology and Laboratory Medicine

Introduction: Carbapenem-resistant Enterobacterales (CREs) are becoming increasingly popular as a cause of hospital-acquired infections that are difficult to treat and are frequently reported as causes of outbreaks in various hospitals. Conventional culturing techniques take at least 2 days to report a case as carbapenem resistant, and it is therefore important to detect such resistance mechanisms as early as possible.
Methods: This study aimed to compare the diagnostic performance of Carba NP, modified Hodge test (MHT), ethylenediaminetetraacetic acid (EDTA) disk synergy test (DST), and the modified carbapenem inactivation method (mCIM). This study was done at Microbiology Laboratory, Aga Khan University Hospital, …

Online Assessment In Undergraduate Medical Education: Challenges And Solutions From A Lmic University, Syeda Sadia Fatima, Romana Idrees, Kauser Jabeen, Saniya Sabzwari, Sadaf Khan

Department of Biological & Biomedical Sciences

Background and objectives: The Covid-19 pandemic has caused large-scale disruption in almost all educational programs across the world. Planning and rapid implementation of assessment through an online format presents the next set of novel challenges that must be addressed by academic administrations across the globe.
Methods: This cross-sectional study was conducted between March to August 2020 at the Aga Khan University Medical College. Two hundred medical students of year 1 and 2 participated in the study. We describe the planning, processes, and outcomes of online assessments using video communication platforms conducted at a private university in Pakistan. Standardized protocols were …

Adenoid Cystic Carcinoma Of External Auditory Canal: A Rare Disease, Abdul Basit Shah Vardag, Muhammad Hassan Danish, Mohammad Sohail Awan, Muhammad Usman Tariq, Omaima Anis Bhatti, Muhammad Hammad Deewani

Section of Otolaryngology, Head & Neck Surgery

External auditory canal, like other epithelialized surfaces is predisposed to malignancies such as Squamous cell carcinomas (SCC), melanomas and adenocarcinomas. In this background, malignancies like adenoid cystic carcinoma (ACC) are a rare occurrence and need to be thoroughly evaluated both locally and for distant extension. The malignancy needs to be addressed with an aggressive approach surgically with adequate marginal clearance. The role of radiation is debatable considering the outcomes in the limited data. Here we present the case of a 35-year-old female who came in with otalgia and otorrhea associated with a mass in the external auditory canal. After biopsy …

A Prospective Observational Study Of Community Acquired Pneumonia In Kenya: The Role Of Viral Pathogens, Jamila Nambafu, Mary Achakolong, Fridah Mwendwa, Jumaa Bwika, Felix Riunga, Samuel Gitau, Hanika Patel, Rodney Adam

Internal Medicine, East Africa

Background: Lower respiratory tract infections continue to contribute significantly to morbidity and mortality across all age groups globally. In sub-Saharan Africa, many studies of community acquired pneumonia in adults have focused on HIV-infected patients and little attention has been given to risk factors and etiologic agents in an urban area with a more moderate HIV prevalence.

Methods: We prospectively enrolled 77 patients admitted to a 280 bed teaching hospital in Kenya with radiographically confirmed community acquired pneumonia from May 2019 to March 2020. The patients were followed for etiology and clinical outcomes. Viral PCR testing was performed using …

Clinical Validation Of A Sensitive Test For Saliva Collected In Healthcare And Community Settings With Pooling Utility For Severe Acute Respiratory Syndrome Coronavirus 2 Mass Surveillance, Panelnikhil S. Sahajpal, Ashis K. Mondal, Sudha Ananth, Allan Njau, Pankaj Ahluwalia, Vamsi Kota, Kevin Caspary, Ted M. Ross, Michael Farrell, Michael P. Shannon

Pathology, East Africa

The clinical performance of saliva compared with nasopharyngeal swabs (NPSs) has shown conflicting results in healthcare and community settings. In the present study, a total of 429 matched NPS and saliva sample pairs, collected in either healthcare or community setting, were evaluated. Phase-1 (protocol U) tested 240 matched NPS and saliva sample pairs; phase 2 (SalivaAll protocol) tested 189 matched NPS and saliva sample pairs, with an additional sample homogenization step before RNA extraction. A total of 85 saliva samples were evaluated with both protocols. In phase-1, 28.3% (68/240) samples tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) …