Pathology Commons^™

Eccrine Spiradenoma: A Rare Adnexal Tumour With Atypical Presentation: A Case Report, Adnan Salim, Muhammad Usman Tariq, Sana Zeeshan

Section of Neurosurgery

First described in 1934, eccrine spiradenoma (ES) is a rare, benign adnexal tumour arising from eccrine sweat glands. It commonly presents as a slow-growing nodule on the upper trunk, and head and neck region, mostly in the age bracket of 15-35 years, with no gender preference. While no established guidelines exist for optimal management of malignant ES, some therapies have been studied. The diagnosis of this entity is extremely important as it can harbour a malignant component with disastrous outcomes which may be missed due to its strong resemblance to benign lesions, such as a papilloma. Here, we present the …

Macrophage-Derived Thrombospondin 1 Promotes Obesity-Associated Non-Alcoholic Fatty Liver Disease, Taesik Gwag, Raja Gopal Reddy Mooli, Dong Li, Sangderk Lee, Eun Young Lee, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

Background

Thrombospondin 1 (TSP1) is a multifunctional matricellular protein. We previously showed that TSP1 has an important role in obesity-associated metabolic complications, including inflammation, insulin resistance, cardiovascular, and renal disease. However, its contribution to obesity-associated non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD or NASH) remains largely unknown; thus, we aimed to determine its role.

Methods

High-fat diet or AMLN (amylin liver NASH) diet-induced obese and insulin-resistant NAFLD/NASH mouse models were utilised, in addition to tissue-specific Tsp1-knockout mice, to determine the contribution of different cellular sources of obesity-induced TSP1 to NAFLD/NASH development.

Results

Liver TSP1 levels were increased in experimental obese …

Gastroenteropancreatic Neuroendocrine Tumours: Clinicopathological Evaluation At Shifa International Hospital, Islamabad, Nadira Mamoon, Hania Naveed, Mariam Abid, Humaira Nasir, Imran Nazir Ahmad, Zujajah Hameed, Asna Haroon Khan

Department of Pathology and Laboratory Medicine

Objective: Clinicopathological features of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have rarely been studied in Pakistani population. We investigated clinical characteristics of these tumours according to updated World Health Organization (WHO) 2010 classification.
Methods: The data of Shifa International Hospital, Islamabad was retrospectively analysed for pathologically confirmed GEP-NETs from January 2013 to March 2018.
Results: One hundred and eighteen patients (mean age, 52.2± 16.4 years; Of these 65(55.1%) were males. Majority, 98(83.1%) of the patients were symptomatic including 6(5.1%) with functional tumours. Pancreas was the most frequent primary site noted in 33(28%) patients. The most common histologic type was well differentiated neuroendocrine …

High Prevalence Of Multidrug-Resistant Clostridioides Difficile Following Extensive Use Of Antimicrobials In Hospitalized Patients In Kenya, Winnie C. Mutai, Marianne W. Mureithi, Omu Anzala, Gunturu Revathi, Brian Kullin, Magdaline Burugu, Cecilia Kyany’A, Erick Odoyo, Peter Otieno, Lillian Musila

Pathology, East Africa

Introduction: Clostridioides difficile is a neglected pathogen in many African countries as it is generally not regarded as one of the major contributors toward the diarrheal disease burden in the continent. However, several studies have suggested that C. difficile infection (CDI) may be underreported in many African settings. The aim of this study was to determine the prevalence of CDI in hospitalized patients, evaluate antimicrobial exposure, and detect toxin and antimicrobial resistance profiles of the isolated C. difficile strains.

Methods: In this cross-sectional study, 333 hospitalized patients with hospital-onset diarrhoea were selected. The stool samples were collected and cultured on …

Regional N-Glycan And Lipid Analysis From Tissues Using Maldi-Mass Spectrometry Imaging, Alexandra E. Stanback, Lindsey R. Conroy, Lyndsay E. A. Young, Tara R. Hawkinson, Kia H. Markussen, Harrison A. Clarke, Derek B. Allison, Ramon C. Sun

Neuroscience Faculty Publications

N-glycans and lipids are structural metabolites that play important roles in cellular processes. Both show unique regional distribution in tissues; therefore, spatial analyses of these metabolites are crucial to our understanding of cellular physiology. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) is an innovative technique that enables in situ detection of analytes with spatial distribution. This workflow details a MALDI-MSI protocol for the spatial profiling of N-glycans and lipids from tissues following application of enzyme and MALDI matrix.

For complete details on the use and execution of this protocol, please refer to Drake et al. (2018) and Andres et al. (2020).

Fludarabine-Based Salvage Therapy For Refractory/Relapsed Acute Leukemias: A Single Center Experience, Abdul Muqtadir Abbasi, Mohammad Usman Shaikh, Natasha Bahadur Ali, Mohammad Nadir Haider

Section of Haematology/Oncology

No abstract provided.

Development Of The Asia Pacific Consortium On Osteoporosis (Apco) Framework: Clinical Standards Of Care For The Screening, Diagnosis, And Management Of Osteoporosis In The Asia-Pacific Region, M Chandran, P J. Mitchell, T Amphansap, S K. Bhadada, M Chadha, D-C Chan, Y-S Chung, P Ebeling, N Gilchrist, Aysha Habib Khan

Department of Pathology and Laboratory Medicine

Guidelines for doctors managing osteoporosis in the Asia-Pacific region vary widely. We compared 18 guidelines for similarities and differences in five key areas. We then used a structured consensus process to develop clinical standards of care for the diagnosis and management of osteoporosis and for improving the quality of care.
Purpose: Minimum clinical standards for assessment and management of osteoporosis are needed in the Asia-Pacific (AP) region to inform clinical practice guidelines (CPGs) and to improve osteoporosis care. We present the framework of these clinical standards and describe its development.
Methods: We conducted a structured comparative analysis of existing CPGs …

Characteristics Of Salmonella Recovered From Stools Of Children Enrolled In The Global Enteric Multicenter Study, Irene N. Kasumba, Caisey V. Pulford, Blanca M. Perez-Sepulveda, Sunil Sen, Nurulla Sayed, Jasnehta Permala-Booth, Sofie Livio Sofie Livio, Darren Heavens Darren Heavens, Ross Low Ross Low, Shahida Qureshi, Anita K. M. Zaidi

Department of Paediatrics and Child Health

Background: The Global Enteric Multicenter Study (GEMS) determined the etiologic agents of moderate-to-severe diarrhea (MSD) in children under 5 years old in Africa and Asia. Here, we describe the prevalence and antimicrobial susceptibility of non-typhoidal Salmonella (NTS) serovars in GEMS and examine the phylogenetics of Salmonella Typhimurium ST313 isolates.
Methods: Salmonella isolated from children with MSD or diarrhea-free controls were identified by classical clinical microbiology and serotyped using antisera and/or whole genome sequence data. We evaluated antimicrobial susceptibility using the Kirby-Bauer disk diffusion method. Salmonella Typhimurium sequence types were determined using multi-locus sequence typing and whole genome sequencing was performed …

Differential Expression Of Αvβ3 And Αvβ6 Integrins In Prostate Cancer Progression, Fabio Quaglia, Shiv Ram Krishn, Yanqing Wang, David W Goodrich, Peter Mccue, Andrew Kossenkov, Amy C Mandigo, Karen Knudsen, Paul H Weinreb, Eva Corey, William Kevin Kelly, Lucia R Languino

Department of Cancer Biology Faculty Papers

Neuroendocrine prostate cancer (NEPrCa) arises de novo or after accumulation of genomic alterations in pre-existing adenocarcinoma tumors in response to androgen deprivation therapies. We have provided evidence that small extracellular vesicles released by PrCa cells and containing the αVβ3 integrin promote neuroendocrine differentiation of PrCa in vivo and in vitro. Here, we examined αVβ3 integrin expression in three murine models carrying a deletion of PTEN (SKO), PTEN and RB1 (DKO), or PTEN, RB1 and TRP53 (TKO) genes in the prostatic epithelium; of these three models, the DKO and TKO tumors develop NEPrCa with a gene signature comparable to those of …

X-Linked Hypophosphatemic Osteomalacia With Phex Mutation Presenting Late In Pakistan, Nawazish Zehra, Lena Jafri, Salman Kirmani, Aysha Habib Khan

Department of Pathology and Laboratory Medicine

Abstract.introduction.and.importance: Autosomal dominant hypophosphatemic rickets is the most common form of rare rickets, commonly manifests in children but sometimes the condition remains undiagnosed due to lack of knowledge &/or awareness of treating physicians or surgeons.
Case presentation: We describe a case of 43 years old female with multiple fragility fractures since childhood, corrected surgically but never investigated. She had stunted growth, bowing deformities and loss of teeth.
Clinical discussion: A detailed history and examination along with metabolic and genetic work up mounted the diagnosis of X linked hypophosphatemic osteomalacia. The pathophysiology involves the mutation or the loss of the …

Calcaneal Ultrasound And Its Relation To Dietary And Lifestyle Factors, Anthropometry, And Vitamin D Deficiency In Young Medical Students, Lena Jafri, Hafsa Majid, Sibtain Ahmed, Ghazala Naureen, Aysha Habib Khan

Department of Pathology and Laboratory Medicine

Background: Bone quality and peak bone mass are greatly affected by lifestyle factors. The objective of the study was to investigate the relationships between anthropometry, dietary and caloric intake, body composition measurements, physical activity, and vitamin D status with quantitative ultrasound-based bone parameters among medical students.
Methods: Both male and female medical college students were included in this study. A detailed questionnaire was administered, collecting clinical, dietary, physical activity information, physical examination details, including body mass index (BMI). Body composition (total body fat, total body water, muscle mass, mean visceral fat mass, basal metabolic rate, bone mass using a bioelectrical …

Clinical Performance Of The Point-Of-Care Cobas Liat For Detection Of Sars-Cov-2 In 20 Minutes: A Multicenter Study., Glen Hansen, Jamie Marino, Zi-Xuan Wang, Kathleen G Beavis, John Rodrigo, Kylie Labog, Lars F Westblade, Run Jin, Nedra Love, Karen Ding, Sachin Garg, Alan Huang, Joanna Sickler, Nam K Tran

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Highly accurate testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the point of care (POC) is an unmet diagnostic need in emergency care and time-sensitive outpatient care settings. Reverse transcription-PCR (RT-PCR) technology is the gold standard for SARS-CoV-2 diagnostics. We performed a multisite U.S. study comparing the clinical performance of the first U.S. Food and Drug Administration (FDA)-authorized POC RT-PCR for detection of SARS-CoV-2 in 20 min, the cobas Liat SARS-CoV-2 and influenza A/B nucleic acid test, to the most widely used RT-PCR laboratory test, the cobas 68/8800 SARS-CoV-2 test. Clinical nasopharyngeal swab specimens from 444 patients with …

Hajdu Cheney Syndrome Due To Notch2 Defect - First Case Report From Pakistan And Review Of Literature, Sibtain Ahmed, Aahan Arif, Saadia Abbas, Muhammad Osama Khan, Salman Kirmani, Aysha Habib Khan

Department of Pathology and Laboratory Medicine

Introduction and importance: Hajdu Cheney Syndrome (HCS) is a rare skeletal disease characterized by severe, progressive focal bone loss with osteoporosis, variable craniofacial, vertebral anomalies and distinctive facial features. It is inherited as an autosomal dominant disease although sporadic cases have been described in literature. Identifying these cases in clinical practice is important for proper diagnosis and management.
Case presentation: We report a case of a 36-year-old male patient presented at metabolic bone disease clinic at the Aga Khan University Hospital with history of multiple fragility fractures and juvenile osteoporosis since childhood. DNA sequence analysis of the NOTCH2 coding sequence …

Risk Factors Of Breast Cancer Among Patients In A Tertiary Care Hospitals In Afghanistan: A Case Control Study, Zekrullah Baset, Jamshid Abdul Ghafar, Yasmin Parpio, Ahmed Maseh Haidary

School of Nursing & Midwifery

Background: Breast cancer is the second most common causes of women's death, worldwide. Data on risk factors associated with female breast cancer in the Afghan population is very limited. The aim of our study was to identifying risk factor associated with female breast cancer in Afghanistan.
Methods: A retrospective case-control study was conducted with inclusion of 201 cases and 201 controls. Patient information was collected by interviewing the patient through a structured questionnaire. Histopathological information was collected from the hospital integrated laboratory management system. The data was analyzed by using logistic regression with univariate and multivariable analyses to determine the …

A Multidisciplinary Approach To Triage Patients With Breast Disease During The Covid-19 Pandemic: Experience From A Tertiary Care Center In The Developing World, Abida K. Sattar, Hania Shahzad, Adnan Abdul Jabbar, Azmina Tajdin Valimohammad, Sadaf Khan, Yasmin Vellani, Romana Idrees, Nasir Ali, Imrana Masroor, Humera Saeed, Gulzar S. Lakhani, Nadia Ayoub, Atif Waqar, Muhammad Zia-Ul Islam, Salman Kirmani, Asad Latif, Ather Enam

Section of General Surgery

Background: The COVID-19 pandemic has created a need to prioritize care because of limitation of resources. Owing to the heterogeneity and high prevalence of breast cancers, the need to prioritize care in this vulnerable population is essential. While various medical societies have published recommendations to manage breast disease during the COVID-19 pandemic, most are focused on the Western world and do not necessarily address the challenges of a resource-limited setting.
Aim: In this article, we describe our institutional approach for prioritizing care for patients presenting with breast disease.
Methods and results: The breast disease management guidelines were developed and approved …

Dystrophic Microglia Are Associated With Neurodegenerative Disease And Not Healthy Aging In The Human Brain, Ryan K. Shahidehpour, Rebecca E. Higdon, Nicole G. Crawford, Janna H. Neltner, Eseosa T. Ighodaro, Ela Patel, Douglas Price, Peter T. Nelson, Adam D. Bachstetter

Spinal Cord and Brain Injury Research Center Faculty Publications

Loss of physiological microglial function may increase the propagation of neurodegenerative diseases. Cellular senescence is a hallmark of aging; thus, we hypothesized age could be a cause of dystrophic microglia. Stereological counts were performed for total microglia, 2 microglia morphologies (hypertrophic and dystrophic) across the human lifespan. An age-associated increase in the number of dystrophic microglia was found in the hippocampus and frontal cortex. However, the increase in dystrophic microglia was proportional to the age-related increase in the total number of microglia. Thus, aging alone does not explain the presence of dystrophic microglia. We next tested if dystrophic microglia could …

Direct And Indirect Effect Of 10 Valent Pneumococcal Vaccine On Nasopharyngeal Carriage In Children Under 2 Years Of Age In Matiari, Pakistan, Muhammad Imran Nisar, Sheraz Ahmed, Fyezah Jehan, Shahira Shahid, Sadia Shakoor, Furqan Kabir, Aneeta Hotwani, Sahrish Munir, Sajid Muhammad, Farah Khalid, Syed Asad Ali, Anita K. M. Zaidi, Najeeha Talat Iqbal

Department of Paediatrics and Child Health

Background: Pakistan introduced Ten-valent pneumococcal-conjugate-vaccine PCV10 in 2012 as a 3 + 0 schedule without catch-up.
Methods: Children <2 years old in Matiari, Sindh provided nasopharyngeal swabs between 2014 and 2018, which were cultured for pneumococcus and serotyped through multiplex PCR at the Aga Khan University Hospital. Carriage rates over time for Vaccine-Type (VT) and Non-VT (NVT) serotypes were used to estimate direct, indirect, total and overall effects of vaccination. Regression analysis was used to determine factors associated with VT carriage.
Results: Pneumococcus was detected in 2370/3140 (75%). VT carriage decreased overall, 16.1-9.6% (p-trend <0.001); vaccinated (all 3 doses of PCV10 received) 11.3-8.1% (p-trend 0.031) and unvaccinated (no PCV10 dose received) 17.4-10.3% (p-trend 0.003) with a decline in serotypes 6B, 9V/9A and 19F. Immunization increased from 41.0% to 68.4% (p-trend 0.001). Direct effect of vaccine was 32.8% (95% CI 14.7-47.0%) and indirect effect 44.6%(95% CI 40.6-48.6%). Factors associated with decreased VT colonization were education 1-5 years (aOR 0.7, 95%CI 0.6-1.0), history of difficulty breathing (aOR 0.7, 95%CI 0.5-1.0), exposure to smoke (aOR 0.8, 95% CI 0.6-1.0), child fully immunized (aOR 0.7, 95%CI 0.5-1.0) and enrolled in 3rd (aOR 0.6, 95%CI 0.4-0.8) and 4th (aOR 0.6, 95%CI 0.5-0.9) year of the study whereas history of runny nose (aOR 1.5, 95% CI 1.2-1.9) was positively associated.
Conclusions: Decrease in VT pneumococcal carriage in vaccinated and unvaccinated children indicates herd immunity. Sustained increase in vaccine coverage and close long-term surveillance is warranted.

The Association Of Chest Radiographic Findings And Severity Scoring With Clinical Outcomes In Patients With Covid-19 Presenting To The Emergency Department Of A Tertiary Care Hospital In Pakistan, Raima Kaleemi, Kiran Hilal, Ainan Arshad, Russell S. Martins, Avinash Nankani, Tanveer Ul Haq, Sundas Basharat, Zeeshan Ansar

Department of Radiology

Introduction: While chest x-rays (CXRs) represent a cost-effective imaging modality for developing countries like Pakistan, their utility for the prognostication of COVID-19 has been minimally explored. Thus, we describe the frequency and distribution of CXR findings, and their association with clinical outcomes of patients with COVID-19.
Methods: All adult (≥ 18 years) patients presenting between 28th February-31st May to the emergency department of a tertiary care hospital in Pakistan, who were COVID-19 positive on RT-PCR with CXR done on presentation, were included. A CXR Severity Score (CXR-SS) of 0-8 was used to quantify the extent of pulmonary infection on CXR, …

The Evolution And Future Of Targeted Cancer Therapy: From Nanoparticles, Oncolytic Viruses, And Oncolytic Bacteria To The Treatment Of Solid Tumors, Kyle M. Pierce, William R. Miklavcic, Kyle P. Cook, Mikayla Sweitzer Hennen, Kenneth W. Bayles, Michael A. Hollingsworth, Amanda E. Brooks, Jessica E. Pullan, Kaitlin M. Dailey

Journal Articles: Pathology and Microbiology

While many classes of chemotherapeutic agents exist to treat solid tumors, few can generate a lasting response without substantial off-target toxicity despite significant scientific advancements and investments. In this review, the paths of development for nanoparticles, oncolytic viruses, and oncolytic bacteria over the last 20 years of research towards clinical translation and acceptance as novel cancer therapeutics are compared. Novel nanoparticle, oncolytic virus, and oncolytic bacteria therapies all start with a common goal of accomplishing therapeutic drug activity or delivery to a specific site while avoiding off-target effects, with overlapping methodology between all three modalities. Indeed, the degree of overlap …

Structure And Activity Of A Selective Antibiofilm Peptide Sk-24 Derived From The Nmr Structure Of Human Cathelicidin Ll-37, Yingxia Zhang, Jayaram Lakshmaiah Narayana, Qianhui Wu, Xiangli Dang, Guangshun Wang

Journal Articles: Pathology and Microbiology

The deployment of the innate immune system in humans is essential to protect us from infection. Human cathelicidin LL-37 is a linear host defense peptide with both antimicrobial and immune modulatory properties. Despite years of studies of numerous peptides, SK-24, corresponding to the long hydrophobic domain (residues 9–32) in the anionic lipid-bound NMR structure of LL-37, has not been investigated. This study reports the structure and activity of SK-24. Interestingly, SK-24 is entirely helical (~100%) in phosphate buffer (PBS), more than LL-37 (84%), GI-20 (75%), and GF-17 (33%), while RI-10 and 17BIPHE2 are essentially randomly coiled (helix%: 7–10%). These results …