Pathology Commons^™

Pharmacological Intervention In Children With Autism Spectrum Disorder With Standard Supportive Therapies Significantly Improves Core Signs And Symptoms: A Single-Center, Retrospective Case Series, Hamza A. Alsayouf, Haitham Talo, Marisa L. Biddappa, Mohammad Qasaymeh, Shadi Qasem, Emily De Los Reyes

Pathology and Laboratory Medicine Faculty Publications

Purpose: Autism spectrum disorder (ASD) is a debilitating neurodevelopmental disorder with high heterogeneity and no clear common cause. Several drugs, in particular risperidone and aripiprazole, are used to treat comorbid challenging behaviors in children with ASD. Treatment with risperidone and aripiprazole is currently recommended by the Food and Drug Administration (FDA) in the USA for children aged 5 and 6 years and older, respectively. Here, we investigated the use of these medications in younger patients aged 4 years and older.

Patients and Methods: This retrospective case series included 18 children (mean age, 5.7 years) with ASD treated at the Kids …

Longitudinal Assessment Of Dementia Measures In Down Syndrome, Lisa Mason Koehl, Jordan P. Harp, Kathryn L. Van Pelt, Elizabeth Head, Frederick A. Schmitt

Neurology Faculty Publications

Introduction: Early detection of dementia symptoms is critical in Down syndrome (DS) but complicated by clinical assessment barriers. The current study aimed to characterize cognitive and behavioral impairment using longitudinal trajectories comparing several measures of cognitive and behavioral functioning.

Methods: Measures included global cognitive status (Severe Impairment Battery [SIB]), motor praxis (Brief Praxis Test [BPT]), and clinical dementia informant ratings (Dementia Questionnaire for People with Learning Disabilities [DLD]). One-year reliability was assessed using a two-way mixed effect, consistency, single measurement intraclass correlation among non-demented participants. Longitudinal assessment of SIB, BPT, and DLD was completed using linear mixed effect models.

Results: …

Near Haploidization Is A Genomic Hallmark Which Defines A Molecular Subgroup Of Giant Cell Glioblastoma., Tiffany G. Baker, Jay Alden, Adrian M. Dubuc, Cynthia T. Welsh, Iya Znoyko, Linda D. Cooley, Midhat S. Farooqi, Stuart Schwartz, Yvonne Y. Li, Andrew D. Cherniack, Scott M. Lindhorst, Melissa Gener, Daynna J. Wolff, David M. Meredith

Manuscripts, Articles, Book Chapters and Other Papers

Background: Giant cell glioblastoma (gcGBM) is a rare histologic subtype of glioblastoma characterized by numerous bizarre multinucleate giant cells and increased reticulin deposition. Compared with conventional isocitrate dehydrogenase (IDH)-wildtype glioblastomas, gcGBMs typically occur in younger patients and are generally associated with an improved prognosis. Although prior studies of gcGBMs have shown enrichment of genetic events, such as

Methods: Through a multi-institutional collaborative effort, we characterized 10 gcGBMs by chromosome studies, single nucleotide polymorphism microarray analysis, and targeted next-generation sequencing. These tumors were subsequently compared to the genomic and epigenomic profile of glioblastomas described in The Cancer Genome Atlas (TCGA) dataset. …

Relationship Of Spot Urine Oxalate To Creatinine Ratio And 24 Hours Urinary Oxalate Excretion In Patients With Urolithiasis, Syed Bilal Hashmi, Lena Jafri, Hafsa Majid, Jamsheer Jehangir Talati, Wajahat Aziz, Aysha Habib Khan

Department of Pathology and Laboratory Medicine

Background: The evaluation of 24 h urinary oxalate excretion is the gold standard for diagnosing hyperoxaluria in patients with recurrent urolithiasis. However, 24 h urine sample collection is cumbersome. Therefore we aim to see if oxalate to creatinine ratio in random urine sample can be used as an alternative.
Materials and methods: A cross-sectional study was conducted at Section of Chemical Pathology, Department of Pathology and Laboratory Medicine Aga Khan University Karachi from 1st February to December 31, 2019. A total of 62 adult patients, 18-60 years of age with history of kidney stones presenting to the clinical laboratory for …

Intracranial Mesenchymal Tumor With Fet-Creb Fusion - A Unifying Diagnosis For The Spectrum Of Intracranial Myxoid Mesenchymal Tumors And Angiomatoid Fibrous Histiocytoma-Like Neoplasms, Emily A. Sloan, Jason Chiang, Javier E. Villanueva-Meyer, Sanda Alexandrescu, Jennifer M. Eschbacher, Wesley Wang, Manuela Mafra, Nasir Ud Din, Emily Carr-Boy, Michael Watson

Department of Pathology and Laboratory Medicine

Intracranial mesenchymal tumors with FET-CREB fusions are a recently described group of neoplasms in children and young adults characterized by fusion of a FET family gene (usually EWSR1, but rarely FUS) to a CREB family transcription factor (ATF1, CREB1, or CREM), and have been variously termed intracranial angiomatoid fibrous histiocytoma or intracranial myxoid mesenchymal tumor. The clinical outcomes, histologic features, and genomic landscape are not well defined. Here we studied twenty patients with intracranial mesenchymal tumors proven to harbor FET-CREB fusion by next-generation sequencing (NGS). The 16 female and 4 male patients had a median age of 14 years (range …

Distinct Clinicopathologic Clusters Of Persons With Tdp-43 Proteinopathy, Yuriko Katsumata, Erin L. Abner, Shama Karanth, Merilee A. Teylan, Charles N. Mock, Matthew D. Cykowski, Edward B. Lee, Kevin L. Boehme, Shubhabrata Mukherjee, John S. K. Kauwe, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Peter T. Nelson

Biostatistics Faculty Publications

To better understand clinical and neuropathological features of TDP-43 proteinopathies, data were analyzed from autopsied research volunteers who were followed in the National Alzheimer’s Coordinating Center (NACC) data set. All subjects (n = 495) had autopsy-proven TDP-43 proteinopathy as an inclusion criterion. Subjects underwent comprehensive longitudinal clinical evaluations yearly for 6.9 years before death on average. We tested whether an unsupervised clustering algorithm could detect coherent groups of TDP-43 immunopositive cases based on age at death and extensive neuropathologic data. Although many of the brains had mixed pathologies, four discernible clusters were identified. Key differentiating features were age at …

Karachi Cancer Registry (Kcr): Age-Standardized Incidence Rate By Age-Group And Gender In A Mega City Of Pakistan, Shahid Pervez, Adnan Jabbar, Ghulam Haider, Shamvil Ashraf, Muhammad Asif Qureshi, Fouzia Lateef, Imtiaz Bashir, Manzoor Zaidi, Mohammad Khurshid, Mohammad Saeed Quraishy

Department of Pathology and Laboratory Medicine

Objectives: To estimate the cancer incidence by age group and gender for the population of Karachi Division by analyzing the Karachi Cancer Registry data of 2017-19.
Settings: The population of Karachi division is 16.1 million according to national census 2017. 'Karachi Cancer Registry' which is a part of 'National Cancer Registry' is collecting data from eight major hospitals in Karachi since 2017. For outcome measures, cancer counts and the age standardized incidence rates (ASIR) per 100,000 population were computed for age groups (0-14, 15-19 and ≥20 years), in both genders and all cancer site/type.
Methods: The population denominators were based …

Implementation Of Surgical Site Infection Surveillance In Low- And Middle-Income Countries: A Position Statement For The International Society For Infectious Diseases, Shaheen Mehtar, Anthony Wanyoro, Folasade Ogunsola, Emmanuel A. Ameh, Peter Nthumba, Claire Kilpatrick, Gunturu Revathi, Anastasia Antoniadou, Helen Giamarelou, Anucha Apisarnthanarak

Pathology, East Africa

Surgical site infection (SSI) rates in low- and middle-income countries (LMICs) range from 8 to 30% of procedures, making them the most frequent healthcare-acquired infection (HAI) with substantial morbidity, mortality, and economic impacts. Presented here is an approach to surgical site infection prevention based on surveillance and focused on five critical areas identified by international experts. These five areas include 1. Collecting valid, high-quality data; 2. Linking HAIs to economic incapacity, underscoring the need to prioritize infection prevention activities; 3. Implementing SSI surveillance within infection prevention and control (IPC) programs to enact structural changes, develop procedural skills, and alter healthcare …

Combating Acquired Resistance To Mapk Inhibitors In Melanoma By Targeting Abl1/2-Mediated Reactivation Of Mek/Erk/Myc Signaling, Rakshamani Tripathi, Zulong Liu, Aditi Jain, Anastasia Lyon, Christina Meeks, Dana Richards, Jinpeng Liu, Daheng He, Chi Wang, Marika Nespi, Andrey Rymar, Peng Wang, Melissa Wilson, Rina Plattner

Pharmacology and Nutritional Sciences Faculty Publications

Metastatic melanoma remains an incurable disease for many patients due to the limited success of targeted and immunotherapies. BRAF and MEK inhibitors reduce metastatic burden for patients with melanomas harboring BRAF mutations; however, most eventually relapse due to acquired resistance. Here, we demonstrate that ABL1/2 kinase activities and/or expression are potentiated in cell lines and patient samples following resistance, and ABL1/2 drive BRAF and BRAF/MEK inhibitor resistance by inducing reactivation of MEK/ERK/MYC signaling. Silencing/inhibiting ABL1/2 blocks pathway reactivation, and resensitizes resistant cells to BRAF/MEK inhibitors, whereas expression of constitutively active ABL1/2 is sufficient to promote resistance. Significantly, nilotinib (2nd generation …

Evaluation Of Semi-Quantitative Compared To Quantitative Cultures Of Tracheal Aspirates For The Yield Of Culturable Respiratory Pathogens - A Cross-Sectional Study, Salima Rattani, Joveria Farooqi, Ghazala Jabeen, Saeeda Chandio, Qaiser Kash, Aijaz Khan, Kauser Jabeen

Department of Pathology and Laboratory Medicine

Background: Diagnosis of lower respiratory tract infections (LRTI) depends on the presence of clinical, radiological and microbiological findings. Endotracheal suction aspirate (ETSA) is the commonest respiratory sample sent for culture from intubated patients. Very few studies have compared quantitative and semi-quantitative processing of ETSA cultures for LRTI diagnosis. We determined the diagnostic accuracy of quantitative and semi-quantitative ETSA culture for LRTI diagnosis, agreement between the quantitative and semi quantitative culture techniques and the yield of respiratory pathogens with both methods.
Methods: This was a cross-sectional study conducted at the Aga Khan University clinical laboratory, Karachi, Pakistan. One hundred and seventy-eight …

Fostering Teaching-Learning Through Workplace Based Assessment In Postgraduate Chemical Pathology Residency Program Using Virtual Learning Environment, Lena Jafri, Imran Siddiqui, Aysha Habib Khan, Muhammed Tariq, Muhammad Umer Naeem Effendi, Azra Naseem, Sibtain Ahmed, Farooq Ghani, Shahnila Alidina, Nadir Shah, Hafsa Majid

Department of Pathology and Laboratory Medicine

Background: The principle of workplace based assessment (WBA) is to assess trainees at work with feedback integrated into the program simultaneously. A student driven WBA model was introduced and perception evaluation of this teaching method was done subsequently by taking feedback from the faculty as well as the postgraduate trainees (PGs) of a residency program.
Methods: Descriptive multimethod study was conducted. A WBA program was designed for PGs in Chemical Pathology on Moodle and forms utilized were case-based discussion (CBD), direct observation of practical skills (DOPS) and evaluation of clinical events (ECE). Consented assessors and PGs were trained on WBA …

Precursor Lymphoblastic Lymphoma In The Extramedullary Tissue: A Rare Manifestation Of Chronic Myeloid Leukemia In Blast Crisis, Huma Mansoori, Maria Faraz, Hira Qadir, Anila Rashid, Maria Ali

Department of Pathology and Laboratory Medicine

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by immature granulocytes in peripheral blood and bone marrow. In 95% of cases, it is always due to the presence of Philadelphia chromosome characterized by the presence of reciprocal translocation between chromosome 9 and 22. However, in 7% -17% of individuals, extramedullary proliferation also occurs, either in skin, lymph nodes, bone or central nervous system (CNS), which could be either myeloid, lymphoid or mixed progenitor in origin. The present case is of a 23-year-old male who presented with lower limb weakness, bowel and urinary incontinence. His complete blood count (CBC) findings …

Distribution Of Microglial Phenotypes As A Function Of Age And Alzheimer's Disease Neuropathology In The Brains Of People With Down Syndrome, Alessandra C. Martini, Alex M. Helman, Katie L. Mccarty, Ira T. Lott, Eric Doran, Frederick A. Schmitt, Elizabeth Head

Sanders-Brown Center on Aging Faculty Publications

Introduction: Microglial cells play an important role in the development of Alzheimer's disease (AD). People with Down syndrome (DS) inevitably develop AD neuropathology (DSAD) by 40 years of age. We characterized the distribution of different microglial phenotypes in the brains of people with DS and DSAD.

Methods: Autopsy tissue from the posterior cingulate cortex (PCC) from people with DS, DSAD, and neurotypical controls was immunostained with the microglial marker Iba1 to assess five microglia morphological types.

Results: Individuals with DS have more hypertrophic microglial cells in their white matter. In the gray matter, individuals with DSAD had significantly fewer ramified …

Development And Interim Analysis Of A Cystic Fibrosis-Specific Antibiogram, Claire Elson, Ellen Meier, Douglas Swanson, Rangaraj Selvarangan, Megan Gripka, Christopher M. Oermann

Posters

Antimicrobial therapy is essential to treat cystic fibrosis (CF) lung infections. Empiric antimicrobial selection is generally based on previous culture information and, if available, an institution-specific antibiogram (ABGM). Most institutions antibiograms exclude cultures from individuals with cystic fibrosis, imposing challenges with empiric antimicrobial selection and monitoring susceptibility patterns over time. A cystic fibrosis-specific antibiogram may help drive population-specific antimicrobial selection and improve antimicrobial stewardship.

Clinical Performance And Utility Of A Comprehensive Next-Generation Sequencing Dna Panel For The Simultaneous Analysis Of Variants, Tmb And Msi For Myeloid Neoplasms, Nikhil Shri Sahajpal, Ashis K. Mondal, Sudha Ananth, Allan Njau, Pankaj Ahluwalia, Kimya Jones, Meenakshi Ahluwalia, Nwogbo Okechukwu, ,Natasha M. Savage, Vamsi Kota

Pathology, East Africa

The extensively employed limited-gene coverage NGS panels lead to clinically inadequate molecular profiling of myeloid neoplasms. The aim of the present investigation was to assess performance and clinical utility of a comprehensive DNA panel for myeloid neoplasms. Sixty-one previously well characterized samples were sequenced using TSO500 library preparation kit on NextSeq550 platform. Variants with a VAF ≥ 5% and a total read depth of >50X were filtered for analysis. The following results were recorded-for clinical samples: clinical sensitivity (97%), specificity (100%), precision (100%) and accuracy (99%) whereas reference control results were 100% for analytical sensitivity, specificity, precision and accuracy, with …

Proposal Of Rt-Pcrebased Mass Population Screening For Severe Acute Respiratory Syndrome Coronavirus 2 (Coronavirus Disease 2019), Nikhil S. Sahajpal, Ashis K. Mondal, Allan Njau, Sudha Ananth, Kimya Jones, Pankaj K. Ahluwalia, Meenakshi Ahluwalia, Yasmeen Jilani, Alka Chaubey, Madhuri Hegde, Vamsi Kota, Amyn Rojiani, Ravindra Kolhe

Pathology, East Africa

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing has lagged in many countries because of test kit shortages and analytical process bottlenecks. This study investigated the feasibility and accuracy of a sample pooling approach for wide-scale population screening for coronavirus disease 2019. A total of 940 nasopharyngeal swab samples (934 negative and 6 positive) previously tested for SARS-CoV-2 were deidentified and assigned random numbers for analysis, and 94 pools of 10 samples each were generated. Automated RNA extraction, followed by RT-PCR, was performed in a 96-well plate. Positive pools were identified, and the individual samples were reanalyzed. Of the 94 …

Immunohistochemical Pattern– A Prognostic Factor For Synchronous Gastrointestinal Cancer, Catalin Alius, Catalin Gabriel Cirstoveanu, Cristinel Dumitru Badiu, Valeriu Ardeleanu, Vasile Adrian Dumitru

Journal of Mind and Medical Sciences

Recent advancements in medical genetics and molecular biology are reflected in the modern understanding and approach to colorectal carcinoma (CRC). Understanding the cellular mechanisms and mutational patterns that promote carcinogenesis could enhance the predictive accuracy of the TNM classification. Furthermore, this will allow for a much more documented stratification and tailored oncological treatment. This paper presents an illustrative case of a relatively young patient (50 years old) with no family history of cancer who was diagnosed with four synchronous gastrointestinal (GI) adenocarcinomas displaying a wild type P53, negative BRAF testing, and mutated MLH1 and PMS2 proteins. This case report contributes …

Paroxysmal Nocturnal Hemoglobinuria: Pandora’S Box?, Mihnea Alexandru Găman, Iulia Ursuleac, Daniel Coriu

Journal of Mind and Medical Sciences

Introduction. Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired non-malignant hematological disorder which affects the pluripotent hematopoietic stem cell. The cause of PNH development is the occurrence of somatic mutations in the phosphatidylinositol glycan-A gene which encodes a protein necessary for the biosynthesis of glycosylphosphatidylinositol anchors. The diagnosis of PNH requires the presence of signs of intravascular hemolysis, thrombosis, and (or) bone marrow failure. Case Report. We report the case of a 42-year-old female, diagnosed with PNH at the age of 27, whose evolution was initially characterized predominantly by hemolytic attacks and whose disease pattern evolved towards thromboembolic episodes …

Staphylococcus Aureus Atp Synthase Promotes Biofilm Persistence By Influencing Innate Immunity, Megan E. Bosch, Blake P. Bertrand, Cortney E. Heim, Abdulelah A. Alqarzaee, Sujata S. Chaudhari, Amy L. Aldrich, Paul D. Fey, Vinai C. Thomas, Tammy Kielian

Journal Articles: Pathology and Microbiology

No abstract provided.

Sequential Complications Of Hypercalcemia, Necrotizing Granulomatous Vasculitis, And Aplastic Anemia Occurring In One Patient With Angioimmunoblastic T-Cell Lymphoma., Sriman Swarup, Jonathan Kopel, Kyaw Zin Thein, Kaiser Tarafdar, Khatrina Swarup, Seshadri Thirumala, Donald P Quick

Articles, Abstracts, and Reports

In this case report of a patient with angioimmunoblastic T-cell lymphoma (AITL), we describe the occurrence of three sequential complications that have been reported uncommonly in this disease subtype. Firstly, the patient developed hypercalcemia due to elevated 1,25-didydroxyvitamin D. Although hypercalcemia in AITL is not rare (1-2% incidence), this case was unusual in that the complication developed when disease appeared stable and symptomatically, he was doing well otherwise. Hypercalcemia surprisingly resolved a few months later at a time when his disease appeared to be progressing. A year later, the patient presented with digital ischemia necessitating partial amputation of a finger. …