Pathology Commons^™

Immunopathogenesis Of Craniotomy Infection And Niche-Specific Immune Responses To Biofilm, Sharon D.B. De Morais, Gunjan Kak, Joseph P. Menousek, Tammy Kielian

Journal Articles: Pathology and Microbiology

Bacterial infections in the central nervous system (CNS) can be life threatening and often impair neurological function. Biofilm infection is a complication following craniotomy, a neurosurgical procedure that involves the removal and replacement of a skull fragment (bone flap) to access the brain for surgical intervention. The incidence of infection following craniotomy ranges from 1% to 3% with approximately half caused by Staphylococcus aureus (S. aureus). These infections present a significant therapeutic challenge due to the antibiotic tolerance of biofilm and unique immune properties of the CNS. Previous studies have revealed a critical role for innate immune responses …

The Mmc Biobank Is A Resource That Supports Biomedical Research, Anne C. Breggia, Sue Lapierre, Christopher Keister, Dawn Charnetzky, Hannah Brown, Joseph Nano, Sydney Robinson, Howard Feller, Susan Nester, Elizabeth Hamir, Heidi Ingersoll, Anthony Sellner, Trevor Jorgensen, Mike Jones

Costas T. Lambrew Research Retreat 2021

Mission: To provide normal and diseased annotated human biospecimens to the research community that supports discoveries leading to improved patient therapies and advances in personalized medicine.

Crosstalk Between Staphylococcus Aureus And Innate Immunity: Focus On Immunometabolism, Christopher M. Horn, Tammy Kielian

Journal Articles: Pathology and Microbiology

Staphylococcus aureus is a leading cause of bacterial infections globally in both healthcare and community settings. The success of this bacterium is the product of an expansive repertoire of virulence factors in combination with acquired antibiotic resistance and propensity for biofilm formation. S. aureus leverages these factors to adapt to and subvert the host immune response. With the burgeoning field of immunometabolism, it has become clear that the metabolic program of leukocytes dictates their inflammatory status and overall effectiveness in clearing an infection. The metabolic flexibility of S. aureus offers an inherent means by which the pathogen could manipulate the …

Developing An Enhanced 7-Color Multiplex Ihc Protocol To Dissect Immune Infiltration In Human Cancers., Zhaoyu Sun, Richard Nyberg, Yaping Wu, Brady Bernard, William L. Redmond

Articles, Abstracts, and Reports

The TSA Opal multiplex immunohistochemistry (mIHC) protocol (PerkinElmer) has been used to characterize immune infiltration in human cancers. This technique allows multiple biomarkers to be simultaneously stained in a single tissue section, which helps to elucidate the spatial relationship among individual cell types. We developed and optimized two improved mIHC protocols for a 7-color panel containing 6 biomarkers (CD3, CD8, CD163, PD-L1, FoxP3, and cytokeratin (CK)) and DAPI. The only difference between these two protocols was the staining sequence of those 6 biomarkers as the first sequence is PD-L1/CD163/CD8/CK/CD3/FoxP3/DAPI and the second sequence is FoxP3/CD163/CD8/CK/CD3/PD-L1/DAPI. By comparing PD-L1/FoxP3 staining in …

Association Of Helicobacter Pylori Caga And Vaca Genotypes With Gastric Adenocarcinoma In Kenya, Priscilla Waithira Njenga

Master of Medicine in Anatomic Pathology

Background: Helicobacter pylori infects approximately half of the world’s population. The main virulence factors, CagA and VacA, are associated with chronic gastritis and cancer. Notable geographic and temporal variations in the prevalence and genotypes of H. pylori in relation to gastric pathologies have been observed, however, their significance and trends in African populations is scantly described. The aim of this study was to investigate the association of H. pylori and its respective CagA and VacA genotypes with gastric adenocarcinoma and to describe the trends of H. pylori genotypes over the last 8 years (2012-2019). Materials and Methods: A total of …

Treatment-Resistant Hypercalcemia From Ectopic Pth Hypersecretion Suspected Secondary To Disseminated Ovarian Cancer, Alexander M. Balinski, Neil J. Khatter, Jeffrey M. Gold, Krishna S. Pothugunta, Vamshi K. Garlapaty, Steven M. Rankin, Christopher A. Thornburn, Jamal Abu-Khaled

Articles

Hypercalcemia of malignancy (HCM) can present secondary to hypersecretion of parathyroid hormone (PTH)-related protein (PTHrP) from malignant tumors, but rare cases of HCM have also been documented due to inappropriate PTH secretion from ectopic neoplasms. Here, we report an unusual case of HCM due to hypersecretion of PTH suspected secondary to a disseminated mucinous ovarian adenocarcinoma. A 45-year-old female presented with severe hypercalcemia and significant elevations in both PTH and PTHrP two weeks after total abdominal hysterectomy with bilateral salpingo-oophorectomy and suboptimal debulking of a newly discovered left ovarian mucinous adenocarcinoma with numerous metastases. Ectopic PTH secretion was highly suspected …

Tisagenlecleucel Infusion In Patients With Relapsed/Refractory All And Concurrent Serious Infection., Erin Hall, Dwight E. Yin, Rakesh K. Goyal, Atif Ahmed, Grace S. Mitchell, Shawn D. St Peter, Terrie Flatt, Ibrahim A. Ahmed, Weijie Li, Richard J. Hendrickson, Keith August, Douglas Myers

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Tisagenlecleucel, an anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy, has demonstrated durable efficacy and a manageable safety profile in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) in the ELIANA pivotal trial and real-world experience. Experience from investigator-led studies prior to ELIANA suggests that infections and inflammatory conditions may exacerbate the severity of cytokine release syndrome (CRS) associated with CAR-T cell therapy, leading to extreme caution and strong restrictions for on-study and commercial infusion of tisagenlecleucel in patients with active infection. CRS intervention with interleukin (IL)-6 blockade and/or steroid therapy was introduced late in …

Chronic Pain, Malingering, And The Word Memory Test, Dawn Marie Emmett Bishop

Walden Dissertations and Doctoral Studies

AbstractThe importance of using scientifically grounded strategies to detect malingering has been established in the literature and past research. Many reliable tools have been established for the detection of malingered neurocognition; however, research on how pain may affect these tools is sparse. The purpose of this study was to investigate the effect of pain on cognitive symptom validity testing and to establish the validity of the Word Memory Test (WMT), a cognitive symptom validity test with good sensitivity and specificity, when the test taker is feigning pain (simulating) or remembering pain. The biopsychosocial model and the gate theory of pain …

Goblet Cell Carcinoma Of The Appendix: A Case Report On Goblet Cell Carcinoid, Sheliza Kabani, Aubtin Saedi, Austin Lehr, Lina O'Brien

HCA Healthcare Journal of Medicine

Goblet cell carcinoid of the appendix is a rare neoplasm with histological features of both neuroendocrine and adenocarcinomas. The combination of its aggressive behavior, infrequent occurrence, and variable clinical presentation convolutes the management of this tumor. We report the case of a 75-year-old female presenting with acute appendicitis. A laparoscopic appendectomy was performed. The pathology report showed goblet cell carcinoid at the base of the appendix with involvement of the proximal surgical margins. At her postoperative visit, the patient’s pathology report and options for management were reviewed, and the patient agreed to proceed with a right hemicolectomy 8-10 weeks after …

Dach1 Mutation Frequency In Endometrial Cancer Is Associated With High Tumor Mutation Burden, Mckayla J. Riggs, Nan Lin, Chi Wang, Dava W. Piecoro, Rachel W. Miller, Oliver A. Hampton, Mahadev Rao, Frederick R. Ueland, Jill M. Kolesar

Obstetrics and Gynecology Faculty Publications

OBJECTIVE: DACH1 is a transcriptional repressor and tumor suppressor gene frequently mutated in melanoma, bladder, and prostate cancer. Loss of DACH1 expression is associated with poor prognostic features and reduced overall survival in uterine cancer. In this study, we utilized the Oncology Research Information Exchange Network (ORIEN) Avatar database to determine the frequency of DACH1 mutations in patients with endometrial cancer in our Kentucky population.

METHODS: We obtained clinical and genomic data for 65 patients with endometrial cancer from the Markey Cancer Center (MCC). We examined the clinical attributes of the cancers by DACH1 status by comparing whole-exome sequencing (WES), …

Malignant Eccrine Adenoma With Sarcomatous (Heterologous) Components: Report Of A Rare Skin Adnexal Neoplasm With Literature Review, Hira Ishtiaq, Muhammad Abdulwaasey, Muhammad Usman Tariq, Saira Fatima

Department of Pathology and Laboratory Medicine

Malignant eccrine spiradenoma (MES) is an exceedingly rare skin adnexal tumor that arises from pre-existing benign eccrine spiradenoma (BES). MES tumors show a wide spectrum of morphological features, posing a diagnostic challenge to the pathologist. Sarcomatous (heterologous) elements are seen in a few of these tumors, further complicating the morphological picture. We herein describe a case of a 66-year-old male who presented with a recently enlarging, ulcerated, nodular skin lesion over the right leg that had been present for the last 25 years. The patient underwent wide local excision of the tumor. Microscopic examination revealed a neoplastic lesion comprising benign …

Newborn Screening For Congenital Hypothyroidism: Improvement In Short-Term Follow-Up By Audit And Monitoring, Hafsa Majid, Sibtain Ahmed, Imran Siddiqui, Khadija N Humayun, Hussain Karimi, Aysha Habib Khan

Department of Pathology and Laboratory Medicine

Objective: Newborn screening for congenital hypothyroidism (CH) at our hospital during this study was by measurement of thyroid stimulating hormone (TSH) in serum samples. This audit was conducted over a 2 year period, to determine the compliance of reporting of results greater than the screening cutoffs for serum TSH. Gaps of non-compliance were identified, and re-audit was undertaken after the corrective actions were taken.
Results: The critical limit was defined as serum TSH (≥ 20 µIU/ml) following consultation with a pediatric endocrinologist. All results above this limit were reported urgently to physicians. During the audit period, 27,407 tests were performed, …

Does Breast Cancer Subtype Impact Margin Status In Patients Undergoing Partial Mastectomy?, Andrew Fenton, Elisabeth Dupont, Theodore Tsangaris, Carlos Garcia-Cantu, Marissa Howard-Mcnatt, Akiko Chiba, Adam Berger, Edward Levine, Jennifer Gass, Kristalyn Gallagher, Sharon Lum, Ricardo Martinez, Alliric Willis, Sonali Pandya, Eric A. Brown, Amanda Mendiola, Naveenraj Solomon, Maheswari Senthil, David Ollila, David Edmonson, Melissa Lazar, Jukes Namm, Fangyong Li, Meghan Butler, Noreen Mcgowan, Maria Herrera, Yoana Avitan, Brian Yoder, Laura L. Walters, Tara Mcpartland, Victor Haddad, Hongwei Ma, Ming Xie, Anees Chagpar

Conference Presentation Abstracts

BACKGROUND: Molecular subtype in invasive breast cancer guides systemic therapy. It is unknown whether molecular subtype should also be considered to tailor surgical therapy. The present investigation was designed to evaluate whether breast cancer subtype impacted surgical margins in patients with invasive breast cancer stage I through III undergoing breast-conserving therapy.

METHODS: Data from 2 randomized trials evaluating cavity shave margins (CSM) on margin status in patients undergoing partial mastectomy (PM) were used for this analysis. Patients were included if invasive carcinoma was present in the PM specimen and data for all 3 receptors (ER, PR, and HER2) were known. …

Clinicopathological And Immunohistochemical Study Of 29 Cases Of Solid-Pseudopapillary Neoplasms Of The Pancreas In Patients Under 20 Years Of Age Along With Detailed Review Of Literature, Nasir Ud Din, Shabina Rahim, Jamshid Abdul-Ghafar, Arsalan Ahmed, Zubair Ahmad

Department of Pathology and Laboratory Medicine

Background: Pancreatic Solid Pseudopapillary Neoplasms (SPNs) are rare low-grade malignant tumors with a marked preponderance for young females. Objective was to describe the morphology, differential diagnosis, and prognosis of SPNs in patients under 20 years of age and present a detailed review of literature.
Methods: A total of 29 cases in patients under 20 years of age reported as SPN during the period January 2014 to December 2019, were included in the study. These included 19 resection specimens, 4 incision biopsies and 6 cases received as blocks for second opinion. Hematoxylin and eosin (H&E) slides as well as immunohistochemistry (IHC) …

Pregabalin-Induced Myopathy In A Double Lung Transplant Recipient, Vishwajit Hegde, Nidhi Shekar, Filip G. Garrett, Maher A. Baz, Michael I. Anstead

Internal Medicine Faculty Publications

Pregabalin is a gamma-aminobutyric acid (GABA) derivative that was commercially approved by the Food and Drug Administration (FDA) in 2004. It is commonly used in the treatment of diabetic neuropathy, peripheral neuropathy, and spinal cord injury. We present the case of a 36-year-old Caucasian male double lung transplant recipient who presented with an 18-month history of fatigue and muscle weakness. He had elevated creatinine kinase level and his muscle biopsy showed evidence of drug-induced myopathy that improved after the cessation of pregabalin. We present a case of drug-induced myopathy as a rare complication of pregabalin therapy in a double lung …

Manf Is Neuroprotective Against Ethanol-Induced Neurodegeneration Through Ameliorating Er Stress, Yongchao Wang, Wen Wen, Hui Li, Marco Clementino, Hong Xu, Mei Xu, Murong Ma, Jacqueline A. Frank, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorders (FASD) are a spectrum of developmental disorders caused by prenatal alcohol exposure. Neuronal loss or neurodegeneration in the central nervous system (CNS) is one of the most devastating features in FASD. It is imperative to delineate the underlying mechanisms to facilitate the treatment of FASD. Endoplasmic reticulum (ER) stress is a hallmark and an underlying mechanism of many neurodegenerative diseases, including ethanol-induced neurodegeneration. Mesencephalic astrocyte-derived neurotrophic factor (MANF) responds to ER stress and has been identified as a protein upregulated in response to ethanol exposure during the brain development. To investigate the role of MANF in …

Epidemiology Of Staphylococcus Aureus Infections In Kenya: Current State, Gaps And Opportunities, Justin Nyasinga, Geoffrey Omuse, John Njenga, Andrew Nyerere, Shima Abdulgader, Mae Newton, Andrew Whitelaw, Gunturu Revathi

Pathology, East Africa

Staphylococcus aureus has maintained its clinical relevance as a major cause of hospital and community acquired infections globally with a high burden of antimicrobial resistance (AMR). Though reported, the burden of infection, antimicrobial resistance and molecular epidemiology of S. aureus are not well defined in Kenya. This descriptive review evaluated reported data on the detection and characterization of S. aureus infections in Kenya. Published data between 2000 and 2020 were evaluated. S. aureus isolation frequencies varied from 1% in blood specimens to 52.6% among skin and soft tissues infections while MRSA rates ranged from 1% to 84.1%. While penicillin resistance …

Trend Analysis Of Lab Tests Requisitions Of Covid-19 Prognostic Biomarkers At A Clinical Chemistry Reference Laboratory-An Observational Study, Sibtain Ahmed, Farooq Ghani

Department of Pathology and Laboratory Medicine

Background: Biochemical parameters, such as C-reactive protein (C-RP), Procalcitonin (PCT), Lactate dehydrogenase (LDH) and Ferritin are associated with COVID-19 severity and prognosis. This trend analysis of COVID-19 prognostic biomarker requisitions is aimed at providing a reflection of the clinical practices adopted amidst the peak of the pandemic. This knowledge of the prognostic biomarkers utilized, will further aid to classify patients based on their risk, for optimal resource allocation and improve outcomes.
Material & methods: This cross-sectional study was conducted at the clinical chemistry laboratory at the Aga Khan University Hospital (AKUH), Karachi Pakistan. A team consisting of two clinical chemistry …

Antimicrobial Resistance In Typhoidal Salmonella: Surveillance For Enteric Fever In Asia Project, 2016-2019, Farah Naz Qamar, Mohammad Tahir Yousafzai, Irum Fatima Dehraj, Sadia Shakoor, Seema Irfan, Aneeta Hotwani, Muhammad J. Hunzai, Rozina Thobani, Najeeb Rahman, Junaid Mehmood, Ashraf M. Memon

Department of Paediatrics and Child Health

Background: Clinicians have limited therapeutic options for enteric as a result of increasing antimicrobial resistance, and therefore typhoid vaccination is recommended as a preventive measure. As a part of the Surveillance for Enteric Fever in Asia Project (SEAP), we investigated the extent measured the burden of antimicrobial resistance (AMR) among confirmed enteric fever cases in Bangladesh, Nepal, and Pakistan.
Methods: From September 2016-September 2019, SEAP recruited study participants of all age groups from its outpatient, inpatient, hospital laboratory, laboratory network, and surgical sites who had a diagnosis of febrile illness that was either suspected or blood culture confirmed for enteric …

Burden Of Culture Confirmed Enteric Fever Cases In Karachi, Pakistan: Surveillance For Enteric Fever In Asia Project (Seap), 2016-2019, Mohammad Tahir Yousafzai, Seema Irfan, Rozina Thobani, Abdul Momin Kazi, Aneeta Hotwani, Ashraf M. Memon, Khalid Iqbal, Saqib Hamid Qazi, Nasir S. Saddal, Najeeb Rehman, Irum Fatima Dehraj, Mohammed J. Hunzai, Junaid Mehmood, Farah Naz Qamar

Department of Paediatrics and Child Health

Background: The Surveillance for Enteric Fever in Asia Project (SEAP) is a multicenter, multicountry study conducted in Pakistan, Nepal, and Bangladesh. The objectives of the study were to characterize disease incidence among patients with enteric fever. We report the burden of enteric fever at selected sites of Karachi, Pakistan.
Methods: During September 2016 to September 2019, prospective surveillance was conducted at inpatient, outpatient, surgical departments, and laboratory networks of Aga Khan University Hospital, Kharadar General Hospital, and surgery units of National Institute of Child Health and Jinnah Postgraduate Medical Centre. Socio-demographic, clinical, and laboratory data were obtained from all suspected …