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Recurrent Hotspot Mutations In Hras Q61 And Pi3k-Akt Pathway Genes As Drivers Of Breast Adenomyoepitheliomas., Felipe C. Geyer, Anqi Li, Anastasios D. Papanastasiou, Alison Smith, Pier Selenica, Kathleen A. Burke, Marcia Edelweiss, Huei-Chi Wen, Salvatore Piscuoglio, Anne M. Schultheis, Luciano G. Martelotto, Fresia Pareja, Rahul Kumar, Alissa Brandes, Dan Fan, Thais Basili, Arnaud Da Cruz Paula, John R. Lozada, Pedro Blecua, Simone Muenst, Achim A. Jungbluth, Maria P. Foschini, Hannah Y. Wen, Edi Brogi, Juan P. Palazzo, Brian P. Rubin, Charlotte K.Y. Ng, Larry Norton, Zsuzsanna Varga, Ian O. Ellis, Emad A. Rakha, Sarat Chandarlapaty, Britta Weigelt, Jorge S. Reis-Filho May 2018

Recurrent Hotspot Mutations In Hras Q61 And Pi3k-Akt Pathway Genes As Drivers Of Breast Adenomyoepitheliomas., Felipe C. Geyer, Anqi Li, Anastasios D. Papanastasiou, Alison Smith, Pier Selenica, Kathleen A. Burke, Marcia Edelweiss, Huei-Chi Wen, Salvatore Piscuoglio, Anne M. Schultheis, Luciano G. Martelotto, Fresia Pareja, Rahul Kumar, Alissa Brandes, Dan Fan, Thais Basili, Arnaud Da Cruz Paula, John R. Lozada, Pedro Blecua, Simone Muenst, Achim A. Jungbluth, Maria P. Foschini, Hannah Y. Wen, Edi Brogi, Juan P. Palazzo, Brian P. Rubin, Charlotte K.Y. Ng, Larry Norton, Zsuzsanna Varga, Ian O. Ellis, Emad A. Rakha, Sarat Chandarlapaty, Britta Weigelt, Jorge S. Reis-Filho

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Adenomyoepithelioma of the breast is a rare tumor characterized by epithelial-myoepithelial differentiation, whose genetic underpinning is largely unknown. Here we show through whole-exome and targeted massively parallel sequencing analysis that whilst estrogen receptor (ER)-positive adenomyoepitheliomas display PIK3CA or AKT1 activating mutations, ER-negative adenomyoepitheliomas harbor highly recurrent codon Q61 HRAS hotspot mutations, which co-occur with PIK3CA or PIK3R1 mutations. In two- and three-dimensional cell culture models, forced expression of HRAS


Ophthalmic Manifestations Of Heimler Syndrome Due To Pex6 Mutations., Nutsuchar Wangtiraumnuay, Waleed Abed Alnabi, Mai Tsukikawa, Avrey Thau, Jenina Capasso, Reuven Sharony, Chris F. Inglehearn, Alex V. Levin May 2018

Ophthalmic Manifestations Of Heimler Syndrome Due To Pex6 Mutations., Nutsuchar Wangtiraumnuay, Waleed Abed Alnabi, Mai Tsukikawa, Avrey Thau, Jenina Capasso, Reuven Sharony, Chris F. Inglehearn, Alex V. Levin

Wills Eye Hospital Papers

BACKGROUND/AIMS: Pigmentary retinal dystrophy and macular dystrophy have been previously reported in Heimler syndrome due to mutations in PEX1. Here we reported the ocular manifestations in Heimler syndrome due to mutations in PEX6.

MATERIALS AND METHODS: Medical records were reviewed to identify patient demographics, ophthalmic and systemic findings, and results of diagnostic testing including whole genome sequencing.

RESULTS: Patient 1 is 12-year-old boy with a novel mutation c.275T>G (p.Val92Gly) and known mutation c.1802G>A (p.Arg601Gln) in PEX6. Patient 2 is a 7-year-old girl with the same known c.1802G>A (p.Arg601Gln) mutation and another novel missense mutation c.296G>T (p.Arg99Leu). …


Synchronous Gastric And Duodenal Metastases From Head And Neck Squamous Cell Carcinoma: A Unique Presentation Of Upper Gastrointestinal Bleeding., Nicholas P. Tarangelo, Charles Andrew Kistler, Zachary Daitch, Wei Jiang, Daniel M. Quirk May 2018

Synchronous Gastric And Duodenal Metastases From Head And Neck Squamous Cell Carcinoma: A Unique Presentation Of Upper Gastrointestinal Bleeding., Nicholas P. Tarangelo, Charles Andrew Kistler, Zachary Daitch, Wei Jiang, Daniel M. Quirk

Department of Medicine Faculty Papers

Metastatic disease to the stomach or duodenum is an infrequent diagnosis, and head and neck squamous cell carcinoma (HNSCC) is one of the least common primary malignancies that lead to gastric or duodenal metastases. We report the case of a 65-year-old man with human immunodeficiency virus infection and previously diagnosed HNSCC who presented with melena. The patient had a percutaneous endoscopic gastrostomy tube placed 3 months prior to his presentation. Laboratory testing was significant for normocytic anemia and a digital rectal examination was positive for melena. Esophagogastroduodenoscopy revealed numerous cratered nodules with contact bleeding in the stomach as well as …


Abrogation Of Transforming Growth Factor-Β-Induced Tissue Fibrosis In Tbricacol1a2cre Transgenic Mice By The Second Generation Tyrosine Kinase Inhibitor Ski-606 (Bosutinib)., Peter J. Wermuth, Sergio A. Jimenez May 2018

Abrogation Of Transforming Growth Factor-Β-Induced Tissue Fibrosis In Tbricacol1a2cre Transgenic Mice By The Second Generation Tyrosine Kinase Inhibitor Ski-606 (Bosutinib)., Peter J. Wermuth, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

Transforming growth factor-β (TGF-β) plays a crucial role in the pathogenesis of Systemic Sclerosis (SSc) and other fibrotic disorders. TGF-β-mediated c-Abl and Src kinase activation induces strong profibrotic cascade signaling. The purpose of this study was to test in vivo the antifibrotic activity of Bosutinib (SKI-606), a second generation c-Abl and Src kinase inhibitor, on TGF-β induced cutaneous and pulmonary fibrosis. For this purpose, we employed the TBRIcaCol1a2Cre transgenic mice expressing an inducible constitutively active TGF-β receptor 1 constitutively activated by Col1a promoter-mediated Cre recombinase. The mice were treated parenterally with 2.5, 5.0 or 10.0 mg/kg/day of Bosutinib for 42 …


The Comparison Of Spectral Domain Optical Coherence Tomography (Sd-Oct) To Histopathology In A Patient With Diffuse Macular Drusen, Harold Salmons, Ralph Eagle, Md May 2018

The Comparison Of Spectral Domain Optical Coherence Tomography (Sd-Oct) To Histopathology In A Patient With Diffuse Macular Drusen, Harold Salmons, Ralph Eagle, Md

Department of Pathology Honors Program Student Research Symposium

Background: Spectral Domain Optical Coherence Tomography (SD-OCT) has become a gold standard technique in ophthalmologic practice, and has revolutionized the diagnosis and treatment of retinal disease. As SD-OCT uses low interference interferometry and mathematical algorithms to produce detailed theoretical cross-sectional images of the retina, it is crucial to examine correlations between SD-OCT images and their corresponding histopathologic slides.

Methods: In the present study, careful correlative light microscopy was performed on the eye that was enucleated from an elderly patient who had a uveal melanoma and early agerelated macular degeneration evident clinically as soft drusen. SD-OCT was performed prior to enucleation …


The Use Of Liquid Biopsy In The Fight Against Cancer, Chamaka Kalutota, Emanual Rubin, Md May 2018

The Use Of Liquid Biopsy In The Fight Against Cancer, Chamaka Kalutota, Emanual Rubin, Md

Department of Pathology Honors Program Student Research Symposium

In recent years, liquid biopsy has emerged as a potential alternative/adjunct to standard tissue biopsy in the diagnosis of malignancies. Current use of this technique, which tracks distinctive molecules released from neoplastic cells including circulating tumor cells (CTCs), exosomes, circulating tumor DNA (ctDNA), cell-free DNA (cfDNA) and miRNA, has generally been limited to determining therapies in lung cancer based on detectable mutations (EFGR, EML4-ALK). However, recent studies have demonstrated the possibility for using these molecules as more efficient prognostic and diagnostic biomarkers in breast, colon, rectum, lung, liver, and pancreatic cancer. Due to the need for standardization in sampled material …


Invasive Trichosporonosis Treated With Voriconazole, Vaibhav Garg, Elizabeth Jones, Ben J. Friedman, Jason B. Lee, Sherry Yang May 2018

Invasive Trichosporonosis Treated With Voriconazole, Vaibhav Garg, Elizabeth Jones, Ben J. Friedman, Jason B. Lee, Sherry Yang

Department of Dermatology and Cutaneous Biology Faculty Papers

Introduction

Trichosporon is a genus of yeast-like fungi. It is perhaps most widely known as the cause of white piedra, a benign superficial mycosis seen in immunocompetent individuals in tropical and subtropical regions. However, the incidence of invasive trichosporonosis has increased in immunocompromised patients, most notably those with hematologic malignancies. The following case illustrates characteristic features of trichosporonosis fungemia.


Genome Editing Technology, Crispr Cas-9, Provides A Potential Future For Xenotransplantation: Can Pigs Become Our New Organ Donors?, Shelby Smith, Bs, Emanual Rubin, Md May 2018

Genome Editing Technology, Crispr Cas-9, Provides A Potential Future For Xenotransplantation: Can Pigs Become Our New Organ Donors?, Shelby Smith, Bs, Emanual Rubin, Md

Department of Pathology Honors Program Student Research Symposium

Organ shortage has been a significant issue in United States for many decades. There were over 116,000 people on the transplant waiting list as of August 2017, with a new person added every 10 minutes. Animals have been considered as potential organ donors for humans, with the pig being the most ideal candidate because of its excellent breeding profile, low maintenance costs, large litters, rapid growth and organ similarity. A notable challenge that comes with porcine organs are endogenous retroviruses that establish themselves in the DNA of offspring in utero, thereby allowing for no time to prevent infection and integration. …


Acquired Resistance Mutations To Egfr Treatment In Non-Small Cell Lung Cancer, Benjamen Schoenberg, Gregory Omerza, Phd May 2018

Acquired Resistance Mutations To Egfr Treatment In Non-Small Cell Lung Cancer, Benjamen Schoenberg, Gregory Omerza, Phd

Department of Pathology Honors Program Student Research Symposium

Non-small cell lung cancer (NSCLC) is currently the number one cause of cancer death in the United States for both men and women.1 Mutations in the epidermal growth factor receptor (EGFR) gene are detected in approximately 30% of individuals with advanced NSCLC in Asia and 10-15% in Western countries.2 For patients harboring activating EGFR mutations, treatment includes the use of first or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), such as afatinib, gefitinib, or erlotinib.

The purpose of this case study is to review the pathophysiology of the progression of NSCLC in a 63-year-old non-smoking Caucasian woman. The patient presented with worsening …


A New Frontier In Breast Cancer Management: Oncotype Dx, Gabriella Rollo, Jeremy Molligan, Md, Juan P. Palazzo, Md May 2018

A New Frontier In Breast Cancer Management: Oncotype Dx, Gabriella Rollo, Jeremy Molligan, Md, Juan P. Palazzo, Md

Department of Pathology Honors Program Student Research Symposium

Diagnosing and prognosticating breast cancer has traditionally relied upon histomorphologic analysis and immunohistochemistry. With the recent advent of multigene molecular assays, traditional methods are being augmented with molecular biomarkers. Implementation of the Oncotype DX assay has led to a change in treatment of patients with early stage, estrogen positive cancer. Oncotype DX uses the expression of 21 genes at the mRNA level to determine a 10 year recurrence risk in node negative and 5 year recurrence risk in node positive cancer. 16 malignancy markers related to estrogen, HER2, cell proliferation, and invasion potential are compared with 5 reference genes and …


Primary Cns Small Mature B-Cell Lymphoma With Plasmacytic Differentiation Presenting As An Amyloidoma: A Case Report And Review Of Literature, Andrew Lynch, Geetha Jagannathan, Md May 2018

Primary Cns Small Mature B-Cell Lymphoma With Plasmacytic Differentiation Presenting As An Amyloidoma: A Case Report And Review Of Literature, Andrew Lynch, Geetha Jagannathan, Md

Department of Pathology Honors Program Student Research Symposium

Primary central nervous system lymphomas (PCNSL) without systemic involvement are rare and account for only 2-3% of all brain tumors and <1% of all non-Hodgkin’s lymphoma (NHL). Close to 40% of PCNSL are associated with immunosuppression, however, the incidence of primary central nervous system (CNS) lymphomas has shown an increasing trend in immunocompetent patients in recent decades due to better control of HIV and drug-induced immunosuppression [2]. Here, we describe a case of a primary CNS non-Hodgkin’s small mature B-cell lymphoma with plasmacytic differentiation in an immunocompetent individual. A previously healthy 87-year-old Caucasian woman presented to the neurology clinic with complaints of slowly progressing left sided weakness, predominantly in the left arm and leg over the last 6 months. Magnetic resonance imaging of the brain revealed a large, confluent white matter T2-hyperintensity in the right frontal lobe with multifocal nodular enhancement involving the left cerebral hemisphere, cerebellum, and leptomeninges, consistent morphologically with lymphoplasmacytic lymphoma. A bone marrow biopsy showed normal trilineage hematopoiesis with no evidence of lymphoma, myeloma or amyloidosis. Our patient was treated with Rituximab but developed an ischemic infarct of the left frontal white matter. She and her family decided to forego further treatment and switch to hospice care.


Ewing’S Sarcoma, Chris Lucasti, Bs, Bruce A. Fenderson, Phd May 2018

Ewing’S Sarcoma, Chris Lucasti, Bs, Bruce A. Fenderson, Phd

Department of Pathology Honors Program Student Research Symposium

Ewing’s sarcoma is the second most common malignant tumor of the bone occurring in children and adolescents. Typically, patients present between the ages of 10 and 20, with the disease having a slight predilection for males.1 Tumors often arise in the mid-shaft with the femur being the most frequently affected bone. The most common chromosome translocation, t(11;22)(q24;q12), occurs between the EWS gene and the FLI-1 gene. This translocation has been implicated in these aggressive and malignant tumors.1–4 Oftentimes, patients present with pain and swelling in the area of the affected bone or joint.5 While there has been some improvement in …


Clinico-Pathological Features And Pd-1/Pd-L1 Expression In Primary Mediastinal Large B Cell Lymphoma, Lydia Glick, Geetha Jagannathan, Md, Guldeep Uppal, Md May 2018

Clinico-Pathological Features And Pd-1/Pd-L1 Expression In Primary Mediastinal Large B Cell Lymphoma, Lydia Glick, Geetha Jagannathan, Md, Guldeep Uppal, Md

Department of Pathology Honors Program Student Research Symposium

Primary Mediastinal Large B Cell Lymphoma (PMBCL) is a distinct subtype of Diffuse Large B Cell Lymphoma (DLBCL) that has been historically reported to have a worse prognosis than DLBCL. Occasional studies have reported PD-L1 expression in PMBCL, which can emerge as an important target for immune-check point therapy. This study aimed to evaluate clinico-pathological features and characterize the expression of PD-1 and PD-L1 in a single cohort of 15 patients with PMBCL.

A total of 15 cases of PMBCL were retrieved from records of the department of Pathology; eleven of these had tissue available for additional immunohistochemistry, specifically, PD-L1 …


Comparative Analysis Of Tumor Capsule Thickness And Other Histologic Features In Encapsulated Follicular Variant Of Papillary Thyroid Carcinoma (Efvptc) And Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (Niftp), Brenda French, Stacey K. Mardekian, Md May 2018

Comparative Analysis Of Tumor Capsule Thickness And Other Histologic Features In Encapsulated Follicular Variant Of Papillary Thyroid Carcinoma (Efvptc) And Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (Niftp), Brenda French, Stacey K. Mardekian, Md

Department of Pathology Honors Program Student Research Symposium

Recent reclassification of a subset of non-invasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) tumors as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has led to important changes in the clinical management of patients with these indolent lesions. Although there are established diagnostic criteria to differentiate NIFTP from EFVPTC, our objective was to determine further differences in histological characteristics between NIFTP and noninvasive EFVPTC. Additionally, we sought to identify histological differences between non-invasive and invasive EFVPTC lesions beyond the key finding of invasion. 68 encapsulated follicular lesions with papillary-like nuclear features from patients treated at Thomas Jefferson …


Implications Of Hobnail Features In Anaplastic Thyroid Carcinoma And Precursor Lesions, Caroline Dunne, Ba, Stacey K. Mardekian, Md May 2018

Implications Of Hobnail Features In Anaplastic Thyroid Carcinoma And Precursor Lesions, Caroline Dunne, Ba, Stacey K. Mardekian, Md

Department of Pathology Honors Program Student Research Symposium

Anaplastic thyroid carcinoma (ATC) has the poorest prognosis of all thyroid cancers. Morphologically, it is characterized by pleomorphic undifferentiated cells. In some cases, a differentiated precursor lesion, either papillary thyroid carcinoma (PTC) or follicular thyroid carcinoma, can be identified adjacent to the anaplastic component. There are certain morphological variants of PTC that are known to be associated with more aggressive behavior, but a recently described, understudied variant is the hobnail variant. It is characterized histologically by micropapillary structures lined by cells with abundant eosinophilic cytoplasm and apically-placed bulging nuclei. The aim of this study was to evaluate the frequency of …


Atypical Presentation Of Upshaw Schulman Syndrome: A Case Report, Goutham Ravipati, Bs, David Strayer, Md, Phd, Douglas Drelich, Md May 2018

Atypical Presentation Of Upshaw Schulman Syndrome: A Case Report, Goutham Ravipati, Bs, David Strayer, Md, Phd, Douglas Drelich, Md

Department of Pathology Honors Program Student Research Symposium

Thrombotic thrombocytopenic purpura (TTP) is a rare coagulation disorder with a typical clinical presentation of low platelets and excessive clotting. Mortality for this disorder may be high if untreated and therefore necessitates a high clinical suspicion. Here we describe a 46-year-old African American woman with a past medical history of multiple cerebrovascular accidents presenting to hematology after a suspected diagnosis of TTP. Presumptive diagnosis of acquired TTP called for treatment with IVIg, but a diagnosis of congenital TTP (Upshaw Schulman syndrome) was made after testing showed a lack of ADAMTS13 antibodies. Treatment with fresh frozen plasma (FFP) showed increase in …


Trunk Motion Visual Feedback During Walking Improves Dynamic Balance In Older Adults: Assessor Blinded Randomized Controlled Trial., Eric Anson, Lei Ma, Tippawan Meetam, Elizabeth Thompson, Roshita Rathore, Victoria Dean, John Jeka May 2018

Trunk Motion Visual Feedback During Walking Improves Dynamic Balance In Older Adults: Assessor Blinded Randomized Controlled Trial., Eric Anson, Lei Ma, Tippawan Meetam, Elizabeth Thompson, Roshita Rathore, Victoria Dean, John Jeka

Department of Physical Therapy Faculty Papers

BACKGROUND: Virtual reality and augmented feedback have become more prevalent as training methods to improve balance. Few reports exist on the benefits of providing trunk motion visual feedback (VFB) during treadmill walking, and most of those reports only describe within session changes.

RESEARCH QUESTION: To determine whether trunk motion VFB treadmill walking would improve over-ground balance for older adults with self-reported balance problems.

METHODS: 40 adults (75.8 years (SD 6.5)) with self-reported balance difficulties or a history of falling were randomized to a control or experimental group. Everyone walked on a treadmill at a comfortable speed 3×/week for 4 weeks …


A Preexisting Rare Pik3ca E545k Subpopulation Confers Clinical Resistance To Mek Plus Cdk4/6 Inhibition In Nras Melanoma And Is Dependent On S6k1 Signaling, Gabriele Romano, Pei-Ling Chen, Ping Song, Jennifer L. Mcquade, Roger J. Liang, Mingguang Liu, Whijae Roh, Dzifa Y. Duose, Fernando C.L. Carapeto, Jun Li, Jessica L.F. Teh, Andrew A. Aplin, Merry Chen, Jianhua Zhang, Alexander J. Lazar, Michael A. Davies, P. Andrew Futreal, Rodabe N. Amaria, David Y. Zhang, Jennifer A. Wargo, Lawrence N. Kwong May 2018

A Preexisting Rare Pik3ca E545k Subpopulation Confers Clinical Resistance To Mek Plus Cdk4/6 Inhibition In Nras Melanoma And Is Dependent On S6k1 Signaling, Gabriele Romano, Pei-Ling Chen, Ping Song, Jennifer L. Mcquade, Roger J. Liang, Mingguang Liu, Whijae Roh, Dzifa Y. Duose, Fernando C.L. Carapeto, Jun Li, Jessica L.F. Teh, Andrew A. Aplin, Merry Chen, Jianhua Zhang, Alexander J. Lazar, Michael A. Davies, P. Andrew Futreal, Rodabe N. Amaria, David Y. Zhang, Jennifer A. Wargo, Lawrence N. Kwong

Department of Cancer Biology Faculty Papers

Combined MEK and CDK4/6 inhibition (MEKi + CDK4i) has shown promising clinical outcomes in patients with NRAS- mutant melanoma. Here, we interrogated longitudinal biopsies from a patient who initially responded to MEKi + CDK4i therapy but subsequently developed resistance. Whole-exome sequencing and functional validation identified an acquired PIK3CA E545K mutation as conferring drug resistance. We demonstrate that PIK3CA E545K preexisted in a rare subpopulation that was missed by both clinical and research testing, but was revealed upon multiregion sampling due to PIK3CA E545K being nonuniformly distributed. This resistant population rapidly expanded after the initiation of MEKi + CDK4i therapy and …


Synaptic Nanomodules Underlie The Organization And Plasticity Of Spine Synapses., Martin Hruska, Nathan T. Henderson, Sylvain J. Le Marchand, Haani Jafri, Matthew B. Dalva May 2018

Synaptic Nanomodules Underlie The Organization And Plasticity Of Spine Synapses., Martin Hruska, Nathan T. Henderson, Sylvain J. Le Marchand, Haani Jafri, Matthew B. Dalva

Department of Neuroscience Faculty Papers

Experience results in long-lasting changes in dendritic spine size, yet how the molecular architecture of the synapse responds to plasticity remains poorly understood. Here a combined approach of multicolor stimulated emission depletion microscopy (STED) and confocal imaging in rat and mouse demonstrates that structural plasticity is linked to the addition of unitary synaptic nanomodules to spines. Spine synapses in vivo and in vitro contain discrete and aligned subdiffraction modules of pre- and postsynaptic proteins whose number scales linearly with spine size. Live-cell time-lapse super-resolution imaging reveals that NMDA receptor-dependent increases in spine size are accompanied both by enhanced mobility of …


Human Gucy2c-Targeted Chimeric Antigen Receptor (Car)-Expressing T Cells Eliminate Colorectal Cancer Metastases., Michael S. Magee, Tara S. Abraham, Trevor R. Baybutt, John C. Flickinger, Natalie A. Ridge, Glen P Marszalowicz, Priyanka Prajapati, Adam R. Hersperger, Scott A. Waldman, Adam E. Snook May 2018

Human Gucy2c-Targeted Chimeric Antigen Receptor (Car)-Expressing T Cells Eliminate Colorectal Cancer Metastases., Michael S. Magee, Tara S. Abraham, Trevor R. Baybutt, John C. Flickinger, Natalie A. Ridge, Glen P Marszalowicz, Priyanka Prajapati, Adam R. Hersperger, Scott A. Waldman, Adam E. Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

One major hurdle to the success of adoptive T-cell therapy is the identification of antigens that permit effective targeting of tumors in the absence of toxicities to essential organs. Previous work has demonstrated that T cells engineered to express chimeric antigen receptors (CAR-T cells) targeting the murine homolog of the colorectal cancer antigen GUCY2C treat established colorectal cancer metastases, without toxicity to the normal GUCY2C-expressing intestinal epithelium, reflecting structural compartmentalization of endogenous GUCY2C to apical membranes comprising the intestinal lumen. Here, we examined the utility of a human-specific, GUCY2C-directed single-chain variable fragment as the basis for a CAR construct targeting …


Determining The Role Of Point-Of-Care Hemoglobin Testing In The Resuscitation Of Acutely Hemorrhaging Patients, Eugene P. Warnick, Alexis R. Peedin, Md May 2018

Determining The Role Of Point-Of-Care Hemoglobin Testing In The Resuscitation Of Acutely Hemorrhaging Patients, Eugene P. Warnick, Alexis R. Peedin, Md

Department of Pathology Honors Program Student Research Symposium

Point-of-care hemoglobin (Hb) testing has not been evaluated in the resuscitation of acutely hemorrhaging patients to guide transfusion therapy. This study assessed the correlation of Hb values determined by point-of-care (EPOC) and traditional laboratory (CBC) methods in patients undergoing massive transfusion. All patients transfused per the massive transfusion protocol (MTP) between February 2013 and October 2017 were identified. The EPOC result was most often within 1 g/dL of the CBC result when EPOC resulted in a Hb between 7-10 g/dL and when drawn within 15 minutes of the CBC specimen. In patients on MTP with an EPOC Hb between 7-10 …


Metastatic Lobular Breast Carcinoma In A Meningioma: A Case Study, Sara Chapin, Msii, Lawrence C. Kenyon, Md, Phd May 2018

Metastatic Lobular Breast Carcinoma In A Meningioma: A Case Study, Sara Chapin, Msii, Lawrence C. Kenyon, Md, Phd

Department of Pathology Honors Program Student Research Symposium

Hormonal relationships between breast carcinoma and meningioma have long been reported in the literature. This association may be related to the widespread expression of progesterone receptors in meningiomas. Indeed, meningiomas are more common in women and may demonstrate increased growth during pregnancy. Women have an increased risk of meningioma following breast carcinoma diagnosis and vice versa. However, much more uncommon is a tumor to tumor metastases of breast carcinoma into a meningioma. We report a case of a 56 year old female with a past medical history of breast cancer, found to have a right sphenoorbital meningioma with metastatic lobular …


Corticosteroid Administration To Prevent Complications Of Anterior Cervical Spine Fusion: A Systematic Review., Shayan Abdollah Zadegan, Seyed Behnam Jazayeri, Aidin Abedi, Hirbod Nasiri Bonaki, Alexander R. Vaccaro, Vafa Rahimi-Movaghar May 2018

Corticosteroid Administration To Prevent Complications Of Anterior Cervical Spine Fusion: A Systematic Review., Shayan Abdollah Zadegan, Seyed Behnam Jazayeri, Aidin Abedi, Hirbod Nasiri Bonaki, Alexander R. Vaccaro, Vafa Rahimi-Movaghar

Rothman Institute Papers

Study Design: Systematic review.

Objectives: Anterior cervical approach is associated with complications such as dysphagia and airway compromise. In this study, we aimed to systematically review the literature on the efficacy and safety of corticosteroid administration as a preventive measure of such complications in anterior cervical spine surgery with fusion.

Methods: Following a systematic literature search of MEDLINE, Embase, and Cochrane databases in July 2016, all comparative human studies that evaluated the effect of steroids for prevention of complications in anterior cervical spine surgery with fusion were included, irrespective of number of levels and language. Risk of bias was assessed …


A Word From The Writing Team (May 2018), Jennifer Wilson, Ms, Els May 2018

A Word From The Writing Team (May 2018), Jennifer Wilson, Ms, Els

A Word From the Writing Team (Newsletter)

This issue includes:

  • Grammar Time
  • What to Do Once Your Manuscript is Accepted
  • Writing Café


Development And Validation Of A 28-Gene Hypoxia-Related Prognostic Signature For Localized Prostate Cancer., Lingjian Yang, Darren Roberts, Mandeep Takhar, Nicholas Erho, Becky A.S. Bibby, Niluja Thiruthaneeswaran, Vinayak Bhandari, Wei-Chen Cheng, Syed Haider, Amy M.B. Mccorry, Darragh Mcart, Suneil Jain, Mohammed Alshalalfa, Ashley Ross, Edward Schaffer, Robert Den, R. Jeffrey Karnes, Eric Klein, Peter J. Hoskin, Stephen J. Freedland, Alastair D. Lamb, David E. Neal, Francesca M. Buffa, Robert G. Bristow, Paul C. Boutros, Elai Davicioni, Ananya Choudhury, Catharine M.L. West May 2018

Development And Validation Of A 28-Gene Hypoxia-Related Prognostic Signature For Localized Prostate Cancer., Lingjian Yang, Darren Roberts, Mandeep Takhar, Nicholas Erho, Becky A.S. Bibby, Niluja Thiruthaneeswaran, Vinayak Bhandari, Wei-Chen Cheng, Syed Haider, Amy M.B. Mccorry, Darragh Mcart, Suneil Jain, Mohammed Alshalalfa, Ashley Ross, Edward Schaffer, Robert Den, R. Jeffrey Karnes, Eric Klein, Peter J. Hoskin, Stephen J. Freedland, Alastair D. Lamb, David E. Neal, Francesca M. Buffa, Robert G. Bristow, Paul C. Boutros, Elai Davicioni, Ananya Choudhury, Catharine M.L. West

Department of Radiation Oncology Faculty Papers

BACKGROUND: Hypoxia is associated with a poor prognosis in prostate cancer. This work aimed to derive and validate a hypoxia-related mRNA signature for localized prostate cancer.

METHOD: Hypoxia genes were identified in vitro via RNA-sequencing and combined with in vivo gene co-expression analysis to generate a signature. The signature was independently validated in eleven prostate cancer cohorts and a bladder cancer phase III randomized trial of radiotherapy alone or with carbogen and nicotinamide (CON).

RESULTS: A 28-gene signature was derived. Patients with high signature scores had poorer biochemical recurrence free survivals in six of eight independent cohorts of prostatectomy-treated patients …


Effects Of Platelet-Activating Factor On Brain Microvascular Endothelial Cells., Eugen Brailoiu, Christine L. Barlow, Servio H. Ramirez, Mary E. Abood, G. Cristina Brailoiu May 2018

Effects Of Platelet-Activating Factor On Brain Microvascular Endothelial Cells., Eugen Brailoiu, Christine L. Barlow, Servio H. Ramirez, Mary E. Abood, G. Cristina Brailoiu

College of Pharmacy Faculty Papers

Platelet-activating factor (PAF) is a potent phospholipid mediator that exerts various pathophysiological effects by interacting with a G protein-coupled receptor. PAF has been reported to increase the permeability of the blood-brain barrier (BBB) via incompletely characterized mechanisms. We investigated the effect of PAF on rat brain microvascular endothelial cells (RBMVEC), a critical component of the BBB. PAF produced a dose-dependent increase in cytosolic Ca2+ concentration; the effect was prevented by the PAF receptor antagonist, WEB2086. The effect of PAF on cytosolic Ca2+ was abolished in Ca2+-free saline or in the presence of L-type voltage-gated Ca2+ …


Stroke Severity Affects Timing: Time From Stroke Code Activation To Initial Imaging Is Longer In Patients With Milder Strokes., Kimberly T. Kwei, John W. Liang, Natalie Wilson, Stanley Tuhrim, Mandip Dhamoon May 2018

Stroke Severity Affects Timing: Time From Stroke Code Activation To Initial Imaging Is Longer In Patients With Milder Strokes., Kimberly T. Kwei, John W. Liang, Natalie Wilson, Stanley Tuhrim, Mandip Dhamoon

Department of Neurology Faculty Papers

Optimizing the time it takes to get a potential stroke patient to imaging is essential in a rapid stroke response. At our hospital, door-to-imaging time is comprised of 2 time periods: the time before a stroke is recognized, followed by the period after the stroke code is called during which the stroke team assesses and brings the patient to the computed tomography scanner. To control for delays due to triage, we isolated the time period after a potential stroke has been recognized, as few studies have examined the biases of stroke code responders. This "code-to-imaging time" (CIT) encompassed the time …


Multimodal Pain Management Protocol Versus Patient Controlled Narcotic Analgesia For Postoperative Pain Control After Shoulder Arthroplasty, Thema Nicholson, Mitchell Maltenfort, Charles Getz, Mark Lazarus, Gerald R. Williams, Surena Namdari May 2018

Multimodal Pain Management Protocol Versus Patient Controlled Narcotic Analgesia For Postoperative Pain Control After Shoulder Arthroplasty, Thema Nicholson, Mitchell Maltenfort, Charles Getz, Mark Lazarus, Gerald R. Williams, Surena Namdari

Rothman Institute Papers

Background: Our institution's traditional pain management strategy after shoulder arthroplasty has involved the utilization of postoperative patient-controlled narcotic analgesia. More recently, we have implemented a protocol (TLC) that utilizes a multimodal approach. The purpose of this study was to determine whether this change has improved pain control and decreased narcotic utilization. Methods: Patients undergoing primary total shoulder or reverse arthroplasty were retrospectively studied. All patients underwent interscalene brachial plexus blockade. "Traditional" patients were provided a patient-controlled analgesic pump postoperatively. TLC patients were given preoperative and postoperative multimodal, non-narcotic analgesic medications and breakthrough narcotics. Morphine equivalent units (MEU) consumed and Visual …


Reuleaux, Sidney Miller May 2018

Reuleaux, Sidney Miller

Program of Industrial Design Capstones

A next-generation system of tools for quickly and intuitively designing in 3D.


Safe Ship, Kristin Renda, Dylan Courtney May 2018

Safe Ship, Kristin Renda, Dylan Courtney

Program of Industrial Design Capstones

SafeShip is the only discrete system that deters opportunistic theft and increases package delivery efficiency.