Medicine and Health Sciences Commons^™

Ferric Chloride-Induced Arterial Thrombosis And Sample Collection For 3d Electron Microscopy Analysis, Smita Joshi, Alexis N. Smith, Kanakanagavalli Shravani Prakhya, Hammodah Rawhi Hammodah Alfar, Joshua Lykins, Ming Zhang, Irina D. Pokrovskaya, Maria A. Aronova, Richard D. Leapman, Brian Storrie, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Cardiovascular diseases are a leading cause of mortality and morbidity worldwide. Aberrant thrombosis is a common feature of systemic conditions like diabetes and obesity, and chronic inflammatory diseases like atherosclerosis, cancer, and autoimmune diseases. Upon vascular injury, usually the coagulation system, platelets, and endothelium act in an orchestrated manner to prevent bleeding by forming a clot at the site of the injury. Abnormalities in this process lead to either excessive bleeding or uncontrolled thrombosis/insufficient antithrombotic activity, which translates into vessel occlusion and its sequelae. The FeCl3-induced carotid injury model is a valuable tool in probing how thrombosis initiates and progresses …

Metallic Implant-Related Osteosarcoma, Frawa Mohsin, Mustafa Bin Ali Zubairi, Kulsoom Fatima, Muhammad Asad Diwan

Department of Radiology

Orthopedic metallic prostheses are commonly used in the current practice of orthopedic surgery. Although, biomaterials used in these implants are generally considered to be biologically inert, there have been consequences of foreign body reactions and potential carcinogenesis. Majority of implant-related malignancies are high grade, and develop in bone or soft tissue around the implant site. No clear association has been identified between the biomaterial implanted and the type of sarcoma. We report the case of a 36-year-old male who underwent intramedullary nailing of femur for mid-shaft fracture secondary to trauma and presented with osteogenic sarcoma of femur 14 months later.

Multimorbidity Research In Sub-Saharan Africa: Proceedings Of An Interdisciplinary Workshop, Gift T. Banda, Edna Bosire, Christopher Bunn, Clare I.R. Chandler, Edith Chikumbu, Jonathan Chiwanda, Justin Dixon, Rashida A. Ferrand, Andre-Pascal Kengne, Felix Limbani

Brain and Mind Institute

As life expectancies rise globally, the number of people living with multiple chronic health conditions – commonly referred to as ‘multimorbidity’ – is rising. Multimorbidity has been recognised as especially challenging to respond to in countries whose health systems are under-funded, fragmented, and designed primarily for acute care, including in sub-Saharan Africa. A growing body of research in sub-Saharan Africa has sought to better understand the particular challenges multimorbidity poses in the region and to develop context-sensitive responses. However, with multimorbidity still crystallising as a subject of enquiry, there remains considerable heterogeneity in conceptualising multimorbidity across disciplines and fields, hindering …

Mental Health And Psychosocial Interventions Integrating Sexual And Reproductive Rights And Health, And Hiv Care And Prevention For Adolescents And Young People (10–24 Years) In Sub-Saharan Africa: A Systematic Scoping Review, Otsetswe Musindo, Sheharbano Jafry, Joseph Nyamiobo, Kimberly D. Becker, Resham Gellatly, Caitlin Maloy, Alvaro Lozano-Ruiz, Borja Romero-Gonzalez, Zul Merali, Manasi Kumar

Brain and Mind Institute

Background: Interventions targeting combined sexual and reproductive health, Human Immunodeficiency Virus (HIV) management and mental health care in sub-Saharan Africa (SSA) are few. There is a need to address common determinants of poor mental, psychosocial and sexual and reproductive health and rights (SRHR) through multimodal and multipronged interventions for adolescents. The main objective of this study was to identify whether and how interventions targeting adolescent SRHR and HIV with a focus on pregnant and parenting adolescents in SSA include mental health components and how these components and their outcomes have been reported in the literature.

Methods: We carried …

Psychosocial Needs Of Pediatric Patients With Cancer Predisposition Syndromes: Standardized Screening Needed, Meredith Ehrhardt, Mirae Fornander, Rachel Moore

Posters

Introduction Cancer predisposition syndromes (CPS; e.g., Li-Fraumeni syndrome, Von Hippel-Lindau syndrome) require routine, standardized medical monitoring with accompanying unique, complex psychosocial needs (e.g., family medical needs). Despite limited research within pediatric populations, emerging literature has begun to support the benefit of routine psychosocial screening in this population. Very few pediatric CPS clinics with dedicated psychosocial care (i.e., psychology) exist in the U.S. and there is currently no standard of care for psychosocial support of CPS patients. This study aims to better understand the psychosocial needs of pediatric CPS patients and support the need for a standardized psychosocial screening protocol among …

Myositis As A Complication Of Dengue Viral Infection, Amina Sadiqa, Usama Hayyan, Zaid Waqar, Taha Pasha

Pakistan Journal of Neurological Sciences (PJNS)

Dengue fever is a febrile illness caused by an arbovirus transmitted by the Aedes aegypti mosquito. It occurs as a seasonal epidemic every year in Pakistan. Apart from febrile illness and its associated hemorrhagic complication, dengue fever is associated with multi-system involvement and their respective complications, including myriad neurological complications. In this case report we describe two patients who developed acute viral myositis.

Clinical Spectrum, Risk Factors & Electrophysiological Evaluation Of Sciatic Nerve Injury In Patients Presenting To A Tertiary Care Hospital, Maryum Khadim Khadim, Safia Bano, Ahsan Numan

Pakistan Journal of Neurological Sciences (PJNS)

No abstract provided.

Frequency Of Tension-Type Headache In Patients With Migraine: A Single-Center Cross-Sectional Study, Haris Majid Rajput, Zahid Hussain Mir, Muhammad Fateen Rashed, Fiza Batool Almosvi, Mazhar Badshah

Pakistan Journal of Neurological Sciences (PJNS)

ABSTRACT Background and objective: Migraine is a common headache disorder characterized by recurrent episodes of moderate to severe headaches which are usually unilateral. Migraine is the second most common headache disorder after tension-type headache. The objective of this study was to determine the frequency of tension-type headache in patients with migraine. Methods: This cross-sectional study was carried out at Pakistan Institute of Medical Sciences, Islamabad for a period of six months between 1st July 2018 and 31st December 2018. This study enrolled patients above the age of 12 years that were diagnosed with “Migraine without aura” or “Migraine with aura”. …

Perceived Business Skills Needs Of Mfts: Implications For A Doctoral Program, Abel Arvizú Whittemore

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was twofold: a) to determine the training that MFTs should have to effectively work in organizational / business settings and with organizational / business issues in the role of clinician, administrator / manager, consultant, coach, and researcher and b) to determine what components should be included in a model curriculum in the area of organizational / management studies in an MFT doctoral program. Using the e-Delphi method, consensus from a panel of experts (in the profession of marriage and family therapy as well as in business / management / organizational issues) was obtained. Panelists identified …

Colon Adenocarcinoma And Birt-Hogg-Dubé Syndrome In A Young Patient: Case Report And Exploration Of Pathologic Implications, Grant W. Jirka, Daniel S. Lefler, Jessica Russo, Babar Bashir

Department of Medical Oncology Faculty Papers

Birt–Hogg–Dubé syndrome (BHD) is an autosomal dominant disorder caused by germline mutations in the folliculin gene (FLCN) that result in the functional loss of the tumor suppressor folliculin. It is classically associated with cutaneous hamartomas, pulmonary cysts with spontaneous pneumothorax, and various renal cancers. In this case, we present a patient initially diagnosed with chromophobe renal cell carcinoma and subsequently found to have colorectal cancer (CRC). The presence of two separate malignancies in a young patient with a strong family history of CRC (father and paternal grandfather) led to genetic testing, which revealed an FLCN c.1177–5_1177-3del mutation, and a diagnosis …

Macrophage-Derived Mlkl In Alcohol-Associated Liver Disease: Regulation Of Phagocytosis, Xiaoqin Wu, Xiude Fan, Megan R Mcmullen, Tatsunori Miyata, Adam Kim, Vai Pathak, Jianguo Wu, Le Z Day, Josiah E Hardesty, Nicole Welch, Jaividhya Dasarathy, Daniela S Allende, Arthur J Mccullough, Jon M Jacobs, Daniel M Rotroff, Srinivasan Dasarathy, Laura E Nagy

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Mixed lineage kinase domain-like pseudokinase (MLKL), a key terminal effector of necroptosis, also plays a role in intracellular vesicle trafficking that is critical for regulating liver inflammation and injury in alcohol-associated liver disease (ALD). Although receptor interacting protein kinase 3 (Rip3)-/- mice are completely protected from ethanol-induced liver injury, Mlkl-/- mice are only partially protected. Therefore, we hypothesized that cell-specific functions of MLKL may contribute to ethanol-induced injury.

APPROACH AND RESULTS: Bone marrow transplants between Mlkl-/- mice and littermates were conducted to distinguish the role of myeloid versus nonmyeloid Mlkl in the Gao-binge model of ALD. Ethanol-induced …

Mining For Equitable Health: Assessing The Impact Of Missing Data In Electronic Health Records, Emily Getzen, Lyle Ungar, Danielle Mowery, Xiaoqian Jiang, Qi Long

Faculty, Staff and Student Publications

Electronic health records (EHR) are collected as a routine part of healthcare delivery, and have great potential to be utilized to improve patient health outcomes. They contain multiple years of health information to be leveraged for risk prediction, disease detection, and treatment evaluation. However, they do not have a consistent, standardized format across institutions, particularly in the United States, and can present significant analytical challenges- they contain multi-scale data from heterogeneous domains and include both structured and unstructured data. Data for individual patients are collected at irregular time intervals and with varying frequencies. In addition to the analytical challenges, EHR …

A Hierarchical Strategy To Minimize Privacy Risk When Linking “De-Identified” Data In Biomedical Research Consortia, Lucila Ohno-Machado, Xiaoqian Jiang, Tsung-Ting Kuo, Shiqiang Tao, Luyao Chen, Pritham M Ram, Guo-Qiang Zhang, Hua Xu

Faculty, Staff and Student Publications

Linking data across studies offers an opportunity to enrich data sets and provide a stronger basis for data-driven models for biomedical discovery and/or prognostication. Several techniques to link records have been proposed, and some have been implemented across data repositories holding molecular and clinical data. Not all these techniques guarantee appropriate privacy protection; there are trade-offs between (a) simple strategies that can be associated with data that will be linked and shared with any party and (b) more complex strategies that preserve the privacy of individuals across parties. We propose an intermediary, practical strategy to support linkage in studies that …

A Potent And Broad Neutralization Of Sars-Cov-2 Variants Of Concern By Darpins, Vikas Chonira, Young D Kwon, Jason Gorman, James Brett Case, Zhiqiang Ku, Rudo Simeon, Ryan G Casner, Darcy R Harris, Adam S Olia, Tyler Stephens, Lawrence Shapiro, Michael F Bender, Hannah Boyd, I-Ting Teng, Yaroslav Tsybovsky, Florian Krammer, Ningyan Zhang, Michael S Diamond, Peter D Kwong, Zhiqiang An, Zhilei Chen

Faculty, Staff and Student Publications

We report the engineering and selection of two synthetic proteins-FSR16m and FSR22-for the possible treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. FSR16m and FSR22 are trimeric proteins composed of DARPin SR16m or SR22 fused with a T4 foldon. Despite selection by a spike protein from a now historical SARS-CoV-2 strain, FSR16m and FSR22 exhibit broad-spectrum neutralization of SARS-CoV-2 strains, inhibiting authentic B.1.351, B.1.617.2 and BA.1.1 viruses, with respective IC

Hla Factors Versus Non-Hla Factors For Haploidentical Donor Selection, Rohtesh S Mehta, Kai Cao, Rima M Saliba, Gheath Al-Atrash, Amin M Alousi, Konstantinos Lontos, Curtis Marcoux, Yudith Carmazzi, Gabriela Rondon, Qaiser Bashir, Chitra M Hosing, Partow Kebriaei, Issa Khouri, David Marin, Yago Nieto, Betul Oran, Uday R Popat, Muzaffar H Qazilbash, Jeremy Ramdial, Katayoun Rezvani, Richard E Champlin, Elizabeth J Shpall

Faculty, Staff and Student Publications

When multiple haploidentical donors are available for transplantation, those of younger generations are generally selected over those of older generations. However, it is unclear who is the optimal donor when selecting candidates from within a generation, such as father versus mother, son versus daughter, or brother versus sister. Although traditionally male donors are favored over female donors, particularly for male recipients, and significant associations of individual HLA mis(matches) on outcomes are being increasingly recognized, the hierarchy of factors for donor selection is indeterminate. To assess whether HLA factors take precedence over non-HLA factors and to isolate the influence of specific …

Naltrexone-Bupropion Combinations Do Not Affect Cocaine Self-Administration In Humans, Sean D Regnier, William W Stoops, Joshua A Lile, Joseph L Alcorn, B Levi Bolin, Anna R Reynolds, Lon R Hays, Abner O Rayapati, Craig R Rush

Faculty, Staff and Student Publications

The FDA has not yet approved a pharmacotherapy for cocaine use disorder despite nearly four decades of research. This study determined the initial efficacy, safety, and tolerability of naltrexone-bupropion combinations as a putative pharmacotherapy for cocaine use disorder. Thirty-one (31) non-treatment seeking participants with cocaine use disorder completed a mixed-design human laboratory study. Participants were randomly assigned to the naltrexone conditions (i.e., 0, 50 mg/day; between-subject factor) and maintained on escalating doses of bupropion (i.e., 0, 100, 200, 400 mg/day; within-subject factor) for at least four days prior to the conduct of experimental sessions. Cocaine self-administration (IN, 0, 40, 80 …

Neoadjuvant Chemotherapy Plus Nivolumab With Or Without Ipilimumab In Operable Non-Small Cell Lung Cancer: The Phase 2 Platform Neostar Trial, Tina Cascone, Cheuk H Leung, Annikka Weissferdt, Apar Pataer, Brett W Carter, Myrna C B Godoy, Hope Feldman, William N William, Yuanxin Xi, Sreyashi Basu, Jing Jing Sun, Shalini S Yadav, Frank R Rojas Alvarez, Younghee Lee, Aditya K Mishra, Lili Chen, Monika Pradhan, Haiping Guo, Ansam Sinjab, Nicolas Zhou, Marcelo V Negrao, Xiuning Le, Carl M Gay, Anne S Tsao, Lauren Averett Byers, Mehmet Altan, Bonnie S Glisson, Frank V Fossella, Yasir Y Elamin, George Blumenschein, Jianjun Zhang, Ferdinandos Skoulidis, Jia Wu, Reza J Mehran, David C Rice, Garrett L Walsh, Wayne L Hofstetter, Ravi Rajaram, Mara B Antonoff, Junya Fujimoto, Luisa M Solis, Edwin R Parra, Cara Haymaker, Ignacio I Wistuba, Stephen G Swisher, Ara A Vaporciyan, Heather Y Lin, Jing Wang, Don L Gibbons, J Jack Lee, Nadim J Ajami, Jennifer A Wargo, James P Allison, Padmanee Sharma, Humam Kadara, John V Heymach, Boris Sepesi

Faculty, Staff and Student Publications

Neoadjuvant ipilimumab + nivolumab (Ipi+Nivo) and nivolumab + chemotherapy (Nivo+CT) induce greater pathologic response rates than CT alone in patients with operable non-small cell lung cancer (NSCLC). The impact of adding ipilimumab to neoadjuvant Nivo+CT is unknown. Here we report the results and correlates of two arms of the phase 2 platform NEOSTAR trial testing neoadjuvant Nivo+CT and Ipi+Nivo+CT with major pathologic response (MPR) as the primary endpoint. MPR rates were 32.1% (7/22, 80% confidence interval (CI) 18.7–43.1%) in the Nivo+CT arm and 50% (11/22, 80% CI 34.6–61.1%) in the Ipi+Nivo+CT arm; the primary endpoint was met in both arms. …

Carbon Fiber-Reinforced Polyetheretherketone Spinal Implants For Treatment Of Spinal Tumors: Perceived Advantages And Limitations, Christopher Alvarez-Breckenridge, Romulo De Almeida, Ali Haider, Matthew Muir, Justin Bird, Robert North, Laurence Rhines, Claudio Tatsui

Faculty, Staff and Student Publications

PURPOSE: Carbon-fiber reinforced polyetheretherketone (CFRP)-based spinal implants are an alternative to titanium, offering less image artifact as their metallic counterparts while maintaining similar biomechanical and biocompatibility properties. Its use in the management of spinal tumors has been reported, however the perceived advantages related to improved imaging quality, radiation treatment planning, and detection of tumor recurrence have not been fully assessed.

METHODS: We performed a retrospective review of medical records amongst oncologic patients treated at MD Anderson Cancer Center with CFRP implants. Histology, tumor location, construct features, time of follow-up, adjuvant radiation, recurrences, overall survival, and hardware-related complications were recorded.

RESULTS: …

Endotrophin Neutralization Through Targeted Antibody Treatment Protects From Renal Fibrosis In A Podocyte Ablation Model, Yu A An, Wei Xiong, Shiuhwei Chen, Dawei Bu, Joseph M Rutkowski, Joel P Berger, Christine M Kusminski, Ningyan Zhang, Zhiqiang An, Philipp E Scherer

Faculty, Staff and Student Publications

OBJECTIVE: Renal fibrosis is a hallmark for chronic kidney disease (CKD), and often leads to end stage renal disease (ESRD). However, limited interventions are available clinically to ameliorate or reverse renal fibrosis.

METHODS: Herein, we evaluated whether blockade of endotrophin through neutralizing antibodies protects from renal fibrosis in the podocyte insult model (the "POD-ATTAC" mouse). We determined the therapeutic effects of endotrophin targeted antibody through assessing renal function, renal inflammation and fibrosis at histological and transcriptional levels, and podocyte regeneration.

RESULTS: We demonstrated that neutralizing endotrophin antibody treatment significantly ameliorates renal fibrosis at the transcriptional, morphological, and functional levels. In …

Immune And Pathologic Responses In Patients With Localized Prostate Cancer Who Received Daratumumab (Anti-Cd38) Or Edicotinib (Csf-1r Inhibitor), Bilal A Siddiqui, Brian F Chapin, Sonali Jindal, Fei Duan, Sreyashi Basu, Shalini S Yadav, Ai-Di Gu, Alexsandra B Espejo, Michelle Kinder, Curtis A Pettaway, John F Ward, Rebecca S S Tidwell, Patricia Troncoso, Paul G Corn, Christopher J Logothetis, Roland Knoblauch, Natalie Hutnick, Marco Gottardis, Charles G Drake, Padmanee Sharma, Sumit K Subudhi

Faculty, Staff and Student Publications

BACKGROUND: The prostate tumor microenvironment (TME) is immunosuppressive, with few effector T cells and enrichment of inhibitory immune populations, leading to limited responses to treatments such as immune checkpoint therapies (ICTs). The immune composition of the prostate TME differs across soft tissue and bone, the most common site of treatment-refractory metastasis. Understanding immunosuppressive mechanisms specific to prostate TMEs will enable rational immunotherapy strategies to generate effective antitumor immune responses. Daratumumab (anti-CD38 antibody) and edicotinib (colony-stimulating factor-1 receptor (CSF-1R) inhibitor) may alter the balance within the prostate TME to promote antitumor immune responses.

HYPOTHESIS: Daratumumab or edicotinib will be safe and …

Respiratory And Cardiometabolic Comorbidities And Stages I To Iii Nsclc Survival: A Pooled Analysis From The International Lung Cancer Consortium, Miguel García-Pardo, Amy Chang, Sabine Schmid, Mei Dong, M Catherine Brown, David Christiani, Hilary Aurora Tindel, Paul Brennan, Chu Chen, Jie Zhang, Brid M Ryan, David Zaridze, Matthew B Schabath, Leticia Ferro Leal, Rui Manuel Reis, Adonina Tardon, Guillermo Fernández-Tardon, Sanjay S Shete, Angeline Andrew, Hermann Brenner, Wei Xu, Rayjean J Hung, Geoffrey Liu

Faculty, Staff and Student Publications

INTRODUCTION: We explored the association of respiratory and cardiometabolic comorbidities with NSCLC overall survival (OS) and lung cancer-specific survival (LCSS), by stage, in a large, multicontinent NSCLC pooled data set.

METHODS: On the basis of patients pooled from 11 International Lung Cancer Consortium studies with available respiratory and cardiometabolic comorbidity data, adjusted hazard ratios (aHRs) were estimated using Cox models for OS. LCSS was evaluated using competing risk Grey and Fine models and cumulative incidence functions. Logistic regression (adjusted OR [aOR]) was applied to assess factors associated with surgical resection.

RESULTS: OS analyses used patients with NSCLC with respiratory health …

Factors That Influence Treatment Decisions: A Qualitative Study Of Racially And Ethnically Diverse Patients With Low- And Very-Low Risk Prostate Cancer, Alice Guan, Janet K Shim, Laura Allen, Mei-Chin Kuo, Kathie Lau, Zinnia Loya, James D Brooks, Peter R Carroll, Iona Cheng, Benjamin I Chung, Mindy C Derouen, Dominic L Frosch, Todd Golden, John T Leppert, Daphne Y Lichtensztajn, Qian Lu, Debora L Oh, Weiva Sieh, Michelle Wadhwa, Scarlett L Gomez, Salma Shariff-Marco

Faculty, Staff and Student Publications

BACKGROUND: Factors that influence prostate cancer treatment decisions are complex, multifaceted, and personal, and may vary by race/ethnicity. Although research has been published to quantify factors involved in decision-making, these studies have been limited to primarily white, and to a lesser extent, Black patients, and quantitative studies are limited for discerning the cultural and contextual processes that shape decision-making.

METHODS: We conducted 43 semi-structured interviews with a racially and ethnically diverse sample of patients diagnosed with low- and very-low risk prostate cancer who had undergone treatment for their prostate cancer. Interviews were transcribed, independently coded, and analyzed to identify themes …

Aapm Medical Physics Practice Guideline 13a: Hdr Brachytherapy, Part A, Susan L Richardson, Ivan M Buzurovic, Gil'ad N Cohen, Wesley S Culberson, Claire Dempsey, Bruce Libby, Christopher S Melhus, Robin A Miller, Daniel J Scanderbeg, Samantha J Simiele

Faculty, Staff and Student Publications

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education, and professional practice of medical physics. The AAPM has more than 8000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines (MPPGs) will be reviewed for the purpose of revision or renewal, as appropriate, on their …

Temporal Multi-Step Predictive Modeling Of Remission In Major Depressive Disorder Using Early Stage Treatment Data; Star*D Based Machine Learning Approach, Haitham Salem, Tung Huynh, Natasha Topolski, Benson Mwangi, Madhukar H Trivedi, Jair C Soares, A John Rush, Sudhakar Selvaraj

Faculty, Staff and Student Publications

BACKGROUND: Artificial intelligence is currently being used to facilitate early disease detection, better understand disease progression, optimize medication/treatment dosages, and uncover promising novel treatments and potential outcomes.

METHODS: Utilizing the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) dataset, we built a machine learning model to predict depression remission rates using same clinical data as features for each of the first three antidepressant treatment steps in STAR*D. We only used early treatment data (baseline and first follow up) in each STAR*D step to temporally analyze predictive features of remission at the end of the step.

RESULTS: Our model showed significant prediction …

Risk Analysis Of The Unity 15 T Mr-Linac Adapt-To-Position Workflow, Jiayi Liang, Paola Godoy Scripes, Neelam Tyagi, Ergys Subashi, Theresa Wunner, Nicolas Cote, Ching-Yun Chan, Angela Ng, Victoria Brennan, Kaveh Zakeri, Cassandra Wildberger, James Mechalakos

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: Newer technologies allow for daily treatment adaptation, providing the ability to account for setup variations and organ motion but comes at the cost of increasing the treatment workflow complexity. One such technology is the adapt-to-position (ATP) workflow on the Unity MR-Linac. Prospective risk assessment of a new workflow allows clinics to catch errors before they occur, especially for processes that include novel and unfamiliar steps.

METHODS: As part of a quality management program, failure modes and effects analysis was performed on the ATP treatment workflow following the recommendations of AAPM's Task Group 100. A multidisciplinary team was …

First-In-Human Phase I Study Of The Ox40 Agonist Gsk3174998 With Or Without Pembrolizumab In Patients With Selected Advanced Solid Tumors (Engage-1), Sophie Postel-Vinay, Vincent K Lam, Willeke Ros, Todd M Bauer, Aaron R Hansen, Daniel C Cho, F Stephen Hodi, Jan H M Schellens, Jennifer K Litton, Sandrine Aspeslagh, Karen A Autio, Frans L Opdam, Meredith Mckean, Neeta Somaiah, Stephane Champiat, Mehmet Altan, Anna Spreafico, Osama Rahma, Elaine M Paul, Christoph M Ahlers, Helen Zhou, Herbert Struemper, Shelby A Gorman, Maura Watmuff, Kaitlin M Yablonski, Niranjan Yanamandra, Michael J Chisamore, Emmett V Schmidt, Axel Hoos, Aurelien Marabelle, Jeffrey S Weber, John V Heymach

Faculty, Staff and Student Publications

BACKGROUND: The phase I first-in-human study ENGAGE-1 evaluated the humanized IgG1 OX40 agonistic monoclonal antibody GSK3174998 alone (Part 1 (P1)) or in combination with pembrolizumab (Part 2 (P2)) in patients with advanced solid tumors.

METHODS: GSK3174998 (0.003-10 mg/kg) ± pembrolizumab (200 mg) was administered intravenously every 3 weeks using a continuous reassessment method for dose escalation. Primary objectives were safety and tolerability; secondary objectives included pharmacokinetics, immunogenicity, pharmacodynamics, and clinical activity.

RESULTS: 138 patients were enrolled (45 (P1) and 96 (P2, including 3 crossovers)). Treatment-related adverse events occurred in 51% (P1) and 64% (P2) of patients, fatigue being the most …

Vidutolimod In Combination With Atezolizumab With And Without Radiation Therapy In Patients With Programmed Cell Death Protein 1 Or Programmed Death-Ligand 1 Blockade-Resistant Advanced Nsclc, Marcelo V Negrao, Vassiliki A Papadimitrakopoulou, Andrew C Price, Alda L Tam, Muhammad Furqan, Sandeep T Laroia, Erminia Massarelli, Jose Pacheco, John V Heymach, Anne S Tsao, Gary V Walker, Lalit Vora, David Mauro, Heather Kelley, James E Wooldridge, Arthur M Krieg, Jiaxin Niu

Faculty, Staff and Student Publications

INTRODUCTION: Vidutolimod, a CpG-A TLR9 agonist, was investigated in a phase 1b study (CMP-001-003; ClinicalTrials.gov, NCT03438318) in combination with atezolizumab with and without radiation therapy (RT) in patients with advanced NSCLC.

METHODS: Patients with progressive disease after anti-programmed cell death protein 1 or programmed death-ligand 1 therapy received either vidutolimod and atezolizumab (part A) or vidutolimod, atezolizumab, and RT (part B). The primary objective was to evaluate the safety of vidutolimod and atezolizumab with and without RT. Key secondary end point was best objective response rate per Response Evaluation Criteria in Solid Tumors, version 1.1.

RESULTS: Between March 28, 2018, …

Persistent Nociceptor Hyperactivity As A Painful Evolutionary Adaptation, Edgar T Walters, Robyn J Crook, G Gregory Neely, Theodore J Price, Ewan St John Smith

Faculty, Staff and Student Publications

Chronic pain caused by injury or disease of the nervous system (neuropathic pain) has been linked to persistent electrical hyperactivity of the sensory neurons (nociceptors) specialized to detect damaging stimuli and/or inflammation. This pain and hyperactivity are considered maladaptive because both can persist long after injured tissues have healed and inflammation has resolved. While the assumption of maladaptiveness is appropriate in many diseases, accumulating evidence from diverse species, including humans, challenges the assumption that neuropathic pain and persistent nociceptor hyperactivity are always maladaptive. We review studies indicating that persistent nociceptor hyperactivity has undergone evolutionary selection in widespread, albeit selected, animal …

Prospective Study Of Pain Outcomes Associated With Breast Surgery In Women With Nonhereditary Breast Cancer, Demetria J Smith-Graziani, Patricia A Parker, Susan K Peterson, Isabelle Bedrosian, Y Shen, Dalliah M Black, Sarah M Desnyder, Kelly K Hunt, Wenli Dong, Abenaa M Brewster

Faculty, Staff and Student Publications

OBJECTIVE: To assess pain severity and interference with life in women after different types of breast cancer surgery and the demographic, treatment-related, and psychosocial variables associated with these pain outcomes.

SUMMARY OF BACKGROUND DATA: Data are conflicting regarding pain outcomes and quality of life (QOL) among women who undergo different types of breast surgery.

METHODS: Women with nonhereditary breast cancer completed the brief pain inventory before surgery and at 1, 6, 12, and 18 months postsurgery. We assessed associations between pain outcomes and CPM status and mastectomy status using multivariable repeated measures models. We assessed associations between pain outcome and …

Novel Genetic Regulators Of Fibrinogen Synthesis Identified By An In Vitro Experimental Platform, Dre'von A Dobson, Lori A Holle, Feng-Chang Lin, Jennifer E Huffman, James P Luyendyk, Matthew J Flick, Nicholas L Smith, Paul S De Vries, Alanna C Morrison, Alisa S Wolberg

Faculty, Staff and Student Publications

BACKGROUND: Fibrinogen has an established, essential role in both coagulation and inflammatory pathways, and these processes are deeply intertwined in the development of thrombotic and atherosclerotic diseases. Previous studies aimed to better understand the (patho) physiological actions of fibrinogen by characterizing the genomic contribution to circulating fibrinogen levels.

OBJECTIVES: Establish an in vitro approach to define functional roles between genes within these loci and fibrinogen synthesis.

METHODS: Candidate genes were selected on the basis of their proximity to genetic variants associated with fibrinogen levels and expression in hepatocytes and HepG2 cells. HepG2 cells were transfected with small interfering RNAs targeting …