Medical Specialties Commons^™

48 Hours Holter Monitoring In Detecting Occult Atrial Fibrillation In Young Patients With Possible Cardioembolic Stroke, Bushra Khalid, Soban Khan, Muhammad Tariq, Sajid Ali, Ijaz Ali, Zaid Waqar

Pakistan Journal of Neurological Sciences (PJNS)

ABSTRACT

Background and objective: Atrial fibrillation (AF) is a common cause of ischemic stroke. AF is usually paroxysmal and could escape detection via single lead electrocardiogram ECG recorder. Holter monitoring is useful in this scenario. The objective of this study was to assess the role of 48 hours Holter monitoring in identifying clinically inapparent AF in young patients with ischemic stroke

Methods: A retrospective cross-sectional study was conducted with patient data from November 2019 to February 2021. It was conducted in Neurology department of Pakistan Institute of Medical Sciences, Islamabad, Pakistan. Study contained medical records of 60 patients which were …

Efficacy And Safety Of Lifileucel, A One-Time Autologous Tumor-Infiltrating Lymphocyte (Til) Cell Therapy, In Patients With Advanced Melanoma After Progression On Immune Checkpoint Inhibitors And Targeted Therapies: Pooled Analysis Of Consecutive Cohorts Of The C-144-01 Study, Jason Chesney, Karl D Lewis, Harriet Kluger, Omid Hamid, Eric Whitman, Sajeve Thomas, Martin Wermke, Mike Cusnir, Evidio Domingo-Musibay, Giao Q Phan, John M Kirkwood, Jessica C Hassel, Marlana Orloff, James Larkin, Jeffrey Weber, Andrew J S Furness, Nikhil I Khushalani, Theresa Medina, Michael E Egger, Friedrich Graf Finckenstein, Madan Jagasia, Parameswaran Hari, Giri Sulur, Wen Shi, Xiao Wu, Amod Sarnaik

Department of Medical Oncology Faculty Papers

Background: Patients with advanced melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 patients who progressed after ICI and targeted therapy. Herein, we report independent review committee (IRC)-assessed outcomes of 153 patients treated with lifileucel in a large multicenter Phase 2 cell therapy trial in melanoma.

Methods: Eligible patients had advanced melanoma that progressed after ICI and targeted therapy, where appropriate. Melanoma lesions were resected (resected tumor diameter ≥1.5 cm) and shipped to a central good manufacturing …

Sars-Cov-2 Infection With Polymyositis- A Case Report, Muhammad Hassan, Fatima Mustafa, Naveed Ullah Khan, Taimoor Hassan, Mansoor Iqbal Chaudhry, Mazhar Badshah

Pakistan Journal of Neurological Sciences (PJNS)

Among the most prevalent and least addressed symptoms of SARS-CoV-2 infection are myalgia, muscle weakness, and body aches. Only a few studies have reported polymyositis in patients with Covid-19 infection. At least one-third of patients with Covid-19 syndrome had elevated CPK levels. The cause of elevated CPK can be a cytokine storm or viral infection of the muscles. We present a case in which our patient developed features of myositis following the resolution of an acute viral prodrome caused by SARS-CoV-2. Our patient had both radiological and biopsy-proven neuromuscular manifestations of SARS-CoV-2 associated with polymyositis. Proximal muscle weakness began shortly …

The Sub-Standardized Approach To Stroke Management In Low And Middle-Income Countries Including Pakistan: Limitations And Suggested Options To Overcome Some Of The Shortcomings Via Teleneurology/Telestroke Application, Rizwana Shahid

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective: Ischemic stroke still poses a significant health concern throughout the world. However, low and middle-income countries (LMIC) in Asia have more devastating outcome. The vascular risk factors are prevalent in most parts of Asia, contributing to increasing incidence. The recommended approved treatment for acute stroke is limited to a few areas in these countries. We aimed to identify stroke risk factors, its incidence and prevalence; treatment opportunities offered in various parts of the region and utilizing the alternate pathways to improve the disease recognition and management outcome.

Method: A comprehensive search using PubMed, MEDLINE, Medline Plus, PubMed …

Covid-19 Vaccine Equity: Codesigning Public Health Interventions With Community Partners, Eva Varotsis, Lauren Schlegel, B. H. Slovis, Patricia C. Henwood, Sandra E Brooks, Robert S. Pugliese, Bon Ku, Morgan Hutchinson

Department of Emergency Medicine Faculty Papers

No abstract provided.

Multispectral Imaging For Microchip Electrophoresis Enables Point-Of-Care Newborn Hemoglobin Variant Screening, Ran An, Yuning Huang, Anne Rocheleau, Qiaochu Zhang, Yuncheng Man, Zoe Sekyonda, Amma Owusu-Ansah, Umut A. Gurkan

Faculty Scholarship

Hemoglobin (Hb) disorders affect nearly 7% of the world's population. Globally, around 400,000 babies are born annually with sickle cell disease (SCD), primarily in sub-Saharan Africa where morbidity and mortality rates are high. Screening, early diagnosis, and monitoring are not widely accessible due to technical challenges and cost. We hypothesized that multispectral imaging will allow sensitive hemoglobin variant identification in existing affordable paper-based Hb electrophoresis. To test this hypothesis, we developed the first integrated point-of-care multispectral Hb variant test: Gazelle-Multispectral. Here, we evaluated the accuracy of Gazelle-Multispectral for Hb variant newborn screening in 265 newborns with known hemoglobin variants including …

Isometric Knee Strength Is Greater In Individuals Who Score Higher On Psychological Readiness To Return To Sport After Primary Anterior Cruciate Ligament Reconstruction., Barrie S Sugarman, Zach B Sullivan, Daniel Le, Carolyn Killelea, Mallory S Faherty, Lee H Diehl, Jocelyn R Wittstein, Jonathan C Riboh, Alison P Toth, Annunziato Amendola, Dean C Taylor, Timothy C Sell

Ambulatory and Primary Care Articles

BACKGROUND: Anterior cruciate ligament (ACL) injury is extremely common among athletes. Rate of second ACL injury due to surgical graft rupture or contralateral limb ACL injury is approximately 15-32%. Psychological readiness to return to sport (RTS) may be an important predictor of successful RTS outcomes. Psychological readiness can be quantified using the ACL Return to Sport after Injury (ACL-RSI) questionnaire, with higher scores demonstrating greater psychological readiness.

PURPOSE: The purpose of this study was to investigate differences in functional performance and psychological readiness to return to sport among athletes who have undergone primary ACL reconstruction (ACLR).

STUDY DESIGN: Descriptive cohort …

The Relationship Between Anti-Müllerian Hormone, Body Mass Index And Weight Loss: A Review Of The Literature, Jacqueline Kloos, Rachel Weinerman

Student Scholarship

Anti-Müllerian hormone (AMH) is commonly used as a proxy for ovarian reserve due to its secretion by antral follicles. It is considered a metric for prediction of ovarian response to certain assisted reproduction therapies. As obesity has a negative impact on fertility, it is important to establish whether obesity-induced hormonal changes influence AMH levels, if and how weight loss affects AMH, and if that influence represents altered reproductive function. The aim of this study was to review the existing literature on the effects of body mass index and weight loss on AMH levels. A PubMed literature keyword search with relevant …

Facilitators And Inhibitors To First Adult Care Visits In The Transition From Paediatric To Adult Orientated Inflammatory Bowel Disease Healthcare, Joanna Rea

Theses

Background: Inflammatory bowel disease (IBD) can be a very debilitating disease and it is found to be more extensive in children with rapid early progression (Van Limbergen et al., 2008). As adolescents, these children transition from paediatric to adult oriented care. The first adult care visits are a pivotal phase of a successful transition process, where adolescents potentially begin to actively take control of their disease. The aim of this study is to explore the inhibitors and facilitators to first adult care visits in the transition process from paediatric to adult oriented IBD healthcare.

Methods: An exploratory, descriptive, qualitative approach …

A Substring Replacement Approach For Identifying Missing Is-A Relations In Snomed Ct, Xubing Hao, Rashmie Abeysinghe, Jay Shi, Licong Cui

Faculty, Staff and Student Publications

Biomedical ontologies provide formalized information and knowledge in the biomedical domain. Over the years, biomedical ontologies have played an important role in facilitating biomedical research and applications. Common quality issues of biomedical ontologies include inconsistent naming of concepts, redundant concepts, redundant relations, incomplete/incorrect concept definitions, and incomplete/incorrect class hierarchies. In this work, we focus on addressing the incompleteness of the class hierarchy in SNOMED CT. We develop a substring replacement approach, leveraging concepts’ lexical features and existing IS-A relations to identify potential missing IS-A relations in SNOMED CT. To evaluate the effectiveness of our approach, we performed both automated and …

Autoantibody Against Tumor-Associated Antigens As Diagnostic Biomarkers In Hispanic Patients With Hepatocellular Carcinoma, Yangcheng Ma

Open Access Theses & Dissertations

Liver cancer is one of the most prevalent malignancies, in which hepatocellular carcinoma (HCC) takes up more than 80% of liver cancer cases. Early diagnosis and treatment are practical approaches to impede HCC progression. Identifying and classifying autoantibodies against tumor-associated antigens (TAAs) have long been interested in cancer diagnosis, especially for HCC. Circulating anti-TAA autoantibodies amplify the antigen expression and are more stable in blood, guaranteeing anti-TAA autoantibodies as valid diagnostic biomarkers in clinical application. Nonetheless, very few studies had focused on the Hispanic HCC group, which might retain distinct etiological risk factors compared to other ethnicities. The high incidence …

Multidisciplinary Simulation Of Trauma In Pregnancy With Resuscitative Endovascular Balloon Occlusion Of The Aorta (Reboa) Utilization., Peter Hopmann, Jaya Sai Varre, Gary Duncan, William B Devoe, Brad D Gable

Trauma and Acute Care Articles

Background Studies have demonstrated the use of resuscitative endovascular balloon occlusion catheters of the aorta (REBOA) in the setting of postpartum hemorrhage and traumatic hemorrhagic shock. However, REBOA is infrequently utilized leading to a lack of clinician comfort. This study's aim was to demonstrate the utility of REBOA in a hemorrhaging pregnant trauma patient and improve clinician comfort with the placement of REBOA while emphasizing collaboration between medical specialties. Methods A multidisciplinary in-situ simulation was developed for the management of a pregnant patient with an abdominal gunshot wound evaluated by obstetrics and surgery teams. A trauma survey, emergency c-section, massive …

Chronic Kidney Disease In Public Renal Practices In Queensland, Australia, 2011–2018, Wendy E Hoy, Zaimin Wang, Jianzhen Zhang, Vishal Diwan, Anne Cameron, Sree K Venuthurupalli, Robert G Fassett, Samuel Chan, Helen G Healy, Ken-Soon Tan, Richard Baer, Andrew J Mallett, Nicholas Gray, Murty Mantha, Roy Cherian, Clyson Mutatiri, Krishan Madhan, George Kan, Geoffrey Mitchell, Shahadat Hossain, Danielle Wu, Thin Han, Adrian Kark, Thomas Titus, Dwarakanatan Ranganathan, Ann Bonner, Sridevi Govindarajulu, Nhmrc Ckd.Cre And The Ckd.Qld Collaborative

Faculty, Staff and Student Publications

AIM: To describe adults with (non-dialysis) chronic kidney disease (CKD) in nine public renal practice sites in the Australian state of Queensland.

METHODS: 7,060 persons were recruited to a CKD Registry in May 2011 and until start of kidney replacement therapy (KRT), death without KRT or June 2018, for a median period of 3.4 years.

RESULTS: The cohort comprised 7,060 persons, 52% males, with a median age of 68 yr; 85% had CKD stages 3A to 5, 45.4% were diabetic, 24.6% had diabetic nephropathy, and 51.7% were obese. Younger persons mostly had glomerulonephritis or genetic renal disease, while older persons …

Single-Cell Crispr Immune Screens Reveal Immunological Roles Of Tumor Intrinsic Factors, Jiakai Hou, Shaoheng Liang, Chunyu Xu, Yanjun Wei, Yunfei Wang, Yukun Tan, Nidhi Sahni, Daniel J Mcgrail, Chantale Bernatchez, Michael Davies, Yumei Li, Rui Chen, S Stephen Yi, Yiwen Chen, Cassian Yee, Ken Chen, Weiyi Peng

Faculty, Staff and Student Publications

Genetic screens are widely exploited to develop novel therapeutic approaches for cancer treatment. With recent advances in single-cell technology, single-cell CRISPR screen (scCRISPR) platforms provide opportunities for target validation and mechanistic studies in a high-throughput manner. Here, we aim to establish scCRISPR platforms which are suitable for immune-related screens involving multiple cell types. We integrated two scCRISPR platforms, namely Perturb-seq and CROP-seq, with both in vitro and in vivo immune screens. By leveraging previously generated resources, we optimized experimental conditions and data analysis pipelines to achieve better consistency between results from high-throughput and individual validations. Furthermore, we evaluated the performance …

Discovery And Systematic Characterization Of Risk Variants And Genes For Coronary Artery Disease In Over A Million Participants, Krishna G Aragam, Tao Jiang, Anuj Goel, Stavroula Kanoni, Brooke N Wolford, Deepak S Atri, Elle M Weeks, Minxian Wang, George Hindy, Wei Zhou, Christopher Grace, Carolina Roselli, Nicholas A Marston, Frederick K Kamanu, Ida Surakka, Loreto Muñoz Venegas, Paul Sherliker, Satoshi Koyama, Kazuyoshi Ishigaki, Bjørn O Åsvold, Michael R Brown, Ben Brumpton, Paul S De Vries, Olga Giannakopoulou, Panagiota Giardoglou, Daniel F Gudbjartsson, Ulrich Güldener, Syed M Ijlal Haider, Anna Helgadottir, Maysson Ibrahim, Adnan Kastrati, Thorsten Kessler, Theodosios Kyriakou, Tomasz Konopka, Ling Li, Lijiang Ma, Thomas Meitinger, Sören Mucha, Matthias Munz, Federico Murgia, Jonas B Nielsen, Markus M Nöthen, Shichao Pang, Tobias Reinberger, Gavin Schnitzler, Damian Smedley, Gudmar Thorleifsson, Moritz Von Scheidt, Jacob C Ulirsch, Biobank Japan, Epic-Cvd, David O Arnar, Noël P Burtt, Maria C Costanzo, Jason Flannick, Kaoru Ito, Dong-Keun Jang, Yoichiro Kamatani, Amit V Khera, Issei Komuro, Iftikhar J Kullo, Luca A Lotta, Christopher P Nelson, Robert Roberts, Gudmundur Thorgeirsson, Unnur Thorsteinsdottir, Thomas R Webb, Aris Baras, Johan L M Björkegren, Eric Boerwinkle, George Dedoussis, Hilma Holm, Kristian Hveem, Olle Melander, Alanna C Morrison, Marju Orho-Melander, Loukianos S Rallidis, Arno Ruusalepp, Marc S Sabatine, Kari Stefansson, Pierre Zalloua, Patrick T Ellinor, Martin Farrall, John Danesh, Christian T Ruff, Hilary K Finucane, Jemma C Hopewell, Robert Clarke, Rajat M Gupta, Jeanette Erdmann, Nilesh J Samani, Heribert Schunkert, Hugh Watkins, Cristen J Willer, Panos Deloukas, Sekar Kathiresan, Adam S Butterworth, Cardiogramplusc4d Consortium

Faculty, Staff and Student Publications

The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in …

Targeting The Mtor Pathway For The Prevention Of Er-Negative Breast Cancer, Abhijit Mazumdar, William M Tahaney, Jamal L Hill, Yun Zhang, Sumankalai Ramachandran, Jitesh Kawedia, Jing Qian, Alejandro Contreras, Michelle I Savage, Lana A Vornik, Shizuko Sei, Altaf Mohammed, Powel H Brown

Faculty, Staff and Student Publications

Our results show that everolimus delays mammary tumor formation in multiple mouse models, suggesting that mTOR inhibitors will be useful for the prevention of ER-negative and triple-negative breast cancer in humans. See related Spotlight, p. 787.

Safety And Efficacy Of Hsp90 Inhibitor Ganetespib For Neoadjuvant Treatment Of Stage Ii/Iii Breast Cancer, Julie E Lang, Andres Forero-Torres, Douglas Yee, Christina Yau, Denise Wolf, John Park, Barbara A Parker, A Jo Chien, Anne M Wallace, Rashmi Murthy, Kathy S Albain, Erin D Ellis, Heather Beckwith, Barbara B Haley, Anthony D Elias, Judy C Boughey, Rachel L Yung, Claudine Isaacs, Amy S Clark, Hyo S Han, Rita Nanda, Qamar J Khan, Kristen K Edmiston, Erica Stringer-Reasor, Elissa Price, Bonnie Joe, Minetta C Liu, Lamorna Brown-Swigart, Emanuel F Petricoin, Julia D Wulfkuhle, Meredith Buxton, Julia L Clennell, Ashish Sanil, Scott Berry, Smita M Asare, Amy Wilson, Gillian L Hirst, Ruby Singhrao, Adam L Asare, Jeffrey B Matthews, Michelle Melisko, Jane Perlmutter, Hope S Rugo, W Fraser Symmans, Laura J Van 'T Veer, Nola M Hylton, Angela M Demichele, Donald A Berry, Laura J Esserman

Faculty, Staff and Student Publications

HSP90 inhibitors destabilize oncoproteins associated with cell cycle, angiogenesis, RAS-MAPK activity, histone modification, kinases and growth factors. We evaluated the HSP90-inhibitor ganetespib in combination with standard chemotherapy in patients with high-risk early-stage breast cancer. I-SPY2 is a multicenter, phase II adaptively randomized neoadjuvant (NAC) clinical trial enrolling patients with stage II-III breast cancer with tumors 2.5 cm or larger on the basis of hormone receptors (HR), HER2 and Mammaprint status. Multiple novel investigational agents plus standard chemotherapy are evaluated in parallel for the primary endpoint of pathologic complete response (pCR). Patients with HER2-negative breast cancer were eligible for randomization to …

Intraoperative Localization And Preservation Of Reading In Ventral Occipitotemporal Cortex, Oscar Woolnough, Kathryn M Snyder, Cale W Morse, Meredith J Mccarty, Samden D Lhatoo, Nitin Tandon

Faculty, Staff and Student Publications

OBJECTIVE: Resective surgery in language-dominant ventral occipitotemporal cortex (vOTC) carries the risk of causing impairment to reading. Because it is not on the lateral surface, it is not easily accessible for intraoperative mapping, and extensive stimulation mapping can be time-consuming. Here the authors assess the feasibility of using task-based electrocorticography (ECoG) recordings intraoperatively to help guide stimulation mapping of reading in vOTC.

METHODS: In 11 patients undergoing extraoperative, intracranial seizure mapping, the authors recorded induced broadband gamma activation (70-150 Hz) during a visual category localizer. In 2 additional patients, whose pathologies necessitated resections in language-dominant vOTC, task-based functional mapping was …

Structural Variants Drive Context-Dependent Oncogene Activation In Cancer, Zhichao Xu, Dong-Sung Lee, Sahaana Chandran, Victoria T Le, Rosalind Bump, Jean Yasis, Sofia Dallarda, Samantha Marcotte, Benjamin Clock, Nicholas Haghani, Chae Yun Cho, Kadir C Akdemir, Selene Tyndale, P Andrew Futreal, Graham Mcvicker, Geoffrey M Wahl, Jesse R Dixon

Faculty, Staff and Student Publications

Higher-order chromatin structure is important for the regulation of genes by distal regulatory sequences. Structural variants (SVs) that alter three-dimensional (3D) genome organization can lead to enhancer-promoter rewiring and human disease, particularly in the context of cancer3. However, only a small minority of SVs are associated with altered gene expression4,5, and it remains unclear why certain SVs lead to changes in distal gene expression and others do not. To address these questions, we used a combination of genomic profiling and genome engineering to identify sites of recurrent changes in 3D genome structure in cancer and determine the effects of specific …

Pan-Cancer Landscape Of Aid-Related Mutations, Composite Mutations, And Their Potential Role In The Ici Response, Isaias Hernández-Verdin, Kadir C Akdemir, Daniele Ramazzotti, Giulio Caravagna, Karim Labreche, Karima Mokhtari, Khê Hoang-Xuan, Matthieu Peyre, Franck Bielle, Mehdi Touat, Ahmed Idbaih, Alex Duval, Marc Sanson, Agustí Alentorn

Faculty, Staff and Student Publications

Activation-induced cytidine deaminase, AICDA or AID, is a driver of somatic hypermutation and class-switch recombination in immunoglobulins. In addition, this deaminase belonging to the APOBEC family may have off-target effects genome-wide, but its effects at pan-cancer level are not well elucidated. Here, we used different pan-cancer datasets, totaling more than 50,000 samples analyzed by whole-genome, whole-exome, or targeted sequencing. AID mutations are present at pan-cancer level with higher frequency in hematological cancers and higher presence at transcriptionally active TAD domains. AID synergizes initial hotspot mutations by a second composite mutation. AID mutational load was found to be independently associated with …

Spinal Metastases And The Evolving Role Of Molecular Targeted Therapy, Chemotherapy, And Immunotherapy, Elena I Fomchenko, James C Bayley, Christopher Alvarez-Breckenridge, Laurence D Rhines, Claudio E Tatsui

Faculty, Staff and Student Publications

Metastatic involvement of the spine is a common complication of systemic cancer progression. Surgery and external beam radiotherapy are palliative treatment modalities aiming to preserve neurological function, control pain and maintain functional status. More recently, with development of image guidance and stereotactic delivery of high doses of conformal radiation, local tumor control has improved; however recurrent or radiation refractory disease remains a significant clinical problem with limited treatment options. This manuscript represents a narrative overview of novel targeted molecular therapies, chemotherapies, and immunotherapy treatments for patients with breast, lung, melanoma, renal cell, prostate, and thyroid cancers, which resulted in improved …

Germline Variants Associated With Toxicity To Immune Checkpoint Blockade, Stefan Groha, Sarah Abou Alaiwi, Wenxin Xu, Vivek Naranbhai, Amin H Nassar, Ziad Bakouny, Talal El Zarif, Renee Maria Saliby, Guihong Wan, Ahmad Rajeh, Elio Adib, Pier V Nuzzo, Andrew L Schmidt, Chris Labaki, Biagio Ricciuti, Joao Victor Alessi, David A Braun, Sachet A Shukla, Tanya E Keenan, Eliezer Van Allen, Mark M Awad, Michael Manos, Osama Rahma, Leyre Zubiri, Alexandra-Chloe Villani, Benjamin Fairfax, Christian Hammer, Zia Khan, Kerry Reynolds, Yevgeniy Semenov, Deborah Schrag, Kenneth L Kehl, Matthew L Freedman, Toni K Choueiri, Alexander Gusev

Faculty, Staff and Student Publications

Immune checkpoint inhibitors (ICIs) have yielded remarkable responses but often lead to immune-related adverse events (irAEs). Although germline causes for irAEs have been hypothesized, no individual variant associated with developing irAEs has been identified. We carried out a genome-wide association study of 1,751 patients on ICIs across 12 cancer types. We investigated two irAE phenotypes: (1) high-grade (3-5) and (2) all-grade events. We identified 3 genome-wide significant associations (P < 5 × 10-8) in the discovery cohort associated with all-grade irAEs: rs16906115 near IL7 (combined P = 3.6 × 10-11; hazard ratio (HR) = 2.1); rs75824728 near IL22RA1 (combined P = 3.5 × 10-8; HR = 1.8); and rs113861051 on 4p15 (combined P = 1.2 × 10-8, HR = 2.0); rs16906115 was replicated in 3 independent studies. The association near IL7 colocalized with the gain of a new cryptic exon for IL7, a critical regulator of lymphocyte homeostasis. Patients carrying the IL7 germline variant exhibited significantly increased lymphocyte stability after ICI initiation, which was itself predictive of downstream irAEs and improved survival.

Quantification Of Manipulation Forces Needed For Robot-Assisted Reduction Of The Ankle Syndesmosis: An Initial Cadaveric Study, Mikias Gebremeskel, Babar Shafiq, Ali Uneri, Niral Sheth, Corey Simmerer, Wojciech Zbijewski, Jeffrey H Siewerdsen, Kevin Cleary, Gang Li

Faculty, Staff and Student Publications

PURPOSE: Manual surgical manipulation of the tibia and fibula is necessary to properly align and reduce the space in ankle fractures involving sprain of the distal tibiofibular syndesmosis. However, manual reduction is highly variable and can result in malreduction in about half of the cases. Therefore, we are developing an image-guided robotic assistant to improve reduction accuracy. The purpose of this study is to quantify the forces associated with reduction of the ankle syndesmosis to define the requirements for our robot design.

METHODS: Using a cadaveric specimen, we designed a fixture jig to fix the tibia securely on the operating …

Mildly Dysplastic Oral Lesions With Optically-Detectable Abnormalities Share Genetic Similarities With Severely Dysplastic Lesions, David R Brenes, Allison J Nipper, Melody T Tan, Frederico O Gleber-Netto, Richard A Schwarz, Curtis R Pickering, Michelle D Williams, Nadarajah Vigneswaran, Ann M Gillenwater, Andrew G Sikora, Rebecca R Richards-Kortum

Faculty, Staff and Student Publications

OBJECTIVE: Optical imaging studies of oral premalignant lesions have shown that optical markers, including loss of autofluorescence and altered morphology of epithelial cell nuclei, are predictive of high-grade pathology. While these optical markers are consistently positive in lesions with moderate/severe dysplasia or cancer, they are positive only in a subset of lesions with mild dysplasia. This study compared the gene expression profiles of lesions with mild dysplasia (stratified by optical marker status) to lesions with severe dysplasia and without dysplasia.

MATERIALS AND METHODS: Forty oral lesions imaged in patients undergoing oral surgery were analyzed: nine without dysplasia, nine with severe …

Characterizing Treatment Resistance In Muscle Invasive Bladder Cancer Using The Chicken Egg Chorioallantoic Membrane Patient-Derived Xenograft Model, Hugo Villanueva, Gabrielle A Wells, Malachi T Miller, Mariana Villanueva, Ravi Pathak, Patricia Castro, Michael M Ittmann, Andrew G Sikora, Seth P Lerner

Faculty, Staff and Student Publications

BACKGROUND: Non-metastatic muscle invasive urothelial bladder cancer (MIBC) has a poor prognosis and standard of care (SOC) includes neoadjuvant cisplatin-based chemotherapy (NAC) combined with cystectomy. Patients receiving NAC have at best

METHODS: We optimized engraftment conditions for primary MIBC tumors using the CAM-PDX model and tested concordance between cisplatin-based chemotherapy response of patients to matching PDX tumors using tumor growth coupled with immunohistochemistry markers of proliferation and apoptosis. We also tested select kinase inhibitor response on chemotherapy-resistant bladder cancers on the CAM-PDX using tumor growth measurements and immuno-detection of proliferation marker, Ki-67.

RESULTS: Our results show primary, NAC-resistant, MIBC tumors …

Learning From The Past: A Century Of Accuracy, Aspirations, And Aspersions In Brachytherapy, Christopher S Melhus, Samantha J Simiele, Manik Aima, Susan Richardson

Faculty, Staff and Student Publications

The oldest form of radiation therapy, brachytherapy, has been investigated and reported in the scientific and medical literature for well over a century. Known by many names over the years, radium-based, empirical practices evolved over decades to contemporary practice. This includes treatment at various dose rates using multiple radionuclides or even electrically generated photon sources. Predictions or prognostications of what may happen in the future enjoy a history that spans centuries, e.g. those by Nostradamus in the 1500s. In this review article, publications from several eras of past practice between the early 1900s and the late 2010s where the authors …

Biobehavioral Factors Predict An Exosome Biomarker Of Ovarian Carcinoma Disease Progression, Susan K Lutgendorf, Premal H Thaker, Michael J Goodheart, Jesusa M G Arevalo, Mamur A Chowdhury, Alyssa E Noble, Laila Dahmoush, George M Slavich, Frank J Penedo, Anil K Sood, Steven W Cole

Faculty, Staff and Student Publications

BACKGROUND: Biobehavioral factors such as social isolation and depression have been associated with disease progression in ovarian and other cancers. Here, the authors developed a noninvasive, exosomal RNA profile for predicting ovarian cancer disease progression and subsequently tested whether it increased in association with biobehavioral risk factors.

METHODS: Exosomes were isolated from plasma samples from 100 women taken before primary surgical resection or neoadjuvant (NACT) treatment of ovarian carcinoma and 6 and 12 months later. Biobehavioral measures were sampled at all time points. Plasma from 76 patients was allocated to discovery analyses in which morning presurgical/NACT exosomal RNA profiles were …

Distinct Germline Genetic Susceptibility Profiles Identified For Common Non-Hodgkin Lymphoma Subtypes, Sonja I Berndt, Joseph Vijai, Yolanda Benavente, Nicola J Camp, Alexandra Nieters, Zhaoming Wang, Karin E Smedby, Geffen Kleinstern, Henrik Hjalgrim, Caroline Besson, Christine F Skibola, Lindsay M Morton, Angela R Brooks-Wilson, Lauren R Teras, Charles Breeze, Joshua Arias, Hans-Olov Adami, Demetrius Albanes, Kenneth C Anderson, Stephen M Ansell, Bryan Bassig, Nikolaus Becker, Parveen Bhatti, Brenda M Birmann, Paolo Boffetta, Paige M Bracci, Paul Brennan, Elizabeth E Brown, Laurie Burdett, Lisa A Cannon-Albright, Ellen T Chang, Brian C H Chiu, Charles C Chung, Jacqueline Clavel, Pierluigi Cocco, Graham Colditz, Lucia Conde, David V Conti, David G Cox, Karen Curtin, Delphine Casabonne, Immaculata De Vivo, Arjan Diepstra, W Ryan Diver, Ahmet Dogan, Christopher K Edlund, Lenka Foretova, Joseph F Fraumeni, Attilio Gabbas, Hervé Ghesquières, Graham G Giles, Sally Glaser, Martha Glenn, Bengt Glimelius, Jian Gu, Thomas M Habermann, Christopher A Haiman, Corinne Haioun, Jonathan N Hofmann, Theodore R Holford, Elizabeth A Holly, Amy Hutchinson, Aalin Izhar, Rebecca D Jackson, Ruth F Jarrett, Rudolph Kaaks, Eleanor Kane, Laurence N Kolonel, Yinfei Kong, Peter Kraft, Anne Kricker, Annette Lake, Qing Lan, Charles Lawrence, Dalin Li, Mark Liebow, Brian K Link, Corrado Magnani, Marc Maynadie, James Mckay, Mads Melbye, Lucia Miligi, Roger L Milne, Thierry J Molina, Alain Monnereau, Rebecca Montalvan, Kari E North, Anne J Novak, Kenan Onel, Mark P Purdue, Kristin A Rand, Elio Riboli, Jacques Riby, Eve Roman, Gilles Salles, Douglas W Sborov, Richard K Severson, Tait D Shanafelt, Martyn T Smith, Alexandra Smith, Kevin W Song, Lei Song, Melissa C Southey, John J Spinelli, Anthony Staines, Deborah Stephens, Heather J Sutherland, Kaitlyn Tkachuk, Carrie A Thompson, Hervé Tilly, Lesley F Tinker, Ruth C Travis, Jenny Turner, Celine M Vachon, Claire M Vajdic, Anke Van Den Berg, David J Van Den Berg, Roel C H Vermeulen, Paolo Vineis, Sophia S Wang, Elisabete Weiderpass, George J Weiner, Stephanie Weinstein, Nicole Wong Doo, Yuanqing Ye, Meredith Yeager, Kai Yu, Anne Zeleniuch-Jacquotte, Yawei Zhang, Tongzhang Zheng, Elad Ziv, Joshua Sampson, Nilanjan Chatterjee, Kenneth Offit, Wendy Cozen, Xifeng Wu, James R Cerhan, Stephen J Chanock, Susan L Slager, Nathaniel Rothman

Faculty, Staff and Student Publications

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9,505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P<5 >× 10−8) for subsets of NHL subtypes, …

Tilsotolimod Exploits The Tlr9 Pathway To Promote Antigen Presentation And Type 1 Ifn Signaling In Solid Tumors: A Multicenter International Phase I/Ii Trial (Illuminate-101), Hani Babiker, Erkut Borazanci, Vivek Subbiah, Sanjiv Agarwala, Alain Algazi, Jacob Schachter, Michael Lotem, Corinne Maurice-Dror, Daniel Hendler, Shah Rahimian, Hans Minderman, Cara Haymaker, Daruka Mahadevan, Chantale Bernatchez, Ravi Murthy, Rolf Hultsch, Nadia Kaplan, Gregory Woodhead, Charles Hennemeyer, Srinivas Chunduru, Peter M Anderson, Adi Diab, Igor Puzanov

Faculty, Staff and Student Publications

PURPOSE: Tilsotolimod is an investigational synthetic Toll-like receptor 9 (TLR9) agonist that has demonstrated antitumor activity in preclinical models. The ILLUMINATE-101 phase I study explored the safety, dose, efficacy, and immune effects of intratumoral (it) tilsotolimod monotherapy in multiple solid tumors.

PATIENTS AND METHODS: Patients with a diagnosis of refractory cancer not amenable to curative therapies received tilsotolimod in doses escalating from 8 to 32 mg into a single lesion at weeks 1, 2, 3, 5, 8, and 11. Additional patients with advanced malignant melanoma were enrolled into an expansion cohort at the 8 mg dose. Objectives included characterizing the …

An Outbreak Of A Novel Recombinant Coxsackievirus A4 In A Kindergarten, Shandong Province, China, 2021, Juan Li, Nan Ni, Yanan Cui, Shuai Zong, Xue Yao, Tao Hu, Mengyuan Cao, Yong Zhang, Peiqiang Hou, Michael J Carr, Weijia Xing, Hong Zhou, Weifeng Shi

Faculty, Staff and Student Publications

In 2021, twenty children exhibiting influenza-like illnesses were reported from a kindergarten in Shandong Province, China. Eleven genomes of Coxsackievirus A4 (CV-A4) were obtained from the pediatric cases, sharing <93% genome sequence identities with known CV-A4 strains. Further analyses suggested potential genetic recombination in the P3 region of the novel strains.