Medical Specialties Commons^™

Considerations For Intensity Modulated Total Body Or Total Marrow And Lymphoid Irradiation, David Parsons, Tze Yee Lim, Jose R Teruel, Paulina Galavis, Stefano Agostinelli, Jieming Liang, Pietro Mancosu, Amanda Cherpak, Dennis N Stanley, Kang-Hyun Ahn, Bingqi Guo, Yesenia Gonzalez, Jay Burmeister, Jeffrey Y C Wong, Xuejun Gu, Grace Gwe-Ya Kim

Faculty, Staff and Student Publications

We compiled a sampling of the treatment techniques of intensity-modulated total body irradiation, total marrow irradiation and total marrow and lymphoid irradiation utilized by several centers across North America and Europe. This manuscript does not serve as a consensus guideline, but rather is meant to serve as a convenient reference for centers that are considering starting an intensity-modulated program.

Circulating Micrornas And Cytokines As Prognostic Biomarkers For Doxorubicin-Induced Cardiac Injury And For Evaluating The Effectiveness Of An Exercise Intervention, Prince Jeyabal, Anchit Bhagat, Fei Wang, Michael Roth, J Andrew Livingston, Susan C Gilchrist, Jose Banchs, Michelle A T Hildebrandt, Joya Chandra, Anita Deswal, Efstratios Koutroumpakis, Jian Wang, Najat C Daw, Theresa A Honey, Eugenie S Kleinerman

Faculty, Staff and Student Publications

Purpose: To define a set of biomarkers that can be used to identify patients at high risk of developing late doxorubicin (DOX)-induced cardiac morbidity with the goal of focused monitoring and early interventions.

Experimental design: Mice received phosphate buffered saline or DOX 2.5 mg/kg 2x/week for 2 weeks. Blood samples were obtained before and after therapy for quantification of miRNAs (6 and 24 hours), cytokines (24 hours), and troponin (24 hours, 4 and 6 weeks). Cardiac function was evaluated using echocardiography before and 24 hours after therapy. To assess the effectiveness of exercise intervention in preventing DOX-induced cardiotoxicity blood samples …

The Androgen Receptor Does Not Directly Regulate The Transcription Of Dna Damage Response Genes, Joshua D Samuels, Katelyn A Moore, Hannah E Ennerfelt, Alexis M Johnson, Adeline E Walsh, Richard J Price, John R Lukens

Faculty, Staff and Student Publications

INTRODUCTION: Mutations in INPP5D, which encodes for the SH2-domain-containing inositol phosphatase SHIP-1, have recently been linked to an increased risk of developing late-onset Alzheimer's disease. While INPP5D expression is almost exclusively restricted to microglia in the brain, little is known regarding how SHIP-1 affects neurobiology or neurodegenerative disease pathogenesis.

METHODS: We generated and investigated 5xFAD Inpp5d

RESULTS: SHIP-1 deletion in microglia led to substantially enhanced recruitment of microglia to Aβ plaques, altered microglial gene expression, and marked improvements in neuronal health. Further, SHIP-1 loss enhanced microglial plaque containment and Aβ engulfment when compared to microglia from Cre-negative 5xFAD Inpp5d

DISCUSSION: …

Importance Of Health Policy And Systems Research For Strengthening Rehabilitation In Health Systems: A Call To Action To Accelerate Progress, Walter R Frontera, Wouter Degroote, Abdul Ghaffar, Health Policy & Systems Research For Rehabilitation Group

Faculty, Staff and Student Publications

No abstract provided.

Use Of Term Reference Infants In Assessing The Developmental Outcome Of Extremely Preterm Infants: Lessons Learned In A Multicenter Study, Charles E Green, Jon E Tyson, Roy J Heyne, Susan R Hintz, Betty R Vohr, Carla M Bann, Abhik Das, Edward F Bell, Sana Boral Debsareea, Emily Stephens, Marie G Gantz, Carolyn M Petrie Huitema, Karen J Johnson, Kristi L Watterberg, Ricardo Mosquera, Myriam Peralta-Carcelen, Deanne E Wilson-Costello, Tarah T Colaizy, Nathalie L Maitre, Stephanie L Merhar, Ira Adams-Chapman, Janell Fuller, Michelle E Hartley-Mcandrew, William F Malcolm, Sarah Winter, Andrea F Duncan, Gary J Myer, Stephen D Kicklighter, Myra H Wyckoff, Sara B Demauro, Anna Maria Hibbs, Barbara J Stoll, Waldemar A Carlo, Krisa P Van Meurs, Matthew A Rysavy, Ravi M Patel, Pablo J Sánchez, Abbot R Laptook, C Michael Cotten, Carl T D'Angio, Michele C Walsh, Human Development Neonatal Research Network

Faculty, Staff and Student Publications

OBJECTIVE: Extremely preterm (EP) impairment rates are likely underestimated using the Bayley III norm-based thresholds scores and may be better assessed relative to concurrent healthy term reference (TR) infants born in the same hospital.

STUDY DESIGN: Blinded, certified examiners in the Neonatal Research Network (NRN) evaluated EP survivors and a sample of healthy TR infants recruited near the 2-year assessment age.

RESULTS: We assessed 1452 EP infants and 183 TR infants. TR-based thresholds showed higher overall EP impairment than Bayley norm-based thresholds (O.R. = 1.86; [95% CI 1.56-2.23], especially for severe impairment (36% vs. 24%; p ≤ 0.001). Difficulty recruiting …

Automated Large Vessel Occlusion Detection Software And Thrombectomy Treatment Times: A Cluster Randomized Clinical Trial, Juan Carlos Martinez-Gutierrez, Youngran Kim, Sergio Salazar-Marioni, Muhammad Bilal Tariq, Rania Abdelkhaleq, Arash Niktabe, Anjan N Ballekere, Ananya S Iyyangar, Mai Le, Hussain Azeem, Charles C Miller, Jon E Tyson, Sandi Shaw, Peri Smith, Mallory Cowan, Isabel Gonzales, Louise D Mccullough, Andrew D Barreto, Luca Giancardo, Sunil A Sheth

Faculty, Staff and Student Publications

Importance

The benefit of endovascular stroke therapy (EVT) in large vessel occlusion (LVO) ischemic stroke is highly time dependent. Process improvements to accelerate in-hospital workflows are critical.

Objective

To determine whether automated computed tomography (CT) angiogram interpretation coupled with secure group messaging can improve in-hospital EVT workflows.

Design, Setting, and Participants

This cluster randomized stepped-wedge clinical trial took place from January 1, 2021, through February 27, 2022, at 4 comprehensive stroke centers (CSCs) in the greater Houston, Texas, area. All 443 participants with LVO stroke who presented through the emergency department were treated with EVT at the 4 CSCs. Exclusion …

Cell-Autonomous Effects Of Apoe4 In Restricting Microglial Response In Brain Homeostasis And Alzheimer’S Disease, Chia-Chen Liu, Na Wang, Yuanxin Chen, Yasuteru Inoue, Francis Shue, Yingxue Ren, Minghui Wang, Wenhui Qiao, Tadafumi C Ikezu, Zonghua Li, Jing Zhao, Yuka Martens, Sydney V Doss, Cassandra L Rosenberg, Suren Jeevaratnam, Lin Jia, Ana-Caroline Raulin, Fangfang Qi, Yiyang Zhu, Alla Alnobani, Joshua Knight, Yixing Chen, Cynthia Linares, Aishe Kurti, John D Fryer, Bin Zhang, Long-Jun Wu, Betty Y S Kim, Guojun Bu

Faculty, Staff and Student Publications

Microglial involvement in Alzheimer's disease (AD) pathology has emerged as a risk-determining pathogenic event. While apolipoprotein E (APOE) is known to modify AD risk, it remains unclear how microglial apoE impacts brain cognition and AD pathology. Here, using conditional mouse models expressing apoE isoforms in microglia and central nervous system-associated macrophages (CAMs), we demonstrate a cell-autonomous effect of apoE3-mediated microglial activation and function, which are negated by apoE4. Expression of apoE3 in microglia/CAMs improves cognitive function, increases microglia surrounding amyloid plaque and reduces amyloid pathology and associated toxicity, whereas apoE4 expression either compromises or has no effects on these outcomes …

Stratification Of Alpha Ganglion Cells And On/Off Directionally Selective Ganglion Cells In The Rabbit Retina, Xinruo Zhang, Katherine Brind'amour, Kelly E King, Susan Hartmaier, Katherine Harris, David A Weinstein, Cynthia J Girman

Faculty, Staff and Student Publications

Introduction

Neurodegenerative diseases cause developmental delays and loss of milestones in infants and children. However, scalable outcome measures that quantify features meaningful to parents/caregivers (P/CGs) and have regulatory precedence are lacking for assessing the effectiveness of treatments in clinical trials of neurodegenerative disorders. To address this gap, we developed an innovative, blinded strategy for single-arm trials with external controls using expert panel review of home video.

Method

We identified meaningful, observable, and objective developmental milestones from iterative interviews with P/CGs and clinical experts. Subsequently, we standardized video recording procedures and instructions to ensure consistency in how P/CGs solicited each activity. …

The Need For Space To Plan The Future For Spondyloarthritis, Louise D Mccullough

Faculty, Staff and Student Publications

A new study indicates that although men and women are equally likely to experience cognitive impairment after acute ischaemic stroke, there are sex differences in particular cognitive domains. Whether these differences are directly linked to biological sex is uncertain, as many factors, including age and pre-stroke factors, could contribute to cognitive outcomes.

A Tale Of 2 Tics: Endoscopic Treatment Of Perforated Periampullary Diverticulum Within A Giant Duodenal Diverticulum, Suchapa Arayakarnkul, Ekin Inal, Amit Mehta, Saowanee Ngamruengphong

Faculty, Staff and Student Publications

Periampullary diverticulum presenting with severe complications, such as perforations, is associated with high morbidity and mortality. Traditionally, only surgical or conservative management has been warranted. In this case, we present a 76-year-old woman with a spontaneously perforated periampullary diverticulum, located within a larger duodenal diverticulum, who achieved complete recovery with endoscopic closure after an initial unsuccessful attempt at surgical management. This case report highlights the role of endoscopy in the treatment of complicated diverticulum perforation.

Surface Charge Effects For The Hydrogen Evolution Reaction On Pt(111) Using A Modified Grand-Canonical Potential Kinetics Method, Mihir Patel, Matthias Franzen, Camille D Hawkins, Matthew Brown, Samir Patel

Faculty, Staff and Student Publications

Supraventricular tachycardia (SVT) is the most common tachyarrhythmia of pregnancy. Catecholamine surges, the use of vasoactive agents during delivery, and increased cardiac output during pregnancy are the most common contributing factors to developing SVT. SVT is usually benign in presentation but can lead to more serious arrhythmias in patients with a history of mitral stenosis secondary to rheumatic heart disease. When an SVT is detected, organic heart causes should be ruled out first. Symptoms of SVT include shortness of breath, palpitations, syncope, sweating, chest pain, and dizziness. In patients who are refractory to pharmacologic management and hemodynamically unstable, electrical cardioversion …

Comprehensive Evaluation And New Recommendations In The Use Of Gafchromic Ebt3 Film, Kevin Liu, Patrik Gonçalves Jorge, Ramesh Tailor, Raphaël Moeckli, Emil Schüler

Faculty, Staff and Student Publications

BACKGROUND: Gafchromic film's unique properties of tissue-equivalence, dose-rate independence, and high spatial resolution make it an attractive choice for many dosimetric applications. However, complicated calibration processes and film handling limits its routine use.

PURPOSE: We evaluated the performance of Gafchromic EBT3 film after irradiation under a variety of measurement conditions to identify aspects of film handling and analysis for simplified but robust film dosimetry.

METHODS: The short- (from 5 min to 100 h) and long-term (months) film response was evaluated for clinically relevant doses of up to 50 Gy for accuracy in dose determination and relative dose distributions. The dependence …

Investigate The Possibility Of Using Phosphorescence In Clinical Oncology As An Early Prognostic Test In Detecting Brain Carcinogenesis, Yuriy O Vinnyk, Igor A Kryvoruchko, Valeriy V Boyko, Yulia V Ivanova, Svetlana Gramatiuk, Karine Sargsyan

Faculty, Staff and Student Publications

Phosphorescence is considered one of the non-invasive glioblastoma testing methods based on studying molecular energy and the metabolism of L-tryptophan (Trp) through KP, which provides essential information on regulating immunity and neuronal function. This study aimed to conduct a feasibility study using phosphorescence in clinical oncology as an early prognostic test in detecting Glioblastoma. This study was conducted on 1039 patients who were operated on with follow-up between January 1, 2014, and December 1, 2022, and retrospectively evaluated in participating institutions in Ukraine (the Department of Oncology, Radiation Therapy, Oncosurgery, and Palliative Care at the Kharkiv National Medical University). Method …

Interplay Of Hypoxia-Inducible Factors And Oxygen Therapy In Cardiovascular Medicine, Yafen Liang, Wei Ruan, Yandong Jiang, Richard Smalling, Xiaoyi Yuan, Holger K Eltzschig

Faculty, Staff and Student Publications

Mammals have evolved to adapt to differences in oxygen availability. Although systemic oxygen homeostasis relies on respiratory and circulatory responses, cellular adaptation to hypoxia involves the transcription factor hypoxia-inducible factor (HIF). Given that many cardiovascular diseases involve some degree of systemic or local tissue hypoxia, oxygen therapy has been used liberally over many decades for the treatment of cardiovascular disorders. However, preclinical research has revealed the detrimental effects of excessive use of oxygen therapy, including the generation of toxic oxygen radicals or attenuation of endogenous protection by HIFs. In addition, investigators in clinical trials conducted in the past decade have …

Identification Of Novel Genetic Loci For Risk Of Multiple Myeloma By Functional Annotation, Angelica Macauda, Klara Briem, Alyssa Clay-Gilmour, Wendy Cozen, Asta Försti, Matteo Giaccherini, Chiara Corradi, Juan Sainz, Yasmeen Niazi, Rob Ter Horst, Yang Li, Mihai G Netea, Ulla Vogel, Kari Hemminki, Susan L Slager, Judit Varkonyi, Vibeke Andersen, Elzbieta Iskierka-Jazdzewska, Joaquin Mártinez-Lopez, Jan Zaucha, Nicola J Camp, S Vincent Rajkumar, Agnieszka Druzd-Sitek, Parveen Bhatti, Stephen J Chanock, Shaji K Kumar, Edyta Subocz, Grzegorz Mazur, Stefano Landi, Mitchell J Machiela, Andrés Jerez, Aaron D Norman, Michelle A T Hildebrandt, Katalin Kadar, Sonja I Berndt, Elad Ziv, Gabriele Buda, Arnon Nagler, Charles Dumontet, Malgorzata Raźny, Marzena Watek, Aleksandra Butrym, Norbert Grzasko, Marek Dudzinski, Malwina Rybicka-Ramos, Eva-Laure Matera, Ramón García-Sanz, Hartmut Goldschmidt, Krzysztof Jamroziak, Artur Jurczyszyn, Esther Clavero, Graham G Giles, Matteo Pelosini, Daria Zawirska, Marcin Kruszewski, Herlander Marques, Eva Haastrup, José Manuel Sánchez-Maldonado, Uta Bertsch, Marcin Rymko, Marc-Steffen Raab, Elizabeth E Brown, Jonathan N Hofmann, Celine Vachon, Daniele Campa, Federico Canzian

Faculty, Staff and Student Publications

No abstract provided.

Cost-Effectiveness Of [99mtc]Tilmanocept Relative To [99mtc]Sulfur Colloid For Sentinel Lymph Node Biopsy In Early Stage Oral Cavity Cancer, Karen Y Choi, Qiang Hao, Kathryn Carlisle, Christopher S Hollenbeak, Stephen Y Lai

Faculty, Staff and Student Publications

BACKGROUND: Several studies have demonstrated varying rates of efficacy, reliability, and sensitivity of sentinel lymph node biopsy (SLNB) in identifying occult nodal disease for early stage oral cavity squamous cell carcinoma (OCSCC) depending on the radionuclide agent utilized. No head-to-head comparison of cost or clinical outcomes of SLNB when utilizing [99mTc]tilmanocept versus [99mTc]sulfur colloid has been performed. The goal of this study was to develop a decision model to compare the cost-effectiveness of [99mTc]tilmanocept versus [99mTc]sulfur colloid in early stage OCSCC.

PATIENTS AND METHODS: A decision model of disease and treatment as a function of SLNB was created. Patients with …

Characteristics And Clinical Outcomes Of Patients With Myeloid Malignancies And Ddx41 Variants, Alex Bataller, Sanam Loghavi, Yoheved Gerstein, Alexandre Bazinet, Koji Sasaki, Kelly S Chien, Danielle Hammond, Guillermo Montalban-Bravo, Gautam Borthakur, Nicholas Short, Ghayas C Issa, Tapan M Kadia, Naval Daver, Guilin Tang, Andres Quesada, Keyur P Patel, Farhad Ravandi, Warren Fiskus, Cristopher P Mill, Hagop M Kantarjian, Kapil Bhalla, Guillermo Garcia-Manero, Betul Oran, Courtney D Dinardo

Faculty, Staff and Student Publications

DDX41 is the most frequently mutated gene in myeloid neoplasms associated with germline predisposition including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We analyzed 3795 patients with myeloid neoplasms and identified 151 (4%) with DDX41 variants and a diagnosis of AML (n = 96), MDS (n = 52), and chronic myelomonocytic leukemia (n = 3). The most frequent DDX41 variants were the somatic variant p.R525H, followed by the germline variants p.M1I and p.D140fs. Most neoplasms had a normal karyotype (59%) and the most frequent co-mutations were TP53 (16%) and ASXL1 (15%). 30% of patients had no concomitant mutations besides …

Geographic Disparity Of Outcome In Patients With Cancer Over Decades: The Surveillance, Epidemiology, And End Results, Koji Sasaki, Kiyomi Morita, Hagop Kantarjian, Guillermo Garcia-Manero, Elias Jabbour, Farhad Ravandi, Marina Konopleva, Gautam Borthakur, William Wierda, Naval Daver, Koichi Takahashi, Courtney Dinardo, Guillermo Montalban Bravo, Ghayas C Issa, Sherry A Pierce, Kelly A Soltysiak, Martha S Tingen, Jorge E Cortes

Faculty, Staff and Student Publications

Background: Improvements in prevention, early detection, and effective cancer therapy have decreased cancer-related mortality; however, significant health disparities exist. Therefore, we investigated the impact of these disparities on survival.

Methods: In the Surveillance, Epidemiology, and End Results, we identified 784,341 patients with cancer between 1990 and 2016 in Georgia, 68,493 between 1990 and 1999; 371,353 between 2000 and 2009; and 322,932 between 2010 and 2016. We assessed the overall survival (OS) of patients with all cancers, chronic myeloid leukemia (CML), and lung cancer, given the dramatic improvement in outcomes in patients with CML since 2000 compared to the generally considerably …

Prevalence And Implications Of Significance Testing For Baseline Covariate Imbalance In Randomised Cancer Clinical Trials: The Table 1 Fallacy, Alexander D Sherry, Pavlos Msaouel, Zachary R Mccaw, Joseph Abi Jaoude, Eric J Hsu, Ramez Kouzy, Roshal Patel, Yumeng Yang, Timothy A Lin, Cullen M Taniguchi, Claus Rödel, Emmanouil Fokas, Chad Tang, Clifton David Fuller, Bruce Minsky, Tomer Meirson, Ryan Sun, Ethan B Ludmir

Faculty, Staff and Student Publications

Background: The 'Table 1 Fallacy' refers to the unsound use of significance testing for comparing the distributions of baseline variables between randomised groups to draw erroneous conclusions about balance or imbalance. We performed a cross-sectional study of the Table 1 Fallacy in phase III oncology trials.

Methods: From ClinicalTrials.gov, 1877 randomised trials were screened. Multivariable logistic regressions evaluated predictors of the Table 1 Fallacy.

Results: A total of 765 randomised controlled trials involving 553,405 patients were analysed. The Table 1 Fallacy was observed in 25% of trials (188 of 765), with 3% of comparisons deemed significant (59 of 2353), approximating …

Development And Implementation Of Optimized Endogenous Contrast Sequences For Delineation In Adaptive Radiotherapy On A 15t Mr-Linear-Accelerator: A Prospective R-Ideal Stage 0–2a Quantitative/Qualitative Evaluation Of In Vivo Site-Specific Quality-Assurance Using A 3d T2 Fat-Suppressed Platform For Head And Neck Cancer, Travis C Salzillo, M Alex Dresner, Ashley Way, Kareem A Wahid, Brigid A Mcdonald, Sam Mulder, Mohamed A Naser, Renjie He, Yao Ding, Alison Yoder, Sara Ahmed, Kelsey L Corrigan, Gohar S Manzar, Lauren Andring, Chelsea Pinnix, R Jason Stafford, Abdallah S R Mohamed, John Christodouleas, Jihong Wang, Clifton David Fuller

Faculty, Staff and Student Publications

Purpose: To improve segmentation accuracy in head and neck cancer (HNC) radiotherapy treatment planning for the 1.5T hybrid magnetic resonance imaging/linear accelerator (MR-Linac), three-dimensional (3D), T2-weighted, fat-suppressed magnetic resonance imaging sequences were developed and optimized.

Approach: After initial testing, spectral attenuated inversion recovery (SPAIR) was chosen as the fat suppression technique. Five candidate SPAIR sequences and a nonsuppressed, T2-weighted sequence were acquired for five HNC patients using a 1.5T MR-Linac. MR physicists identified persistent artifacts in two of the SPAIR sequences, so the remaining three SPAIR sequences were further analyzed. The gross primary tumor volume, metastatic lymph nodes, parotid glands, …

Tolerability And Efficacy Of The Anticluster Of Differentiation 47 Antibody Magrolimab Combined With Azacitidine In Patients With Previously Untreated Aml: Phase Ib Results, Naval G Daver, Paresh Vyas, Suman Kambhampati, Monzr M Al Malki, Richard A Larson, Adam S Asch, Gabriel Mannis, Wanxing Chai-Ho, Tiffany N Tanaka, Terrence J Bradley, Deepa Jeyakumar, Eunice S Wang, Kendra Sweet, Hagop M Kantarjian, Guillermo Garcia-Manero, Rami Komrokji, Guan Xing, Giridharan Ramsingh, Camille Renard, Joshua F Zeidner, David A Sallman

Faculty, Staff and Student Publications

Purpose: Magrolimab is a first-in-class humanized monoclonal antibody against cluster of differentiation 47, an antiphagocytic signal used by cancer cells to evade phagocytosis. Azacitidine upregulates prophagocytic signals on AML cells, further increasing phagocytosis when combined with magrolimab. We report final phase Ib data for magrolimab with azacitidine in patients with untreated AML ineligible for intensive chemotherapy (ClinicalTrials.gov identifier: NCT03248479).

Patients and methods: Patients with previously untreated AML, including TP53-mutant AML, received magrolimab intravenously as an initial dose (1 mg/kg, days 1 and 4), followed by 15 mg/kg once on day 8 and 30 mg/kg once weekly or every …

Patient-Reported Quality Of Life After Breast-Conserving Surgery With Radiotherapy Versus Mastectomy And Reconstruction, Kevin Diao, Xiudong Lei, Weiguo He, Reshma Jagsi, Sharon H Giordano, Grace L Smith, Abigail Caudle, Yu Shen, Susan K Peterson, Benjamin D Smith

Faculty, Staff and Student Publications

Objective: To compare long-term quality of life (QOL) outcomes in breast cancer survivors who received breast-conserving surgery with radiotherapy (BCS+RT) with those who received a mastectomy and reconstructive surgery (Mast+Recon) without radiotherapy and identify other important factors.

Background: The long-term differences in patient-reported QOL outcomes following BCS+RT and Mast+Recon are not well understood.

Methods: We identified patients from the Texas Cancer Registry with stage 0-II breast cancer diagnosed in 2009-2014 after BCS+RT or Mast+Recon without radiotherapy. Sampling was stratified by age and race and ethnicity. A paper survey was sent to 4800 patients which included validated BREAST-Q and PROMIS modules. …

High-Dose Chemotherapy And Autologous Stem Cell Transplantation For Relapsed Or Refractory Primary Mediastinal Large B-Cell Lymphoma, Hanan Alkhaldi, Alec Reinhardt, Melissa Barnett, Suprateek Kundu, Chitra Hosing, Jeremy Ramdial, Neeraj Saini, Samer Srour, Amin Alousi, Partow Kebriaei, Uday Popat, Muzaffar Qazilbash, Richard Champlin, Elizabeth J Shpall, Allison Gulbis, Terri Lynn Shigle, Bouthaina Dabaja, Chelsea Pinnix, Sairah Ahmed, Raphael Steiner, Borje S Andersson, Yago Nieto

Faculty, Staff and Student Publications

Primary mediastinal large B-cell lymphoma (PMBCL) is an uncommon, aggressive type of non-Hodgkin lymphoma. Rituximab-containing chemoimmunotherapy with or without radiation therapy (RT) is standard first-line treatment. Relapsed or refractory (R/R) disease has long been treated with salvage chemotherapy followed by high-dose chemotherapy (HDC), with autologous stem cell transplantation (ASCT) in appropriate patients. We retrospectively analyzed all patients with R/R PMBCL treated with HDC/ASCT at our center between January 2000 and August 2022. The 60 study patients received either rituximab-BEAM (n = 37) or rituximab-gemcitabine/busulfan/melphalan (R-GemBuMel) with or without vorinostat (n = 23), followed by ASCT. Forty-six patients received mediastinal RT, …

Aortic Arch Reconstruction Using Nonvalved Femoral Vein Homograft In High-Risk Neonates, Kyle G Mitchell, Julija Dobrila, Blaz Podgorsek, Christopher Greenleaf, Peter Chen, Jorge D Salazar, Damien J Lapar

Faculty, Staff and Student Publications

Aortic arch obstruction is often present with complex concomitant congenital heart defects (CHDs). The use of nonvalved femoral vein homograft (FVH) to reconstruct the aortic arch has distinct surgical advantages, including simplified reconstruction. We present an intraoperative video of a Yasui procedure utilizing FVH for aortic reconstruction in a 12-day-old (2.2 kg) neonate with right ventricular outflow tract obstruction, malalignment ventricular septal defect, aortic valve atresia, aortic arch hypoplasia, atrial septal defect, and ductal dependent systemic circulation. Further, we report outcomes for a series of three additional neonatal patients with complex CHD and aortic arch obstruction who underwent FVH arch …

Changes In Renal-Mesenteric Duplex Ultrasound Velocities After Fenestrated And Branched Endovascular Aortic Aneurysm Repair, Titia A L Sulzer, Thanila A Macedo, Nicole Strissel, Gina K Hesley, Alexander Lekah, Tiziano Tallarita, Marina Dias-Neto, Ying Huang, Emanuel R Tenorio, Andrea Vacirca, Thomas Mesnard, Aidin Baghbani-Oskouei, Safa Savadi, Jorg L De Bruin, Hence J M Verhagen, Bernardo Mendes, Gustavo S Oderich

Faculty, Staff and Student Publications

Objective: Stenting of renal and mesenteric vessels may result in changes in velocity measurements due to arterial compliance, potentially giving rise to confusion about the presence of stenosis during follow-up. The aim of our study was to compare preoperative and postoperative changes in peak systolic velocity (PSV, cm/s) after placement of the celiac axis (CA), superior mesenteric artery (SMA) and renal artery (RAs) bridging stent grafts during fenestrated-branched endovascular aortic repair (FB-EVAR) for treatment of complex abdominal aortic aneurysms (AAA) and thoracoabdominal aortic aneurysms.

Methods: Patients were enrolled in a prospective, nonrandomized single-center study to evaluate FB-EVAR for treatment of …

Hidroadenocarcinoma Mimicking Epidermal Inclusion Cyst Of The Palm, Connor L Zale, Sean Kelly, Kevin Krul

Faculty, Staff and Student Publications

Hidradenocarcinoma is a rare malignant tumor of sweat glands of the skin that has been reported several times in the hand. We report a case of hidradenocarcinoma of the palm in a 55-year-old woman that presented as a painless volar hand mass. A staged rotational forearm flap was used after resection.

Exosomes Modified With Anti-Mek1 Sirna Lead To An Effective Silencing Of Triple Negative Breast Cancer Cells, Débora Ferreira, Cátia Santos-Pereira, Marta Costa, Julieta Afonso, Sujuan Yang, Janine Hensel, Kathleen M Mcandrews, Adhemar Longatto-Filho, Rui Fernandes, Joana B Melo, Fátima Baltazar, João N Moreira, Raghu Kalluri, Ligia R Rodrigues

Faculty, Staff and Student Publications

Triple negative breast cancer (TNBC) is a highly heterogenous disease not sensitive to endocrine or HER2 therapy and standardized treatment regimens are still missing. Therefore, development of novel TNBC treatment approaches is of utmost relevance. Herein, the potential of MAPK/ERK downregulation by RNAi-based therapeutics in a panel of mesenchymal stem-like TNBC cell lines was uncovered. Our data revealed that suppression of one of the central nodes of this signaling pathway, MEK1, affects proliferation, migration, and invasion of TNBC cells, that may be explained by the reversion of the epithelial-mesenchymal transition phenotype, which is facilitated by the MMP-2/MMP-9 downregulation. Moreover, an …

Engineering A Tunable Micropattern-Array Assay To Sort Single Extracellular Vesicles And Particles To Detect Rna And Protein In Situ, Jingjing Zhang, Xilal Y Rima, Xinyu Wang, Luong T H Nguyen, Kristin Huntoon, Yifan Ma, Paola Loreto Palacio, Kim Truc Nguyen, Karunya Albert, Minh-Dao Duong-Thi, Nicole Walters, Kwang Joo Kwak, Min Jin Yoon, Hong Li, Jacob Doon-Ralls, Colin L Hisey, Daeyong Lee, Yifan Wang, Jonghoon Ha, Kelsey Scherler, Shannon Fallen, Inyoul Lee, Andre F Palmer, Wen Jiang, Setty M Magaña, Kai Wang, Betty Y S Kim, L James Lee, Eduardo Reátegui

Faculty, Staff and Student Publications

The molecular heterogeneity of extracellular vesicles (EVs) and the co-isolation of physically similar particles, such as lipoproteins (LPs), confounds and limits the sensitivity of EV bulk biomarker characterization. Herein, we present a single-EV and particle (siEVP) protein and RNA assay (siEVPPRA) to simultaneously detect mRNAs, miRNAs, and proteins in subpopulations of EVs and LPs. The siEVPPRA immobilizes and sorts particles via positive immunoselection onto micropatterns and focuses biomolecular signals in situ. By detecting EVPs at a single-particle resolution, the siEVPPRA outperformed the sensitivities of bulk-analysis benchmark assays for RNA and protein. To assess the specificity of RNA detection in complex …

Cardiac Muscle-Restricted Partial Loss Of Nos1ap Expression Has Limited But Significant Impact On Electrocardiographic Features, Alexa Smith, Dallas Auer, Morgan Johnson, Ernesto Sanchez, Holly Ross, Christopher Ward, Aravinda Chakravarti, Ashish Kapoor

Faculty, Staff and Student Publications

Genome-wide association studies have identified sequence polymorphisms in a functional enhancer of the NOS1AP gene as the most common genetic regulator of QT interval and human cardiac NOS1AP gene expression in the general population. Functional studies based on in vitro overexpression in murine cardiomyocytes and ex vivo knockdown in zebrafish embryonic hearts, by us and others, have also demonstrated that NOS1AP expression levels can alter cellular electrophysiology. Here, to explore the role of NOS1AP in cardiac electrophysiology at an organismal level, we generated and characterized constitutive and heart muscle-restricted Nos1ap knockout mice to assess whether NOS1AP disruption alters the QT …

Adavosertib Enhances Antitumor Activity Of Trastuzumab Deruxtecan In Her2-Expressing Cancers, Timothy P Diperi, Kurt W Evans, Maria Gabriela Raso, Ming Zhao, Yasmeen Q Rizvi, Xiaofeng Zheng, Bailiang Wang, Bryce P Kirby, Kathleen Kong, Michael Kahle, Timothy A Yap, Ecaterina E Dumbrava, Jaffer A Ajani, Siqing Fu, Khandan Keyomarsi, Funda Meric-Bernstam

Faculty, Staff and Student Publications

PURPOSE: Cyclin E (CCNE1) has been proposed as a biomarker of sensitivity to adavosertib, a Wee1 kinase inhibitor, and a mechanism of resistance to HER2-targeted therapy.

EXPERIMENTAL DESIGN: Copy number and genomic sequencing data from The Cancer Genome Atlas and MD Anderson Cancer Center databases were analyzed to assess ERBB2 and CCNE1 expression. Molecular characteristics of tumors and patient-derived xenografts (PDX) were assessed by next-generation sequencing, whole-exome sequencing, fluorescent in situ hybridization, and IHC. In vitro, CCNE1 was overexpressed or knocked down in HER2+ cell lines to evaluate drug combination efficacy. In vivo, NSG mice bearing PDXs were subjected to …