Medical Specialties Commons^™

A Phase I, Open-Label, Dose Confirmation, Escalation, And Expansion Trial Of Bi 1810631 As Monotherapy In Patients With Advanced Or Metastatic Solid Tumors With Her2 Aberrations, John Heymach, Frans Opdam, Minal Barve, Neil Gibson, Behbood Sadrolhefazi, Josep Serra, Noboru Yamamoto

Faculty, Staff and Student Publications

Background: BI 1810631 is a human HER2-selective tyrosine kinase inhibitor that covalently binds to both wild-type and mutated HER2 receptors, including exon 20 insertion mutations, whilst sparing EGFR signaling. This phase Ia/Ib, open-label, non-randomized study will determine the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of BI 1810631 in patients with HER2 aberration-positive solid tumors (NCT04886804).

Patients and methods: In phase Ia, patients with histologically/cytologically confirmed HER2 aberration-positive advanced/metastatic solid tumors will receive BI 1810631 orally twice daily (BID) or once daily (QD) at escalating doses. Starting dose level is 15 mg BID; QD …

What Are Risk Factors For And Outcomes Of Late Amputation After Treatment For Lower Extremity Sarcoma: A Childhood Cancer Survivor Study Report, Erik J Geiger, Wei Liu, Deo Kumar Srivastava, Nicholas M Bernthal, Brent R Weil, Yutaka Yasui, Kirsten K Ness, Kevin R Krull, Robert E Goldsby, Kevin C Oeffinger, Leslie L Robison, Bryan V Dieffenbach, Christopher B Weldon, Mark C Gebhardt, Rebecca Howell, Andrew J Murphy, Wendy M Leisenring, Gregory T Armstrong, Eric J Chow, Rosanna L Wustrack

Faculty, Staff and Student Publications

Background: Although pediatric lower extremity sarcoma once was routinely treated with amputation, multiagent chemotherapy as well as the evolution of tumor resection and reconstruction techniques have enabled the wide adoption of limb salvage surgery (LSS). Even though infection and tumor recurrence are established risk factors for early amputation (< 5 years) after LSS, the frequency of and factors associated with late amputation (≥ 5 years from diagnosis) in children with sarcomas are not known. Additionally, the resulting psychosocial and physical outcomes of these patients compared with those treated with primary amputation or LSS that was not complicated by subsequent amputation are not well studied. Studying these outcomes is critical to enhancing the quality of life of patients with sarcomas.

Questions/purposes: (1) How have treatments changed over time in patients with lower extremity sarcoma who are included in the Childhood Cancer Survivor Study (CCSS), and did primary treatment with amputation or LSS affect overall survival at 25 years among patients who had survived at least 5 years from diagnosis? (2) What …

Immune-Checkpoint Inhibitor Therapy Response Evaluation Using Oncophysics-Based Mathematical Models, Mustafa Syed, Matthew Cagely, Prashant Dogra, Lauren Hollmer, Joseph D Butner, Vittorio Cristini, Eugene J Koay

Faculty, Staff and Student Publications

The field of oncology has transformed with the advent of immunotherapies. The standard of care for multiple cancers now includes novel drugs that target key checkpoints that function to modulate immune responses, enabling the patient's immune system to elicit an effective anti-tumor response. While these immune-based approaches can have dramatic effects in terms of significantly reducing tumor burden and prolonging survival for patients, the therapeutic approach remains active only in a minority of patients and is often not durable. Multiple biological investigations have identified key markers that predict response to the most common form of immunotherapy-immune checkpoint inhibitors (ICI). These …

Tubers Affecting The Fusiform Face Area Are Associated With Autism Diagnosis, Alexander L Cohen, Mallory R Kroeck, Juliana Wall, Peter Mcmanus, Arina Ovchinnikova, Mustafa Sahin, Darcy A Krueger, E Martina Bebin, Hope Northrup, Joyce Y Wu, Simon K Warfield, Jurriaan M Peters, Michael D Fox, Acern Study Group

Faculty, Staff and Student Publications

OBJECTIVE: Tuberous sclerosis complex (TSC) is associated with focal brain "tubers" and a high incidence of autism spectrum disorder (ASD). The location of brain tubers associated with autism may provide insight into the neuroanatomical substrate of ASD symptoms.

METHODS: We delineated tuber locations for 115 TSC participants with ASD (n = 31) and without ASD (n = 84) from the Tuberous Sclerosis Complex Autism Center of Excellence Research Network. We tested for associations between ASD diagnosis and tuber burden within the whole brain, specific lobes, and at 8 regions of interest derived from the ASD neuroimaging literature, including the anterior …

Impact Of Time To Treatment On Endovascular Thrombectomy Outcomes In The Early Versus Late Treatment Time Windows, Negar Asdaghi, Kefeng Wang, Hannah Gardener, Angus Jameson, David Z Rose, Ayham Alkhachroum, Carolina M Gutierrez, Hao Ying, Nils Mueller-Kronast, Nicole B Sur, Chuanhui Dong, Gillian Gordon Perue, Marissa Lepain, Sebastian Koch, Nastajjia Krementz, Erika Marulanda-Londoño, Ricardo Hanel, Brijesh Mehta, Dileep R Yavagal, Tatjana Rundek, Ralph L Sacco, Jose G Romano

Faculty, Staff and Student Publications

BACKGROUND: The impact of time to treatment on outcomes of endovascular thrombectomy (EVT) especially in patients presenting after 6 hours from symptom onset is not well characterized. We studied the differences in characteristics and treatment timelines of EVT-treated patients participating in the Florida Stroke Registry and aimed to characterize the extent to which time impacts EVT outcomes in the early and late time windows.

METHODS: Prospectively collected data from Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry from January 2010 to April 2020 were reviewed. Participants were EVT patients with onset-to-puncture time (OTP) of ≤24 hours and …

Building The Foundation For A Community-Generated National Research Blueprint For Inherited Bleeding Disorders: Research Priorities To Transform The Care Of People With Hemophilia, Duc Q Tran, Craig C Benson, Judith A Boice, Meera Chitlur, Amy L Dunn, Miguel A Escobar, Kalpna Gupta, Jill M Johnsen, James Jorgenson, Scott D Martin, Suzanne Martin, Shannon L Meeks, Alfredo A Narvaez, Doris V Quon, Mark T Reding, Ulrike M Reiss, Brittany Savage, Kim Schafer, Bruno Steiner, Courtney Thornburg, Lena M Volland, Annette Von Drygalski

Faculty, Staff and Student Publications

BACKGROUND: Decades of research have transformed hemophilia from severely limiting children's lives to a manageable disorder compatible with a full, active life, for many in high-income countries. The direction of future research will determine whether exciting developments truly advance health equity for all people with hemophilia (PWH). National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive inclusive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them.

RESEARCH DESIGN AND METHODS: Working group (WG) 1 of the NHF State of the Science Research Summit distilled the community-identified priorities for …

Association Of Insurance Type With Inpatient Surgical 30-Day Readmissions, Emergency Department Visits/Observation Stays, And Costs, Michael A Jacobs, Jeongsoo Kim, Jasmine C Tetley, Susanne Schmidt, Bradley B Brimhall, Virginia Mika, Chen-Pin Wang, Laura S Manuel, Paul Damien, Paula K Shireman

Faculty, Staff and Student Publications

Objective: To assess the association of Private, Medicare, and Medicaid/Uninsured insurance type with 30-day Emergency Department visits/Observation Stays (EDOS), readmissions, and costs in a safety-net hospital (SNH) serving diverse socioeconomic status patients.

Summary background data: Medicare's Hospital Readmission Reduction Program (HRRP) disproportionately penalizes SNHs.

Methods: This retrospective cohort study used inpatient National Surgical Quality Improvement Program (2013-2019) data merged with cost data. Frailty, expanded Operative Stress Score, case status, and insurance type were used to predict odds of EDOS and readmissions, as well as index hospitalization costs.

Results: The cohort had 1,477 Private; 1,164 Medicare; and 3,488 Medicaid/Uninsured cases with …

Meniscal And Articular Cartilage Predictors Of Outcome After Revision Acl Reconstruction: A 6-Year Follow-Up Cohort Study, Rick W Wright, Laura J Huston, Amanda K Haas, Jacquelyn S Pennings, Christina R Allen, Daniel E Cooper, Thomas M Deberardino, Warren R Dunn, Brett Brick A Lantz, Kurt P Spindler, Michael J Stuart, John P Albright, Annunziato Ned Amendola, Jack T Andrish, Christopher C Annunziata, Robert A Arciero, Bernard R Bach, Champ L Baker, Arthur R Bartolozzi, Keith M Baumgarten, Jeffery R Bechler, Jeffrey H Berg, Geoffrey A Bernas, Stephen F Brockmeier, Robert H Brophy, Charles A Bush-Joseph, J Brad Butler, John D Campbell, James L Carey, James E Carpenter, Brian J Cole, Jonathan M Cooper, Charles L Cox, R Alexander Creighton, Diane L Dahm, Tal S David, David C Flanigan, Robert W Frederick, Theodore J Ganley, Elizabeth A Garofoli, Charles J Gatt, Steven R Gecha, James Robert Giffin, Sharon L Hame, Jo A Hannafin, Christopher D Harner, Norman Lindsay Harris, Keith S Hechtman, Elliott B Hershman, Rudolf G Hoellrich, David C Johnson, Timothy S Johnson, Morgan H Jones, Christopher C Kaeding, Ganesh V Kamath, Thomas E Klootwyk, Bruce A Levy, C Benjamin Ma, G Peter Maiers, Robert G Marx, Matthew J Matava, Gregory M Mathien, David R Mcallister, Eric C Mccarty, Robert G Mccormack, Bruce S Miller, Carl W Nissen, Daniel F O'Neill, Brett D Owens, Richard D Parker, Mark L Purnell, Arun J Ramappa, Michael A Rauh, Arthur C Rettig, Jon K Sekiya, Kevin G Shea, Orrin H Sherman, James R Slauterbeck, Matthew V Smith, Jeffrey T Spang, Ltc Steven J Svoboda, Timothy N Taft, Joachim J Tenuta, Edwin M Tingstad, Armando F Vidal, Darius G Viskontas, Richard A White, James S Williams, Michelle L Wolcott, Brian R Wolf, James J York

Faculty, Staff and Student Publications

Background: Meniscal and chondral damage is common in the patient undergoing revision anterior cruciate ligament (ACL) reconstruction.

Purpose: To determine if meniscal and/or articular cartilage pathology at the time of revision ACL surgery significantly influences a patient's outcome at 6-year follow-up.

Study design: Cohort study; Level of evidence, 3.

Methods: Patients undergoing revision ACL reconstruction were prospectively enrolled between 2006 and 2011. Data collection included baseline demographics, surgical technique, pathology, treatment, and scores from 4 validated patient-reported outcome instruments: International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and …

Ras Nanoclusters Are Cell Surface Transducers That Convert Extracellular Stimuli To Intracellular Signalling, Yong Zhou, John F Hancock

Faculty, Staff and Student Publications

Mutations of rat sarcoma virus (RAS) oncogenes (HRAS, KRAS and NRAS) can contribute to the development of cancers and genetic disorders (RASopathies). The spatiotemporal organization of RAS is an important property that warrants further investigation. In order to function, wild-type or oncogenic mutants of RAS must be localized to the inner leaflet of the plasma membrane (PM), which is driven by interactions between their C-terminal membrane-anchoring domains and PM lipids. The isoform-specific RAS-lipid interactions promote the formation of nanoclusters on the PM. As main sites for effector recruitment, these nanoclusters are biologically important. Since the spatial distribution of lipids is …

A Bidirectional Single-Cell Migration And Retrieval Chip For Quantitative Study Of Dendritic Cell Migration, Ning Shao, Yufu Zhou, Jun Yao, Pengchao Zhang, Yanni Song, Kai Zhang, Xin Han, Bin Wang, Xuewu Liu

Faculty, Staff and Student Publications

Dendritic cell (DC) migration is a fundamental step during execution of its adaptive immunity functions. Studying DC migration characteristics is critical for development of DC-dependent allergy treatments, vaccines, and cancer immunotherapies. Here, a microfluidics-based single-cell migration platform is described that enables high-throughput and precise bidirectional cell migration assays. It also allows selective retrieval of cell subpopulations that have different migratory potentials. Using this microfluidic platform, DC migration is investigated in response to different chemoattractants and inhibitors, quantitatively describe DC migration patterns and retrieve DC subpopulations of different migratory potentials for differential gene expression analysis. This platform opens an avenue for …

Smurf1 Attenuates Endoplasmic Reticulum Stress By Promoting The Degradation Of Keap1 To Activate Nrf2 Antioxidant Pathway, Amita Singh, Gabriel Bonnell, Justin De Prey, Natalie Buchwald, Kyrillos Eskander, Keith J Kincaid, Christina A Wilson

Faculty, Staff and Student Publications

Cerebral small-vessels are generally located in the brain at branch points from major cerebral blood vessels and perfuse subcortical structures such as the white matter tracts, basal ganglia, thalamus, and pons. Cerebral small-vessel disease (CSVD) can lead to several different clinical manifestations including ischemic lacunar stroke, intracerebral hemorrhage, and vascular dementia. Risk factors for CSVD overlap with conventional vascular risk factors including hypertension, diabetes mellitus, and hypercholesterolemia, as well as genetic causes. As in cardiovascular disease, treatment of CSVD involves both primary and secondary prevention. Aspirin has not been established as a primary prevention strategy for CSVD among the general …

Burn Resuscitation Practices In North America: Results Of The Acute Burn Resuscitation Multicenter Prospective Trial (Abrupt), David G Greenhalgh, Robert Cartotto, Sandra L Taylor, Jeffrey R Fine, Giavonni M Lewis, David J Smith, Michael A Marano, Angela Gibson, Lucy A Wibbenmeyer, James H Holmes, Julie A Rizzo, Kevin N Foster, Anjay Khandelwal, Sarah Fischer, Mark R Hemmila, David Hill, Ariel M Aballay, Edward E Tredget, Jeremy Goverman, Herbert Phelan, Carlos J Jimenez, Anthony Baldea, Rajiv Sood

Faculty, Staff and Student Publications

Objectives: ABRUPT was a prospective, noninterventional, observational study of resuscitation practices at 21 burn centers. The primary goal was to examine burn resuscitation with albumin or crystalloids alone, to design a future prospective randomized trial.

Summary background data: No modern prospective study has determined whether to use colloids or crystalloids for acute burn resuscitation.

Methods: Patients ≥18 years with burns ≥ 20% total body surface area (TBSA) had hourly documentation of resuscitation parameters for 48 hours. Patients received either crystalloids alone or had albumin supplemented to crystalloid based on center protocols.

Results: Of 379 enrollees, two-thirds (253) were resuscitated with …

Gender-Associated Cardiometabolic Risk Profiles And Health Behaviors In Patients With Type 2 Diabetes: A Cross-Sectional Analysis Of The Joint Asia Diabetes Evaluation (Jade) Program, Lee-Ling Lim, Eric S H Lau, Alice P S Kong, Amy W C Fu, Vanessa Lau, Weiping Jia, Wayne H H Sheu, Leorino Sobrepena, K H Yoon, Alexander T B Tan, Yook-Chin Chia, Aravind Sosale, Banshi D Saboo, Jothydev Kesavadev, Su-Yen Goh, Thy Khue Nguyen, Yotsapon Thewjitcharoen, Raymond Suwita, Ronald C W Ma, Elaine Y K Chow, Andrea O Y Luk, Juliana C N Chan

Faculty, Staff and Student Publications

Background

In Asia, diabetes-associated death due to cardiorenal diseases were 2–3 times higher in women than men which might be due to gender disparity in quality of care and health habits.

Methods

Adults with type 2 diabetes (T2D) from 11 Asian countries/areas were assessed using the same protocol (2007–2015). We compared treatment target attainment (HbA_1c < 7%, blood pressure [BP] < 130/80 mmHg, risk-based LDL-cholesterol, lack of central obesity [waist circumference <90 cm in men or <80 cm in women), use of cardiorenal-protective drugs (renin-angiotensin system [RAS] inhibitors, statins), and self-reported health habits including self-monitoring blood glucose (SMBG) by gender. Analyses were stratified by countries/areas, age of natural menopause (<50 vs. ≥50 years), and comorbidities (atherosclerotic cardiovascular disease [ASCVD], heart failure, kidney impairment [eGFR < 60 mL/min/1.73 m²]).

Findings

Among 106,376 patients (53.2% men; median (interquartile range) diabetes duration: 6.0 (2.0–12.0) years; mean ± SD HbA_1c 8.0 ± 1.9%; 27% insulin-treated), women were older and …

Author Correction: Neoadjuvant Relatlimab And Nivolumab In Resectable Melanoma, Rodabe N Amaria, Michael Postow, Elizabeth M Burton, Michael T Tetzlaff, Merrick I Ross, Carlos Torres-Cabala, Isabella C Glitza, Fei Duan, Denái R Milton, Klaus Busam, Lauren Simpson, Jennifer L Mcquade, Michael K Wong, Jeffrey E Gershenwald, Jeffrey E Lee, Ryan P Goepfert, Emily Z Keung, Sarah B Fisher, Allison Betof-Warner, Alexander N Shoushtari, Margaret Callahan, Daniel Coit, Edmund K Bartlett, Danielle Bello, Parisa Momtaz, Courtney Nicholas, Aidi Gu, Xuejun Zhang, Brinda Rao Korivi, Madhavi Patnana, Sapna P Patel, Adi Diab, Anthony Lucci, Victor G Prieto, Michael A Davies, James P Allison, Padmanee Sharma, Jennifer A Wargo, Charlotte Ariyan, Hussein A Tawbi

Faculty, Staff and Student Publications

No abstract provided.

A National, Electronic Health Record-Based Study Of Perinatal Hemorrhagic And Ischemic Stroke, Stuart Fraser, Samantha M Levy, Yashar Talebi, Sean I Savitz, Alicia Zha, Gen Zhu, Hulin Wu

Faculty, Staff and Student Publications

BACKGROUND: Perinatal stroke occurs in approximately 1 in 1100 live births. Large electronic health record (EHR) data can provide information on exposures associated with perinatal stroke in a larger number of patients than is achievable through traditional clinical studies. The objective of this study is to assess prevalence and odds ratios of known and theorized comorbidities with perinatal ischemic and hemorrhagic stroke.

METHODS: The data for patients aged 0-28 days with a diagnosis of either ischemic or hemorrhagic stroke were extracted from the Cerner Health Facts Electronic Medical Record (EMR) database. Incidence of birth demographics and perinatal complications were recorded. …

Stem Cell Mobilization Yields With Daratumumab- And Lenalidomide-Containing Quadruplet Induction Therapy In Newly Diagnosed Multiple Myeloma: Findings From The Master And Griffin Trials, Saurabh Chhabra, Natalie Callander, Nicole L Watts, Luciano J Costa, Bicky Thapa, Jonathan L Kaufman, Jacob Laubach, Douglas W Sborov, Brandi Reeves, Cesar Rodriguez, Ajai Chari, Rebecca Silbermann, Larry D Anderson, Susan Bal, Binod Dhakal, Nitya Nathwani, Nina Shah, Eva Medvedova, Naresh Bumma, Sarah A Holstein, Caitlin Costello, Andrzej Jakubowiak, Tanya M Wildes, Timothy Schmidt, Robert Z Orlowski, Kenneth H Shain, Andrew J Cowan, Bhagirathbhai Dholaria, R Frank Cornell, James H Jerkins, Huiling Pei, Annelore Cortoos, Sharmila Patel, Thomas S Lin, Saad Z Usmani, Paul G Richardson, Peter M Voorhees

Faculty, Staff and Student Publications

For eligible patients with newly diagnosed multiple myeloma (NDMM), standard of care includes induction therapy followed by autologous stem cell transplantation (ASCT). Daratumumab as monotherapy and in combination treatment is approved across multiple lines of therapy for multiple myeloma (MM), and lenalidomide is an effective and commonly used agent for induction and maintenance therapy in MM. However, there is concern that lenalidomide and daratumumab given as induction therapy might impair mobilization of stem cells for ASCT. Therefore, we assessed stem cell mobilization in patients following frontline induction therapy in the MASTER and GRIFFIN phase 2 clinical studies by examining stem …

Ninety-Day Mortality Following Transoral Robotic Surgery Or Radiation At Commission On Cancer-Accredited Facilities, James R Janopaul-Naylor, Manali Rupji, Rachel A Tobillo, Joshua W Lorenz, Jeffrey M Switchenko, Sibo Tian, Azeem S Kaka, David C Qian, Ashley J Schlafstein, Conor E Steuer, Jill S Remick, Soumon Rudra, Mark W Mcdonald, Nabil F Saba, William A Stokes, Mihir R Patel, James E Bates

Faculty, Staff and Student Publications

BACKGROUND: Postoperative mortality for oropharynx squamous cell carcinoma (OPSCC) with transoral robotic surgery (TORS) varies from 0.2% to 6.5% on trials; the real-world rate is unknown.

METHODS: NCDB study from 2010 to 2017 for patients with cT1-2N0-2M0 OPSCC with Charleson-Deyo score 0-1. Ninety-day mortality assessed from start and end of treatment at Commission on Cancer-accredited facilities.

RESULTS: 3639 patients were treated with TORS and 1937 with radiotherapy. TORS cohort had more women and higher income, was younger, more often treated at academic centers, and more likely to have private insurance (all p < 0.05). Ninety-day mortality was 1.3% with TORS and 0.7% or 1.4% from start or end of radiotherapy, respectively. From end of therapy, there was no significant difference on MVA between treatment modality.

CONCLUSIONS: There is minimal difference between 90-day mortality …

Blood Neutrophil Count And Neutrophil-To-Lymphocyte Ratio For Prediction Of Disease Progression And Mortality In Two Independent Systemic Sclerosis Cohorts, Nancy Wareing, Vishnu Mohan, Rana Taherian, Elizabeth R Volkmann, Marka A Lyons, Holly Wilhalme, Michael D Roth, Rosa M Estrada-Y-Martin, Brian Skaug, Maureen D Mayes, Donald P Tashkin, Shervin Assassi

Faculty, Staff and Student Publications

OBJECTIVE: To assess the predictive significance of blood neutrophil count and the ratio between neutrophil and lymphocyte count (neutrophil-to-lymphocyte ratio [NLR]) for disease severity and mortality in systemic sclerosis (SSc).

METHODS: Neutrophil and lymphocyte counts were prospectively measured in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) and the Scleroderma Lung Study II (SLS II). Forced vital capacity percent predicted (FVC%) and modified Rodnan skin thickness score (MRSS) were used as surrogate measures for disease severity. Longitudinal analyses were performed using generalized linear mixed models. Cox proportional hazards models evaluated the predictive significance of these cell counts for mortality. …

Physician Perspectives On Telemedicine In Radiation Oncology, Sean Maroongroge, Brian De, Kristina D Woodhouse, Roland L Bassett, Percy Lee, Elizabeth S Bloom, Grace L Smith, Steven J Frank, Jing Li, George Perkins, Prajnan Das, Albert C Koong, Benjamin D Smith, Chenyang Wang

Faculty, Staff and Student Publications

PURPOSE: Telemedicine enthusiasm and uptake in radiation oncology rapidly increased during the COVID-19 pandemic, but it is unclear if and how telemedicine should be used after the COVID-19 public health emergency ends is unclear. Herein, we report on our institution's provider experience after the mature adoption of telemedicine.

METHODS AND MATERIALS: We distributed a survey to all radiation oncology attending physicians at our institution in October 2021 to assess satisfaction, facilitators, and barriers to telemedicine implementation. We performed quantitative and qualitative analyses to characterize satisfaction and identify influencing factors whether telemedicine is employed. We calculated the average proportion of visits …

Spatial Pd-L1, Immune-Cell Microenvironment, And Genomic Copy-Number Alteration Patterns And Drivers Of Invasive-Disease Transition In Prospective Oral Precancer Cohort, William N William, Jianjun Zhang, Xin Zhao, Edwin R Parra, Naohiro Uraoka, Heather Y Lin, S Andrew Peng, Adel K El-Naggar, Jaime Rodriguez-Canales, Jaejoon Song, Ann M Gillenwater, Ignacio I Wistuba, Jeffrey N Myers, Kathryn A Gold, Renata Ferrarotto, Patrick Hwu, Teresa Davoli, J Jack Lee, John V Heymach, Vassiliki A Papadimitrakopoulou, Scott M Lippman

Faculty, Staff and Student Publications

BACKGROUND: Studies of the immune landscape led to breakthrough trials of programmed death-1 (PD-1) inhibitors for recurrent/metastatic head and neck squamous cell carcinoma therapy. This study investigated the timing, influence of somatic copy-number alterations (SCNAs), and clinical implications of PD-L1 and immune-cell patterns in oral precancer (OPC).

METHODS: The authors evaluated spatial CD3, CD3/8, and CD68 density (cells/mm

RESULTS: Epithelial, but not CD68 immune-cell, PD-L1 expression was detected in 28% of OPCs, correlated with immune-cell infiltration, 9p21.3 loss of heterozygosity (LOH), and inferior oral cancer-free survival (OCFS), notably in OPCs with low CD3/8 cell density, dysplasia, and/or 9p21.3 LOH. High …

High Pulse Pressure Impairs Cerebral Artery Endothelial Function In Young, But Not Old, Mice, Nick R Winder, Emily H Reeve, Elise K Kronquist, Aleena Khurana, Byron Lee, Thuan Nguyen, Grant D Henson, Ashley E Walker

Faculty, Staff and Student Publications

One of the hallmarks of vascular aging is increased pulse pressure. This elevated pulse pressure is associated with deleterious effects on cerebral vascular function; however, it is unknown if age modulates the susceptibility to high pulse pressure. To examine the effects of age on the cerebral artery response to pulse pressure, we studied isolated cerebral arteries collected from young (6.1 ± 0.2 mo) and old (26.7 ± 0.5 mo) male C57BL/6 mice. Isolated cerebral arteries were exposed ex vivo to static pressure, low pulse pressure (25 mmHg), and high pulse pressure (50 mmHg). In cerebral arteries from young mice, endothelium-dependent …

Covariate Adjustment In Continuous Biomarker Assessment, Ziyi Li, Yijian Huang, Dattatraya Patil, Martin G Sanda

Faculty, Staff and Student Publications

Continuous biomarkers are common for disease screening and diagnosis. To reach a dichotomous clinical decision, a threshold would be imposed to distinguish subjects with disease from nondiseased individuals. Among various performance metrics, specificity at a controlled sensitivity level (or vice versa) is often desirable because it directly targets the clinical utility of the intended clinical test. Meanwhile, covariates, such as age, race, as well as sample collection conditions, could impact the biomarker distribution and may also confound the association between biomarker and disease status. Therefore, covariate adjustment is important in such biomarker evaluation. Most existing covariate adjustment methods do not …

Effect Of Neoadjuvant Chemotherapy On Intraoperative Core Temperature In Patients With Breast Cancer: A Retrospective Cohort Study, Daniel D Kim, Sarah M Desnyder, Patrick M Dougherty, Juan P Cata

Faculty, Staff and Student Publications

Background: Clinical evidence suggests that chemotherapeutic agents are associated with neuropathy and peripheral autonomic dysfunction. However, the possible effects of neoadjuvant chemotherapy on intraoperative temperature remain poorly characterised.

Methods: We evaluated patients who underwent a mastectomy for breast cancer between April 2016 and July 2020. Propensity scores were used to match patients who received neoadjuvant chemotherapy with those who did not, and intraoperative core temperature patterns were analysed in the matched cohort. The independent associations between vasopressor use and heart rate during general anaesthesia in the matched cohort were also analysed.

Results: Data from 1764 patients were analysed (882 patients …

Predictors Of Emergency Room Visits After Ambulatory Breast Cancer Surgery In The Medicare Population, Susie X Sun, Zhigang Duan, Henry M Kuerer, Sarah M Desnyder, Carrie Cunningham, Hui Zhao, Sharon H Giordano

Faculty, Staff and Student Publications

Background: Emergency department (ED) overuse is a large contributor to healthcare spending in the USA. We examined the rate of and risk factors for ED visits following outpatient breast cancer surgery.

Patients and methods: Using linked data from the Surveillance, Epidemiology, and End Results (SEER) program and Medicare, we identified women who underwent curative breast cancer surgery between 2003 and 2015. Our outcome of interest was ED visits within 30 days of surgery. Multivariate regression was used to evaluate the odds of ED visit while controlling for clinical and socioeconomic variables. Secondary analyses assessed admission from the ED as well …

Community-Onset Bacterial Coinfection In Children Critically Ill With Severe Acute Respiratory Syndrome Coronavirus 2 Infection., Kristin L. Moffitt, Mari M. Nakamura, Cameron C. Young, Margaret M. Newhams, Natasha B. Halasa, J Nelson Reed, Julie C. Fitzgerald, Philip C. Spinella, Vijaya L. Soma, Tracie C. Walker, Laura L. Loftis, Aline B. Maddux, Michele Kong, Courtney M. Rowan, Charlotte V. Hobbs, Jennifer E. Schuster, Becky J. Riggs, Gwenn E. Mclaughlin, Kelly N. Michelson, Mark W. Hall, Christopher J. Babbitt, Natalie Z. Cvijanovich, Matt S. Zinter, Mia Maamari, Adam J. Schwarz, Aalok R. Singh, Heidi R. Flori, Shira J. Gertz, Mary A. Staat, John S. Giuliano, Saul R. Hymes, Katharine N. Clouser, John Mcguire, Christopher L. Carroll, Neal J. Thomas, Emily R. Levy, Adrienne G. Randolph

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Community-onset bacterial coinfection in adults hospitalized with coronavirus disease 2019 (COVID-19) is reportedly uncommon, though empiric antibiotic use has been high. However, data regarding empiric antibiotic use and bacterial coinfection in children with critical illness from COVID-19 are scarce.

METHODS: We evaluated children and adolescents agedadmission, we adjudicated whether patients had community-onset bacterial coinfection. We compared demographic and clinical characteristics of those who did and did not (1) receive antibiotics and (2) have bacterial coinfection early in admission. Using Poisson regression models, we assessed factors associated with these outcomes.

RESULTS: Of the 532 patients, 63.3% received empiric antibiotics, but …

Elastic Priors To Dynamically Borrow Information From Historical Data In Clinical Trials, Liyun Jiang, Lei Nie, Ying Yuan

Faculty, Staff and Student Publications

Use of historical data and real-world evidence holds great potential to improve the efficiency of clinical trials. One major challenge is to effectively borrow information from historical data while maintaining a reasonable type I error and minimal bias. We propose the elastic prior approach to address this challenge. Unlike existing approaches, this approach proactively controls the behavior of information borrowing and type I errors by incorporating a well-known concept of clinically significant difference through an elastic function, defined as a monotonic function of a congruence measure between historical data and trial data. The elastic function is constructed to satisfy a …

An Echogenic Clot Method For Thrombolysis Monitoring In Thrombotic Stroke Models, Dalton E Carter, Tao Peng, Melanie R Moody, Shao-Ling Huang, David D Mcpherson, Melvin E Klegerman

Faculty, Staff and Student Publications

To demonstrate thrombolytic efficacy of a tissue plasminogen activator (tPA)-loaded echogenic liposome (TELIP) formulation in a rabbit thrombotic stroke model (the most relevant animal model for evaluation of directed thrombolytic therapy for ischemic stroke), we sought to develop a means of monitoring thrombus dissolution quantitatively by ultrasound imaging methods. We hypothesized that a gas-free ultrasound contrast agent can be incorporated into blood clots at a concentration that does not affect the tPA-mediated clot dissolution rate, while enabling quantitative assessment of the clot dissolution rate. Clots were formed from a mixture of whole rabbit blood, 1 M calcium chloride, human thrombin …

Invasive Mold Infections Following Hurricane Harvey-Houston, Texas, Mitsuru Toda, Samantha Williams, Brendan R Jackson, Sebastian Wurster, Jose A Serpa, Masayuki Nigo, Carolyn Z Grimes, Robert L Atmar, Tom M Chiller, Luis Ostrosky-Zeichner, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

BACKGROUND: Characterizing invasive mold infection (IMI) epidemiology in the context of large flooding events is important for public health planning and clinical decision making.

METHODS: We assessed IMI incidence (per 10 000 healthcare encounters) 1 year before and after Hurricane Harvey at 4 hospitals in Houston, Texas. Potential IMI cases were assigned as proven or probable cases using established definitions, and surveillance cases using a novel definition. We used rate ratios to describe IMI incidence and multivariable logistic regression to examine patient characteristics associated with IMI case status.

RESULTS: IMI incidence was significantly higher posthurricane (3.69 cases) than prehurricane (2.50 …

Imaging Features Of Immune Checkpoint Inhibitor-Related Nephritis With Clinical Correlation: A Retrospective Series Of Biopsy-Proven Cases, Muhammad O Awiwi, Ala Abudayyeh, Noha Abdel-Wahab, Adi Diab, Migena Gjoni, Guofan Xu, Raghu Vikram, Khaled Elsayes

Faculty, Staff and Student Publications

OBJECTIVES: Imaging appearances of immune checkpoint inhibitor-related nephritis have not yet been described. The primary objective of this study is to describe the appearances of immunotherapy-related nephritis on computerized tomography (CT) and positron emission tomography (PET). The secondary objectives are to investigate the association of radiologic features with clinical outcomes.

METHODS: CT and PET-CT scans before the initiation of immunotherapy (baseline), at nephritis, and after resolution of pathology-proven nephritis cases were reviewed. Total kidney volume, renal parenchymal SUVmax, renal pelvis SUVmax, and blood pool SUVmean were obtained.

RESULTS: Thirty-four patients were included. The total kidney volume was significantly higher at …

Linoleic Acid Improves Piezo2 Dysfunction In A Mouse Model Of Angelman Syndrome, Luis O Romero, Rebeca Caires, A Kaitlyn Victor, Juanma Ramirez, Francisco J Sierra-Valdez, Patrick Walsh, Vincent Truong, Jungsoo Lee, Ugo Mayor, Lawrence T Reiter, Valeria Vásquez, Julio F Cordero-Morales

Faculty, Staff and Student Publications

Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability and atypical behaviors. AS results from loss of expression of the E3 ubiquitin-protein ligase UBE3A from the maternal allele in neurons. Individuals with AS display impaired coordination, poor balance, and gait ataxia. PIEZO2 is a mechanosensitive ion channel essential for coordination and balance. Here, we report that PIEZO2 activity is reduced in Ube3a deficient male and female mouse sensory neurons, a human Merkel cell carcinoma cell line and female human iPSC-derived sensory neurons with UBE3A knock-down, and de-identified stem cell-derived neurons from individuals with AS. We find that loss …