Digital Commons Network^™

Gestational Diabetes Knowledge Improves With Interactive Online Training Modules, Petra Krutilova, Roxann Williams, Rebecca Morey, Carole Field, Veronda Byrth, Melissa Tepe, Amy Mcqueen, Cynthia Herrick

2020-Current year OA Pubs

BACKGROUND: The risk of developing type 2 diabetes mellitus (T2DM) is up to 50% among women with gestational diabetes mellitus (GDM). However, diabetes education during and after pregnancy is limited. To bridge this gap, our team developed four training modules on GDM for nurses and community health workers. This pilot study assesses changes in knowledge, self-efficacy for providing diabetes education, attitudes, and intentions to recommend diabetes prevention before and after training completion.

METHODS: Interactive online modules were disseminated to clinical staff providing care for women with GDM in the United States. Optional pre- and post-training surveys were conducted to gauge …

Substitution Of A Single Non-Coding Nucleotide Upstream Of Tmem216 Causes Non-Syndromic Retinitis Pigmentosa And Is Associated With Reduced Tmem216 Expression, Samantha Malka, Pooja Biswas, Anne-Marie Berry, Riccardo Sangermano, Mukhtar Ullah, Siying Lin, Matteo D'Antonio, Aleksandr Jestin, Xiaodong Jiao, Mathieu Quinodoz, Lori Sullivan, Jessica C Gardner, Emily M Place, Michel Michaelides, Karolina Kaminska, Omar A Mahroo, Elena Schiff, Genevieve Wright, Francesca Cancellieri, Veronika Vaclavik, Cristina Santos, Atta Ur Rehman, Sudeep Mehrotra, Hafiz Muhammad Azhar Baig, Muhammad Iqbal, Muhammad Ansar, Luisa Coutinho Santos, Ana Berta Sousa, Viet H Tran, Hiroko Matsui, Anjana Bhatia, Muhammad Asif Naeem, Shehla J Akram, Javed Akram, Sheikh Riazuddin, Carmen Ayuso, Eric A Pierce, Alison J Hardcastle, S Amer Riazuddin, Kelly A Frazer, J Fielding Hejtmancik, Carlo Rivolta, Kinga M Bujakowska, Gavin Arno, Andrew R Webster, Radha Ayyagari

Faculty, Staff and Student Publications

Genome analysis of individuals affected by retinitis pigmentosa (RP) identified two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]), in individuals of South Asian and African ancestry, respectively. Genotypes included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations. Clinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation …

Targeting Igf2 To Reprogram The Tumor Microenvironment For Enhanced Viro-Immunotherapy, Min Hye Noh, Jin Muk Kang, Alexandra A Miller, Grace Nguyen, Minxin Huang, Ji Seon Shim, Alberto J Bueso-Perez, Sara A Murphy, Kimberly A Rivera-Caraballo, Yoshihiro Otani, Eunju Kim, Seung-Hee Yoo, Yuanqing Yan, Yeshavanth Banasavadi-Siddegowda, Hiroshi Nakashima, E Antonio Chiocca, Balveen Kaur, Zhongming Zhao, Tae Jin Lee, Ji Young Yoo

Faculty, Staff and Student Publications

BACKGROUND: The FDA approval of oncolytic herpes simplex-1 virus (oHSV) therapy underscores its therapeutic promise and safety as a cancer immunotherapy. Despite this promise, the current efficacy of oHSV is significantly limited to a small subset of patients largely due to the resistance in tumor and tumor microenvironment (TME).

METHODS: RNA sequencing (RNA-Seq) was used to identify molecular targets of oHSV resistance. Intracranial human and murine glioma or breast cancer brain metastasis (BCBM) tumor-bearing mouse models were employed to elucidate the mechanism underlying oHSV therapy-induced resistance.

RESULTS: Transcriptome analysis identified IGF2 as one of the top-secreted proteins following oHSV treatment. …

Physiological And Communicative Emotional Disconcordance In Children On The Autism Spectrum, Emma Finkel, Eric Sah, Mckenna Spaulding, John Herrington, Liza Tomczuk, Aaron Masino, Xueqin Pang, Anushua Bhattacharya, Darren Hedley, Yelena Kushleyeva, Phoebe Thomson, Natalie Doppelt, Jessica Tan, Jeffrey Pennington, Cheryl Dissanayake, Christopher Bonafide, Heather Nuske

SKMC Student Presentations and Publications

BACKGROUND: Individuals on the autism spectrum commonly have differences from non-autistic people in expressing their emotions using communicative behaviors, such as facial expressions. However, it is not yet clear if this reduced expressivity stems from reduced physiological reactivity in emotional contexts or if individuals react internally, but do not show these reactions externally to others. We hypothesized that autism is characterized by a discordance between in-the-moment internal psychophysiological arousal and external communicative expressions of emotion.

METHODS: Forty-one children on the autism spectrum and 39 non-autistic, typically developing (TD) children of two age groups (2-4 and 8-12 years) participated in a …

Different Sensory Information Is Used For State Estimation When Stationary Or Moving., Aaron Wong, Alyssa Eyssalenne, Luke Carter, Amanda S Therrien

Moss-Magee Rehabilitation Papers

The accurate estimation of limb state is necessary for movement planning and execution. While state estimation requires both feedforward and feedback information, we focus here on the latter. Prior literature has shown that integrating visual and proprioceptive feedback improves estimates of static limb position. However, differences in visual and proprioceptive feedback delays suggest that multisensory integration could be disadvantageous when the limb is moving. We formalized this hypothesis by modeling feedback-based state estimation using the long-standing maximum likelihood estimation model of multisensory integration, which we updated to account for sensory delays. Our model predicted that the benefit of multisensory integration …

Racial And Ethnic Representation In Food Allergen Immunotherapy Trial Participants: A Systematic Review., Hannah Suffian, Aarti Pandya, Lauren Davidson, Vincent Staggs, Bridgette Jones

Manuscripts, Articles, Book Chapters and Other Papers

IMPORTANCE: The lack of inclusion of diverse population samples in food allergy immunotherapy clinical trials not only leads to decreased applicability to the general population in terms of results and treatments but can also be seen as a broader social injustice contributing to inequity within the health care system.

OBJECTIVES: To investigate the racial and ethnic distribution of participants included in food allergy immunotherapy clinical trials, and determine whether the racial and ethnic representation in trials accurately reflects the patients who experience food allergy.

EVIDENCE REVIEW: Data were collected from articles found on PubMed and ClinicalTrials.gov using key terms of …

Prognostic Significance And Biologic Associations Of Senescence-Associated Secretory Phenotype Biomarkers In Heart Failure, Oday Salman, Ali Javaheri, Douglas L Mann, Et Al.

2020-Current year OA Pubs

BACKGROUND: The role of cellular senescence in human heart failure (HF) remains unclear. The senescence-associated secretory phenotype (SASP) is composed of proteins released by senescent cells. We assessed the prognostic significance and biologic pathways associated with the SASP in human HF using a plasma proteomics approach.

METHODS AND RESULTS: We measured 25 known SASP proteins among 2248 PHFS (Penn HF Study) participants using the SOMAScan V4 assay. We extracted the common variance in these proteins to generate SASP factor scores and assessed the relationship between these SASP factor scores and (1) all-cause death and (2) the composite of death or …

Proteomic Correlates And Prognostic Significance Of Kidney Injury In Heart Failure With Preserved Ejection Fraction, Oday Salman, Ali Javaheri, Douglas L Mann, Et Al.

2020-Current year OA Pubs

BACKGROUND: Kidney disease is common in heart failure with preserved ejection fraction (HFpEF). However, the biologic correlates and prognostic significance of kidney injury (KI), in HFpEF, beyond the estimated glomerular filtration rate (eGFR), are unclear.

METHODS AND RESULTS: Using baseline plasma samples from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, we measured the following KI biomarkers: cystatin-C, fatty acid-binding protein-3, Beta-2 microglobulin, neutrophil gelatinase-associated lipocalin, and kidney-injury molecule-1. Factor analysis was used to extract the common variability underlying these biomarkers. We assessed the relationship between the KI-factor score and the risk of death …

Positive Airway Pressure, Mortality, And Cardiovascular Risk In Older Adults With Sleep Apnea, Diego R Mazzotti, Lemuel R Waitman, Jennifer Miller, Krishna M Sundar, Nancy H Stewart, David Gozal, Xing Song

Faculty, Staff and Student Publications

Importance: Positive airway pressure (PAP) is the first-line treatment for obstructive sleep apnea (OSA), but evidence on its beneficial effect on major adverse cardiovascular events (MACE) and mortality prevention is limited.

Objective: To determine whether PAP initiation and utilization are associated with lower mortality and incidence of MACE among older adults with OSA living in the central US.

Design, setting, and participants: This retrospective clinical cohort study included Medicare beneficiaries with 2 or more distinct OSA claims identified from multistate, statewide, multiyear (2011-2020) Medicare fee-for-service claims data. Individuals were followed up until death or censoring on December 31, 2020. Analyses …

Prognostic Impact Of Notch1 Intracellular Domain, P63, And C-Myc In Lacrimal Gland Adenoid Cystic Carcinoma, Jiawei Zhao, Michelle D Williams, Mike Hernandez, Grace Kuang, Hila Goldberg, Janet Fan, Jing Ning, Renata Ferrarotto, Bita Esmaeli

Faculty, Staff and Student Publications

PURPOSE: We assessed whether NICD1 expression, c-MYC expression, and P63 expression by immunohistochemistry (IHC) correlate with prognosis and high-risk clinicopathological features in lacrimal gland adenoid cystic carcinoma (ACC).

METHODS: Records of patients with lacrimal gland ACC who underwent surgery between 1998 to 2018 were reviewed. Clinicopathologic and treatment data were collected. Tumor tissues were subjected to light microscopy and IHC.

RESULTS: Of 43 patients treated during the study period, 21 had archived tumor tissue available and were included. The median age at diagnosis was 47 years, and 13 patients (62%) were male. Thirteen patients (62%) had T2 disease, and none …

Folate Metabolism And Risk Of Childhood Acute Lymphoblastic Leukemia: A Genetic Pathway Analysis From The Childhood Cancer And Leukemia International Consortium, Catherine Metayer, Logan G Spector, Michael E Scheurer, Soyoung Jeon, Rodney J Scott, Masatoshi Takagi, Jacqueline Clavel, Atsushi Manabe, Xiaomei Ma, Elleni M Hailu, Philip J Lupo, Kevin Y Urayama, Audrey Bonaventure, Motohiro Kato, Aline Meirhaeghe, Charleston W K Chiang, Libby M Morimoto, Joseph L Wiemels

Faculty, Staff and Students Publications

BACKGROUND: Prenatal folate supplementation has been consistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Previous germline genetic studies examining the one carbon (folate) metabolism pathway were limited in sample size, scope, and population diversity and led to inconclusive results.

METHODS: We evaluated whether ∼2,900 single-nucleotide polymorphisms (SNP) within 46 candidate genes involved in the folate metabolism pathway influence the risk of childhood ALL, using genome-wide data from nine case-control studies in the Childhood Cancer and Leukemia International Consortium (n = 9,058 cases including 4,510 children of European ancestry, 3,018 Latinx, and 1,406 Asians, and 92,364 controls). …

Fetal Mavs And Type I Ifn Signaling Pathways Control Zikv Infection In The Placenta And Maternal Decidua, Yael Alippe, Leran Wang, Reyan Coskun, Stéfanie P Muraro, Fang R Zhao, Michelle Elam-Noll, J Michael White, Daiana M Vota, Vanesa C Hauk, Jeffrey I Gordon, Scott A Handley, Michael S Diamond

2020-Current year OA Pubs

The contribution of placental immune responses to congenital Zika virus (ZIKV) syndrome remains poorly understood. Here, we leveraged a mouse model of ZIKV infection to identify mechanisms of innate immune restriction exclusively in the fetal compartment of the placenta. ZIKV principally infected mononuclear trophoblasts in the junctional zone, which was limited by mitochondrial antiviral-signaling protein (MAVS) and type I interferon (IFN) signaling mechanisms. Single nuclear RNA sequencing revealed MAVS-dependent expression of IFN-stimulated genes (ISGs) in spongiotrophoblasts but not in other placental cells that use alternate pathways to induce ISGs. ZIKV infection of Ifnar1-/- or Mavs-/- placentas was associated with greater …

Analysis Of Ductal Carcinoma In Situ By Self-Reported Race Reveals Molecular Differences Related To Outcome, Siri H Strand, Graham A Colditz, Et Al.

2020-Current year OA Pubs

BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-obligate precursor to invasive breast cancer (IBC). Studies have indicated differences in DCIS outcome based on race or ethnicity, but molecular differences have not been investigated.

METHODS: We examined the molecular profile of DCIS by self-reported race (SRR) and outcome groups in Black (n = 99) and White (n = 191) women in a large DCIS case-control cohort study with longitudinal follow up.

RESULTS: Gene expression and pathway analyses suggested that different genes and pathways are involved in diagnosis and ipsilateral breast outcome (DCIS or IBC) after DCIS treatment in White versus …

Toward Reliable Symptom Coding In Electronic Health Records For Symptom Assessment And Research: Identification And Categorization Of International Classification Of Diseases, Ninth Revision, Clinical Modification Symptom Codes, Tru Cao, Veronica Brady, Meagan Whisenant, Xueying Wang, Yuxuan Gu, Hulin Wu

Faculty, Staff and Student Publications

To date, symptom documentation has mostly relied on clinical notes in electronic health records or patient-reported outcomes using disease-specific symptom inventories. To provide a common and precise language for symptom recording, assessment, and research, a comprehensive list of symptom codes is needed. The International Classification of Diseases, Ninth Revision or its clinical modification ( International Classification of Diseases, Ninth Revision, Clinical Modification ) has a range of codes designated for symptoms, but it does not contain codes for all possible symptoms, and not all codes in that range are symptom related. This study aimed to identify and categorize the first …

Systematically Assessing The Quality Of Dental Electronic Health Record Data For An Investigation Into Oral Health Care Disparities, Krishna Kumar Kookal, Muhammad F Walji, Ryan Brandon, Ferit Kivanc, Elizabeth Mertz, Aubri Kottek, Joanna Mullins, Shuang Liang, Larry E Jenson, Joel M White

Faculty, Staff and Student Publications

Objectives: This work describes the process by which the quality of electronic health care data for a public health study was determined. The objectives were to adapt, develop, and implement data quality assessments (DQAs) based on the National Institutes of Health Pragmatic Trials Collaboratory (NIHPTC) data quality framework within the three domains of completeness, accuracy, and consistency, for an investigation into oral health care disparities of a preventive care program.

Methods: Electronic health record data for eligible children in a dental accountable care organization of 30 offices, in Oregon, were extracted iteratively from January 1, 2014, through March 31, 2022. …

Automatic Vessel Attenuation Measurement For Quality Control Of Contrast-Enhanced Ct: Validation On The Portal Vein, Kevin Mccoy, Sujay Marisetty, Dominique Tan, Corey T Jensen, Jeffrey H Siewerdsen, Christine B Peterson, Moiz Ahmad

Faculty, Staff and Student Publications

Background: Adequate image enhancement of organs and blood vessels of interest is an important aspect of image quality in contrast-enhanced computed tomography (CT). There is a need for an objective method for evaluation of vessel contrast that can be automatically and systematically applied to large sets of CT exams.

Purpose: The purpose of this work was to develop a method to automatically segment and measure attenuation Hounsfield Unit (HU) in the portal vein (PV) in contrast-enhanced abdomen CT examinations.

Methods: Input CT images were processed by a vessel enhancing filter to determine candidate PV segmentations. Multiple machine learning (ML) classifiers …

Artificial Intelligence-Based Segmentation Of Residual Pancreatic Cancer In Resection Specimens Following Neoadjuvant Treatment (Isgpp-2): International Improvement And Validation Study, Boris V Janssen, Bart Oteman, Mahsoem Ali, Pieter A Valkema, Volkan Adsay, Olca Basturk, Deyali Chatterjee, Angela Chou, Stijn Crobach, Michael Doukas, Paul Drillenburg, Irene Esposito, Anthony J Gill, Seung-Mo Hong, Casper Jansen, Mike Kliffen, Anubhav Mittal, Jas Samra, Marie-Louise F Van Velthuysen, Aslihan Yavas, Geert Kazemier, Joanne Verheij, Ewout Steyerberg, Marc G Besselink, Huamin Wang, Caroline Verbeke, Arantza Fariña, Onno J De Boer, Pancreatobiliary And Hepatic Artificial Intelligence Research (Phair) Consortium, International Study Group Of Pancreatic Pathologists (Isgpp);

Faculty, Staff and Student Publications

Neoadjuvant therapy (NAT) has become routine in patients with borderline resectable pancreatic cancer. Pathologists examine pancreatic cancer resection specimens to evaluate the effect of NAT. However, an automated scoring system to objectively quantify residual pancreatic cancer (RPC) is currently lacking. Herein, we developed and validated the first automated segmentation model using artificial intelligence techniques to objectively quantify RPC. Digitized histopathological tissue slides were included from resected pancreatic cancer specimens from 14 centers in 7 countries in Europe, North America, Australia, and Asia. Four different scanner types were used: Philips (56%), Hamamatsu (27%), 3DHistech (10%), and Leica (7%). Regions of interest …

Utilization Of Blood Flow Restriction Therapy With A Former Triathlete After Total Knee Arthroplasty: A Case Report, Christopher Keating, Stephanie Muth, Pt, Phd, Cameron Hui, Lisa T. Hoglund

Department of Physical Therapy Faculty Papers

INTRODUCTION AND PURPOSE: Knee osteoarthritis (OA) is a common condition that limits function and reduces quality of life. Total knee arthroplasty (TKA) is a surgical procedure that replaces the joint surfaces to address anatomical changes due to knee OA. While TKA improves symptoms and function, postoperative impairments are common, including reduced quadriceps strength. Blood flow restriction (BFR) may be a viable option for patients following TKA, as it can improve strength with a minimal amount of joint loading compared to traditional strength training. The purpose of this case report is to describe the impact of BFR use in an individual …

The Burden Of Diagnostic Error In Dentistry: A Study On Periodontal Disease Misclassification, Bunmi Tokede, Alfa Yansane, Ryan Brandon, Guo-Hao Lin, Chun-Teh Lee, Joel White, Xiaoqian Jiang, Eric Lee, Alaa Alsaffar, Muhammad Walji, Elsbeth Kalenderian

Faculty, Staff and Student Publications

Background: Periodontal disease constitutes a widely prevalent category of non-communicable diseases and ranks among the top 10 causes of disability worldwide. Little however is known about diagnostic errors in dentistry. In this work, by retrospectively deploying an electronic health record (EHR)-based trigger tool, followed by gold standard manual review, we provide epidemiological estimates on the rate of diagnostic misclassification in dentistry through a periodontal use case.

Methods: An EHR-based trigger tool (a retrospective record review instrument that uses a list of triggers (or clues), i.e., data elements within the health record, to alert reviewers to the potential presence of a …

Psychiatric Polygenic Risk Scores: Experience, Hope For Utility, And Concerns Among Child And Adolescent Psychiatrists, Amanda R Merner, Page M Trotter, Lauren A Ginn, Jason Bach, Katherine J Freedberg, Takahiro Soda, Eric A Storch, Stacey Pereira, Gabriel Lázaro-Muñoz

Center for Medical Ethics and Health Policy Staff Publications

Recent advances in psychiatric genetics have enabled the use of polygenic risk scores (PRS) to estimate genetic risk for psychiatric disorders. However, the potential use of PRS in child and adolescent psychiatry has raised concerns. This study provides an in-depth examination of attitudes among child and adolescent psychiatrists (CAP) regarding the use of PRS in psychiatry. We conducted semi-structured interviews with U.S.-based CAP (n=29) who possess expertise in genetics. The majority of CAP indicated that PRS have limited clinical utility in their current form and are not ready for clinical implementation. Most clinicians stated that nothing would motivate them to …

Dominant Missense Variants In Srebf2 Are Associated With Complex Dermatological, Neurological, And Skeletal Abnormalities, Matthew J Moulton, Kristhen Atala, Yiming Zheng, Debdeep Dutta, Dorothy K Grange, Wen-Wen Lin, Daniel J Wegner, Jennifer A Wambach, Angela L Duker, Michael B Bober, Lisa Kratz, Carol A Wise, Ila Oxendine, Anas Khanshour, Undiagnosed Diseases Network, Michael F Wangler, Shinya Yamamoto, F Sessions Cole, Jonathan Rios, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

Purpose: We identified 2 individuals with de novo variants in SREBF2 that disrupt a conserved site 1 protease (S1P) cleavage motif required for processing SREBP2 into its mature transcription factor. These individuals exhibit complex phenotypic manifestations that partially overlap with sterol regulatory element binding proteins (SREBP) pathway-related disease phenotypes, but SREBF2-related disease has not been previously reported. Thus, we set out to assess the effects of SREBF2 variants on SREBP pathway activation.

Methods: We undertook ultrastructure and gene expression analyses using fibroblasts from an affected individual and utilized a fly model of lipid droplet (LD) formation to investigate the consequences …

An Ordinal Clinical Score Predicts Seizure Freedom After Minimally Invasive Epilepsy Surgery, Adam S Dickey, Katie L Bullinger, Dayton Grogan, Melissa M Asmar, Abdulrahman Alwaki, Ammar Kheder, Veeresh Kumar N Shivamurthy, Razan R Faraj, Alexander Greven, Jon T Willie, Daniel L Drane, Robert E Gross

2020-Current year OA Pubs

OBJECTIVE: To predict one-year seizure freedom, using a combination of relevant clinical variables, following stereotactic laser amygdalohippocampotomy for mesial temporal lobe epilepsy in a series of 101 patients.

METHODS: Eight predictors of seizure freedom were selected based on their association with medial temporal lobe epilepsy: (1) MRI evidence of mesial temporal sclerosis (MTS); (2) unitemporal interictal epileptiform discharges; (3) absence of generalized tonic-clonic seizures; (4) history of febrile seizures; (5) onset of epilepsy ≤16 years; (6) absence of an auditory, visual, or vertiginous aura; and (7) unitemporal ictal onset; (8) unitemporal PET hypometabolism. We compared four multivariate models: "MTS," using …

Long-Term Results Of The Sequential Combination Of Cladribine And Rituximab In Hairy Cell Leukemia, Jennifer Marvin-Peek, Wei-Ying Jen, Hagop M Kantarjian, David Mccue, Fadi G Haddad, William Wierda, Alessandra Ferrajoli, Jan Burger, Tareq Abusab, Jeffrey Jorgensen, Sa A Wang, Keyur Patel, Sanam Loghavi, Susan O'Brien, Farhad Ravandi

Faculty, Staff and Student Publications

We report on the long-term efficacy and safety of a phase 2 trial of sequential cladribine and rituximab in hairy cell leukemia (HCL). One-hundred and thirty-nine patients were enrolled: 111 in the frontline setting, 18 in first relapse, and 10 with variant HCL (HCLv). A complete response (CR) was achieved in 133 of 137 evaluable participants (97%) with measurable residual disease (MRD) negativity in 102 (77%). MRD status was not associated with significant differences in event free survival (EFS) or overall survival (OS). With a median follow up of 7·8 years (range: 0·40–18·8), eight patients have experienced disease relapse (5·8%), …

Oric-101, A Glucocorticoid Receptor Antagonist, In Combination With Nab-Paclitaxel In Patients With Advanced Solid Tumors, Christopher T Chen, Vishesh Khanna, Shivaani Kummar, Raghad M Abdul-Karim, David Sommerhalder, Anthony W Tolcher, Naoto T Ueno, Sarah Lindsey Davis, Douglas W Orr, Erika Hamilton, Manish R Patel, Alexander I Spira, Shekeab Jauhari, Vaia Florou, Maureen Duff, Rongda Xu, Jian Wang, Shravani R Barkund, Haiying Zhou, Aleksandr Pankov, Wayne Kong, Nadine S Jahchan, Erica L Jackson, Jessica D Sun, Melissa R Junttila, Pratik S Multani, Anneleen Daemen, Edna Chow Maneval, Pamela N Munster

Faculty, Staff and Student Publications

Purpose: In preclinical models, glucocorticoid receptor (GR) signaling drives resistance to taxane chemotherapy in multiple solid tumors via upregulation of antiapoptotic pathways. ORIC-101 is a potent and selective GR antagonist that was investigated in combination with taxane chemotherapy as an anticancer regimen preclinically and in a phase 1 clinical trial.

Patients and methods: The ability of ORIC-101 to reverse taxane resistance was assessed in cell lines and xenograft models, and a phase 1 study (NCT03928314) was conducted in patients with advanced solid tumors to determine the dose, safety, and antitumor activity of ORIC-101 with nab-paclitaxel.

Results: ORIC-101 reversed …

Image-Guided Patient-Specific Optimization Of Catheter Placement For Convection-Enhanced Nanoparticle Delivery In Recurrent Glioblastoma, Chengyue Wu, David A Hormuth, Chase D Christenson, Ryan T Woodall, Michael R A Abdelmalik, William T Phillips, Thomas J R Hughes, Andrew J Brenner, Thomas E Yankeelov

Faculty, Staff and Student Publications

Background: Proper catheter placement for convection-enhanced delivery (CED) is required to maximize tumor coverage and minimize exposure to healthy tissue. We developed an image-based model to patient-specifically optimize the catheter placement for rhenium-186 (186Re)-nanoliposomes (RNL) delivery to treat recurrent glioblastoma (rGBM).

Methods: The model consists of the 1) fluid fields generated via catheter infusion, 2) dynamic transport of RNL, and 3) transforming RNL concentration to the SPECT signal. Patient-specific tissue geometries were assigned from pre-delivery MRIs. Model parameters were personalized with either 1) individual-based calibration with longitudinal SPECT images, or 2) population-based assignment via leave-one-out cross-validation. The concordance correlation coefficient …

Ablative Margin Quantification Using Deformable Versus Rigid Image Registration In Colorectal Liver Metastasis Thermal Ablation: A Retrospective Single-Center Study, Yuan-Mao Lin, Iwan Paolucci, Jessica Albuquerque Marques Silva, Caleb S O'Connor, Jun Hong, Ketan Y Shah, Mohamed E Abdelsalam, Peiman Habibollahi, Kyle A Jones, Kristy K Brock, Bruno C Odisio

Faculty, Staff and Student Publications

Purpose: To investigate the correlation of minimal ablative margin (MAM) quantification using biomechanical deformable (DIR) versus intensity-based rigid image registration (RIR) with local outcomes following colorectal liver metastasis (CLM) thermal ablation.

Methods: This retrospective single-institution study included consecutive patients undergoing thermal ablation between May 2016 and October 2021. Patients who did not have intraprocedural pre- and post-ablation contrast-enhanced CT images for MAM quantification or follow-up period less than 1 year without residual tumor or local tumor progression (LTP) were excluded. DIR and RIR methods were used to quantify the MAM. The registration accuracy was compared using Dice similarity coefficient (DSC). …

Surgical Necrotizing Enterocolitis And Spontaneous Intestinal Perforation Lead To Severe Growth Failure In Infants, Allison L Speer, Kevin P Lally, Claudia Pedroza, Yuxin Zhang, Brenda B Poindexter, Walter J Chwals, Susan R Hintz, Gail E Besner, David K Stevenson, Robin K Ohls, William E Truog, Barbara J Stoll, Matthew A Rysavy, Abhik Das, Jon E Tyson, Martin L Blakely

Faculty, Staff and Student Publications

Objective: We aimed to determine the incidence of growth failure in infants with necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP) and whether initial laparotomy versus peritoneal drainage (PD) impacted the likelihood of growth failure.

Summary background data: Infants with surgical NEC and SIP have high mortality, and most have neurodevelopmental impairment and poor growth. Existing literature on growth outcomes for these infants is limited.

Methods: This is a preplanned secondary study of the Necrotizing Enterocolitis Surgery Trial dataset. The primary outcome was growth failure (Z-score for weight < -2.0) at 18 to 22 months. We used logistic regression, including diagnosis and treatment, as covariates. Secondary outcomes were analyzed using the Fisher exact or Pearson χ2 test for categorical variables and the Wilcoxon rank sum test or one-way ANOVA for continuous variables.

Results: Among 217 survivors, 207 infants (95%) had primary outcome data. Growth …

Quantitative Evaluation Of 90y-Pet/Ct And 90y-Spect/Ct-Based Dosimetry Following Yttrium-90 Radioembolization, Srinivas Cheenu Kappadath, Eric Courtney Henry, Benjamin P Lopez, Armeen Mahvash

Faculty, Staff and Student Publications

Background: Following yttrium-90 radioembolization (90Y-RE), 90Y-PET/CT and 90Y-SPECT/CT imaging provide the means to calculate the voxelized absorbed dose distribution. Given the widespread use of the two imaging modalities and lack of well-established standardized dosimetry protocols for 90Y-RE, there is a clinical need to systematically investigate and evaluate differences in the performance of voxel-based dosimetry between 90Y-PET/CT and 90Y-SPECT/CT.

Purpose: To quantitatively analyze and compare 90Y-PET/CT and 90Y-SPECT/CT-based dosimetry following 90Y-RE.

Methods: 90Y-PET/CT and 90Y-SPECT/CT imaging was acquired for 35 patients following 90Y-RE with TheraSphere for the treatment of unresectable hepatocellular carcinoma. Dosimetry was performed using the local deposition method with …

A Comparison Of Methods For In Vivo Activity And Absorbed Dose Quantification With Pet/Ct Following Yttrium-90 Radioembolization, Eric Courtney Henry, Armeen Mahvash, Benjamin P Lopez, Srinivas Cheenu Kappadath

Faculty, Staff and Student Publications

Background: Yttrium-90 (90Y) positron emission tomography (PET)/computed tomography (CT) imaging is increasingly being used to perform tumor (T) and normal liver (NL) voxel dosimetry after 90Y-radioembolization (90Y-RE). Yet, the accuracy of in vivo 90Y-PET/CT imaging, subject to motion blur and co-registration inaccuracies, and 90Y-PET/CT dose quantification, subject to availability of different voxel dosimetry algorithms, are not well understood.

Purpose: The purpose of this study was to investigate the accuracy of 90Y-PET/CT-based activity estimates following 90Y-RE and characterize differences between 90Y-PET/CT-based voxel dosimetry algorithms.

Methods: Thirty-five patients underwent 90Y-PET/CT imaging after 90Y-RE with TheraSphere. The net administered 90Y activity (Aadmin) was …

High-Sensitivity Troponin T, Nt-Probnp, And Cognitive Outcomes In Sprint, Devin Haney, Yuan Ma, Djhenne Dalmacy, Nicholas M Pajewski, Ihab Hajjar, James A De Lemos, Wenxin Zhang, Elsayed Z Soliman, Christie M Ballantyne, Vijay Nambi, Naveed Sattar, Anthony A Killeen, Joachim H Ix, Michael G Shlipak, Jarett D Berry, Simon B Ascher

Faculty, Staff and Students Publications

Background: Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets.

Methods: In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories.

Results: Over a median …