Digital Commons Network^™

A Multicenter, Randomized, Non-Comparative, Phase Ii Study Of Nivolumab ± Ipilimumab For Patients With Metastatic Sarcoma (Alliance A091401): Expansion Cohorts And Correlative Analyses, Nathan D Seligson, James L Chen, Austin C Goodrich, Brian A Van Tine, Jordan D Campbell, Allison L Richards, Cristina R Antonescu, David A Liebner, Mohammed M Milhem, Howard Streicher, William D Tap, Gary K Schwartz, Suzanne George, Sandra P D'Angelo

2020-Current year OA Pubs

BACKGROUND: In this open-label, randomized, non-comparative, multicenter phase II study (Alliance A091401) we report on three expansion cohorts treated with nivolumab (N) with and without ipilimumab (N+I) and provide a multi-omic correlative analysis of actionable biomarkers.

METHODS: Patients were randomized (non-comparative) to receive either N or N+I. The primary endpoint was a 6-month confirmed response rate (CRR) defined by Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included treatment-related adverse events (TRAEs), progression-free survival, and overall survival. Multi-omic correlative analyses were conducted using samples from both the primary and expansion cohorts.

RESULTS: A total of 66 patients were …

Efficacy And Safety Of Glp-1 Analog Ecnoglutide In Adults With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial, Dalong Zhu, Weimin Wang, Guoyu Tong, Guoqing Ma, Jianhua Ma, Jie Han, Xin Zhang, Yang Liu, Shenglian Gan, Hong Qin, Qing Zheng, Jing Ning, Zhiyi Zhu, Mengying Guo, Yue Bu, Yao Li, Catherine L Jones, Martijn Fenaux, Mohammed K Junaidi, Susan Xu, Hai Pan

Faculty, Staff and Student Publications

Glucagon-like peptide-1 (GLP-1) analogs are important therapeutics for type 2 diabetes and obesity. Ecnoglutide (XW003) is a novel, long-acting GLP-1 analog. We conducted a Phase 2, randomized, double-blind, placebo-controlled study enrolling 145 adults with T2DM. Participants were randomized to 0.4, 0.8, or 1.2 mg ecnoglutide or placebo as once-weekly injections for 20 weeks. The primary objective was to evaluate the efficacy of ecnoglutide, as measured by HbA1c change from baseline at Week 20. Secondary endpoints included body weight, glucose and lipid parameters, as well as safety. We show that, at end of treatment, the 0.4, 0.8, and 1.2 mg groups …

Noninvasive Multi-Cancer Detection Using Blood-Based Cell-Free Micrornas, Jason Zhang, Hallgeir Rui, Hai Hu

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Patients diagnosed with early-stage cancers have a substantially higher chance of survival than those with late-stage diseases. However, the option for early cancer screening is limited, with most cancer types lacking an effective screening tool. Here we report a miRNA-based blood test for multi-cancer early detection based on examination of serum microRNA microarray data from cancer patients and controls. First, a large multi-cancer training set that included 1,408 patients across 7 cancer types and 1,408 age- and gender-matched non-cancer controls was used to develop a 4-microRNA diagnostic model using 10-fold cross-validation. In three independent validation sets comprising a total of …

Prevalence Of Cardiometabolic Risk Factors In Women: Insights From The Houston Heartreach Study, Arjun R Raghuram, Matthew W Segar, Stephanie Coulter, Joseph G Rogers

The Texas Heart Institute Journal

BACKGROUND: Cardiovascular disease is the leading cause of death among women in the United States. Past research has highlighted the importance of the relationship between female-specific demographics and traditional risk factors. The present analysis aimed to identify the prevalence of modifiable risk factors in women attending a community cardiovascular health screening.

METHODS: Data collected between 2011 and 2019 were obtained from the Houston HeartReach Registry. Participants were classified as having or not having each of 4 traditional cardiometabolic risk factors: hypertension, diabetes, body mass index indicating overweight or obesity, and dyslipidemia. Differences in prevalence were compared using the Pearson χ2 …

Use Of Web-Based Decision Support To Improve Informed Choice For Chemoprevention: A Qualitative Analysis Of Pre-Implementation Interviews (Swog S1904), Alissa M Michel, Haeseung Yi, Jacquelyn Amenta, Nicole Collins, Anna Vaynrub, Subiksha Umakanth, Garnet Anderson, Katie Arnold, Cynthia Law, Sandhya Pruthi, Ana Sandoval-Leon, Rachel Shirley, Maria Grosse Perdekamp, Sarah Colonna, Stacy Krisher, Tari King, Lisa D Yee, Tarah J Ballinger, Christa Braun-Inglis, Debra A Mangino, Kari Wisinski, Claudia A Deyoung, Masey Ross, Justin Floyd, Andrea Kaster, Lindi Vanderwalde, Thomas J Saphner, Corrine Zarwan, Shelly Lo, Cathy Graham, Alison Conlin, Kathleen Yost, Doreen Agnese, Cheryl Jernigan, Dawn L Hershman, Marian L Neuhouser, Banu Arun, Katherine D Crew, Rita Kukafka

Faculty, Staff and Student Publications

Background: Women with high-risk breast lesions, such as atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS), have a 4- to tenfold increased risk of breast cancer compared to women with non-proliferative breast disease. Despite high-quality data supporting chemoprevention, uptake remains low. Interventions are needed to break down barriers.

Methods: The parent trial, MiCHOICE, is a cluster randomized controlled trial evaluating the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. For this pre-implementation analysis, 25 providers participated in semi-structured interviews prior to accessing decision support tools. …

Study Protocol For Writing To Heal: A Culturally Based Brief Expressive Writing Intervention For Chinese Immigrant Breast Cancer Survivors, Qian Lu, Di Lun, Lenna Dawkins-Moultin, Yisheng Li, Minxing Chen, Sharon Hermes Giordano, James W Pennebaker, Lucy Young, Carol Wang

Faculty, Staff and Student Publications

BACKGROUND: This study uses a randomized controlled trial (RCT) to test the health benefits of expressive writing that is culturally adapted for Chinese immigrant breast cancer survivors (BCSs) and to characterize how acculturation moderates the effects of expressive writing interventions.

METHODS: We will recruit Chinese immigrant BCSs (N = 240) diagnosed with stage 0-III breast cancer and within 5 years of completion of primary treatment. Recruitment will occur primarily through community-based organizations and cancer registries. Participants will be randomly assigned either to a control condition to write about neutral topics or to one of two intervention conditions, self-regulation or self-cultivation, …

Treatment Outcomes Among Patients With A Positive Candida Culture Close To Randomization Receiving Rezafungin Or Caspofungin In The Restore Study, Alex Soriano, Marin Kollef, Et Al.

2020-Current year OA Pubs

BACKGROUND: Rezafungin, a novel, once-weekly echinocandin for the treatment of candidemia and/or invasive candidiasis (IC) was noninferior to caspofungin for day 30 all-cause mortality (ACM) and day 14 global cure in the phase 3 ReSTORE trial (NCT03667690). We conducted preplanned subgroup analyses for patients with a positive culture close to randomization in ReSTORE.

METHODS: ReSTORE was a multicenter, double-blind, double-dummy, randomized trial in patients aged ≥18 years with candidemia and/or IC treated with once-weekly intravenous rezafungin (400 mg/200 mg) or once-daily intravenous caspofungin (70 mg/50 mg). This analysis comprised patients with a positive blood culture drawn between 12 hours before …

Untargeted Metabolomic Biomarker Discovery For The Detection Of Ectopic Pregnancy, Onur Turkoglu, Ayse Citil, Ceren Katar, Ismail Mert, Robert A Quinn, Ray O Bahado-Singh, Stewart F Graham

Faculty, Staff and Students Publications

Ectopic pregnancy (EP) is the leading cause of maternal morbidity and mortality in the first trimester. Using an untargeted metabolomic approach, we sought to identify putative plasma biomarkers using tandem liquid chromatography-mass spectrometry for the detection of tubal EP. This case-control study included the prospective recruitment of 50 tubal EP cases and 50 early intrauterine pregnancy controls. To avoid over-fitting, logistic regression models were developed in a randomly selected discovery group (30 cases vs. 30 controls) and validated in the test group (20 cases vs. 20 controls). In total, 585 mass spectral features were detected, of which 221 molecular features …

Intracranial Aneurysms In Sickle Cell Disease Are Associated With Hemodynamic Stress And Anemia, Yan Wang, Jared S Garland, Slim Fellah, Martin N Reis, Matthew S Parsons, Kristin P Guilliams, Melanie E Fields, Amy E Mirro, Josiah B Lewis, Chunwei Ying, Rachel A Cohen, Monica L Hulbert, Allison A King, Yasheng Chen, Jin-Moo Lee, Hongyu An, Andria L Ford

2020-Current year OA Pubs

Although hemodynamic stress plays a key role in aneurysm formation outside of sickle cell disease (SCD), its role is understudied in patients with SCD. We hypothesized that tissue-based markers of hemodynamic stress are associated with aneurysm presence in a prospective SCD cohort. Children and adults with SCD, with and without aneurysms, underwent longitudinal brain magnetic resonance imaging/magnetic resonance angiography (MRA) to assess cerebral blood flow (CBF) and oxygen extraction fraction (OEF). Baseline characteristics were recorded. In the subgroup of adults, stepwise mixed-effect logistic regression examined clinical variables, CBF, and OEF as predictors of aneurysm presence. Cumulative rates of new aneurysm …

Dek::Aff2 Fusion-Associated Squamous Cell Carcinoma: A Case Series With Literature Review On An Emerging And Challenging Entity, Sara E Amin, James S Lewis, Julia A Bridge, Jen-Fan Hang, Udit Naik, Justin A Bishop, Karan Saluja

Faculty, Staff and Student Publications

Purpose: DEK::AFF2 fusion-associated squamous cell carcinoma (DEK::AFF2 SCC), also reported in the literature as low-grade papillary sinonasal (Schneiderian) carcinoma (LGPSC), is a rare, primarily bland-appearing, but locally aggressive neoplasm. Morphologically, these tumors can closely resemble sinonasal papilloma (SP), especially on small or limited biopsy, often leading to misdiagnosis. DEK::AFF2 SCC is devoid of the underlying mutually exclusive EGFR or KRAS driver mutations of SP, suggesting it may represent a distinct unique entity.

Methods: In this study, we conducted a retrospective search of "unusual" SP reported either as atypical, dysplastic, or suspicious for malignant transformation at our institution in the last …

Examining Management And Employees' Perceptions Of Occupational Heat Exposure And The Effectiveness Of A Heat Stress Prevention Intervention On Safety And Well-Being Among Natural Gas Construction Workers: A Qualitative Field-Based Study, Muinat Abolore Idris, Christine Markham, Kristina D Mena, William B Perkison

Faculty, Staff and Student Publications

BACKGROUND: Numerous risk factors have been identified as significantly influencing outdoor workers' risk for heat stress and heat-related conditions, impacting their health, well-being, and productivity. However, the specific effects of these factors on construction workers' safety, health, and well-being remain under-researched. With climate change increasing temperatures, assessing heat stress among construction workers is imperative.

OBJECTIVE: To identify the barriers and facilitators influencing the safety of natural gas construction workers and evaluate an implemented heat stress intervention.

METHODS: In the summer of 2023, two semi-structured interviews and six focus groups were conducted with twenty-one stakeholders at a Texas natural gas construction …

Exploring The Complexity Of Systemic Sclerosis Etiology By Trio Whole Genome Sequencing, Hongzheng Dai, Shamika Ketkar, Taotao Tan, Elizabeth G Atkinson, Lindsay Burrage, Kim C Worley, Brian Christopher, Marka A Lyons, Shervin Assassi, Maureen D Mayes, Brendan Lee

Faculty, Staff and Students Publications

Systemic sclerosis (SSc) is a heterogeneous rare autoimmune fibrosing disorder affecting connective tissue. The etiology of systemic sclerosis is largely unknown and many genes have been suggested as susceptibility loci of modest impact by genome-wide association study (GWAS). Multiple factors can contribute to the pathological process of the disease, which makes it more difficult to identify possible disease-causing genetic alterations. In this study, we have applied whole genome sequencing (WGS) in 101 indexed family trios, supplemented with transcriptome sequencing on cultured fibroblast cells of four patients and five family controls where available. Single nucleotide variants (SNVs) and copy number variants …

Axatilimab In Recurrent Or Refractory Chronic Graft-Versus-Host Disease, Daniel Wolff, Iskra Pusic, Et Al.

2020-Current year OA Pubs

BACKGROUND: Colony-stimulating factor 1 receptor (CSF1R)-dependent monocytes and macrophages are key mediators of chronic graft-versus-host disease (GVHD), a major long-term complication of allogeneic hematopoietic stem-cell transplantation. The CSF1R-blocking antibody axatilimab has shown promising clinical activity in chronic GVHD.

METHODS: In this phase 2, multinational, pivotal, randomized study, we evaluated axatilimab at three different doses in patients with recurrent or refractory chronic GVHD. Patients were randomly assigned to receive axatilimab, administered intravenously, at a dose of 0.3 mg per kilogram of body weight every 2 weeks (0.3-mg dose group), at a dose of 1 mg per kilogram every 2 weeks (1-mg …

Generalized Encoding Of The Relative Subjective Value Of Cognitive Effort In The Dorsal Acc, Jennifer L Crawford, Rachel E Brough, Sarah A Eisenstein, Jonathan E Peelle, Todd S Braver

2020-Current year OA Pubs

Making choices about whether and when to engage cognitive effort are a common feature of everyday experience, with important consequences for academic, career, and health outcomes. Yet, despite their hypothesized importance, very little is understood about the underlying mechanisms that support this form of human cost-benefit decision-making. To investigate these mechanisms, we used the Cognitive Effort Discounting Paradigm (Cog-ED) during fMRI scanning to precisely quantify the neural encoding of varying cognitive effort demands relative to reward outcomes, within two distinct cognitive domains (working memory, speech comprehension). The findings provide strong evidence that the dorsal anterior cingulate cortex (dACC) plays a …

Design Of A Tool Capable Of Assessing Environmental Sociocultural Physical Factors Influencing Women's Decisions On When And Where To Toilet Within Real-World Settings: Protocol For The Build And Usability Testing Of A Mobile App For Use By Community-Dwelling Women, Janis M Miller, Jean F Wyman, Lawrence An, Haitao Chu, Cynthia S Fok, Missy Lavender, Cora Elizabeth Lewis, Alayne D Markland, Leslie M Rickey, Ying Sheng, Siobhan Sutcliffe, Lisa Kane Low, Elizabeth R Mueller

2020-Current year OA Pubs

BACKGROUND: Although surveys and apps are available for women to report urination and bladder symptoms, they do not include their decisions regarding toileting. Real-world factors can interfere with toileting decisions, which may then influence bladder health. This premise lacks data per want of a robust data collection tool.

OBJECTIVE: The Prevention of Lower Urinary Tract Symptoms (PLUS) research consortium engaged a transdisciplinary team to build and test WhereIGo, a mobile data collection app for Android and iOS. The design goal was a comprehensive reporting system for capturing environmental, sociocultural, and physical factors that influence women's decisions for toileting. Aims include …

Impact Of An Online Decision Support Tool For Ductal Carcinoma In Situ (Dcis) Using A Pre-Post Design (Aft-25), Elissa Ozanne, Kellyn Maves, Angela Tramontano, Thomas Lynch, Alastair Thompson, Ann Partridge, Elizabeth Frank, Deborah Collyar, Desiree Basila, Donna Pinto, Terry Hyslop, Marc Ryser, Shoshana Rosenberg, E. Shelley Hwang, Rinaa Punglia

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: The heterogeneous biology of ductal carcinoma in situ (DCIS), as well as the variable outcomes, in the setting of numerous treatment options have led to prognostic uncertainty. Consequently, making treatment decisions is challenging and necessitates involved communication between patient and provider about the risks and benefits. We developed and investigated an interactive decision support tool (DST) designed to improve communication of treatment options and related long-term risks for individuals diagnosed with DCIS.

FINDINGS: The DST was developed for use by individuals aged > 40 years with DCIS and is based on a disease simulation model that integrates empirical data and …

Association Between Non-Injection Drug Use And Hepatitis C Infection Among Hiv-Negative Men Who Have Sex With Men, Jing Zhao, Charles Green, Christine Markham, Kayo Fujimoto, Alan G Nyitray, Lu-Yu Hwang

Faculty, Staff and Student Publications

Background: Prior research predominantly examined the association between HIV-positive men who have sex with men (MSM) or those using injection drugs and hepatitis C virus (HCV) infection. However, limited attention has been given to understanding the association among HIV-negative MSM who do not inject drugs. This gap leaves apportion of the population unexamined, potentially overlooking important factor that may contribute to the transmission and prevalence of HCV. This study aims to investigate the relationship between non-injection drug use and HCV infection in this population.

Methods: In this cross-sectional study, we analyzed data on 118 MSM who reported use of non-injection …

Perfusion-Weighted Imaging With Dynamic Contrast Enhancement (Pwi/Dce) Morphologic, Qualitative, Semiquantitative, And Radiomics Features Predicting Undifferentiated Pleomorphic Sarcoma (Ups) Treatment Response, R F Valenzuela, E Duran-Sierra, M Canjirathinkal, B Amini, K E Torres, R S Benjamin, J Ma, W L Wang, K P Hwang, R J Stafford, C Wu, A M Zarzour, A J Bishop, S Lo, J E Madewell, R Kumar, W A Murphy, C M Costelloe

Faculty, Staff and Student Publications

Undifferentiated pleomorphic sarcoma (UPS) is the largest subgroup of soft tissue sarcomas. This study determined the value of perfusion-weighted imaging with dynamic-contrast-enhancement (PWI/DCE) morphologic, qualitative, and semiquantitative features for predicting UPS pathology-assessed treatment effect (PATE). This retrospective study included 33 surgically excised extremity UPS patients with pre-surgical MRI. Volumetric tumor segmentation from PWI/DCE was obtained at Baseline (BL), Post-Chemotherapy (PC), and Post-Radiation Therapy (PRT). The surgical specimens' PATE separated cases into Responders (R) (≥ 90%, 16 patients), Partial-Responders (PR) (89 - 31%, 10 patients), and Non-Responders (NR) (≤ 30%, seven patients). Seven semiquantitative kinetic parameters and maps were extracted from …

Gut Phageome In Mexican Americans: A Population At High Risk For Metabolic Dysfunction-Associated Steatotic Liver Disease And Diabetes, Suet-Ying Kwan, Caroline M Sabotta, Lorenzo R Cruz, Matthew C Wong, Nadim J Ajami, Joseph B Mccormick, Susan P Fisher-Hoch, Laura Beretta

Faculty, Staff and Student Publications

Mexican Americans are disproportionally affected by metabolic dysfunction-associated steatotic liver disease (MASLD), which often co-occurs with diabetes. Despite extensive evidence on the causative role of the gut microbiome in MASLD, studies determining the involvement of the gut phageome are scarce. In this cross-sectional study, we characterized the gut phageome in Mexican Americans of South Texas by stool shotgun metagenomic sequencing of 340 subjects, concurrently screened for liver steatosis by transient elastography. Inter-individual variations in the phageome were associated with gender, country of birth, diabetes, and liver steatosis. The phage signatures for diabetes and liver steatosis were subsequently determined. Enrichment of …

A Qualitative Exploration Of Disseminating Research Findings Among Public Health Researchers In China, Yiluan Hu, Xuejun Yin, Yachen Wang, Enying Gong, Xin Xin, Jing Liu, Xia Liu, Ruitai Shao, Juan Zhang, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Research dissemination is essential to accelerate the translating of evidence into practice. Little is known about dissemination among Chinese public health researchers. This study aimed to explore the understanding and practices of disseminating research findings and to identify barriers and facilitators that influence dissemination activities to non-research audiences.

METHODS: This study deployed an exploratory qualitative design with purposive and snowball sampling. One focus group with 5 participants and 12 in-depth interviews were conducted with participants working in diverse fields from universities (n = 10), the National Chinese Center for Disease Control and Prevention (n = 4), the Chinese National …

Association Of Chronic Kidney Disease With Postoperative Outcomes: A National Surgical Quality Improvement Program (Nsqip) Multi-Specialty Surgical Cohort Analysis, Carlos Riveros, Sanjana Ranganathan, Yash B. Shah, Emily Huang, Jiaqiong Xu, Enshuo Hsu, Michael Geng, Siqi Hu, Zachary Melchiode, Brian J. Miles, Nestor Esnaola, Zachary Klaassen, Angela Jerath, Christopher J.D. Wallis, Raj Satkunasivam

Student Papers, Posters & Projects

BACKGROUND: Chronic kidney disease (CKD) is associated with higher incidence of major surgery. No studies have evaluated the association between preoperative kidney function and postoperative outcomes across a wide spectrum of procedures. We aimed to evaluate the association between CKD and 30-day postoperative outcomes across surgical specialties.

METHODS: We selected adult patients undergoing surgery across eight specialties. The primary study endpoint was major complications, defined as death, unplanned reoperation, cardiac complication, or stroke within 30 days following surgery. Secondary outcomes included Clavien-Dindo high-grade complications, as well as cardiac, pulmonary, infectious, and thromboembolic complications. Multivariable regression was performed to evaluate the …

The Impact Of Hypertension On Clinical Outcomes In Moyamoya Disease: A Multicenter, Propensity Score-Matched Analysis, Basel Musmar, Joanna Roy, Hammam Abdalrazeq, Elias Atallah, Kareem El Naamani, Ching-Jen Chen, Roland Jabre, Hassan Saad, Jonathan Grossberg, Adam Dmytriw, Aman Patel, Mirhojjat Khorasanizadeh, Christopher Ogilvy, Ajith Thomas, Andre Monteiro, Adnan Siddiqui, Gustavo Cortez, Ricardo Hanel, Guilherme Porto, Alejandro Spiotta, Anthony Piscopo, David Hasan, Mohammad Ghorbani, Joshua Weinberg, Shahid Nimjee, Kimon Bekelis, Mohamed Salem, Jan-Karl Burkhardt, Akli Zetchi, Charles Matouk, Brian Howard, Rosalind Lai, Rose Du, Rawad Abbas, Georgios Sioutas, Abdelaziz Amllay, Alfredo Munoz, Nabeel Herial, Stavropoula Tjoumakaris, Michael Gooch, Robert Rosenwasswer, Pascal Jabbour

Department of Neurosurgery Faculty Papers

BACKGROUND: Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive steno-occlusive changes in the internal carotid arteries, leading to an abnormal vascular network. Hypertension is prevalent among MMD patients, raising concerns about its impact on disease outcomes. This study aims to compare the clinical characteristics and outcomes of MMD patients with and without hypertension.

METHODS: We conducted a multicenter, retrospective study involving 598 MMD patients who underwent surgical revascularization across 13 academic institutions in North America. Patients were categorized into hypertensive (n=292) and non-hypertensive (n=306) cohorts. Propensity score matching (PSM) was performed to adjust for baseline differences.

RESULTS: …

Bacteroides Ovatus Alleviates Dysbiotic Microbiota-Induced Graft-Versus-Host Disease, Eiko Hayase, Tomo Hayase, Akash Mukherjee, Stuart C Stinson, Mohamed A Jamal, Miriam R Ortega, Christopher A Sanchez, Saira S Ahmed, Jennifer L Karmouch, Chia-Chi Chang, Ivonne I Flores, Lauren K Mcdaniel, Alexandria N Brown, Rawan K El-Himri, Valerie A Chapa, Lin Tan, Bao Q Tran, Yao Xiao, Christopher Fan, Dung Pham, Taylor M Halsey, Yimei Jin, Wen-Bin Tsai, Rishika Prasad, Israel K Glover, Altai Enkhbayar, Aqsa Mohammed, Maren Schmiester, Katherine Y King, Robert A Britton, Pavan Reddy, Matthew C Wong, Nadim J Ajami, Jennifer A Wargo, Samuel Shelburne, Pablo C Okhuysen, Chen Liu, Stephanie W Fowler, Margaret E Conner, Zoe Katsamakis, Natalie Smith, Marina Burgos Da Silva, Doris M Ponce, Jonathan U Peled, Marcel R M Van Den Brink, Christine B Peterson, Gabriela Rondon, Jeffrey J Molldrem, Richard E Champlin, Elizabeth J Shpall, Philip L Lorenzi, Rohtesh S Mehta, Eric C Martens, Amin M Alousi, Robert R Jenq

Faculty, Staff and Student Publications

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects …

Diagnostic Utility Of Brain Mri Volumetry In Comparing Traumatic Brain Injury, Alzheimer Disease And Behavioral Variant Frontotemporal Dementia, Cyrus A Raji, Somayeh Meysami, Verna R Porter, David A Merrill, Mario F Mendez

2020-Current year OA Pubs

BACKGROUND: Brain MRI with volumetric quantification, MRI volumetry, can improve diagnostic delineation of patients with neurocognitive disorders by identifying brain atrophy that may not be evident on visual assessments.

OBJECTIVE: To investigate diagnostic utility of MRI volumetry in traumatic brain injury (TBI), early-onset Alzheimer disease (EOAD), late-onset Alzheimer disease, and behavioral variant frontotemporal dementia (bvFTD).

METHOD: We utilized 137 participants of TBI (n = 40), EOAD (n = 45), LOAD (n = 32), and bvFTD (n = 20). Participants had 3D T1 brain MRI imaging amendable to MRI volumetry. Scan volumes were analyzed with Neuroreader. One-way ANOVA compared brain volumes …

Final Outcomes From A Phase 2 Trial Of Posoleucel In Allogeneic Hematopoietic Cell Transplant Recipients., Sanjeet S. Dadwal, Rajat Bansal, Michael W. Schuster, Jean A. Yared, Douglas Myers, Michelle Matzko, Sama Adnan, David Mcneel, Julie Ma, Sarah A. Gilmore, Spyridoula Vasileiou, Ann M. Leen, Joshua A. Hill, Jo-Anne H. Young

Manuscripts, Articles, Book Chapters and Other Papers

Allogeneic hematopoietic cell transplantation (allo-HCT) recipients are susceptible to viral infections. We conducted a phase 2 trial evaluating the safety and rate of clinically significant infections (CSIs; viremia requiring treatment or end-organ disease) after infusion of posoleucel, a partially HLA-matched, allogeneic, off-the-shelf, multivirus-specific T-cell investigational product for preventing CSIs with adenovirus, BK virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus-6, or JC virus. This open-label trial enrolled allo-HCT recipients at high risk based on receiving grafts from umbilical cord blood, haploidentical, mismatched, or matched unrelated donors; post-HCT lymphocytes of <180/mm3; or use of T-cell depletion. Posoleucel dosing was initiated within 15 to 49 days of allo-HCT and subsequently every 14 days for up to 7 doses. The primary end point was the number of CSIs due to the 6 target viruses by week 14. Of the 26 patients enrolled, only 3 (12%) had a CSI by week 14, each with a single target virus. In vivo expansion of functional virus-specific T cells detected via interferon-γ enzyme-linked immunosorbent spot assay was associated with viral control. Persistence of posoleucel-derived T-cell clones for up to 14 weeks after the last infusion was confirmed by T-cell-receptor deep sequencing. Five patients (19%) had acute graft-versus-host disease grade 2 to 4. No patient experienced cytokine release syndrome. All 6 deaths were due to relapse or disease progression. allo-HCT recipients at high risk who received posoleucel had low rates of CSIs from 6 targeted viruses. Repeat posoleucel dosing was generally safe and well tolerated and associated with functional immune reconstitution. This trial was registered at www.ClinicalTrials.gov as #NCT04693637.

Immunoactive Signatures Of Circulating Trna- And Rrna-Derived Rnas In Chronic Obstructive Pulmonary Disease, Megumi Shigematsu, Takuya Kawamura, Deepak Deshpande, Yohei Kirino

Computational Medicine Center Faculty Papers

Chronic obstructive pulmonary disease (COPD) is the most prevalent lung disease, and macrophages play a central role in the inflammatory response in COPD. We here report a comprehensive characterization of circulating short non-coding RNAs (sncRNAs) in plasma from patients with COPD. While circulating sncRNAs are increasingly recognized for their regulatory roles and biomarker potential in various diseases, the conventional RNA sequencing (RNA-seq) method cannot fully capture these circulating sncRNAs due to their heterogeneous terminal structures. By pre-treating the plasma RNAs with T4 polynucleotide kinase, which converts all RNAs to those with RNA-seq susceptible ends (5′-phosphate and 3′-hydroxyl), we comprehensively sequenced …

Variants In Lrrc7 Lead To Intellectual Disability, Autism, Aggression And Abnormal Eating Behaviors, Jana Willim, Weimin Yuan, Anika Lindsey, Omar Itani, Gary A Silverman, Stephen C Pak, Tim Schedl, Et Al.

2020-Current year OA Pubs

Members of the leucine rich repeat (LRR) and PDZ domain (LAP) protein family are essential for animal development and histogenesis. Densin-180, encoded by LRRC7, is the only LAP protein selectively expressed in neurons. Densin-180 is a postsynaptic scaffold at glutamatergic synapses, linking cytoskeletal elements with signalling proteins such as the α-subunit of Ca

Final Outcomes From A Phase 2 Trial Of Posoleucel In Allogeneic Hematopoietic Cell Transplant Recipients, Sanjeet S Dadwal, Rajat Bansal, Michael W Schuster, Jean A Yared, Gary Douglas Myers, Michelle Matzko, Sama Adnan, David Mcneel, Julie Ma, Sarah A Gilmore, Spyridoula Vasileiou, Ann M Leen, Joshua A Hill, Jo-Anne H Young

Faculty, Staff and Students Publications

Allogeneic hematopoietic cell transplantation (allo-HCT) recipients are susceptible to viral infections. We conducted a phase 2 trial evaluating the safety and rate of clinically significant infections (CSIs; viremia requiring treatment or end-organ disease) after infusion of posoleucel, a partially HLA-matched, allogeneic, off-the-shelf, multivirus-specific T-cell investigational product for preventing CSIs with adenovirus, BK virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus-6, or JC virus. This open-label trial enrolled allo-HCT recipients at high risk based on receiving grafts from umbilical cord blood, haploidentical, mismatched, or matched unrelated donors; post-HCT lymphocytes of < 180/mm3; or use of T-cell depletion. Posoleucel dosing was initiated within 15 to 49 days of allo-HCT and subsequently every 14 days for up to 7 doses. The primary end point was the number of CSIs due to the 6 target viruses by week 14. Of the 26 patients enrolled, only 3 (12%) had a CSI by week 14, each with a single target virus. In vivo expansion of functional virus-specific T cells detected via interferon-γ enzyme-linked immunosorbent spot assay was associated with viral control. Persistence of posoleucel-derived T-cell clones for up to 14 weeks after the last infusion was confirmed by T-cell–receptor deep sequencing. Five patients (19%) had acute graft-versus-host disease grade 2 to 4. No patient experienced cytokine release syndrome. All 6 deaths were due to relapse or disease progression. allo-HCT recipients at high risk who received posoleucel had low rates of CSIs from 6 targeted viruses. Repeat posoleucel dosing was generally safe and well tolerated and associated with functional immune reconstitution.

Lessons Learned From Developing Dashboards To Support Decision-Making For Community Opioid Response By Community Stakeholders: Mixed Methods And Multisite Study., Naleef Fareed, Ramona G. Olvera, Yiting Wang, Michael Hayes, Elizabeth Liz Larimore, Peter Balvanz, Ronald Langley, Corinna A. Noel, Peter J. Rock, Daniel Redmond, Jessica Neufeld, Sarah Kosakowski, Daniel R. Harris, Marc Larochelle, Timothy R. Huerta, Lashawn Glasgow, Emmanuel Oga, Jennifer Villani, Elwin Wu

Center on Drug and Alcohol Research Faculty Publications

BACKGROUND: Data dashboards are published tools that present visualizations; they are increasingly used to display data about behavioral health, social determinants of health, and chronic and infectious disease risks to inform or support public health endeavors. Dashboards can be an evidence-based approach used by communities to influence decision-making in health care for specific populations. Despite widespread use, evidence on how to best design and use dashboards in the public health realm is limited. There is also a notable dearth of studies that examine and document the complexity and heterogeneity of dashboards in community settings.

OBJECTIVE: Community stakeholders engaged in the …

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 …