Digital Commons Network^™

Oral Sebetralstat For On-Demand Treatment Of Hereditary Angioedema Attacks, Marc A Riedl, H James Wedner, Et Al.

2020-Current year OA Pubs

BACKGROUND: Approved on-demand treatments for hereditary angioedema attacks need to be administered parenterally, a route of administration that is associated with delays in treatment or withholding of therapy.

METHODS: In this phase 3, double-blind, three-way crossover trial, we randomly assigned participants at least 12 years of age with type 1 or type 2 hereditary angioedema to take up to two oral doses of sebetralstat (300 mg or 600 mg) or placebo for an angioedema attack. The primary end point, assessed in a time-to-event analysis, was the beginning of symptom relief, defined as a rating of "a little better" on the …

Hur Controls Glutaminase Rna Metabolism, Douglas Adamoski, Larissa M Dos Reis, Ana Carolina Paschoalini Mafra, Felipe Corrêa-Da-Silva, Pedro Manoel Mendes De Moraes-Vieira, Ioana Berindan-Neagoe, George A Calin, Sandra Martha Gomes Dias

Faculty, Staff and Student Publications

Glutaminase (GLS) is directly related to cell growth and tumor progression, making it a target for cancer treatment. The RNA-binding protein HuR (encoded by the ELAVL1 gene) influences mRNA stability and alternative splicing. Overexpression of ELAVL1 is common in several cancers, including breast cancer. Here we show that HuR regulates GLS mRNA alternative splicing and isoform translation/stability in breast cancer. Elevated ELAVL1 expression correlates with high levels of the glutaminase isoforms C (GAC) and kidney-type (KGA), which are associated with poor patient prognosis. Knocking down ELAVL1 reduces KGA and increases GAC levels, enhances glutamine anaplerosis into the TCA cycle, and …

Urban-Rural Disparities In Food Insecurity And Weight Status Among Children In The United States, Jayna M Dave, Tzuan A Chen, Alexandra N Castro, Mamie A White, Elizabeth A Onugha, Sloane Zimmerman, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Place of residence (urban versus rural) is a contextual determinant of health that has received less attention in the food insecurity literature. The purpose of this study was to assess the urban–rural disparity in the prevalence of food insecurity and weight status among US children. Using data from the National Health and Nutrition Examination Survey (NHANES) 2013–2016 with three age groups of children (2–5, 6–11, and 12–17 years old), the associations of weight status and child and household food security status by urban–rural residence were examined using Rao–Scott Chi-square tests. Statistical significance was set at p < 0.05. Children living in urban areas were significantly more likely to experience household food insecurity (29.15%) compared to their rural counterparts (19.10%), among those aged 6–11 years. The associations between children’s weight status and child and household food security status were significant for children living in urban areas overall and different age groups but not for children living in rural areas. These trends were more pronounced in older age groups. Given the link between food insecurity and higher obesity rates, particularly among urban children, this study highlights the importance of incorporating food security interventions into future obesity prevention programs.

Genomic Determinants Of Response And Resistance To Inotuzumab Ozogamicin In B-Cell All, Yaqi Zhao, Nicholas J Short, Hagop M Kantarjian, Ti-Cheng Chang, Pankaj S Ghate, Chunxu Qu, Walid Macaron, Nitin Jain, Beenu Thakral, Aaron H Phillips, Joseph Khoury, Guillermo Garcia-Manero, Wenchao Zhang, Yiping Fan, Hui Yang, Rebecca S Garris, Lewis F Nasr, Richard W Kriwacki, Kathryn G Roberts, Marina Konopleva, Elias J Jabbour, Charles G Mullighan

Faculty, Staff and Student Publications

Inotuzumab ozogamicin (InO) is an antibody-drug conjugate that delivers calicheamicin to CD22-expressing cells. In a retrospective cohort of InO-treated patients with B-cell acute lymphoblastic leukemia, we sought to understand the genomic determinants of the response and resistance to InO. Pre- and post-InO-treated patient samples were analyzed by whole genome, exome, and/or transcriptome sequencing. Acquired CD22 mutations were observed in 11% (3/27) of post-InO-relapsed tumor samples, but not in refractory samples (0/16). There were multiple CD22 mutations per sample and the mechanisms of CD22 escape included epitope loss (protein truncation and destabilization) and epitope alteration. Two CD22 mutant cases were post-InO …

Caregiver Recruitment Strategies For Interventions Designed To Optimize Transitions From Hospital To Home: Lessons From A Randomized Trial, Allison M Gustavson, Molly J Horstman, Jodie A Cogswell, Diane E Holland, Catherine E Vanderboom, Jay Mandrekar, William S Harmsen, Brystana G Kaufman, Cory Ingram, Joan M Griffin

Faculty, Staff and Students Publications

Challenges to recruitment of family caregivers exist and are amplified when consent must occur in the context of chaotic healthcare circumstances, such as the transition from hospital to home. The onset of the COVID-19 pandemic during our randomized controlled trial provided an opportunity for a natural experiment exploring and examining different consent processes for caregiver recruitment. The purpose of this publication is to describe different recruitment processes (in-person versus virtual) and compare diversity in recruitment rates in the context of a care recipient's hospitalization. We found rates of family caregiver recruitment for in-person versus virtual were 28% and 23%, respectively …

Task And Stimulus Coding In The Multiple-Demand Network, Sneha Shashidhara, Moataz Assem, Matthew F Glasser, John Duncan

2020-Current year OA Pubs

In the human brain, a multiple-demand (MD) network plays a key role in cognitive control, with core components in lateral frontal, dorsomedial frontal and lateral parietal cortex, and multivariate activity patterns that discriminate the contents of many cognitive activities. In prefrontal cortex of the behaving monkey, different cognitive operations are associated with very different patterns of neural activity, while details of a particular stimulus are encoded as small variations on these basic patterns (Sigala et al, 2008). Here, using the advanced fMRI methods of the Human Connectome Project and their 360-region cortical parcellation, we searched for a similar result in …

O-Glcnacylation Of Mitf Regulates Its Activity And Cdk4/6 Inhibitor Resistance In Breast Cancer, Yi Zhang, Shuyan Zhou, Yan Kai, Ya-Qin Zhang, Changmin Peng, Zhuqing Li, Muhammad Jameel Mughal, Belmar Julie, Xiaoyan Zheng, Junfeng Ma, Cynthia X Ma, Min Shen, Matthew D Hall, Shunqiang Li, Wenge Zhu

2020-Current year OA Pubs

Cyclin-dependent kinases 4 and 6 (CDK4/6) play a pivotal role in cell cycle and cancer development. Targeting CDK4/6 has demonstrated promising effects against breast cancer. However, resistance to CDK4/6 inhibitors (CDK4/6i), such as palbociclib, remains a substantial challenge in clinical settings. Using high-throughput combinatorial drug screening and genomic sequencing, we find that the microphthalmia-associated transcription factor (MITF) is activated via O-GlcNAcylation by O-GlcNAc transferase (OGT) in palbociclib-resistant breast cancer cells and tumors. Mechanistically, O-GlcNAcylation of MITF at Serine 49 enhances its interaction with importin α/β, thus promoting its translocation to nuclei, where it suppresses palbociclib-induced senescence. Inhibition of MITF or …

Ledoxy-Sl: A Placebo-Controlled, Double-Blind, Randomized, 24-Month Trial Of Six Weeks Of Daily Doxycycline Plus Hygiene-Based Essential Care For Reducing Progression Of Filarial Lymphedema In Sri Lanka, Thishan Channa Yahathugoda, Nirmitha Lalindi De Silva, Janaka Ruben, Sharmini Gunawardena, Mirani Vasanthamala Weerasooriya, John Horton, Philip Budge, Eric Ottesen, Sarah Mary Sullivan, Mariana Stephens, John Shen, Ute Klarmann-Schulz, Achim Hoerauf, Joseph Patrick Shott, Charles Mackenzie

2020-Current year OA Pubs

Morbidity management of filarial lymphedema remains a challenge even during the post-lymphatic filariasis elimination era in Sri Lanka despite provision of the predominantly hygiene-based WHO Essential Package of Care. Because prior studies have suggested that 6 weeks of doxycycline may reduce progression of limb lymphedema, we conducted a randomized, placebo-controlled, superiority study to evaluate this possibility in Sri Lanka. Patients aged 14 to 65 years with lymphedema in one or both legs received either 200 mg of doxycycline daily for 6 weeks or matching placebo. The primary efficacy endpoint was improvement or lack of progression in lymphedema stage at 24 …

Validating A Curvature-Based Marker Of Cervical Carotid Tortuosity For Risk Assessment In Heritable Aortopathies, Jin Vivian Lee, Anna L Huguenard, Ralph G Dacey, Alan C Braverman, Joshua W Osbun

2020-Current year OA Pubs

BACKGROUND: Cervical arterial tortuosity is associated with adverse outcomes in Loeys-Dietz syndrome and other heritable aortopathies.

METHODS AND RESULTS: A method to assess tortuosity based on curvature of the vessel centerline in 3-dimensional space was developed. We measured cervical carotid tortuosity in 65 patients with Loeys-Dietz syndrome from baseline computed tomography angiogram/magnetic resonance angiogram and all serial images during follow-up. Relations between baseline carotid tortuosity, age, aortic root diameter, and its change over time were compared. Patients with unoperated aortic roots were assessed for clinical end point (type A aortic dissection or aortic root surgery during 4 years of follow-up). …

Pathogenic Variants In Autism Gene Katnal2 Cause Hydrocephalus And Disrupt Neuronal Connectivity By Impairing Ciliary Microtubule Dynamics, Tyrone Despenza, Shujuan Zhao, Sheng Chih Jin, Et Al.

2020-Current year OA Pubs

Enlargement of the cerebrospinal fluid (CSF)-filled brain ventricles (cerebral ventriculomegaly), the cardinal feature of congenital hydrocephalus (CH), is increasingly recognized among patients with autism spectrum disorders (ASD).

Baseline Levels And Longitudinal Changes In Plasma Aβ42/40 Among Black And White Individuals, Chengjie Xiong, Jingqin Luo, Rachel L Henson, Tammie L S Benzinger, Quoc Bui, Folasade Agboola, Elizabeth Grant, Emily N Gremminger, Krista L Moulder, Ganesh Babulal, Carlos Cruchaga, David M Holtzman, Randall J Bateman, John C Morris, Suzanne E Schindler, Et Al.

2020-Current year OA Pubs

Blood-based biomarkers of Alzheimer disease (AD) may facilitate testing of historically under-represented groups. The Study of Race to Understand Alzheimer Biomarkers (SORTOUT-AB) is a multi-center longitudinal study to compare AD biomarkers in participants who identify their race as either Black or white. Plasma samples from 324 Black and 1,547 white participants underwent analysis with C

Post-Immunotherapy Ctla-4 Ig Treatment Improves Antitumor Efficacy, Stephen Mok, Didem Ağaç Çobanoğlu, Huey Liu, James J Mancuso, James P Allison

Faculty, Staff and Student Publications

Immune checkpoint therapies (ICT) improve overall survival of patients with cancer but may cause immune-related adverse events (irAEs) such as myocarditis. Cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA-4 Ig), an inhibitor of T cell costimulation through CD28, reverses irAEs in animal models. However, concerns exist about potentially compromising antitumor response of ICT. In mouse tumor models, we administered CTLA-4 Ig 1) concomitantly with ICT or 2) after ICT completion. Concomitant treatment reduced antitumor efficacy, while post-ICT administration improved efficacy without affecting frequency and function of CD8 T cells. The improved response was independent of the ICT used, whether …

Celecoxib-Tramadol Co-Crystal In Patients With Moderate-To-Severe Pain Following Bunionectomy With Osteotomy: Secondary Analyses By Baseline Pain Intensity And Use Of Rescue Medication Of A Phase 3, Randomized, Double-Blind, Factorial, Active- And Placebo-Controlled Trial, Eugene R. Viscusi, Oscar De Leon-Casasola, Jesús Cebrecos, Adam Jacobs, Adelaida Morte, Esther Ortiz, Mariano Sust, Anna Vaqué, Ira Gottlieb, Stephen Daniels, Derek Muse, Michael E. Kuss, Sebastián Videla, Neus Gascón, Carlos Plata-Salamán

Department of Anesthesiology Faculty Papers

BACKGROUND: In the randomized, phase 3, SUSA-301 trial, celecoxib-tramadol co-crystal (CTC) provided significantly greater analgesia compared with celecoxib, tramadol, or placebo in adults with acute, moderate-to-severe, postoperative pain. This post hoc, secondary analysis further evaluated the use of rescue medication and the incidence of treatment-emergent adverse events (TEAEs).

METHODS: Patients (N = 637) were randomized 2:2:2:1 to receive oral CTC 200 mg twice daily (BID; n = 184), tramadol 50 mg four times daily (QID; n = 183), celecoxib 100 mg BID (n = 181), or placebo QID (n = 89). Post hoc analyses were conducted on the use of …

Loss Of The Dna Repair Gene Rnase H2 Identifies A Unique Subset Of Ddr-Deficient Leiomyosarcomas, Michael S Nakazawa, Ian M Silverman, Victoria Rimkunas, Artur Veloso, Dominik Glodzik, Adrienne Johnson, Toshiro K Ohsumi, Shreyaskumar R Patel, Anthony P Conley, Christina L Roland, Pamela T Soliman, Hannah C Beird, Chia-Chin Wu, Davis R Ingram, Rossana Lazcano, Dawon Song, Khalida M Wani, Alexander J Lazar, Timothy A Yap, Wei-Lien Wang, J Andrew Livingston

Faculty, Staff and Student Publications

Targeting the DNA damage response (DDR) pathway is an emerging therapeutic approach for leiomyosarcoma (LMS), and loss of RNase H2, a DDR pathway member, is a potentially actionable alteration for DDR-targeted treatments. Therefore, we designed a protein- and genomic-based RNase H2 screening assay to determine its prevalence and prognostic significance. Using a selective RNase H2 antibody on a pan-tumor microarray (TMA), RNase H2 loss was more common in LMS (11.5%, 9/78) than across all tumors (3.8%, 32/843). In a separate LMS cohort, RNase H2 deficiency was confirmed in uterine LMS (U-LMS, 21%, 23/108) and soft-tissue LMS (ST-LMS; 30%, 39/102). In …

Home Blood Pressure Telemonitoring And Nurse Case Management In Black And Hispanic Patients With Stroke: A Randomized Clinical Trial, Gbenga Ogedegbe, Jeanne A Teresi, Stephen K Williams, Adebayo Ogunlade, Chigozirim Izeogu, Joseph P Eimicke, Jian Kong, Stephanie A Silver, Olajide Williams, Helen Valsamis, Susan Law, Steven R Levine, Salina P Waddy, Tanya M Spruill

Faculty, Staff and Student Publications

Importance: Black and Hispanic patients have high rates of recurrent stroke and uncontrolled hypertension in the US. The effectiveness of home blood pressure telemonitoring (HBPTM) and telephonic nurse case management (NCM) among low-income Black and Hispanic patients with stroke is unknown.

Objective: To determine whether NCM plus HBPTM results in greater systolic blood pressure (SBP) reduction at 12 months and lower rate of stroke recurrence at 24 months than HBPTM alone among Black and Hispanic stroke survivors with uncontrolled hypertension.

Design, setting, and participants: Practice-based, multicenter, randomized clinical trial in 8 stroke centers and ambulatory practices in New York City. …

Experiences From Patients In Mental Healthcare Accessing Their Electronic Health Records: Results From A Cross-National Survey In Estonia, Finland, Norway, And Sweden, A. J. Fagerlund, Annika Bärkås, A. Kharko, C. R. Blease, J. Hagström, I. Huvila, I. Hörhammer, B. Kane, E. Kristiansen, S. Kujala, J. Moll, H. Rexhepi, I. Scandurra, S. Simola, H. Soone, B. Wang, R. M. Åhlfeldt, M. Hägglund, M. A. Johansen

School of Psychology

Background: Patients’ online record access (ORA) enables patients to read and use their health data through online digital solutions. One such solution, patient-accessible electronic health records (PAEHRs) have been implemented in Estonia, Finland, Norway, and Sweden. While accumulated research has pointed to many potential benefits of ORA, its application in mental healthcare (MHC) continues to be contested. The present study aimed to describe MHC users’ overall experiences with national PAEHR services. Methods: The study analysed the MHC-part of the NORDeHEALTH 2022 Patient Survey, a large-scale multi-country survey. The survey consisted of 45 questions, including demographic variables and questions related to …

Individual And Joint Associations Of High-Sensitivity Troponin I And High-Sensitivity Troponin T With Cardiac Phenotypes And Outcomes In The General Population: An Analysis From The Dallas Heart Study, Rebecca Vigen, Colby Ayers, Jarett Berry, Anand Rohatgi, Vijay Nambi, Christie M Ballantyne, Torbjorn Omland, Christopher R De Filippi, James De Lemos

Faculty, Staff and Students Publications

Background: High-sensitivity troponin I (hs-cTnI) and T (hs-cTnT) provide complementary information regarding cardiovascular disease risk. The explanation for their distinct risk profiles is incompletely understood.

Methods and results: hs-cTnI and hs-cTnT were measured in Dallas Heart Study participants. Associations of hs-cTnI and hs-cTnT with demographics and phenotypes were assessed using linear regression. Associations with incident heart failure, atherosclerotic cardiovascular disease, global cardiovascular disease, and cardiovascular and all-cause mortality were assessed using Cox models. Among 3276 participants (56% women, 50% Black persons, median age 43 years), the correlation between hs-cTnI and hs-cTnT was modest (Spearman rho=0.35). Variables associated with hs-cTnI but …

A Prognostic Model For Use Before Elective Surgery To Estimate The Risk Of Postoperative Pulmonary Complications (Gsu-Pulmonary Score), Nihr Global Health Research Unit On Global Surgery, Starsurg Collaborative

Department of Surgery Faculty Publications

Background: Pulmonary complications are the most common cause of death after surgery. This study aimed to derive and externally validate a novel prognostic model that can be used before elective surgery to estimate the risk of postoperative pulmonary complications and to support resource allocation and prioritisation during pandemic recovery. Methods: Data from an international, prospective cohort study were used to develop a novel prognostic risk model for pulmonary complications after elective surgery in adult patients (aged ≥18 years) across all operation and disease types. The primary outcome measure was postoperative pulmonary complications at 30 days after surgery, which was a …

In Vivo Validation Of Late-Onset Alzheimer's Disease Genetic Risk Factors., Michael Sasner, Christoph Preuss, Ravi S Pandey, Asli Uyar, Dylan Garceau, Kevin P Kotredes, Harriet M. Jackson, Adrian L Oblak, Peter Bor-Chian Lin, Bridget Perkins, Disha Soni, Cindy Ingraham, Audrey Lee-Gosselin, Bruce T Lamb, Gareth R Howell, Gregory W. Carter

Faculty Research 2024

INTRODUCTION: Genome-wide association studies have identified over 70 genetic loci associated with late-onset Alzheimer's disease (LOAD), but few candidate polymorphisms have been functionally assessed for disease relevance and mechanism of action.

METHODS: Candidate genetic risk variants were informatically prioritized and individually engineered into a LOAD-sensitized mouse model that carries the AD risk variants APOE ε4/ε4 and Trem2*R47H. The potential disease relevance of each model was assessed by comparing brain transcriptomes measured with the Nanostring Mouse AD Panel at 4 and 12 months of age with human study cohorts.

RESULTS: We created new models for 11 coding and loss-of-function risk variants. …

Assessment Of Neurovascular Uncoupling: Apoe Status Is A Key Driver Of Early Metabolic And Vascular Dysfunction., Kristen D. Onos, Peter B Lin, Ravi S Pandey, Scott A Persohn, Charles P Burton, Ethan W Miner, Kierra Eldridge, Jonathan Nyandu Kanyinda, Kate E Foley, Gregory W. Carter, Gareth R Howell, Paul R Territo

Faculty Research 2024

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia worldwide, with apolipoprotein Eε4 (APOEε4) being the strongest genetic risk factor. Current clinical diagnostic imaging focuses on amyloid and tau; however, new methods are needed for earlier detection.

METHODS: PET imaging was used to assess metabolism-perfusion in both sexes of aging C57BL/6J, and hAPOE mice, and were verified by transcriptomics, and immunopathology.

RESULTS: All hAPOE strains showed AD phenotype progression by 8 months, with females exhibiting the regional changes, which correlated with GO-term enrichments for glucose metabolism, perfusion, and immunity. Uncoupling analysis revealed APOEε4/ε4 exhibited significant Type-1 uncoupling (↓ …

New Labor Curves Of Dilation And Station To Improve The Accuracy Of Predicting Labor Progress., Emily F Hamilton, Tilekbek Zhoroev, Philip A Warrick, Adi L Tarca, Thomas J Garite, Aaron B Caughey, Jason Melillo, Mona Prasad, Duncan Neilson, Peter Singson, Kimberlee Mckay, Roberto Romero

Women’s Health Articles

BACKGROUND: The diagnosis of failure to progress, the most common indication for intrapartum cesarean delivery, is based on the assessment of cervical dilation and station over time. Labor curves serve as references for expected changes in dilation and fetal descent. The labor curves of Friedman, Zhang et al, and others are based on time alone and derived from mothers with spontaneous labor onset. However, labor induction is now common, and clinicians also consider other factors when assessing labor progress. Labor curves that consider the use of labor induction and other factors that influence labor progress have the potential to be …

Predicting Nutrition And Environmental Factors Associated With Female Reproductive Disorders Using A Knowledge Graph And Random Forests., Lauren E Chan, Elena Casiraghi, Justin Reese, Quaker E Harmon, Kevin Schaper, Harshad Hegde, Giorgio Valentini, Charles Schmitt, Alison Motsinger-Reif, Janet E Hall, Christopher J Mungall, Peter N Robinson, Melissa A Haendel

Faculty Research 2024

OBJECTIVE: Female reproductive disorders (FRDs) are common health conditions that may present with significant symptoms. Diet and environment are potential areas for FRD interventions. We utilized a knowledge graph (KG) method to predict factors associated with common FRDs (for example, endometriosis, ovarian cyst, and uterine fibroids).

MATERIALS AND METHODS: We harmonized survey data from the Personalized Environment and Genes Study (PEGS) on internal and external environmental exposures and health conditions with biomedical ontology content. We merged the harmonized data and ontologies with supplemental nutrient and agricultural chemical data to create a KG. We analyzed the KG by embedding edges and …

Healthy Dietary Patterns Are Associated With Exposure To Environmental Chemicals In A Pregnancy Cohort, Guoqi Yu, Ruijin Lu, Jiaxi Yang, Mohammad L Rahman, Ling-Jun Li, Dong D Wang, Qi Sun, Wei Wei Pang, Claire Guivarch, Anna Birukov, Jagteshwar Grewal, Zhen Chen, Cuilin Zhang

2020-Current year OA Pubs

Healthy dietary patterns, such as the alternate Mediterranean diet and alternate Healthy Eating Index, benefit cardiometabolic health. However, several food components of these dietary patterns are primary sources of environmental chemicals. Here, using data from a racially and ethnically diverse US cohort, we show that healthy dietary pattern scores were positively associated with plasma chemical exposure in pregnancy, particularly for the alternate Mediterranean diet and alternate Healthy Eating Index with polychlorinated biphenyls and per- and poly-fluoroalkyl substances. The associations appeared stronger among Asian and Pacific Islanders. These findings suggest that optimizing the benefits of a healthy diet requires concerted regulatory …

Momelotinib Vs. Ruxolitinib In Myelofibrosis Patient Subgroups By Baseline Hemoglobin Levels In The Simplify-1 Trial, Vikas Gupta, Stephen Oh, Et Al.

2020-Current year OA Pubs

A key hallmark of myelofibrosis is anemia, which ranges from mild to severe based on hemoglobin levels. To more clearly define outcomes with the Janus kinase (JAK) 1/JAK2/activin A receptor type 1 inhibitor momelotinib by anemia severity, we performed a descriptive post hoc exploratory analysis of the double-blind, randomized, phase 3 SIMPLIFY-1 study (NCT01969838;

Efficacy Of Tezepelumab In Patients With Severe, Uncontrolled Asthma Across Multiple Clinically Relevant Subgroups In The Navigator Study, Tara F Carr, Wendy C Moore, Monica Kraft, Guy Brusselle, Mario Castro, Geoffrey L Chupp, Michael E Wechsler, Gillian Hunter, Andrew W Lindsley, Jean-Pierre Llanos, Luke K Burke, Shradha Chandarana, Christopher S Ambrose

Faculty, Staff and Student Publications

INTRODUCTION: Many patients with severe asthma continue to experience symptoms and exacerbations despite treatment with standard-of-care therapy. In the phase 3 NAVIGATOR study, tezepelumab significantly reduced exacerbations over 52 weeks compared with placebo in patients with severe, uncontrolled asthma. This analysis assessed the efficacy of tezepelumab in reducing asthma exacerbations in various clinically relevant subgroups of patients in NAVIGATOR.

METHODS: NAVIGATOR was a phase 3, multicentre, randomized, double-blind, placebo-controlled study. Participants (12-80 years old) with severe, uncontrolled asthma were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Pre-specified and post hoc analyses …

Inhibition Of Cathepsin S In Autoimmune Cd25ko Mouse Improves Sjögren Disease-Like Lacrimal Gland Pathology, Kaitlin K Scholand, Jeremias Galletti, Wolfgang Haap, Tiago Santos-Ferreira, Christoph Ullmer, Cintia S De Paiva

Faculty, Staff and Students Publications

PURPOSE: CD25KO mice are a model of Sjögren disease (SjD) driven by autoreactive T cells. Cathepsin S (CTSS) is a protease crucial for major histocompatibility complex class II presentation that primes T cells. We investigated if a diet containing CTSS inhibitor would improve autoimmune signs in CD25KO mice.

METHODS: Four-week female CD25KO mice were randomly chosen to receive chow containing a CTSS inhibitor (R05461111, 262.5 mg/kg chow) or standard chow for 4 weeks. Cornea sensitivity was measured. Inflammatory score was assessed in lacrimal gland (LG) histologic sections. Flow cytometry of LG and ocular draining lymph nodes (dLNs) investigated expression of …

Clinical Exome Sequencing Uncovers Genetic Disorders In Neonates With Suspected Hypoxic-Ischemic Encephalopathy: A Retrospective Analysis, Christian M Parobek, Roni Zemet, Matthew A Shanahan, Brian A Burnett, Elizabeth Mizerik, Jill A Rosenfeld, Liesbeth Vossaert, Steven L Clark, Jill V Hunter, Seema R Lalani

Faculty, Staff and Students Publications

Hypoxic-ischemic encephalopathy (HIE) occurs in up to 7 out of 1000 births and accounts for almost a quarter of neonatal deaths worldwide. Despite the name, many newborns with HIE have little evidence of perinatal hypoxia. We hypothesized that some infants with HIE have genetic disorders that resemble encephalopathy. We reviewed genetic results for newborns with HIE undergoing exome or genome sequencing at a clinical laboratory (2014-2022). Neonates were included if they had a diagnosis of HIE and were delivered ≥35 weeks. Neonates were excluded for cardiopulmonary pathology resulting in hypoxemia or if neuroimaging suggested postnatal hypoxic-ischemic injury. Of 24 patients …

Perinatal Mental Healthcare Utilization Among Patients With Placenta Accreta Spectrum, Sarah R Casey, Alison N Goulding, Christina C Reed, Amir A Shamshirsaz, Hennie A Lombaard, Michael A Belfort, Lisa M Noll, Karin A Fox

Faculty, Staff and Students Publications

No abstract provided.

Pregnancy Outcomes Of Nifedipine Compared With Labetalol For Oral Treatment Of Mild Chronic Hypertension, Ayodeji A Sanusi, Justin Leach, Kim Boggess, Lorraine Dugoff, Baha Sibai, Kirsten Lawrence, Brenna L Hughes, Joseph Bell, Kjersti Aagaard, Rodney K Edwards, Kelly S Gibson, David M Haas, Lauren Plante, Torri D Metz, Brian Casey, Sean Esplin, Sherri Longo, Matthew K Hoffman, George R Saade, Kara K Hoppe, Janelle Foroutan, Methodius Tuuli, Michelle Y Owens, Hyagriv N Simhan, Heather Frey, Todd Rosen, Anna Palatnik, Susan Baker, Phyllis August, Uma M Reddy, Emily J Su, Iris Krishna, Nguyet A Nguyen, Mary E Norton, Daniel Skupski, Yasser Y El-Sayed, Dotun Ogunyemi, Zorina S Galis, Lorie Harper, Namasivayam Ambalavanan, Nancy L Geller, Hui-Chien Kuo, Rachel G Sinkey, Ronald Librizzi, Leonardo Pereira, Everett F Magann, Mounira Habli, Shauna Williams, Giancarlo Mari, Gabriella Pridjian, David S Mckenna, Marc Parrish, Eugene Chang, Sarah Osmundson, Joanne Quinones, Jeff M Szychowski, Alan T N Tita

Faculty, Staff and Students Publications

Objective: To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial.

Methods: We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care …

Mean Arterial Pressure And Neonatal Outcomes In Pregnancies Complicated By Mild Chronic Hypertension, Matthew D Moore, Hui-Chien Kuo, Rachel G Sinkey, Kim Boggess, Lorraine Dugoff, Baha Sibai, Kirsten Lawrence, Brenna L Hughes, Joseph Bell, Kjersti Aagaard, Rodney K Edwards, Kelly S Gibson, David M Haas, Lauren Plante, Torri D Metz, Brian Casey, Sean Esplin, Sherri Longo, Matthew K Hoffman, George R Saade, Kara K Hoppe, Janelle Foroutan, Methodius Tuuli, Michelle Y Owens, Hyagriv N Simhan, Heather A Frey, Todd Rosen, Anna Palatnik, Susan Baker, Phyllis August, Uma M Reddy, Wendy Kinzler, Emily J Su, Iris Krishna, Nguyet A Nguyen, Mary E Norton, Daniel Skupski, Yasser Y El-Sayed, Dotun Ogunyemi, Ronald Librizzi, Leonardo Pereira, Everett F Magann, Mounira Habli, Shauna Williams, Giancarlo Mari, Gabriella Pridjian, David S Mckenna, Marc Parrish, Eugene Chang, Sarah Osmundson, Joanne N Quiñones, Justin Leach, Ayodeji Sanusi, Zorina S Galis, Lorie Harper, Namasivayam Ambalavanan, Jeff M Szychowski, Alan T N Tita

Faculty, Staff and Students Publications

Objective: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial.

Methods: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 …