Digital Commons Network^™

Effect Of Semaglutide On Regression And Progression Of Glycemia In People With Overweight Or Obesity But Without Diabetes In The Select Trial, Steven E Kahn, John E Deanfield, Ole Kleist Jeppesen, Scott S Emerson, Trine Welløv Boesgaard, Helen M Colhoun, Robert F Kushner, Ildiko Lingvay, Bartolome Burguera, Grzegorz Gajos, Deborah Bade Horn, Irene M Hramiak, Ania M Jastreboff, Alexander Kokkinos, Michael Maeng, Ana Laura S A Matos, Francisco J Tinahones, A Michael Lincoff, Donna H Ryan, Select Trial Investigators

Faculty, Staff and Student Publications

OBJECTIVE: To determine whether semaglutide slows progression of glycemia in people with cardiovascular disease and overweight or obesity but without diabetes.

RESEARCH DESIGN AND METHODS: In a multicenter, double-blind trial, participants aged ≥45 years, with BMI ≥27 kg/m2, and with preexisting cardiovascular disease but without diabetes (HbA1c

RESULTS: Of 17,604 participants, 8,803 were assigned to semaglutide and 8,801 to placebo. Mean ± SD intervention exposure was 152 ± 56 weeks and follow-up 176 ± 40 weeks. In both treatment arms mean nadir HbA1c for participants was at 20 weeks. Thereafter, HbA1c increased similarly in both arms, with a mean difference …

Association Between Intravenous Fluids During Labor And Primary Postpartum Hemorrhage: A Retrospective Cohort Study, Belinda R Bruce, Heather L Shepherd, Saleem Ahmed Khan, Charlotte R Haunton, Julie Leask, Bradley S De Vries

Faculty, Staff and Student Publications

INTRODUCTION: There is a major research gap relating to the impact of intravenous (IV) fluids administration during labor on maternal and neonatal outcomes. It is biologically plausible that a relationship between volume of IV fluids and primary postpartum hemorrhage (PPH) exists. The primary objective of this study was to evaluate whether the administration of high-volume IV fluids during labor (≥ 2500 mL) increases the risk of primary PPH and other adverse outcomes for women with a term, singleton pregnancy, in comparison to low-volume IV fluids during labor (<2500 >mL).

MATERIAL AND METHODS: A retrospective cohort study was conducted at a …

Assessment Of Thrombectomy Versus Combined Thrombolysis And Thrombectomy In Patients With Acute Ischemic Stroke And Medium Vessel Occlusion, Adam A Dmytriw, Sherief Ghozy, Hamza Adel Salim, Basel Musmar, James E Siegler, Hassan Kobeissi, Hamza Shaikh, Jane Khalife, Mohamad Abdalkader, Piers Klein, Thanh N Nguyen, Jeremy J Heit, Robert W Regenhardt, Nicole M Cancelliere, Kareem El Naamani, Abdelaziz Amllay, Lukas Meyer, Anne Dusart, Flavio Bellante, Géraud Forestier, Aymeric Rouchaud, Suzana Saleme, Charbel Mounayer, Jens Fiehler, Anna Luisa Kühn, Ajit S Puri, Christian Dyzmann, Peter T Kan, Marco Colasurdo, Gaultier Marnat, Jérôme Berge, Xavier Barreau, Igor Sibon, Simona Nedelcu, Nils Henninger, Thomas R Marotta, Christopher J Stapleton, James D Rabinov, Takahiro Ota, Shogo Dofuku, Leonard L L Yeo, Benjamin Y Q Tan, Juan Carlos Martinez-Gutierrez, Sergio Salazar-Marioni, Sunil Sheth, Leonardo Renieri, Carolina Capirossi, Ashkan Mowla, Nimer Adeeb, Hugo H Cuellar-Saenz, Stavropoula I Tjoumakaris, Pascal Jabbour, Priyank Khandelwal, Arundhati Biswas, Frédéric Clarençon, Mahmoud Elhorany, Kevin Premat, Iacopo Valente, Alessandro Pedicelli, João Pedro Filipe, Ricardo Varela, Miguel Quintero-Consuegra, Nestor R Gonzalez, Markus A Möhlenbruch, Jessica Jesser, Vincent Costalat, Adrien Ter Schiphorst, Vivek Yedavalli, Pablo Harker, Lina M Chervak, Yasmin Aziz, Benjamin Gory, Christian Paul Stracke, Constantin Hecker, Ramanathan Kadirvel, Monika Killer-Oberpfalzer, Christoph J Griessenauer, Ajith J Thomas, Cheng-Yang Hsieh, David S Liebeskind, Răzvan Alexandru Radu, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Robert Fahed, Charlotte S Weyland, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Adrien Guenego, Worldwide Web Workgroup

Faculty, Staff and Student Publications

The Woven EndoBridge (WEB) device is FDA-approved for the treatment of bifurcation aneurysms. Despite its wide popularity, it has been under scrutiny for its association with potential aneurysm recanalization and retreatment due to device shape modification. This study aims to analyze the shape modification rate of WEB devices and identify factors associated with this phenomenon, as well as its correlation with aneurysm retreatment. We conducted a retrospective review of the WorldWide WEB Consortium database, including adult patients treated for intracranial aneurysms with the WEB device. We assessed aneurysm occlusion using the WEB Occlusion Scale and defined WEB shape modification as …

Genomic Testing And Molecular Diagnosis Among Infants With Congenital Heart Disease In The Neonatal Intensive Care Unit, Erica E D'Souza, Tina O Findley, Rachel Hu, Zahra S H Khazal, Rachel Signorello, Camille Dash, Alissa M D'Gama, Henry A Feldman, Pankaj B Agrawal, Monica H Wojcik, Sarah U Morton

Faculty, Staff and Student Publications

Objective: To evaluate patterns of genetic testing among infants with CHD at a tertiary care center.

Study design: We conducted a retrospective observational cohort study of infants in the NICU with suspicion of a genetic disorder. 1075 of 7112 infants admitted to BCH had genetic evaluation including 329 with CHD and 746 without CHD. 284 of 525 infants with CHD admitted to CMHH had genetic evaluation. Patterns of testing and diagnoses were compared.

Results: The rate of diagnosis after testing was similar for infants with or without CHD (38% [121/318] vs. 36% [246/676], p = 0.14). In a multiple logistic …

Adverse Childhood Experiences And Adult Household Firearm Ownership, Alexander Testa, Karyn Fu, Dylan B Jackson, Daniel C Semenza, Sandra Mckay

Faculty, Staff and Student Publications

This survey study examines exposure to abuse, neglect, and household dysfunction during childhood and likelihood of gun ownership in adulthood.

Myeloablation Followed By Hematopoietic Stem Cell Transplantation And Long-Term Normalization Of Systemic Sclerosis Molecular Signatures, Nancy Wareing, Xuan Wang, Lynette Keyes-Elstein, Ellen A Goldmuntz, Marka A Lyons, Peter Mcsweeney, Daniel E Furst, Richard A Nash, Leslie J Crofford, Beverly Welch, Ashley Pinckney, Maureen D Mayes, Keith M Sullivan, Shervin Assassi

Faculty, Staff and Student Publications

Objective: In the randomized Scleroderma: Cyclophosphamide or Transplantation (SCOT) trial, myeloablation, followed by hematopoietic stem cell transplantation (HSCT), led to the normalization of systemic sclerosis (SSc) peripheral blood cell (PBC) gene expression signature at the 26-month visit. Herein, we examined long-term molecular changes ensuing 54 months after randomization for individuals receiving an HSCT or 12 months of intravenous cyclophosphamide (CYC).

Methods: Global PBC transcript studies were performed in study participants at pretreatment baseline and at 38 months and 54 months after randomization, as well as in healthy controls using Illumina HT-12 arrays.

Results: Thirty (HSCT = 19 and CYC = …

Quantitative Myocardial Perfusion In Liver Transplantation Candidates: Poorly Metabolized Caffeine Inhibition Of Vasodilatory Stress, Danai Kitkungvan, Nils P Johnson, Amanda E Roby, Patricia Mendoza, Linh Bui, Monica B Patel, Kelly Sander, Lindsey Harmon, Richard Kirkeeide, K Lance Gould

Faculty, Staff and Student Publications

Background: Data on cardiac positron emission tomography (PET) in liver transplantation (LT) candidates are limited with no prior study accounting for poorly metabolized caffeine reducing stress perfusion.

Method: Consecutive LT candidates (n = 114) undergoing cardiac rest/stress PET were instructed to abstain from caffeine for 2 days extended to 5 and 7 days. Due to persistently high prevalence of measurable blood caffeine after 5-day caffeine abstinence, dipyridamole (n = 41) initially used was changed to dobutamine (n = 73). Associations of absolute flow, coronary flow reserve (CFR), detectable blood caffeine, and Modified End-Stage Liver Disease (MELD) score for liver failure …

A Multi-National Survey To Identify Clinicians’ Perspectives Concerning Proton Pump Inhibitors In Patients With Systemic Sclerosis, Giulia Bandini, Alessia Alunno, Filipe Oliveira Pinheiro, Corrado Campochiaro, Ilaria Galetti, Pietro Matucci Cerinic, Barbara Ruaro, Alberto Moggi Pignone, Silvia Bellando Randone, Lorenzo Dagna, Marco Matucci Cerinic, Zsuzsanna H Mcmahan, Michael Hughes

Faculty, Staff and Student Publications

Objectives: Proton Pump Inhibitors (PPIs) are widely used in SSc for gastroesophageal reflux disease (GERD). However, there is little evidence to support their empirical use and long-term safety has been questioned. Our objective was to better describe clinicians' attitudes toward PPIs prescription and use in SSc patients.

Methods: Clinicians involved in the care of SSc patients were invited through international physician networks and social media to participate in an online survey.

Results: Responses from 227 clinicians from 36 countries were evaluable. The majority 'agreed' (41.4 %) or 'strongly agreed' (45.4 %) that GERD is a major cause of morbidity in …

Acetaminophen For Patent Ductus Arteriosus And Risk Of Mortality And Pulmonary Morbidity, Erik A Jensen, Sara B Demauro, Matthew A Rysavy, Ravi M Patel, Matthew M Laughon, Eric C Eichenwald, Barbara T Do, Abhik Das, Clyde J Wright

Faculty, Staff and Student Publications

Objective: Emerging data indicate that acetaminophen may adversely affect lung health. We examined whether acetaminophen compared with cyclooxygenase (COX) inhibitor alone for patent ductus arteriosus (PDA) is associated with mortality or respiratory morbidity in extremely preterm infants.

Methods: This is a retrospective cohort study using data from the National Institute of Child Health and Human Development Neonatal Research Network. Infants were born at 22 to 28 weeks' gestation or weighing 401 to 1000 g between 2016 and 2020 and received acetaminophen, ibuprofen, and/or indomethacin for PDA closure. The primary outcome was death or grade 2 to 3 bronchopulmonary dysplasia (BPD) …

A Qualitative Narrative Study Of Rescue And Recovery Workers Responding To The Terrorist Bombing Of Oklahoma City's Murrah Building, E Whitney Pollio, Jennifer Wang, Edward Randle, David E Pollio, Carol S North

Faculty, Staff and Student Publications

OBJECTIVE: Much of disaster mental health research uses quantitative methods, focusing on numerical prevalence, services, and outcomes.

METHODS: Qualitative methods can provide more detailed, rich, and spontaneous insights into personal disaster experiences, yielding important insights beyond deductive methods. This large-scale qualitative narrative study examined experiences of 181 Oklahoma City bombing rescue/recovery workers.

RESULTS: Thematic narrative content of the bombing experience arose from personal accounts of the bomb blast by rescue/recovery workers proceeding chronologically from initial awareness and deployment to harrowing onsite search and rescue/recovery missions to the aftermath with reflections on the bombing.

CONCLUSIONS: Beyond disaster recovery/rescue worker stories published …

Combination Of Dasatinib And Venetoclax In Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia, Elias Jabbour, Fadi G Haddad, Koji Sasaki, Bing Z Carter, Yesid Alvarado, Cedric Nasnas, Lewis Nasr, Lucia Masarova, Naval Daver, Naveen Pemmaraju, Nicholas J Short, Jeffrey Skinner, Tapan Kadia, Gautam Borthakur, Guillermo Garcia-Manero, Farhad Ravandi, Ghayas C Issa, Michael Andreeff, Hagop Kantarjian

Faculty, Staff and Student Publications

Background: The dual inhibition of the BCR::ABL1 tyrosine kinase and BCL-2 could potentially deepen the response rates of chronic myeloid leukemia in chronic phase (CML-CP). This study evaluated the safety and efficacy of the combination of dasatinib and venetoclax.

Methods: In this phase 2 trial, patients with CML-CP or accelerated phase (clonal evolution) received dasatinib 50 mg/day for three courses; venetoclax was added in course 4 for 3 years. The initial venetoclax dose was 200 mg/day continuously but reduced later to 200 mg/day for 14 days, and to 100 mg/day for 7 days per course once a molecular response (MR)4.5 …

Eculizumab For Management Of Hyperhemolysis Syndrome In Pediatric Patients With Sickle Cell Disease: A Single-Center Case Series, Ajibike Lapite, Saleh Bhar, Titilope Fasipe

Faculty, Staff and Students Publications

Chronic hemolytic anemia and vascular occlusion are hallmarks of sickle cell disease (SCD). Blood transfusions are critical for supportive and preventive management of SCD complications. Patients with SCD are at risk for hyperhemolysis syndrome (HHS), a subtype of delayed hemolytic transfusion reactions. HHS management includes intravenous immunoglobulin, corticosteroids, and avoidance of further transfusions. Not all patients respond to first-line agents. Eculizumab, which blocks terminal complement activation, has been proposed as second-line management of HHS. We describe two patients who received eculizumab for refractory HHS. In our experience, eculizumab is a safe and effective option for refractory pediatric HHS.

Fetal Malrotation With Midgut Volvulus: Prenatal Diagnosis And Planning, Jai Sidpra, Sniya Sudhakar, Asthik Biswas, Flavia Massey, Valentina Turchetti, Tracy Lau, Edward Cook, Javeria Raza Alvi, Hasnaa M Elbendary, Jerry L Jewell, Antonella Riva, Alessandro Orsini, Aglaia Vignoli, Zara Federico, Jessica Rosenblum, An-Sofie Schoonjans, Matthias De Wachter, Ignacio Delgado Alvarez, Ana Felipe-Rucián, Nourelhoda A Haridy, Shahzad Haider, Mashaya Zaman, Selina Banu, Najwa Anwaar, Fatima Rahman, Shazia Maqbool, Rashmi Yadav, Vincenzo Salpietro, Reza Maroofian, Rajan Patel, Rupa Radhakrishnan, Sanjay P Prabhu, Klaske Lichtenbelt, Helen Stewart, Yoshiko Murakami, Ulrike Löbel, Felice D'Arco, Emma Wakeling, Wendy Jones, Eleanor Hay, Sanjay Bhate, Thomas S Jacques, David M Mirsky, Matthew T Whitehead, Maha S Zaki, Tipu Sultan, Pasquale Striano, Anna C Jansen, Maarten Lequin, Linda S De Vries, Mariasavina Severino, Andrew C Edmondson, Lara Menzies, Philippe M Campeau, Henry Houlden, Amy Mctague, Stephanie Efthymiou, Kshitij Mankad

Faculty, Staff and Students Publications

Inherited glycosylphosphatidylinositol deficiency disorders (IGDs) are a group of rare multisystem disorders arising from pathogenic variants in glycosylphosphatidylinositol anchor pathway (GPI-AP) genes. Despite associating 24 of at least 31 GPI-AP genes with human neurogenetic disease, prior reports are limited to single genes without consideration of the GPI-AP as a whole and with limited natural history data. In this multinational retrospective observational study, we systematically analyse the molecular spectrum, phenotypic characteristics and natural history of 83 individuals from 75 unique families with IGDs, including 70 newly reported individuals; the largest single cohort to date. Core clinical features were developmental delay or …

Loneliness Among Black/African American Adults Living With Hiv: Sociodemographic And Psychosocial Correlates And Implications For Adherence., Nipher Malika, Laura M. Bogart, Matt G. Mutchler, Kathy Goggin, David J. Klein, Sean J. Lawrence, Glenn J. Wagner

Manuscripts, Articles, Book Chapters and Other Papers

Loneliness, an emerging public health problem, is higher among people living with HIV and is associated with negative health outcomes. Black/African Americans have a high burden of HIV, and little is known about the characteristics of loneliness among Black adults living with HIV; therefore, this study sought to understand the sociodemographic and psychosocial correlates of Black adults living with HIV who are lonely and the implications of loneliness for their health outcomes. A sample of 304 Black adults living with HIV (73.8% sexual minority men) in Los Angeles County, CA, USA, completed the survey items assessing sociodemographic and psychosocial characteristics, …

Stratifying Heart Failure Patients With Graph Neural Network And Transformer Using Electronic Health Records To Optimize Drug Response Prediction, Shaika Chowdhury, Yongbin Chen, Pengyang Li, Sivaraman Rajaganapathy, Andrew Wen, Xiao Ma, Qiying Dai, Yue Yu, Sunyang Fu, Xiaoqian Jiang, Zhe He, Sunghwan Sohn, Xiaoke Liu, Suzette J Bielinski, Alanna M Chamberlain, James R Cerhan, Nansu Zong

Faculty, Staff and Student Publications

Objectives: Heart failure (HF) impacts millions of patients worldwide, yet the variability in treatment responses remains a major challenge for healthcare professionals. The current treatment strategies, largely derived from population based evidence, often fail to consider the unique characteristics of individual patients, resulting in suboptimal outcomes. This study aims to develop computational models that are patient-specific in predicting treatment outcomes, by utilizing a large Electronic Health Records (EHR) database. The goal is to improve drug response predictions by identifying specific HF patient subgroups that are likely to benefit from existing HF medications.

Materials and methods: A novel, graph-based model capable …

Patient Education Practices And Preferences Of Radiation Oncologists And Interprofessional Radiation Therapy Care Teams: A Mixed-Methods Study Exploring Strategies For Effective Patient Education Delivery, Jie Jane Chen, Anna M Brown, Allison E Garda, Ellen Kim, Sarah A Mcavoy, Subha Perni, Michael K Rooney, Kevin Shiue, Kristi L Tonning, Laura E Warren, Daniel W Golden, Jennifer M Croke

Faculty, Staff and Student Publications

Purpose: Patients' understanding of radiation therapy (RT) and data regarding optimal approaches to patient education (PE) within radiation oncology (RO) are limited. We aimed to evaluate PE practices of radiation oncologists and interprofessional RT care team members to inform recommendations for delivering inclusive and accessible PE.

Methods and materials: An anonymous survey was administered to all Radiation Oncology Education Collaborative Study Group members (10/5/22-11/23/22). Respondent demographics, individual practices/preferences, and institutional practices were collected. Qualitative items explored strategies, challenges, and desired resources for PE. Descriptive statistics summarized survey responses. The Fisher exact test compared PE practices by respondent role and PE …

Frontiers In Congenital Disorders Of Glycosylation Consortium, A Cross-Sectional Study Report At Year 5 Of 280 Individuals In The Natural History Cohort, Christina Lam, Fernando Scaglia, Gerard T Berry, Austin Larson, Kyriakie Sarafoglou, Hans C Andersson, Evgenia Sklirou, Queenie K G Tan, Rodrigo T Starosta, Mustafa Sadek, Lynne Wolfe, Seishu Horikoshi, May Ali, Rita Barone, Teresa Campbell, Irene J Chang, Kiaira Coles, Edward Cook, Erik A Eklund, Nicole M Engelhardt, Mary Freeman, Jennifer Friedman, Debbie Y T Fu, Grace Botzo, Brandy Rawls, Christien Hernandez, Christin Johnsen, Kierstin Keller, Sara Kramer, Bryce Kuschel, Angela Leshinski, Ivan Martinez-Duncker, Gina L Mazza, Saadet Mercimek-Andrews, Bradley S Miller, Karthik Muthusamy, Juanita Neira, Marc C Patterson, Natalie Pogorelc, Lex N Powers, Elizabeth Ramey, Michaela Reinhart, Audrey Squire, Jenny Thies, Jerry Vockley, Hayden Vreugdenhil, Peter Witters, Mehdi Youbi, Aziza Zeighami, Roni Zemet, Andrew C Edmondson, Eva Morava

Faculty, Staff and Students Publications

Objective: Our report describes clinical, genetic, and biochemical features of participants with a molecularly confirmed congenital disorder of glycosylation (CDG) enrolled in the Frontiers in Congenital Disorders of Glycosylation (FCDGC) Natural History cohort at year 5 of the study.

Methods: We enrolled individuals with a known or suspected CDG into the FCDGC Natural History Study, a multicenter prospective and retrospective natural history study of all genetic causes of CDG. We conducted a cross-sectional analysis of baseline study visit data from participants with confirmed CDG who were consented into the FCDGC Natural History Study (5U54NS115198) from October 2019 to November 2023. …

Histone Serotonylation Regulates Ependymoma Tumorigenesis, Hsiao-Chi Chen, Peihao He, Malcolm Mcdonald, Michael R Williamson, Srinidhi Varadharajan, Brittney Lozzi, Junsung Woo, Dong-Joo Choi, Debosmita Sardar, Emmet Huang-Hobbs, Hua Sun, Siri M Ippagunta, Antrix Jain, Ganesh Rao, Thomas E Merchant, David W Ellison, Jeffrey L Noebels, Kelsey C Bertrand, Stephen C Mack, Benjamin Deneen

Faculty, Staff and Students Publications

Bidirectional communication between tumors and neurons has emerged as a key facet of the tumor microenvironment that drives malignancy1,2. Another hallmark feature of cancer is epigenomic dysregulation, where alterations in gene expression influences cell states and interactions with the tumor microenvironment3. Ependymoma (EPN) is a pediatric brain tumor that relies on epigenomic remodeling to engender malignancy4,5; how these epigenetic mechanisms intersect with extrinsic neuronal signaling during EPN tumor progression is unknown. Here we show that activity of serotonergic neurons regulates EPN tumorigenesis, while serotonin itself also serves as an activating …

Breast Cancer, Jane E Visvader, Jeffrey M Rosen, Samuel Aparicio

Faculty, Staff and Students Publications

Breast cancer kills hundreds of thousands of people every year. Rapid progress over the past two decades has increased our understanding of the genetic and environmental risk factors for disease. It has also shed light on drivers of tumor progression and the molecular landscape underpinning tumor heterogeneity, as well as the role of the microenvironment and the immune system. These strides forward should lead to more effective and tailored therapies for early- and late-stage patients.

Epigenetic Disease Markers In Primary Sclerosing Cholangitis And Primary Biliary Cholangitis-Methylomics Of Cholestatic Liver Disease, Brian D Juran, Bryan M Mccauley, Elizabeth J Atkinson, Erik M Schlicht, Jackie K Bianchi, Jason M Vollenweider, Hong Ye, Nicholas F Larusso, Gregory J Gores, Zhifu Sun, Konstantinos N Lazaridis

Faculty, Staff and Students Publications

Background: The epigenome, the set of modifications to DNA and associated molecules that control gene expression, cellular identity, and function, plays a major role in mediating cellular responses to outside factors. Thus, evaluation of the epigenetic state can provide insights into cellular adaptions occurring over the course of disease.

Methods: We performed epigenome-wide association studies of primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) using the Illumina MethylationEPIC Bead Chip.

Results: We found evidence of increased epigenetic age acceleration and differences in predicted immune cell composition in patients with PSC and PBC. Epigenetic profiles demonstrated differences in predicted protein …

Associations Of Mid-To-Late-Life Inflammation With Late-Life Mobility And The Influences Of Chronic Comorbidities, Race, And Social Determinants Of Health: The Atherosclerosis Risk In Communities Study, Kirby G Parker, B Gwen Windham, Chad Blackshear, Keenan A Walker, Sara B Parker, Ron C Hoogeveen, Christie M Ballantyne, Anna Kucharska-Newton, Priya Palta, Elizabeth Selvin, Maria Vassilaki, Thomas H Mosley, Michael E Griswold

Faculty, Staff and Students Publications

Background: Relationships of midlife inflammation with late-life mobility and influences of chronic health conditions, race, and social determinants of health (SDoH) on these relationships are poorly understood.

Methods: Among 4758 community-dwelling participants (41% men, 20% Black), high-sensitivity C-reactive protein (hsCRP) was measured over 20+ years: in midlife at study visit 2 (V2: 1990-1992, 47-68 years); at V4 (1996-1998, 53-74 years); and with concurrent late-life 4-m gait speed at V5 (2011-2013, 67-88 years, mean 75 years). SDoH measures included race, the national-rank area deprivation index, education, and income. We examined associations of late-life gait speed with midlife hsCRP (V2 continuous and …

Aging-Associated Metabolite Methylmalonic Acid Increases Susceptibility To Pulmonary Fibrosis, Kai Xu, Linke Ding, Wenwen Li, Yaxuan Wang, Shuaichen Ma, Hui Lian, Xiaoyue Pan, Ruyan Wan, Weiming Zhao, Juntang Yang, Ivan Rosas, Lan Wang, Guoying Yu

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by pulmonary fibroblast overactivation, resulting in the accumulation of abnormal extracellular matrix and lung parenchymal damage. Although the pathogenesis of IPF remains unclear, aging was proposed as the most prominent nongenetic risk factor. Propionate metabolism undergoes reprogramming in the aging population, leading to the accumulation of the by-product methylmalonic acid (MMA). This study aimed to explore alterations in propionate metabolism in IPF and the impact of the by-product MMA on pulmonary fibrosis. It revealed alterations in the expression of enzymes involved in propionate metabolism within IPF lung tissues, characterized …

Amoxicillin And Penicillin G Dosing In Pediatric Community-Acquired Pneumococcal Pneumonia In The Era Of Conjugate Pneumococcal Vaccines, Dustin Huynh, Norint Tung, Quang Dam, Tri Tran, Kristina G Hulten, Christopher J Harrison, Sheldon L Kaplan, Allison Nguyen, Tyler H Do, Amartya Setty, Jennifer Le

Faculty, Staff and Students Publications

Background: Parenteral penicillin G (PENG) and oral amoxicillin (AMOX) are recommended as treatment for pediatric community-acquired pneumonia (CAP). With recent epidemiologic penicillin susceptibility data for Streptococcus pneumoniae, the most common etiology of CAP, the objective of this study was to evaluate optimal dosing regimens of PENG and AMOX based on population pharmacokinetics linked to current susceptibility data.

Methods: Using NONMEM v7.3, Monte Carlo simulations (N = 10,000) were conducted for AMOX 15 mg/kg/dose PO every 8 h (standard-dose), AMOX 45 mg/kg/dose PO every 12 h (high-dose), and PENG 62,500 units/kg/day IV every 6 h using six virtual subjects with ages …

Pediatric Mental Health Emergency Department Visits From 2017 To 2022: A Multicenter Study, Jennifer A Hoffmann, Camille P Carter, Cody S Olsen, David Ashby, Kamali L Bouvay, Susan J Duffy, James M Chamberlain, Sofia S Chaudhary, Nicolaus W Glomb, Jacqueline Grupp-Phelan, Maya Haasz, Erin P O'Donnell, Mohsen Saidinejad, Bashar S Shihabuddin, Leah Tzimenatos, Neil G Uspal, Joseph J Zorc, Lawrence J Cook, Elizabeth R Alpern

Faculty, Staff and Students Publications

Background: The COVID-19 pandemic adversely affected children's mental health (MH) and changed patterns of MH emergency department (ED) utilization. Our objective was to assess how pediatric MH ED visits during the COVID-19 pandemic differed from expected prepandemic trends.

Methods: We retrospectively studied MH ED visits by children 5 to < 18 years old at nine U.S. hospitals participating in the Pediatric Emergency Care Applied Research Network Registry from 2017 to 2022. We described visit length by time period: prepandemic (January 2017-February 2020), early pandemic (March 2020-December 2020), midpandemic (2021), and late pandemic (2022). We estimated expected visit rates from prepandemic data using multivariable Poisson regression models. We calculated rate ratios (RRs) of observed to expected visits per 30 days during each pandemic time period, overall and by sociodemographic and clinical characteristics.

Results: We identified 175,979 pediatric MH ED visits. Visit length exceeded 12 h for 7.3% prepandemic, 8.4% early pandemic, 15.0% midpandemic, and 19.2% late pandemic visits. During the early pandemic, observed visits per 30 days decreased relative to expected rates (RR 0.80, 95% confidence interval [CI] 0.78-0.84), were similar to expected …

Long-Term Prospective Outcomes Of Intensity Modulated Radiotherapy For Locally Advanced Lung Cancer: A Secondary Analysis Of A Randomized Clinical Trial, Stephen G Chun, Chen Hu, Ritsuko U Komaki, Robert D Timmerman, Steven E Schild, Jeffrey A Bogart, Michael C Dobelbower, Walter Bosch, Vivek S Kavadi, Samir Narayan, Puneeth Iyengar, Clifford Robinson, Jan Rothman, Adam Raben, Mark E Augspurger, Robert M Macrae, Rebecca Paulus, Jeffrey D Bradley

Faculty, Staff and Students Publications

Importance: The optimal radiotherapy technique for unresectable locally advanced non-small cell lung cancer (NSCLC) is controversial, so evaluating long-term prospective outcomes of intensity-modulated radiotherapy (IMRT) is important.

Objective: To compare long-term prospective outcomes of patients receiving IMRT and 3-dimensional conformal radiotherapy (3D-CRT) with concurrent carboplatin/paclitaxel for locally advanced NSCLC.

Design, setting, and participants: A secondary analysis of a prospective phase 3 randomized clinical trial NRG Oncology-RTOG 0617 assessed 483 patients receiving chemoradiotherapy (3D-CRT vs IMRT) for locally advanced NSCLC based on stratification.

Main outcomes and measures: Long-term outcomes were analyzed, including overall survival (OS), progression-free survival (PFS), time to local …

Parkinson’S Disease Variant Detection And Disclosure: Pd Generation, A North American Study, Lola Cook, Jennifer Verbrugge, Tae-Hwi Schwantes-An, Jeanine Schulze, Tatiana Foroud, Anne Hall, Karen S Marder, Ignacio F Mata, Niccolò E Mencacci, Martha A Nance, Michael A Schwarzschild, Tanya Simuni, Susan Bressman, Anne-Marie Wills, Hubert H Fernandez, Irene Litvan, Kelly E Lyons, Holly A Shill, Carlos Singer, Thomas F Tropea, Nora Vanegas Arroyave, Janfreisy Carbonell, Rossy Cruz Vicioso, Linn Katus, Joseph F Quinn, Priscila D Hodges, Yan Meng, Samuel P Strom, Cornelis Blauwendraat, Katja Lohmann, Cynthia Casaceli, Shilpa C Rao, Kamalini Ghosh Galvelis, Anna Naito, James C Beck, Roy N Alcalay

Faculty, Staff and Students Publications

Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson's disease; however, individuals with Parkinson's disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson's disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson's …

Structure Of Adenylyl Cyclase 5 In Complex With Gβγ Offers Insights Into Adcy5-Related Dyskinesia, Yu-Chen Yen, Yong Li, Chun-Liang Chen, Thomas Klose, Val J Watts, Carmen W Dessauer, John J G Tesmer

Faculty, Staff and Student Publications

The nine different membrane-anchored adenylyl cyclase isoforms (AC1-9) in mammals are stimulated by the heterotrimeric G protein, Gαs, but their response to Gβγ regulation is isoform specific. In the present study, we report cryo-electron microscope structures of ligand-free AC5 in complex with Gβγ and a dimeric form of AC5 that could be involved in its regulation. Gβγ binds to a coiled-coil domain that links the AC transmembrane region to its catalytic core as well as to a region (C1b) that is known to be a hub for isoform-specific regulation. We confirmed the Gβγ interaction with both purified proteins and cell-based …

Patterns Of Social Needs Predict Quality-Of-Life And Healthcare Utilization Outcomes In Patients From A Large Hospital System, Chengbo Zeng, Manraj N Kaur, Sri Harshini Malapati, Jason B Liu, Allison S Bryant, Peter M Meyers, David W Bates, Nadine J Mccleary, Andrea L Pusic, Maria O Edelen

Faculty, Staff and Students Publications

Background: Unmet social needs (SNs) often coexist in distinct patterns within specific population subgroups, yet these patterns are understudied.

Objective: To identify patterns of social needs (PSNs) and characterize their associations with health-related quality-of-life (HRQoL) and healthcare utilization (HCU).

Design: Observational study using data on SNs screening, HRQoL (i.e., low mental and physical health), and 90-day HCU (i.e., emergency visits and hospital admission). Among patients with any SNs, latent class analysis was conducted to identify unique PSNs. For all patients and by race and age subgroups, compared with no SNs, we calculated the risks of poor HRQoL and time to …

Early Cold Stored Platelet Transfusion Following Severe Injury: A Randomized Clinical Trial, Jason L Sperry, Francis X Guyette, Bedda L Rosario-Rivera, Matthew E Kutcher, Lucy Z Kornblith, Bryan A Cotton, Chad T Wilson, Kenji Inaba, Eva V Zadorozny, Laura E Vincent, Ashley M Harner, Emily T Love, Joseph E Doherty, Joseph Cuschieri, Aaron E Kornblith, Erin E Fox, Yu Bai, Marcus K Hoffman, Catherine P Seger, Jay Hudgins, Sheila Mallett-Smith, Matthew D Neal, Christine M Leeper, Philip C Spinella, Mark H Yazer, Stephen R Wisniewski, Cold Stored Platelet For Hemorrhagic Shock (Crisp-Hs) Study Group

Faculty, Staff and Student Publications

OBJECTIVE: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared with standard care resuscitation in patients with hemorrhagic shock.

BACKGROUND: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury.

METHODS: A phase 2, multicenter, randomized, open label, clinical trial was performed at 5 US trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days versus …

De Novo Variants In Immune Regulatory Genes In Down Syndrome Regression Disorder, Saba Jafarpour, Abhik K Banerjee, Mellad M Khoshnood, Benjamin N Vogel, Natalie K Boyd, Lina Nguyen, Rebecca Partridge, Stephanie L Santoro, Grace Y Gombolay, Kristen S Fisher, Diego Real De Asua, Maria Carmen Del Ortega, Cathy Franklin, Michael S Rafii, Jonathan D Santoro

Faculty, Staff and Students Publications

Background: Down Syndrome Regression Disorder (DSRD) is a rare and poorly understood disorder of the central nervous system, characterized by acute or subacute neuropsychiatric symptoms in previously healthy individuals with Down syndrome (DS). Many patients exhibit immunotherapy-responsiveness, indicative of immune dysregulation as a potential underlying etiology. While hypotheses are emerging regarding the role of interferon signaling in DSRD and other autoimmune conditions associated with DS, it is unclear why a small subset of individuals with DS develop DSRD. The aim of this study was to investigate genes of immune regulation in persons with DSRD.

Methods: This study included individuals with …