Digital Commons Network^™

Plasma P-Tau217 And Tau-Pet Predict Future Cognitive Decline Among Cognitively Unimpaired Individuals: Implications For Clinical Trials, Rik Ossenkoppele, Tammie L S Benzinger, Suzanne E Schindler, Randall J Bateman, Et Al.

2020-Current year OA Pubs

Plasma p-tau217 and tau positron emission tomography (PET) are strong prognostic biomarkers in Alzheimer's disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In a head-to-head comparison study including nine cohorts and 1,474 individuals, we show that plasma p-tau217 and medial temporal lobe tau-PET signal display similar associations with cognitive decline on a global cognitive composite test (R

Regulation Of Tfeb In Human Placental Cytotrophoblasts And Syncytiotrophoblasts, A Mathew, J S Trausch-Azar, C Azar, M Schuetz, M R Mahjoub, A L Schwartz

2020-Current year OA Pubs

While cellular proteins exist in a dynamic state maintained by the balance of synthesis and degradation, there is a paucity of information on these processes in placental trophoblasts, including within cytotrophoblasts which differentiate into multi-nucleate syncytiotrophoblasts. TFEB, a transcription factor with a myriad of cellular activities, is one of the most abundant genes expressed in syncytiotrophoblasts compared to cytotrophoblasts. TFEB is localized to the nucleus of human BeWo differentiated syncytiotrophoblasts and to the cytoplasm of the undifferentiated cytotrophoblasts. Within both the cytotrophoblasts and syncytiotrophoblasts, TFEB exists in subcellular compartments as both phosphorylated and unphosphorylated forms and translocates between cytoplasm and …

Combining Exercise Training And Testosterone Therapy In Older Women After Hip Fracture: The Step-Hi Randomized Clinical Trial, Ellen F Binder, Peter M Doré, Camelia Guild, Kelly M Monroe, Dominic Reeds, Kenneth B Schechtman, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Despite receiving postacute rehabilitation services, many older women with a recent hip fracture repair are unable to return to their prefracture level of function. Whether testosterone therapy can enhance recovery after hip fracture in older women with persistent mobility impairments has not been fully examined.

OBJECTIVE: To evaluate the effects of a supervised exercise program combined with topical testosterone therapy on functional outcomes in older women with a recent hip fracture.

DESIGN, SETTING, AND PARTICIPANTS: This phase 3 double-blind, placebo-controlled randomized clinical trial, Starting a Testosterone and Exercise Program After Hip Injury (STEP-HI), was conducted at 8 US sites …

Multiregional Implementation Initiative's Impact On Guideline-Based Performance Measures For Patients Hospitalized With Heart Failure: Implement-Hf, Andrew J. Sauer, Nancy Sweitzer, Et Al.

2020-Current year OA Pubs

BACKGROUND: Despite randomized data for survival benefit (with class 1 recommendations) for treating heart failure (HF) with reduced ejection fraction using quadruple medical therapy (QMT)-defined as evidence-based β-blockers, sodium-glucose cotransporter 2 inhibitor, preferably angiotensin receptor/neprilysin inhibitor, and mineralocorticoid receptor antagonist-it is underutilized. IMPLEMENT-HF is a multiregional HF quality improvement initiative to improve care and outcomes for patients with HF by enhancing the use of QMT in routine practice.

METHODS: This analysis of HF with reduced ejection fraction treatment in patients from hospitals participating in the American Heart Association's Get With The Guidelines-HF who volunteered to participate in IMPLEMENT-HF in 7 …

Clerkship Students' Use Of Clinical Reasoning Concepts After A Pre-Clinical Reasoning Course, Shradha A Kulkarni, Gurpreet Dhaliwal, Arianne Teherani, Denise M Connor

Faculty, Staff and Students Publications

Background: Many medical schools have incorporated clinical reasoning (CR) courses into their pre-clinical curricula to address the quality and safety issue of diagnostic error. It is unknown how students use concepts and practices from pre-clinical CR courses once in clerkships.

Objective: We sought to understand how students utilize CR concepts from a pre-clinical course during clerkships and to identify facilitators and barriers to the use of reasoning concepts.

Design: We used structured interviews to gain insight into medical students' experiences with CR concepts in clerkships.

Participants: We interviewed 16 students who had completed a pre-clinical CR course and subsequently completed …

Establishing A Peritoneal Dialysis Technique Survival Core Outcome Measure: A Standardised Outcomes In Nephrology-Peritoneal Dialysis Consensus Workshop Report, Emma H Elphick, Karine E Manera, Andrea K Viecelli, Jonathan C Craig, Yeoungjee Cho, Angela Ju, Jenny I Shen, Martin Wilkie, Samaya Anumudu, Neil Boudville, Josephine Sf Chow, Simon J Davies, Patricia Gooden, Tess Harris, Arsh K Jain, Adrian Liew, Andrea Matus-Gonzalez, Noa Amir, Annie-Claire Nadeau-Fredette, Thu Nguyen, Angela Yee-Moon Wang, Daniela Ponce, Rob Quinn, Alison Jaure, David W Johnson, Mark Lambie, Peritoneal Dialysis International

Faculty, Staff and Students Publications

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Methods

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Otolaryngology-Assisted Approach For Anterior Cervical Discectomy And Fusion, M Benjamin Larkin, Anthony K Allam, Cyrus B King, N Eddie Liou, Alexander E Ropper

Faculty, Staff and Students Publications

First introduced in 1955, anterior cervical discectomy and fusion (ACDF) surgery has seen minimal changes over the years. Its reproducibility, impressive long-term results, and minimal complication rates have established it as one of the most frequently performed cervical spinal fusion surgeries. Yet, postoperative dysphagia remains a concern with a 60% incidence rate. An otolaryngologist's expertise regarding cervical fascial anatomy can inform the spine surgeon's approach to an ACDF to potentially reduce postoperative dysphagia rates. We describe an illustrative case of a 35-year-old woman who presented with 8/10 neck and arm pain along with numbness in her fourth and fifth digits …

Early Prediction Of Mortality And Morbidities In Vlbw Preterm Neonates Using Machine Learning, Chi-Hung Shu, Rema Zebda, Camilo Espinosa, Jonathan Reiss, Anne Debuyserie, Kristina Reber, Nima Aghaeepour, Mohan Pammi

Faculty, Staff and Students Publications

Background: Predicting mortality and specific morbidities before they occur may allow for interventions that may improve health trajectories.

Hypothesis: Integrating key maternal and postnatal infant variables in the first 2 weeks of age into machine learning (ML) algorithms will reliably predict survival and specific morbidities in VLBW preterm infants.

Methods: ML algorithms were developed to integrate 47 features for predicting mortality, bronchopulmonary dysplasia (BPD), neonatal sepsis, necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), cystic periventricular leukomalacia (PVL), and retinopathy of prematurity (ROP). A retrospective cohort (n = 3341) was used to train and validate the models with a repeated 10-fold cross-validation …

Uncovering Shared Genetic Features Between Inflammatory Bowel Disease And Systemic Lupus Erythematosus, Vikram R Shaw, Jinyoung Byun, Catherine Zhu, Rowland W Pettit, Jeffrey M Cohen, Younghun Han, Christopher I Amos

Faculty, Staff and Students Publications

Inflammatory bowel disease (IBD) is an autoimmune disease (AD) characterized by chronic, relapsing intestinal inflammation. Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multisystem involvement and overactivation of both innate and adaptive immunity. The extra intestinal manifestations (EIMs) that commonly occur in IBD include many of the organ sites that are affected by SLE. ADs are often comorbid with one another and may have shared underlying genetic features and architectures contributing to their pathogenesis and disease course. We performed both epidemiological and post-genome wide association study (GWAS) analyses to investigate the shared genetic features between IBD and systemic …

For Girls And Women (4gw) Hpv Rct Protocol: A Crowdsourced, Pragmatic Stepped-Wedge Cluster Randomized Trial To Improve Uptake Of Hpv Vaccination And Screening Among Mother-Daughter Dyads In Nigeria, Juliet Iwelunmor, Ekenechukwu Kokelu, Temitope Ojo, Olufunto Olusanya, Titilola Gbaja-Biamila, Peter Kalulu, Angel Obiorah, Maria Afadapa, Nkiruka Obodoechina, Onyeka Anikamadu, Et Al.

2020-Current year OA Pubs

BACKGROUND: Expanding human papillomavirus (HPV) vaccination for girls and HPV self-collection for women can reduce the global burden of cervical cancer. However, HPV vaccination and self-collection services are rarely implemented simultaneously in mother-daughter dyads, leaving a critical gap in cervical cancer prevention. From 2023 to 2024, a community-engaged model for combined HPV vaccination and screening was co-designed using crowdsourcing open calls and designathons with mother-daughter teams and pilot-tested by trained research facilitators. This study explores the impact of this crowdsourced, community-engaged mother-daughter campaign and implementation strategy bundle on HPV vaccination among girls and HPV screening among their mothers in Nigeria …

Translational Genomics Of Osteoarthritis In 1,962,069 Individuals, Konstantinos Hatzikotoulas, Lorraine Southam, Lilja Stefansdottir, Cindy G Boer, Merry-Lynn Mcdonald, J Patrick Pett, Young-Chan Park, Margo Tuerlings, Rick Mulders, Andrei Barysenka, Ana Luiza Arruda, Vinicius Tragante, Alison Rocco, Norbert Bittner, Shibo Chen, Susanne Horn, Vinodh Srinivasasainagendra, Ken To, Georgia Katsoula, Peter Kreitmaier, Amabel M M Tenghe, Arthur Gilly, Liubov Arbeeva, Lane G Chen, Agathe M De Pins, Daniel Dochtermann, Cecilie Henkel, Jonas Höijer, Shuji Ito, Penelope A Lind, Bitota Lukusa-Sawalena, Aye Ko Ko Minn, Marina Mola-Caminal, Akira Narita, Chelsea Nguyen, Ene Reimann, Micah D Silberstein, Anne-Heidi Skogholt, Hemant K Tiwari, Michelle S Yau, Ming Yue, Wei Zhao, Jin J Zhou, George Alexiadis, Karina Banasik, Søren Brunak, Archie Campbell, Jackson T S Cheung, Joseph Dowsett, Tariq Faquih, Jessica D Faul, Lijiang Fei, Anne Marie Fenstad, Takamitsu Funayama, Maiken E Gabrielsen, Chinatsu Gocho, Kirill Gromov, Thomas Hansen, Georgi Hudjashov, Thorvaldur Ingvarsson, Jessica S Johnson, Helgi Jonsson, Saori Kakehi, Juha Karjalainen, Elisa Kasbohm, Susanna Lemmelä, Kuang Lin, Xiaoxi Liu, Marieke Loef, Massimo Mangino, Daniel Mccartney, Iona Y Millwood, Joshua Richman, Mary B Roberts, Kathleen A Ryan, Dino Samartzis, Manu Shivakumar, Søren T Skou, Sachiyo Sugimoto, Ken Suzuki, Hiroshi Takuwa, Maris Teder-Laving, Laurent Thomas, Kohei Tomizuka, Constance Turman, Stefan Weiss, Tian T Wu, Eleni Zengini, Yanfei Zhang, Arcogen Consortium, Argo Consortium, Dbds Genomic Consortium, Estonian Biobank Research Team, Finngen, Genes & Health Research Team, Hunt All-In Pain, Million Veteran Program, Regeneron Genetics Center, Manuel Allen Revez Ferreira, George Babis, Aris Baras, Tyler Barker, David J Carey, Kathryn S E Cheah, Zhengming Chen, Jason Pui-Yin Cheung, Mark Daly, Renée De Mutsert, Charles B Eaton, Christian Erikstrup, Ove Nord Furnes, Yvonne M Golightly, Daniel F Gudbjartsson, Nils P Hailer, Caroline Hayward, Marc C Hochberg, Georg Homuth, Laura M Huckins, Kristian Hveem, Shiro Ikegawa, Muneaki Ishijima, Minoru Isomura, Marcus Jones, Jae H Kang, Sharon L R Kardia, Margreet Kloppenburg, Peter Kraft, Nobuyuki Kumahashi, Suguru Kuwata, Ming Ta Michael Lee, Phil H Lee, Robin Lerner, Liming Li, Steve A Lietman, Luca Lotta, Michelle K Lupton, Reedik Mägi, Nicholas G Martin, Timothy E Mcalindon, Sarah E Medland, Karl Michaëlsson, Braxton D Mitchell, Dennis O Mook-Kanamori, Andrew P Morris, Toru Nabika, Fuji Nagami, Amanda E Nelson, Sisse Rye Ostrowski, Aarno Palotie, Ole Birger Pedersen, Frits R Rosendaal, Mika Sakurai-Yageta, Carsten Oliver Schmidt, Pak Chung Sham, Jasvinder A Singh, Diane T Smelser, Jennifer A Smith, You-Qiang Song, Erik Sørensen, Gen Tamiya, Yoshifumi Tamura, Chikashi Terao, Gudmar Thorleifsson, Anders Troelsen, Aspasia Tsezou, Yuji Uchio, A G Uitterlinden, Henrik Ullum, Ana M Valdes, David A Van Heel, Robin G Walters, David R Weir, J Mark Wilkinson, Bendik S Winsvold, Masayuki Yamamoto, John-Anker Zwart, Kari Stefansson, Ingrid Meulenbelt, Sarah A Teichmann, Joyce B J Van Meurs, Unnur Styrkarsdottir, Eleftheria Zeggini

Faculty, Staff and Students Publications

Osteoarthritis is the third most rapidly growing health condition associated with disability, after dementia and diabetes1. By 2050, the total number of patients with osteoarthritis is estimated to reach 1 billion worldwide2. As no disease-modifying treatments exist for osteoarthritis, a better understanding of disease aetiopathology is urgently needed. Here we perform a genome-wide association study meta-analyses across up to 489,975 cases and 1,472,094 controls, establishing 962 independent associations, 513 of which have not been previously reported. Using single-cell multiomics data, we identify signal enrichment in embryonic skeletal development pathways. We integrate orthogonal lines of evidence, including …

Misconceptions Among Mental Health Treatment Providers About Ocd And Ptsd, Caitlin M Pinciotti, Gabriella T Ponzini, Gianna M Colombo, Carmen P Mclean, Terri L Fletcher, Natalie E Hundt, Lauren P Wadsworth, Nathaniel Van Kirk, Stephanie Y Wells, Jonathan S Abramowitz, Wayne K Goodman, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) share overlapping features for which similar cognitive behavioral treatment (CBT) strategies can be employed. However, the comorbid presence of these conditions poses unique clinical considerations, and a nuanced approach to assessment, conceptualization, and treatment is needed when working with individuals with co-occurring OCD and PTSD. Treatment providers may not be aware of these nuances and may hold misconceptions about co-occurring OCD and PTSD, impacting their approach to assessment, conceptualization, and treatment. The current study sought to examine possible misconceptions among mental health treatment providers of differing specializations. Among 146 primarily CBT-oriented treatment …

Antibiotic Prophylaxis With Urodynamic Studies In Spinal Cord Injury: Assessing Practice Patterns And Outcomes To Guide Future Practice In A Single Center, Du Pham, Bradley Chi, Felicia Skelton, Donna Huang

Faculty, Staff and Students Publications

Context/objective: Despite urinary tract infections (UTIs) being a common problem in patients with spinal cord injuries (SCIs), and a well-known complication of invasive urologic procedures, little consensus exists regarding the standard of care for peri-procedural antibiotic use for SCI patients undergoing urodynamics studies (UDS). Our research seeks to evaluate local antibiotic prophylaxis pattern in SCI patients undergoing UDS, assess incidence of post-procedural UTI, describe local antibiotic resistance trends, and provide antibiotic stewardship considerations to guide future practice.

Design/setting/participants: Retrospective cohort study of SCI patients undergoing UDS from January 2010 to January 2020 at a Veterans Affairs SCI Center. Data on …

Treatment Of Rapid Recurrence Of Severe Steatosis With Combined Glucagon-Like Peptide-1 Agonist And Growth Hormone Therapy In A Pediatric Patient Transplanted For Metabolic Dysfunction-Associated Steatohepatitis Cirrhosis In The Setting Of Hypopituitarism, Stephanie R Saaybi, Henry Shiau, Goo Lee, Babak John Orandi, Luz Helena Gutierrez Sanchez

Faculty, Staff and Students Publications

The association between hypopituitarism and metabolic dysfunction-associated steatotic liver disease is increasingly recognized, although data about therapies targeting recurrence posttransplant is limited. An 8-year-old with hypopituitarism-associated metabolic dysfunction-associated steatotic liver disease underwent a liver transplant due to rapid progression of metabolic dysfunction-associated steatohepatitis. Hepatosteatosis recurred within weeks. Her therapeutic plan included a glucagon-like peptide-1 agonist and growth hormone replacement. Her transaminases normalized in 2.5 months, and her macrosteatosis significantly improved on the 1-year surveillance biopsy. This case highlights one of the youngest reported children with hypopituitarism to have undergone transplantation for rapidly progressing metabolic dysfunction-associated steatohepatitis and its recurrence post-operatively. …

Repeat Ascaris Challenge Reduces Worm Intensity Through Gastric Cellular Reprograming, Yifan Wu, Charlie Suarez-Reyes, Nina L Tang, Alexander R Kneubehl, Jill E Weatherhead

Faculty, Staff and Students Publications

Ascariasis (roundworm) is the most prevalent parasitic nematode infection worldwide, impacting approximately 500 million people predominantly in low- and middle-income countries (LMICs). While people of all ages are infected with Ascaris, infection intensity (defined by worm burden) paradoxically peaks in pre-school and school-aged children but then declines with age. The cause of age-dependent Ascaris worm intensity is not well understood but may be dependent on cellular changes in mucosal barrier sites. We have previously found that the gastric mucosa is a critical barrier site for Ascaris infection as ingested Ascaris larvae use acidic mammalian chitinase (AMCase) secreted by gastric chief …

Bi-Allelic Uggt1 Variants Cause A Congenital Disorder Of Glycosylation, Zain Dardas, Laura Harrold, Daniel G Calame, Claire G Salter, Takashi Kikuma, Kevin P Guay, Bobby G Ng, Kanae Sano, Ahmad K Saad, Haowei Du, Riccardo Sangermano, Sohil G Patankar, Shalini N Jhangiani, Semra Gürsoy, Mohamed S Abdel-Hamid, Mahmoud K H Ahmed, Reza Maroofian, Rauan Kaiyrzhanov, Kamran Salayev, Wendy D Jones, Ana Pérez Caballero, Lucy Mcgavin, Michael Spiller, Miranda Durkie, Nick Wood, Lauren O'Grady, Paula Goldenberg, Ann M Neumeyer, Amber Begtrup, Sherif F Abdel-Ghafar, Maha S Zaki, Hilde Van Esch, Jennifer E Posey, Olivia K Wenger, Ethan M Scott, Kinga M Bujakowska, Richard A Gibbs, Davut Pehlivan, Dana Marafi, Joseph S Leslie, Nishanka Ubeyratna, Jacob Day, Martina Owens, Jessica Settle, Soher Balkhy, Abdullah Tamim, Lama Alabdi, Fowzan S Alkuraya, Yoichi Takeda, Hudson H Freeze, Daniel N Hebert, James R Lupski, Andrew H Crosby, Emma L Baple

Faculty, Staff and Students Publications

Congenital disorders of glycosylation (CDGs) comprise a large heterogeneous group of metabolic conditions caused by defects in glycoprotein and glycolipid glycan assembly and remodeling, a fundamental molecular process with wide-ranging biological roles. Herein, we describe bi-allelic UGGT1 variants in fifteen individuals from ten unrelated families of various ethnic backgrounds as a cause of a distinctive CDG of variable severity. The cardinal clinical features of UGGT1-CDG involve developmental delay, intellectual disability, seizures, characteristic facial features, and microcephaly in the majority (9/11 affected individuals for whom measurements were available). The more severely affected individuals display congenital heart malformations, variable skeletal abnormalities including …

Feasibility And Acceptability Of The Team Pilot Trial With African American And Latino Families, Ashley M Butler, Marisa E Hilliard, Krystal Christopher, Marissa Baudino, Charles Minard, Lefkothea Karaviti

Faculty, Staff and Students Publications

Objective: We adapted the empirically supported Family Teamwork intervention protocol to support collaborative parent involvement in type 1 diabetes (T1D) management among African American and Latino parents of children with T1D. This randomized pilot study aimed to evaluate feasibility and acceptability of the Type 1 Diabetes Empowerment and Management (TEAM) intervention.

Methods: African American and Latino parents (n = 59; 65% recruitment rate) of youth (ages 5-10 years, M = 8.9 ± 1.6 years; 59% female, M hemoglobin A1c 9.0% ± 1.9%) with diabetes duration of ≥1 year and who were fluent in English and not planning to leave the …

Functional Vision Assessment Over 4 Years In Ush2a Using The Veteran Affairs Low-Vision Visual Functioning Questionnaire, Bela Parekh, Nicholas Peck-Dimit, Jacque L Duncan, Lassana Samarakoon, Maria Fernanda Abalem, Chris A Andrews, Isabelle Audo, Allison R Ayala, Chris Bradley, Janet K Cheetham, Gislin Dagnelie, Todd A Durham, Rachel M Huckfeldt, Gabrielle D Lacy, Brett Malbin, Michel Michaelides, David C Musch, Katarina Stingl, Christina Y Weng, Alex Z Zmejkoski, Michele Melia, K Thiran Jayasundera, Foundation Fighting Blindness Clinical Consortium Investigator Group

Faculty, Staff and Students Publications

Purpose: The purpose of this study was to evaluate the validity of the Veterans Affairs Low Vision Visual Functioning Questionnaire (VALVVFQ-48) functional vision scores (FVS) in patients with USH2A-associated retinal degeneration. In addition, to correlate the change in the VALVVFQ-48 FVS with the change in visual function (VF) measurements.

Methods: The VALVVFQ-48 was administered verbally to participants ≥18 years of age at baseline, and after 2 and 4 years. Associations among changes in FVS and changes in VF measures were assessed using the Spearman correlation coefficients. Mixed effects regression models with a random intercept were used to estimate annual rates …

Efficacy And Safety Of Epicutaneous Immunotherapy In Peanut-Allergic Toddlers: Open-Label Extension To Epitope, Matthew Greenhawt, Deborah Albright, Sara Anvari, Nicolette Arends, Peter D Arkwright, Philippe Bégin, Katharina Blümchen, Terri Brown-Whitehorn, Heather Cassell, Edmond S Chan, Christina E Ciaccio, Antoine Deschildre, Amandine Divaret-Chauveau, Stacy Dorris, Morna Dorsey, George Du Toit, Thomas Eiwegger, Michel Erlewyn-Lajeunesse, David M Fleischer, Lara S Ford, Maria Garcia-Lloret, Jonathan O'B Hourihane, Nicola Jay, Stacie M Jones, Edwin H Kim, Kirsten Kloepfer, Stephanie Leonard, Guillaume Lezmi, Jay Lieberman, Jeanne Lomas, Melanie Makhija, Michael O'Sullivan, Christopher Parrish, Jane Peake, Kirsten P Perrett, Daniel Petroni, Jacqueline A Pongracic, Patrick Quinn, Rachel G Robison, Georgiana Sanders, Lynda Schneider, Hemant Sharma, Sayantani B Sindher, Juan Trujillo, Paul J Turner, Katherine Tuttle, Julia Upton, Pooja Varshney, Brian P Vickery, Christian Vogelberg, Brynn Wainstein, Julie Wang, Robert Wood, Katharine J Bee, Dianne E Campbell, Todd D Green, Rihab Rouissi, Henry T Bahnson, Timothée Bois, Hugh A Sampson, A Wesley Burks

Faculty, Staff and Students Publications

Background: The pivotal phase 3 EPITOPE trial, a 12-month, double-blind, placebo-controlled study of epicutaneous immunotherapy with the VIASKIN patch containing 250 μg of peanut protein (VP250), previously reported significant treatment response versus placebo in peanut-allergic toddlers aged 1 through 3 years.

Objective: To assess the interim efficacy and safety of VP250 from the first year of the EPITOPE open-label extension (OLE) study.

Methods: Eligible participants enrolled in the OLE study for up to 3 years of total treatment with annual double-blind, placebo-controlled food challenges (DBPCFCs) and safety assessments; here we report the first-year OLE (year 2) results.

Results: A total …

Malperfusion In Patients With Acute Type A Aortic Dissection: A Nationwide Analysis, Nicholas J Goel, John J Kelly, William L Patrick, Yu Zhao, Joseph E Bavaria, Maral Ouzounian, Anthony L Estrera, Hiroo Takayama, Edward P Chen, T Brett Reece, G Chad Hughes, Eric E Roselli, Karen M Kim, Himanshu J Patel, Michael E Bowdish, Jason S Sperling, Bradley G Leshnower, Ourania Preventza, William T Brinkman, Nimesh D Desai

Faculty, Staff and Student Publications

Background: This study describes in detail the clinical burden of malperfusion associated with acute type A aortic dissection (ATAAD) in a large, national cohort and the effect of treatment strategy on outcomes.

Methods: All patients undergoing repair of ATAAD between 2017 and 2020 in The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database were studied. Malperfusion was defined using STS definitions on the basis of imaging or the surgeon's evaluation. Multivariable logistic regression was used to analyze the effect of patient and treatment factors on outcomes in patients with and without malperfusion.

Results: A total of 9958 patients undergoing …

Longevity Humans Have Youthful Erythrocyte Function And Metabolic Signatures, Fang Yu, Changhan Chen, Wuping Liu, Zhixiang Zhao, Yuhua Fan, Zhenjiang Li, Weilun Huang, Tingting Xie, Cheng Luo, Zhouzhou Yao, Qi Guo, Zhiyu Yang, Juan Liu, Yujin Zhang, Rodney E Kellems, Jian Xia, Ji Li, Yang Xia

Faculty, Staff and Student Publications

Longevity individuals have lower susceptibility to chronic hypoxia, inflammation, oxidative stress, and aging-related diseases. It has long been speculated that "rejuvenation molecules" exist in their blood to promote extended lifespan. We unexpectedly discovered that longevity individuals exhibit erythrocyte oxygen release function similar to young individuals, whereas most elderly show reduced oxygen release capacity. Untargeted erythrocyte metabolomics profiling revealed that longevity individuals are characterized by youth-like metabolic reprogramming and these metabolites effectively differentiate the longevity from the elderly. Quantification analyses led us to identify multiple novel longevity-related metabolites within erythrocytes including adenosine, sphingosine-1-phosphate (S1P), and glutathione (GSH) related amino acids. Mechanistically, …

Neuroimaging-Based Variability In Subtyping Biomarkers For Psychiatric Heterogeneity, Zhenfu Wen, Mira Z Hammoud, Carole E Siegel, Eugene M Laska, Duna Abu-Amara, Amit Etkin, Mohammed R Milad, Charles R Marmar

Faculty, Staff and Student Publications

Neuroimaging-based subtyping is increasingly used to explain heterogeneity in psychiatric disorders. However, the clinical utility of these subtyping efforts remains unclear, and replication has been challenging. Here we examined how the choice of neuroimaging measures influences the derivation of neuro-subtypes and the consequences for clinical delineation. On a clinically heterogeneous dataset (total n = 566) that included controls (n = 268) and cases (n = 298) of psychiatric conditions, including individuals diagnosed with post-traumatic stress disorder (PTSD), traumatic brain injury (TBI), and comorbidity of both (PTSD&TBI), we identified neuro-subtypes among the cases using either structural, resting-state, or task-based measures. The …

Maternal Dysbiosis Produces Long-Lasting Behavioral Changes In Offspring, Jacob Hudobenko, Claudia M Di Gesù, Patrick R Mooz, Joseph Petrosino, Nagireddy Putluri, Bhanu P Ganesh, Kristen Rebeles, Frank W Blixt, Venugopal R Venna, Louise D Mccullough

Faculty, Staff and Student Publications

Advanced maternal age (AMA) is defined as a pregnancy in a woman older than 35 years of age. AMA increases the risk for both maternal and neonatal complications, including miscarriage and stillbirth. AMA has also been linked to neurodevelopmental and neuropsychiatric disorders in the offspring. Recent studies have found that age-associated compositional shifts in the gut microbiota contribute to altered microbial metabolism and enhanced inflammation in the host. We investigated the specific contribution of the maternal microbiome on pregnancy outcomes and offspring behavior by recolonizing young female mice with aged female microbiome prior to pregnancy. We discovered that pre-pregnancy colonization …

Genome-Wide Association Meta-Analyses Of Drug-Resistant Epilepsy, Costin Leu, Andreja Avbersek, Remi Stevelink, Helena Martins Custodio, Siwei Chen, Doug Speed, Caitlin A Bennett, Lina Jonsson, Unnur Unnsteinsdóttir, Andrea L Jorgensen, Gianpiero L Cavalleri, Norman Delanty, John J Craig, Chantal Depondt, Michael R Johnson, Bobby P C Koeleman, Emadeldin Hassanin, Maryam Erfanian Omidvar, Roland Krause, Holger Lerche, Anthony G Marson, Terence J O'Brien, Josemir W Sander, Graeme J Sills, Pasquale Striano, Federico Zara, Hreinn Stefansson, Kari Stefansson, Patrick May, Benjamin M Neale, Dennis Lal, Samuel F Berkovic, Epi25 Collaborative, Epipgx Consortium, Sanjay M Sisodiya

Faculty, Staff and Student Publications

Background: Epilepsy is one of the most common neurological disorders, affecting over 50 million people worldwide. One-third of people with epilepsy do not respond to currently available anti-seizure medications, constituting one of the most important problems in epilepsy. Little is known about the molecular pathology of drug resistance in epilepsy, in particular, possible underlying genetic factors are largely unknown.

Methods: We performed a genome-wide association study (GWAS) in two epilepsy cohorts of European ancestry, comparing drug-resistant (N = 4208) to drug-responsive individuals (N = 2618) followed by meta-analyses across the studies. Next, we performed subanalyses split into two broad subtypes: …

Dosimetric Predictors Of Toxicity For Brainstem Metastases And Avms Treated With Stereotactic Radiosurgery: An International, Multi-Institutional Analysis, Raj Singh, Samantha Dayawansa, Duy Pham, Georgios Mantziaris, Selcuk Peker, Yavuz Samanci, Ali Haluk Duzkalir, David Mathieu, Anne-Marie Langlois, Molly L Egnot, Ronald E Warnick, Herwin Speckter, Erwin Lazo, Laura Mendez, Angel I Blanco, Mark J Amsbaugh, Collin Liu, Andrea Becerril-Gaitan, Yoshua Esquenazi, Ching-Jen Chen, Peter Zaki, Yun Liang, Rodney Wegner, Manjul Tripathi, Zhishuo Wei, Shivani A Jajoo, Ajay Niranjan, L Dade Lunsford, Joshua D Palmer, Jason P Sheehan

Faculty, Staff and Student Publications

Background: There are limited data on dosimetric predictors of radiation-induced changes (RICs) for brainstem metastases or arteriovenous malformations (AVMs) following single-fraction stereotactic radiosurgery (SRS).

Methods: We examined a multi-institutional cohort of patients with brainstem metastases or AVMs treated with SRS. We evaluated predictors of RICs graded per CTCAE(Common Terminology Criteria for Adverse Events), including D5%, D95%, D0.03 cc, and D0.5 cc (brainstem minus lesion). Univariate logistic regressions were initially performed with independent variables trending towards significance included on multivariate logistic regression.

Results: A total of 124 brainstem lesions treated with SRS were analyzed (21 AVMs and 103 metastases). The median …

Targeting Discrepancies In Linear Growth Measurements In The Neonatal Intensive Care Unit Through Nursing Interventions: A Quality Improvement Initiative, Gail Snyder, Rebekah Wilkinson, Raina Evans, Meagan Owen, Akram Yazdani, Covi Tibe, Catherine Perez, Lindsay F Holzapfel

Faculty, Staff and Student Publications

Objective: Accurate length measurements are essential for infants to identify growth deficiencies and adjust nutrition accordingly. The gold standard for length measurement in infants is using a length board with two people to obtain an accurate clinical assessment. We aimed to improve the number of measurements with the desired minimal difference, defined as a discrepancy ≤1 cm between nurse and audit measurements, in our center. Our secondary aim was to increase and maintain the number of length boards available.

Methods: This quality improvement (QI) study used a before-and-after intervention comparison design in a single-level IV neonatal intensive care unit between …

First Step To Environmentally Sustainable Endoscopy Practice: A Prospective Study Of Minimizing Multiple Device Use During Screening Colonoscopy At A Large Tertiary Center, Prateek S Harne, Vaishali Harne, Asad Rehman, Nirav Thosani, Madhav Desai

Faculty, Staff and Student Publications

The healthcare sector generates 8% of greenhouse gas emissions in the USA, of which gastrointestinal (GI) endoscopy is the third largest contributor. Single-use tools are a major contributor to modifiable waste generation during GI endoscopy. Through a quality improvement initiative, we aimed to reduce endoscopy waste by urging gastroenterologists to be mindful of tools used during polypectomies by avoiding using multiple tools.We discussed green endoscopy initiatives in monthly journal club and business meetings. Over 14 weeks, 210 patients were included in the pre-intervention group and 112 in the post-intervention group.At baseline, 34% of colonoscopies required no intervention, 32% required one …

Overlapping Clinical Phenotypes In Patients With Primary Ciliary Dyskinesia Or Activated Phosphoinositide 3-Kinase Delta Syndrome, Adam J Shapiro, Eveline Y Wu, Deborah J Morris-Rosendahl, Kenneth N Olivier, Sharon D Dell, Scott D Sagel, Cullen M Dutmer, Ricardo A Mosquera, Markus Rose, Michael G O'Connor, Chi A Ma, Gulbu Uzel, Timothy J Vece, Maimoona A Zariwala, Michael R Knowles, Margaret W Leigh, Stephanie D Davis, Thomas W Ferkol

Faculty, Staff and Student Publications

Primary ciliary dyskinesia and activated phosphoinositide 3-kinase delta syndrome type 1 present similarly, with recurrent respiratory infections and reduced nasal nitric oxide levels. When diagnostic confirmation of primary ciliary dyskinesia with genetic testing and/or ciliary electron microscopy is inconclusive, activated phosphoinositide 3-kinase delta syndrome type 1 and other inborn errors of immunity must be investigated.

Tumour Size Is Associated With Growth Rates Of >0.5 Cm/Year And Delayed Intervention In Small Renal Masses In Patients On Active Surveillance, Maximilian Pallauf, Michael Rezaee, Roy Elias, Tina Wlajnitz, Sean A Fletcher, Joseph Cheaib, Khalid Alkhatib, Peter Chang, Andrew A Wagner, James M Mckiernan, Mohamad E Allaf, Phillip M Pierorazio, Nirmish Singla

Faculty, Staff and Student Publications

Objective: To evaluate the association between tumour size and the growth rate (GR) of small renal masses (SRMs) in patients managed by active surveillance (AS).

Materials and methods: We queried the prospective, multi-institutional Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) registry for patients on AS with an imaging interval of ≥6 months, identifying 456 patients. We tracked tumour size over time; a GR >0.5 cm/year was defined as a GR event. We used multivariable recurrent events and time-to-event Cox regression modelling to evaluate the association between tumour size and GR events (primary outcome) and tumour size and delayed …

Older Adults' Experiences Of Emergency Department Admission Decisions: A Qualitative Study In A Public Safety Net Hospital, Anita N Chary, Annika Bhananker, Beatrice Torres, Victoria Sofia Martell, Manish N Shah, Aanand D Naik

Faculty, Staff and Student Publications

Background: Hospital admission is a significant event in the healthcare trajectory of older adults (age 60 +). Numerous harms such as delirium, falls, and adverse medication events can arise that outweigh the benefits of admission. Little is known about how older adults feel about being hospitalized or what they think admission will achieve for them. These issues are particularly important to understand in socioeconomically disadvantaged patients, who have poor access to outpatient care and higher hospitalization rates.

Methods: We performed semi-structured interviews with emergency department (ED) patients aged 60 and older who were being admitted. The study site was a …