Digital Commons Network^™

The Dialysis Foot- The Impact Of Presenting Estimated Glomerular Filtration Rate On Clinical Outcomes In Patients Hospitalized With Diabetic Foot Infections, Arthur Tarricone, Tyler L Coye, Allen Gee, Bijan Najafi, Michael C Siah, Lawrence A Lavery

Center on Aging Staff Publications

To evaluate the association between presenting estimated glomerular filtration rate (eGFR) and clinical outcomes in patients hospitalized with diabetic foot infections. This retrospective cohort study included 344 patients with moderate to severe diabetic foot infections. Patients were categorized into three groups based on presenting estimated eGFR: eGFR ≥60 (eGFR >60 mL/min), eGFR 30-60 (eGFR 30-60 mL/min) and eGFR < 30 (eGFR < 30 mL/min). Outcomes assessed included wound healing, time to heal, re-infection, amputation, mortality and re-hospitalization for infection. Compared with patients with eGFR < 30, patients with eGFR ≥60 had significantly lower rates of retinopathy, peripheral arterial disease and use of beta blockers or calcium channel blockers. Glycated haemoglobin levels were inversely related to eGFR, decreasing as eGFR severity increased. Haemoglobin levels were significantly lower, and inflammatory markers (ESR and CRP) were significantly higher in patients with eGFR < 30. There were no significant differences among eGFR groups in rates of wound healing, time to heal, re-infection or amputation. However, mortality increased with decreasing eGFR (1.9% in eGFR ≥60 vs. 3.2% in eGFR 30-60 vs. 8.1% in eGFR < 30; p = 0.04). Similarly, re-hospitalization for infection at a different site also increased with decreasing eGFR (20.5% in eGFR ≥60 vs. 28.1% in eGFR 30-60 vs. 48.4% in eGFR < 30; p <  0.01). In diabetic foot infections, presenting eGFR severity did not affect rates of wound healing, time to heal, re-infection or amputation. However, decreasing eGFR was associated with increased mortality and re-hospitalization for infection at a different site. In this study, presenting eGFR was not a predictive value for wound healing or time until healing, however was associated with rehospitalization and overall mortality this diabetic foot population.

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 …

Navacaprant, A Novel And Highly Selective Kappa Opioid Receptor Antagonist, In Adults With Major Depressive Disorder: A Randomized, Double-Blind Phase 2 Clinical Trial, Sanjay J Mathew, Andrew J Cutler, Nicole C Visitacion, Michael Gold, Jason Yuan, Bill Aurora

Staff and Researcher Publications

PURPOSE/BACKGROUND: This phase 2a randomized, double-blind, placebo-controlled, 8-week trial assessed the efficacy and safety of navacaprant, a highly selective kappa opioid receptor antagonist, in adults with major depressive disorder (MDD).

METHODS/PROCEDURES: Participants with 17-Item Hamilton Depression Rating Scale (HAMD-17) scores of 14 to 30 were randomized 1:1 to once-daily navacaprant 80 mg or placebo (n = 102 each). The primary endpoint was HAMD-17 change from baseline (CFB) to week 8. Secondary endpoints included CFB in Snaith-Hamilton Pleasure Scale (SHAPS). No adjustment for multiple comparisons was made.

FINDINGS/RESULTS: At week 8, HAMD-17 CFB was not statistically significantly improved with navacaprant vs …

Azetukalner, A Novel Kv7 Potassium Channel Opener, In Adults With Major Depressive Disorder: A Randomized Clinical Trial, Noam N Butterfield, Constanza Luzon Rosenblut, Maurizio Fava, Christoph U Correll, Anthony J Rothschild, James W Murrough, Sanjay J Mathew, Gregory N Beatch, Celene Grayson, Cynthia Harden, Jenny Qian, Joe Mcintosh, Rostam Namdari, Christopher Kenney

Staff and Researcher Publications

Importance: Available antidepressants provide inadequate therapeutic responses in many patients with major depressive disorder (MDD), highlighting a substantial unmet need.

Objective: To evaluate the efficacy and safety of azetukalner, a novel, potent KV7 potassium channel opener, in participants with MDD.

Design, setting, and participants: X-NOVA was a multicenter, proof-of-concept, phase 2, randomized, double-blind, parallel-group, placebo-controlled clinical trial that evaluated azetukalner in participants (adults aged ≥18 to ≤65 years) with moderate to severe MDD in a current depressive episode. Participants were enrolled between April 2022 and October 2023, and data analysis occurred from January 2023 to January 2024.

Intervention: Participants were …

Trajectories Of Attention Problems In Preschoolers Born Very Preterm., Marie Camerota, Francisco Xavier Castellanos, Brian S. Carter, Jennifer Check, Jennifer Helderman, Julie A. Hofheimer, Elisabeth C. Mcgowan, Charles R. Neal, Steven L. Pastyrnak, Lynne M. Smith, Thomas Michael O'Shea, Carmen J. Marsit, Barry M. Lester

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Children born preterm are at heightened risk for neurodevelopmental impairment, including specific deficits in attention. Few studies have investigated change over time in attention problems prior to school entry. The current study aims to describe trajectories of attention problems from age 2 through 5 years in a cohort of children born(GA), identify sociodemographic, medical, and neurobehavioral characteristics associated with attention trajectories, and test whether attention problem trajectories predict the risk of a reported attention-deficit/hyperactivity disorder (ADHD) diagnosis.

METHODS: We studied 608 infants from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study, a prospective, multisite study of …

A Scoping Review Of Sexual And Reproductive Health Interventions With Youth In U.S. Juvenile Facilities., April Mcneill-Johnson, Jason Glenn, Nekia Ivory Daniel, Mira Menon, Basil H. Aboul-Enein, Patricia J. Kelly, Megha Ramaswamy

Manuscripts, Articles, Book Chapters and Other Papers

Youth placed in U.S. juvenile detention facilities face multilevel barriers that contribute to disparate sexual and reproductive health (SRH) outcomes when compared to their peers in the general adolescent population. Minimal information is available about evidence-based interventions that have been effective in changing these outcomes. The aim of this scoping review was to focus on the current state of SRH and identify recommendations for SRH care. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for scoping reviews guidelines, we searched electronic databases for publications published through March 2024. The search terms were designed to find intervention studies focusing …

Brain Morphometry In Infants Later Diagnosed With Autism Is Related To Later Language Skills, Luke E Moraglia, Kelly N Botteron, Natasha Marrus, Et Al.

2020-Current year OA Pubs

Autism spectrum disorder (ASD) presents early in life with distinct social and language differences. This study explores the association between infant brain morphometry and language abilities using an infant-sibling design. Participants included infants who had an older sibling with autism (high likelihood, HL) who were later diagnosed with autism (HL-ASD; n = 31) and two non-autistic control groups: HL-Neg (HL infants not diagnosed with autism; n = 126) and LL-Neg (typically developing infants who did not have an older sibling with autism; n = 77). Using a whole-brain approach, we measured cortical thickness and surface area at 6 and 12 …

Demographics And Clinical Features Associated With Abnormal Small Bowel Motility In Systemic Sclerosis, Jenice X Cheah, Jamie Perin, Michael Hughes, Christopher A Mecoli, Julie J Paik, Laura K Hummers, Ami A Shah, Zsuzsanna H Mcmahan

Faculty, Staff and Student Publications

Objective: The small bowel is affected in up to 50% of systemic sclerosis (SSc) patients, and some patients experience severe complications. Our aim was to use specific statistical methods to compare demographic and clinical features of SSc patients with and without abnormal small bowel to better characterize patients at risk for this complication.

Methods: SSc patients with gastrointestinal symptoms were prospectively enrolled and underwent a scintigraphy-based whole gut transit (WGT) study. A cross-sectional analysis was performed comparing clinical features between patients with and without abnormal small bowel transit by WGT. Univariate logistic regression models and multivariable models were used to …

Author Correction: Predictive Equation Derived From 6,497 Doubly Labelled Water Measurements Enables The Detection Of Erroneous Self-Reported Energy Intake, Rania Bajunaid, Chaoqun Niu, Catherine Hambly, Zongfang Liu, Yosuke Yamada, Heliodoro Aleman-Mateo, Liam J Anderson, Lenore Arab, Issad Baddou, Linda Bandini, Kweku Bedu-Addo, Ellen E Blaak, Carlijn V C Bouten, Soren Brage, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Regina Casper, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Peter S W Davies, Prasangi Dabare, Lara R Dugas, Simon Eaton, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Melanie Gillingham, Annelies H Goris, Michael Gurven, Asmaa El Hamdouchi, Hinke H Haisma, Daniel Hoffman, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Misaka Kimura, William E Kraus, Wantanee Kriengsinyos, Rebecca Kuriyan, Robert F Kushner, Estelle V Lambert, Pulani Lanerolle, Christel L Larsson, William R Leonard, Nader Lessan, Marie Löf, Corby K Martin, Eric Matsiko, Anine C Medin, James C Morehen, James P Morton, Aviva Must, Marian L Neuhouser, Theresa A Nicklas, Christine D Nyström, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, John J Reilly, Rebecca Reynolds, Susan B Roberts, Dulani Samaranayakem, Luis B Sardinha, Analiza M Silva, Anders M Sjödin, Marina Stamatiou, Eric Stice, Samuel S Urlacher, Ludo M Van Etten, Edgar G A H Van Mil, George Wilson, Jack A Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Srishti Sinha, Cornelia U Loechl, Amy H Luke, Herman Pontzer, Jennifer Rood, Hiroyuki Sagayama, Dale A Schoeller, Klaas R Westerterp, William W Wong, John R Speakman

Children’s Nutrition Research Center Staff Publications

No abstract provided.

Cord Blood Treatment For Children With Cerebral Palsy: Individual Participant Data Meta-Analysis, Megan Finch-Edmondson, Madison C B Paton, Annabel Webb, Mahmoud Reza Ashrafi, Remy K Blatch-Williams, Charles S Cox, Kylie Crompton, Alexandra R Griffin, Minyoung Kim, Steven Kosmach, Joanne Kurtzberg, Masoumeh Nouri, Mi Ri Suh, Jessica Sun, Morteza Zarrabi, Iona Novak

The Brown Foundation: Institute of Molecular Medicine

Context: Umbilical cord blood (UCB) is a novel treatment for cerebral palsy (CP), with trials indicating UCB can improve gross motor function. However, heterogeneity has limited the ability to interpret findings.

Objective: Assess the safety and efficacy of UCB for improving gross motor function in children with CP, including exploring cell dose effect and responder subgroups.

Data sources: Individual participant data from published reports and registered trials identified via systematic searches.

Study selection: Studies administering UCB to individuals with CP collecting Gross Motor Function Measure (GMFM) scores.

Data extraction: A 1-stage individual participant data meta-analysis was conducted in R to …

Clinical Implications Of Mismatch Repair Deficiency In Pancreatic Ductal Adenocarcinoma, Zachary Kaplan, Elizabeth Prezioso, Aditi Jain, Harish Lavu, Charles Yeo, Wilbur Bowne, Avinoam Nevler

Kimmel Cancer Center Faculty Papers

BACKGROUND: Pancreatic cancer is a highly aggressive and lethal disease, characterized by a limited response to chemotherapy and overall poor prognosis. Pancreatic cancers with a distinct mismatch repair deficiency, although relatively rare, have been shown to be associated with markedly better outcomes in comparison. Furthermore, whereas pancreatic cancers are generally unresponsive to current immunotherapy, this specific group of tumors has been shown to have a notable susceptibility to immune checkpoint inhibitors.

AIMS: In this review, we aim to summarize the relevant literature regarding mismatch-repair associated pancreatic cancers, the impacted biological mechanisms, and the resulting vulnerabilities for potential opportunistic immunotherapeutic treatment …

Characterization Of Human Senescent Cell Biomarkers For Clinical Trials, Joshua N Farr, David G Monroe, Elizabeth J Atkinson, Mitchell N Froemming, Ming Ruan, Nathan K Lebrasseur, Sundeep Khosla

Faculty, Staff and Students Publications

There is an increasing need for biomarkers of senescent cell burden to facilitate the selection of participants for clinical trials. p16 Ink4a is encoded by the CDKN2A locus, which produces five variant transcripts in humans, two of which encode homologous p16 proteins: p16Inka4a, encoded by p16_variant 1, and p16ɣ, encoded by p16_variant 5. While distinct quantitative polymerase chain reaction primers can be designed for p16_variant 5, primers for p16_variant 1 also measure p16_variant 5 (p16_variant 1 + 5). In a recent clinical trial evaluating the effects of the senolytic combination, dasatinib + quercetin (D + Q), on …

User Actions Within A Clinical Decision Support Alert For The Management Of Hypertension In Chronic Kidney Disease, Lipika Samal, Sarah W Chen, Stuart Lipsitz, Heather J Baer, John L Kilgallon, Michael Gannon, Ryan Dunk, Weng Ian Chay, Richard Fay, Michael Sainlaire, Chenxi Gao, Matthew Wien, Pamela M Garabedian, Edward Wu, Hojjat Salmasian, David W Bates, Patricia C Dykes, Adam Wright, Allison B Mccoy

Faculty, Staff and Students Publications

This study aimed to examine user actions within a clinical decision support (CDS) alert addressing hypertension (HTN) in chronic kidney disease (CKD).A pragmatic randomized controlled trial of a CDS alert for primary care patients with CKD and uncontrolled blood pressure included prechecked default orders for medication initiation or titration, basic metabolic panel (BMP), and nephrology electronic consult (e-consult). We examined each type of action and calculated percentages of placed and signed orders for subgroups of firings.There were firings for medication initiation (813) and medication titration (430), and every firing also included orders for nephrology e-consult (1,243) and BMP (1,243). High …

The Influence Of The American Association For Thoracic Surgery On Clinical Trial Development By Cardiothoracic Surgeons, Adishesh K Narahari, Taylor M Horgan, Anirudha S Chandrabhatla, Abhinav Kareddy, Ajami Gikandi, Marco A Zenati, David Harpole, David Jones, Leora T Yarboro, Bryan Burt, A Sasha Krupnick, J Hunter Mehaffey

Faculty, Staff and Students Publications

Objective: Clinical trials play a critical role in the rapidly evolving field of cardiothoracic surgery and the American Association for Thoracic Surgery Clinical Trials Methods Course has provided a biannual symposium led by preeminent surgeons with vast experience in planning, conducting, and analyzing surgical clinical trials. This study hypothesizes that participation in the course is associated with future success in clinical trial leadership.

Methods: A list of course attendees (2014-2022) was queried in ClinicalTrials.gov, a database of clinical trials funded by the US Department of Health and Human Services and the National Institutes of Health. The type of clinical trial …

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 …

Temi: Tissue-Expansion Mass-Spectrometry Imaging, Hua Zhang, Lang Ding, Amy Hu, Xudong Shi, Penghsuan Huang, Haiyan Lu, Paul W Tillberg, Meng C Wang, Lingjun Li

Faculty, Staff and Students Publications

The spatial distribution of diverse biomolecules in multicellular organisms is essential for their physiological functions. High-throughput in situ mapping of biomolecules is crucial for both basic and medical research, and requires high scanning speed, spatial resolution, and chemical sensitivity. Here we developed a tissue-expansion method compatible with matrix-assisted laser desorption/ionization mass-spectrometry imaging (TEMI). TEMI reaches single-cell spatial resolution without sacrificing voxel throughput and enables the profiling of hundreds of biomolecules, including lipids, metabolites, peptides (proteins), and N-glycans. Using TEMI, we mapped the spatial distribution of biomolecules across various mammalian tissues and uncovered metabolic heterogeneity in tumors. TEMI can be easily …

Recommendations For Design, Execution, And Reporting Of Studies On Experimental Thoracic Aortopathy In Preclinical Models, Alan Daugherty, Dianna M Milewicz, David A Dichek, Ketan B Ghaghada, Jay D Humphrey, Scott A Lemaire, Yanming Li, Ziad Mallat, Yvan Saeys, Hisashi Sawada, Ying H Shen, Toru Suzuki, Zhen Zhou

Faculty, Staff and Students Publications

There is a recent dramatic increase in research on thoracic aortic diseases that includes aneurysms, dissections, and rupture. Experimental studies predominantly use mice in which aortopathy is induced by chemical interventions, genetic manipulations, or both. Many parameters should be deliberated in experimental design in concert with multiple considerations when providing dimensional data and characterization of aortic tissues. The purpose of this review is to provide recommendations on guidance in (1) the selection of a mouse model and experimental conditions for the study, (2) parameters for standardizing detection and measurements of aortic diseases, (3) meaningful interpretation of characteristics of diseased aortic …

Atp1a3 Variants, Variably Penetrant Short Qt Intervals, And Lethal Ventricular Arrhythmias, Mary E Moya-Mendez, Minu-Tshyeto Bidzimou, Padmapriya Muralidharan, Zhushan Zhang, Jordan E Ezekian, Robin M Perelli, Lauren E Parker, Lyndsey Prange, April Boggs, Jeffrey J Kim, Taylor S Howard, Tarah A Word, Xander H T Wehrens, Gabriela Reyes Valenzuela, Roberto Caraballo, Giacomo Garone, Federico Vigevano, Sarah Weckhuysen, Charissa Millevert, Monica Troncoso, Mario Matamala, Simona Balestrini, Sanjay M Sisodiya, Josephine Poole, Claudio Zucca, Eleni Panagiotakaki, Maria T Papadopoulou, Sébile Tchaicha, Marta Zawadzka, Maria Mazurkiewicz-Beldzinska, Carmen Fons, Jennifer Anticona, Elisa De Grandis, Ramona Cordani, Livia Pisciotta, Sergiu Groppa, Sandra Paryjas, Francesca Ragona, Elena Mangia, Tiziana Granata, Andrey Megvinov, Mirjana Pavlicek, Kevin Ess, Christine Q Simmons, Alfred L George, Rosaria Vavassori, Mohamad A Mikati, Andrew P Landstrom

Faculty, Staff and Students Publications

Importance: Alternating hemiplegia of childhood (AHC) is a disorder that can result from pathogenic variants in ATP1A3-encoded sodium-potassium adenosine triphosphatase alpha 3 (ATP1A3). While AHC is primarily a neurologic disease, some individuals experience sudden unexplained death (SUD) potentially associated with cardiac arrhythmias.

Objective: To determine the impact of ATP1A3 variants on cardiac electrophysiology and whether lethal ventricular arrhythmias are associated with SUD in patients with AHC.

Design, setting, and participants: In this international, multicenter case-control study from 12 centers across 10 countries, patients with AHC were grouped by ATP1A3 variant status (positive vs negative) and into subgroups with the most …

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. …

Pediatric Predictive Artificial Intelligence Implemented In Clinical Practice From 2010 To 2021: A Systematic Review, Swaminathan Kandaswamy, Lindsey A Knake, Adam C Dziorny, Sean M Hernandez, Allison B Mccoy, Lauren M Hess, Evan Orenstein, Mia S White, Eric S Kirkendall, Matthew J Molloy, Philip A Hagedorn, Naveen Muthu, Avinash Murugan, Jonathan M Beus, Mark Mai, Brooke Luo, Juan D Chaparro

Faculty, Staff and Students Publications

To review pediatric artificial intelligence (AI) implementation studies from 2010 to 2021 and analyze reported performance measures.We searched PubMed/Medline, Embase CINHAL, Cochrane Library CENTRAL, IEEE, and Web of Science with controlled vocabulary. Inclusion criteria: AI intervention in a pediatric clinical setting that learns from data (i.e., data-driven, as opposed to rule-based) and takes actions to make patient-specific recommendations; published between 01/2010 and 10/2021; must have agency (AI must provide guidance that affects clinical care, not merely running in the background). We extracted study characteristics, target users, implementation setting, time span, and performance measures.Of 126 articles reviewed as full text, 17 …

Computational And Functional Prioritization Identifies Genes That Rescue Behavior And Reduce Tau Protein In Fly And Human Cell Models Of Alzheimer Disease, Morgan C Stephens, Jiayang Li, Megan Mair, Justin Moore, Katy Zhu, Akash Tarkunde, Bismark Amoh, Alma M Perez, Arya Bhakare, Fangfei Guo, Joshua M Shulman, Ismael Al-Ramahi, Juan Botas

Faculty, Staff and Students Publications

Genome-wide association studies (GWASs) in Alzheimer disease (AD) have uncovered over 70 loci significantly associated with AD risk, but identifying the true causal gene(s) at these loci requires systematic functional validation that is rarely performed due to limitations of time and cost. Here, we integrate transcriptome-wide association study (TWAS) with colocalization analysis, fine-mapping, and additional annotation of AD GWAS variants to identify 123 genes at known and suggestive AD risk loci. A comparison with human AD brain transcriptome data confirmed that many of these candidate genes are dysregulated in human AD and correlate with neuropathology. We then tested all available …

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

Background

Methods

Results

Changes In Adequacy Of Splanchnic Oxygen Delivery And Splanchnic Artery Doppler After Bolus Feedings In Infants: A Systematic Review And Meta-Analysis, Rohit S Loomba, Saloni P Sheth, Joshua Wong, Megan Davis, Juan S Farias, Enrique G Villarreal, Saul Flores

Faculty, Staff and Students Publications

Background: Current practice regarding timing of feed initiation and feed tolerance largely relies on anecdotal practice and protocols. This study aims to provide an objective measure to guide clinical practice by analyzing changes in splanchnic regional oxygen saturation and Doppler patterns with feeds.

Methods: A systematic review was performed. Inclusion criteria were: 1) patients under 1 year of age; 2) splanchnic regional oxygen saturation with near infrared spectroscopy before and after feeds or mesenteric Doppler findings before and after feeds; and 3) clinical parameters must have been presented as either mean and standard deviation or median and range. Endpoints of …

Optimal Delay Time To Initiate Anticoagulation After Ischemic Stroke In Atrial Fibrillation: A Pragmatic, Response-Adaptive Randomized Clinical Trial, Steven J Warach, Lisa A Davis, Patrick Lawrence, Byron Gajewski, Jo Wick, Fred Shi, Ty T Shang, Daiwai M Olson, Sidarrth Prasad, Lee Birnbaum, Jody M Richardson, Sean I Savitz, Mark P Goldberg, Salvador Cruz-Flores, Israel Alba, Jane Anderson, Barbara Kimmel, Chethan P Venkatasubba Rao, Ben King, Adrienne N Dula, Truman J Milling

Faculty, Staff and Students Publications

Importance: Clinical practice guidelines recommend initiation of anticoagulation within 2 weeks after stroke with atrial fibrillation. It is unknown whether there is an optimal starting day within the 14-day period that balances the risks of recurrent embolic events against serious hemorrhagic events.

Objective: To determine if there is an optimal delay time to initiate treatment with a direct oral anticoagulant after atrial fibrillation-related stroke that minimizes the risk of a composite outcome of ischemic or hemorrhagic events.

Design, setting, and participants: This phase 2, pragmatic, response-adaptive randomized clinical trial was conducted between June 2017 and June 2023 at acute care …

The Contribution Of De Novo Coding Mutations To Meningomyelocele, Yoo-Jin Jiny Ha, Ashna Nisal, Isaac Tang, Chanjae Lee, Ishani Jhamb, Cassidy Wallace, Robyn Howarth, Sarah Schroeder, Keng Ioi Vong, Naomi Meave, Fiza Jiwani, Chelsea Barrows, Sangmoon Lee, Nan Jiang, Arzoo Patel, Krisha Bagga, Niyati Banka, Liana Friedman, Francisco A Blanco, Seyoung Yu, Soeun Rhee, Hui Su Jeong, Isaac Plutzer, Michael B Major, Béatrice Benoit, Christian Poüs, Caleb Heffner, Zoha Kibar, Gyang Markus Bot, Hope Northrup, Kit Sing Au, Madison Strain, Allison E Ashley-Koch, Richard H Finnell, Joan T Le, Hal S Meltzer, Camila Araujo, Helio R Machado, Roger E Stevenson, Anna Yurrita, Sara Mumtaz, Awais Ahmed, Mulazim Hussain Khara, Osvaldo M Mutchinick, José Ramón Medina-Bereciartu, Friedhelm Hildebrandt, Gia Melikishvili, Ahmed I Marwan, Valeria Capra, Mahmoud M Noureldeen, Aida M S Salem, Mahmoud Y Issa, Maha S Zaki, Libin Xu, Ji Eun Lee, Donghyuk Shin, Anna Alkelai, Alan R Shuldiner, Stephen F Kingsmore, Stephen A Murray, Heon Yung Gee, W Todd Miller, Kimberley F Tolias, John B Wallingford, Spina Bifida Sequencing Consortium, Sangwoo Kim, Joseph G Gleeson

Faculty, Staff and Students Publications

Meningomyelocele (also known as spina bifida) is considered to be a genetically complex disease resulting from a failure of the neural tube to close. Individuals with meningomyelocele display neuromotor disability and frequent hydrocephalus, requiring ventricular shunting. A few genes have been proposed to contribute to disease susceptibility, but beyond that it remains unexplained1. We postulated that de novo mutations under purifying selection contribute to the risk of developing meningomyelocele2. Here we recruited a cohort of 851 meningomyelocele trios who required shunting at birth and 732 control trios, and found that de novo likely gene disruption or …

Discharge Practice Variability In Pediatric Chronic Home Invasive Ventilation, Guillermo Beltran-Ale, Ryne Simpson, Terri Magruder, Ajay S Kasi, Amit Agarwal, Jake A Kaslow

Faculty, Staff and Students Publications

Introduction: The Pediatric Mechanical Ventilation Society is a collaboration of pediatric pulmonologists with a focus on pediatric chronic home invasive ventilation (PCHIV). Since the initial discharge on PCHIV is not always directed by pediatric pulmonologists, we sought to understand how this variability between centers impact adherence to American Thoracic Society (ATS) guidelines for PCHIV.

Methods: A survey was distributed to pediatric pulmonologists across multiple platforms inquiring about discharging practices for PCHIV and adherence to six of the nine ATS recommendations for PCHIV. Two subgroups were created based on common practices - discharge by pediatric pulmonologists from a non-ICU unit (pulmonary …

Digital Interventions For Suicide Prevention, Sean K Burr, Miao Yu, Danny Clark, Dana Alonzo, Robin E Gearing

Faculty, Staff and Students Publications

Background: Digital-based mobile interventions hold significant promise in preventing suicide. Although mixed, some evidence suggests these interventions are effective and capable of overcoming barriers such as cost and stigma. Aim(s): This review aimed to determine the effectiveness of digital interventions designed to address suicidal ideation and behaviors and the impacts of age, gender, and control group type on these outcomes.

Methods: Databases were searched for randomized controlled trials (RCTs) on digital suicide interventions (apps/online programs) published before January 1, 2022. Data were analyzed using a random-effects model in Stata 17.

Results: The search identified 4,317 articles, and 16 were included. …

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 …

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 …

Cdc’S Core Elements To Promote Diagnostic Excellence, Daniel J Morgan, Hardeep Singh, Arjun Srinivasan, Andrea Bradford, L Clifford Mcdonald, Preeta K Kutty

Faculty, Staff and Students Publications

Nearly a decade after the National Academy of Medicine released the "Improving Diagnosis in Health Care" report, diagnostic errors remain common, often leading to physical, psychological, emotional, and financial harm. Despite a robust body of research on potential solutions and next steps, the translation of these efforts to patient care has been limited. Improvement initiatives are still narrowly focused on selective themes such as diagnostic stewardship, preventing overdiagnosis, and enhancing clinical reasoning without comprehensively addressing vulnerable systems and processes surrounding diagnosis. To close this implementation gap, the US Centers for Disease Control and Prevention (CDC) released the Core Elements of …