Digital Commons Network^™

A New Multiple Imputation Method For High-Dimensional Neuroimaging Data, Tong Lu, Peter Kochunov, Chixiang Chen, Hsin-Hsiung Huang, L Elliot Hong, Shuo Chen

Faculty, Staff and Student Publications

Missing data are a prevalent challenge in neuroimaging, with significant implications for downstream statistical analysis. Neglecting this issue can introduce bias and lead to erroneous inferential conclusions, making it crucial to employ appropriate statistical methods for handling missing data. Although the multiple imputation is a widely used technique, its application in neuroimaging is severely hindered by the high dimensionality of neuroimaging data, and the substantial computational demands. To tackle the critical computational challenges, we propose a novel approach, High dimensional Multiple Imputation (HIMA), based on Bayesian models specifically designed for large-scale neuroimaging datasets. HIMA introduces a new computational strategy to …

The Impact Of Atlas Parcellation On Functional Connectivity Analysis Across Six Psychiatric Disorders, Xiaoya Wu, Chuang Liang, Juan Bustillo, Peter Kochunov, Xuyun Wen, Jing Sui, Rongtao Jiang, Xiao Yang, Zening Fu, Daoqiang Zhang, Vince D Calhoun, Shile Qi

Faculty, Staff and Student Publications

Neuropsychiatric disorders are associated with altered functional connectivity (FC); however, the reported regional patterns of functional alterations suffered from low replicability and high variability. This is partly because of differences in the atlas and delineation techniques used to measure FC-related deficits within/across disorders. We systematically investigated the impact of the brain parcellation approach on the FC-based brain network analysis. We focused on identifying the replicable FCs using three structural brain atlases, including Automated Anatomical Labeling (AAL), Brainnetome atlas (BNA) and HCP_MMP_1.0, and four functional brain parcellation approaches: Yeo-Networks (Yeo), Gordon parcel (Gordon) and two Schaefer parcelletions, among correlation, group difference, …

Selected Social And Lifestyle Correlates Of Brain Health Markers: The Cross-Cohort Collaboration Consortium, Leslie Grasset, Joshua C Bis, Stefan Frenzel, Daniel Kojis, Jeannette Simino, Amber Yaqub, Alexa Beiser, Claudine Berr, Jan Bressler, Robin Bülow, Charles S Decarli, Alison E Fohner, Laura B Harrington, Catherine Helmer, M Arfan Ikram, Rozenn N Lemaitre, Oscar L Lopez, W T Longstreth, Julia Neitzel, Michelle C Odden, Priya Palta, Carsten O Schmidt, Rajesh Talluri, Meike W Vernooij, Henry Völzke, Trudy Voortman, Quest Whalen, Katharina Wittfeld, Hans J Grabe, Thomas H Mosley, Bruce M Psaty, Frank J Wolters, Sudha Seshadri, Carole Dufouil

Faculty, Staff and Student Publications

Introduction: To investigate the associations of education level, marital status, and physical activity with dementia risk and brain MRI markers.

Methods: Data from six community-based samples from the Cross-Cohort Collaboration Consortium were analyzed. Self-reported education level, marital status, and physical activity at age 60 to 75 years were harmonized. Subsamples of participants with brain MRI markers at time of exposure were selected. Associations with dementia risk and cross-sectional MRI markers were meta-analyzed.

Results: Higher education level was associated with lower dementia risk (hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.59; 0.72 vs low level) but not significantly …

Il13rα2-Targeting Antibodies For Immuno-Pet In Solid Malignancies, Leah Gajecki, Irina V Lebedeva, Yu-Rou Liao, Daisy Ambriz, Lukas M Carter, Melina Kumpf, Samantha Lovibond, Justin S Hachey, Maya S Graham, Michael Postow, Jason S Lewis, David P Andrew, Manuel Baca, Heiko Schöder, Steven M Larson, Darren R Veach, Simone Krebs

Faculty, Staff and Student Publications

Interleukin-13 receptor α-2 (IL13Rα2) is a cell surface receptor frequently expressed in solid malignancies, such as glioblastoma and melanoma, with limited expression in healthy tissue, rendering it an ideal target for noninvasive and specific tumor delineation. In this study, we report the development of 5 novel IL13Rα2-targeted human monoclonal antibodies (mAbs) KLG-1-5; in subsequent in vitro and in vivo studies after radiolabeling with 89Zr, we evaluate their performance to identify a lead candidate.

Methods: Five novel human anti-IL13Rα2 mAbs KLG-1-5 were developed and in vitro binding properties and target specificity assessed. In vivo 89Zr-immuno-PET using KLG-1-5 was conducted in a …

In Vivo Antibody Labeling Route And Fluorophore Dictate Labeling Efficiency, Sensitivity, And Longevity, Natalie B Hagan, Charles Inaku, Nikesh Kunder, Tayleur White, Thierry Iraguha, Anna Meyer, Kristen E Pauken, Jason M Schenkel

Faculty, Staff and Student Publications

Leukocytes migrate through the blood and extravasate into organs to surveil the host for infection or cancer. Recently, we demonstrated that intravenous (IV) anti-CD45.2 antibody labeling allowed for precise tracking of leukocyte migration. However, the narrow labeling window can make this approach challenging for tracking rare migration events. Here, we show that altering antibody administration route and fluorophore can significantly extend the antibody active labeling time. We found that while both IV and intraperitoneal (IP) anti-CD45.2 antibody labeled circulating leukocytes after injection, they had different kinetic properties that impacted labeling time and intensity. Quantification of circulating antibody revealed that while …

Manual Therapy For Fibrosis-Related Late Effect Dysphagia In Head And Neck Cancer Survivors: The Mantle Nonrandomized Clinical Trial, Holly Mcmillan, Carla L Warneke, Sheila Buoy, Christine Porsche, Kiara Savage, Stephen Y Lai, Clifton D Fuller, Katherine A Hutcheson

Faculty, Staff and Student Publications

Importance: Late radiation-associated dysphagia (RAD) after head and neck cancer (HNC) treatment is challenging and commonly treatment refractory, with fibrosis stiffening connective tissues and compressing peripheral nerve tracts, contributing to diminished strength and possibly denervation of swallowing muscles. Manual therapy (MT), while common for cancer-related pain and other indications, remains largely unstudied for fibrosis-related late RAD.

Objective: To determine the feasibility and safety of MT, estimate effect size and durability of MT for associated improvements in cervical range of motion (CROM), and examine functional outcomes after MT in survivors of HNC with fibrosis-related late RAD.

Design, setting, and participants: This …

Defining A 'Cells To Society' Research Framework For Appendiceal Tumours, Andreana N Holowatyj, Michael J Overman, Konstantinos I Votanopoulos, Andrew M Lowy, Patrick Wagner, Mary K Washington, Cathy Eng, Wai Chin Foo, Richard M Goldberg, Mojgan Hosseini, Kamran Idrees, Douglas B Johnson, Ardaman Shergill, Erin Ward, Nicholas C Zachos, Deborah Shelton

Faculty, Staff and Student Publications

Tumours of the appendix — a vestigial digestive organ attached to the colon — are rare. Although we estimate that around 3,000 new appendiceal cancer cases are diagnosed annually in the USA, the challenges of accurately diagnosing and identifying this tumour type suggest that this number may underestimate true population incidence. In the current absence of disease-specific screening and diagnostic imaging modalities, or well-established risk factors, the incidental discovery of appendix tumours is often prompted by acute presentations mimicking appendicitis or when the tumour has already spread into the abdominal cavity — wherein the potential misclassification of appendiceal tumours as …

Statins And Middle Meningeal Artery Embolization: A Literature Review In The Treatment Of Chronic Subdural Hematoma, Basel Musmar, Joanna M. Roy, Samantha Spellicy, Stavropoula I. Tjoumakaris, Michael R. Gooch, Robert H. Rosenwasswer, David Hasan, Pascal Jabbour

Department of Neurosurgery Faculty Papers

Chronic subdural hematoma (cSDH) presents a multifaceted challenge in contemporary neurological practice, necessitating innovative therapeutic strategies. This comprehensive review explores the convergence of two promising interventions: statins and middle meningeal artery (MMA) Embolization. With cSDH incidence on the rise, particularly among the aging population and those with long-term anticoagulant usage, the traditional surgical avenues face limitations in recurrence rates and associated risk factors. Statins, heralded for their anti-inflammatory, vasculogenic, and angiogenic properties, are emerging as potential allies in cSDH management. Concurrently, MMA embolization offers a nuanced approach to target the neomembrane's blood supply, with evidence supporting its efficacy and safety. …

Opioid Prescribing Patterns And The Effect Of Chronic Kidney Disease In Pediatric Urology Population: A Retrospective Cohort Analysis., Kristen M. Meier, Darren Ha, Carter Sevick, Eliza D. Blanchette, Megan A. Brockel, Vijaya M. Vemulakonda, Kyle O. Rove

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Significant efforts have been undertaken to decrease opioid prescribing, but there is little research into patient-specific factors presenting as barriers in the pediatric surgical population. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be a safe and effective alternative to opioids for pain control, however, concerns about their impact on renal function limit their use in patients with chronic kidney disease (CKD). Data is limited on the interplay of CKD on opioid prescribing.

OBJECTIVE: We hypothesized that opioid reduction efforts were successful, but patients with CKD would be more likely to receive an opioid prescription than those without CKD. …

Symptom Documentation In Unstructured Palliative Care Notes Of Children And Adolescents With Cancer., Katherine Bernier Carney, Jacob Wilkes, Tumilara Aderibigbe, Kristin Stegenga, Holly Spraker-Perlman, Lauri A. Linder

Manuscripts, Articles, Book Chapters and Other Papers

CONTEXT: Children and adolescents with cancer experiencing complex symptoms can benefit from subspeciality palliative care. However, standardized methods of symptom documentation by pediatric palliative care teams are lacking. Understanding current approaches to symptom documentation will inform next steps to optimize symptom support.

OBJECTIVE: To explore the documentation of symptom prevalence and characteristics in unstructured clinical notes by pediatric palliative care clinicians caring for children and adolescents with cancer.

METHODS: We reviewed unstructured clinical notes documented by the pediatric palliative care team for 115 children and adolescents with cancer. Symptom-related data were abstracted and evaluated using content analysis based on the …

Unleashing The Power Of Multiomics: Unraveling The Molecular Landscape Of Peripheral Neuropathy, Julie Choi, Zitian Tang, Wendy Dong, Jenna Ulibarri, Elvisa Mehinovic, Simone Thomas, Ahmet Höke, Sheng Chih Jin

Faculty, Staff and Student Publications

Peripheral neuropathies (PNs) affect over 20 million individuals in the United States, manifesting as a wide range of sensory, motor, and autonomic nerve symptoms. While various conditions such as diabetes, metabolic disorders, trauma, autoimmune disease, and chemotherapy-induced neurotoxicity have been linked to PN, approximately one-third of PN cases remain idiopathic, underscoring a critical gap in our understanding of these disorders. Over the years, considerable efforts have focused on unraveling the complex molecular pathways underlying PN to advance diagnosis and treatment. Traditional methods such as linkage analysis, fluorescence in situ hybridization, polymerase chain reaction, and Sanger sequencing identified initial genetic variants …

Age-Associated Proteins Explain The Role Of Medial Temporal Lobe Networks In Alzheimer’S Disease, Adam Turnbull, Yejin Kim, Kai Zhang, Xiaoqian Jiang, Zihuai He, Victor W Henderson, F Vankee Lin

Faculty, Staff and Student Publications

The structural connectivity (SC) of the medial temporal lobe and its associated cortical anterior temporal and posterior medial networks (MTL-AT-PM) is linked to pathologies and memory decline in Alzheimer's disease (AD). However, neuroimaging analyses cannot tell us how SC changes occur in AD at the molecular level and do not provide a means of intervening to slow/prevent pathology-related changes in MTL-AT-PM SC. The current study aimed to understand how and where AD-related changes occur within MTL-AT-PM using proteomics. We used a 4-step approach in 101 older adults from a local sample, aiming to understand how proteins and SC in combination …

Correction To: Selinexor In Combination With Carboplatin And Paclitaxel In Patients With Advanced Solid Tumors: Results Of A Single-Center, Multi-Arm Phase Ib Study, Kyaw Z Thein, Daniel D Karp, Apostolia Tsimberidou, Jing Gong, Selma Sulovic, Jatin Shah, Denái R Milton, David S Hong, Filip Janku, Lacey Mcquinn, Bettzy A Stephen, Rivka Colen, Brett W Carter, Timothy A Yap, Sarina A Piha-Paul, Siqing Fu, Funda Meric-Bernstam, Aung Naing

Faculty, Staff and Student Publications

No abstract provided.

Ethics Of Learning Surgical Autonomy In Safety-Net Hospital Systems With Patients Who Are Incarcerated, Kala T Pham, Rachel W Davis

Faculty, Staff and Students Publications

Safety-net hospitals care for patients who are incarcerated and are key environments in which surgical trainees learn to wield their professional autonomy. This article explores ethical questions raised by surgical trainees' participation in carceral care and canvasses possible responses to those questions.

Clinical Management And Therapeutic Optimization Of Patients With Heart Failure With Reduced Ejection Fraction And Low Blood Pressure. A Clinical Consensus Statement Of The Heart Failure Association (Hfa) Of The Esc, Hadi Skouri, Nicolas Girerd, Luca Monzo, Mark C Petrie, Michael Böhm, Marianna Adamo, Wilfried Mullens, Gianluigi Savarese, Mehmet Birhan Yilmaz, Offer Amir, Antoni Bayes-Genis, Biykem Bozkurt, Javed Butler, Ovidiu Chioncel, Alexandre Mebazaa, Jose L Merino, Brenda Moura, Piotr Ponikowski, Petar Seferovic, Giuseppe M C Rosano, Marco Metra

Faculty, Staff and Students Publications

Despite major advancements in heart failure (HF) management and guideline recommendations over the past two decades, real-world evidence highlights suboptimal implementation of guideline-directed medical therapy (GDMT) for HF with reduced ejection fraction (HFrEF). Low blood pressure (BP) is common in HFrEF patients and represents a major perceived barrier to implementing life-saving treatments in clinical practice, as physicians are often concerned about symptomatic hypotension and its consequences. Although low BP can be seen in those hospitalized with signs of shock, the most common scenario involves non-severe, asymptomatic hypotension in patients receiving foundational therapy for HFrEF, where premature down-titration or discontinuation of …

Familial Chylomicronemia Syndrome And Treatments To Target Hepatic Apoc3 Mrna, Eliot A Brinton, Robert H Eckel, Daniel Gaudet, Christie M Ballantyne, Brenda F Baker, Henry N Ginsberg, Joseph L Witztum

Faculty, Staff and Students Publications

Familial chylomicronemia syndrome (FCS) is a rare, recessive monogenic disorder characterized by severely elevated plasma triglyceride (TG) levels due to absent or markedly impaired lipoprotein lipase activity, leading to a greatly increased risk of acute pancreatitis. Naturally occurring very low levels of apoC-III are associated with low TG levels; thus, apoC-III is a target for TG lowering, and therapies have been developed to reduce apoC-III. Strategies to inhibit hepatic apoC-III synthesis include antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs). In the last decade, technologies have been developed to enhance hepatic delivery of these potential therapeutic agents by conjugation of …

Guideline-Directed Medical Therapy And Outcomes In The Ischemia Trial, David J Maron, Jonathan D Newman, Rebecca Anthopolos, Ying Lu, Susanna Stevens, William E Boden, Kreton Mavromatis, Jason Linefsky, Rajesh G Nair, Olga Bockeria, Gilbert Gosselin, Gian P Perna, Elena Demchenko, David Foo, Michael D Shapiro, Mary Ann Champagne, Christie Ballantyne, Peter Mccullough, Jose Luis Lopez-Sendon, Frank Rockhold, Frank Harrell, Yves Rosenberg, Gregg W Stone, Sripal Bangalore, Harmony R Reynolds, John A Spertus, Judith S Hochman

Faculty, Staff and Students Publications

Background: Guideline-directed medical therapy (GDMT) with multiple risk factor goals is recommended for patients with chronic coronary disease (CCD), yet achieving all GDMT goals is uncommon. The relative importance of these goals and timing of their attainment on cardiovascular events is uncertain.

Objectives: This study aims to describe the relationship between achieving specific GDMT goals, when they are achieved, and clinical outcomes.

Methods: This was an observational study of participants with CCD in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial. The primary outcome was cardiovascular (CV) death or myocardial infarction (MI). GDMT goals …

Demographic And Clinical Risk Factors Of Developing Clinically Recognized Varicose Veins In Older Adults, Yejin Mok, Shoshana H Ballew, Anna Kucharska-Newton, Kenneth Butler, Peter Henke, Pamela L Lutsey, Maya Salameh, Ron C Hoogeveen, Christie M Ballantyne, Elizabeth Selvin, Kunihiro Matsushita

Faculty, Staff and Students Publications

INTRODUCTION: Varicose veins are common in older adults and are associated with adverse clinical outcomes such as deep venous thrombosis. Established risk factors for varicose veins include female sex, height, and obesity, but other risk factors are relatively uncharacterized.

METHODS: This was a prospective cohort analysis of 6,241 participants aged 66-70 years from the Atherosclerosis Risk in Communities (ARIC) Study. Incident varicose veins were defined as two outpatient encounters (at least a week apart) or inpatient diagnoses through 2018 with ICD-9 code 454 or ICD-10 code I83. Participants with a history of clinically recognized varicose veins at baseline were excluded. …

New Onset Refractory Status Epilepticus: Long-Term Outcomes Beyond Seizures, Poul H Espino, Krista Eschbach, Leah J Blank, Mackenzie C Cervenka, Eyal Muscal, Raquel Farias-Moeller, Emily J Gilmore, Margaret T Gopaul, Hiba A Haider, Aurelie Hanin, Lawrence J Hirsch, Marissa A Kellogg, Gerhard Kluger, Soon-Tae Lee, Alexandria E Melendez-Zaidi, Vincent Navarro, Audrey C Oliger, Elena Pasini, Gitta Reuner, Cynthia M Sharpe, Zubeda B Sheikh, Leon Steigleder, Claude Steriade, Coral M Stredny, Adam Strzelczyk, Olga Taraschenko, Andreas Van Baalen, Sarah A Vinette, Ronny Wickström, Nora W Wong, Jiyeoun Yoo, Teneille E Gofton

Faculty, Staff and Students Publications

We propose and prioritize important outcome domains that should be considered for future research investigating long-term outcomes (LTO) after new onset refractory status epilepticus (NORSE). The study was led by the international NORSE Institute LTO Working Group. First, literature describing the LTO of NORSE survivors was identified using a PubMed search and summarized to identify knowledge gaps. Subsequently, a consensus-building process was performed to prioritize and rank important LTO domains for further research. The prioritization of LTO domains was qualitative, enabling the expert panel to generate ideas, share opinions, and provide reasons for the rankings. A second round took place …

Comparing Rituximab And Cyclophosphamide In Induction Therapy For Childhood-Onset Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: An Archive Registry Cohort Study, Samuel J Gagne, Vidya Sivaraman, Else S Bosman, Brett Klamer, Kimberly A Morishita, Adam Huber, Alvaro Orjuela, Barbara Eberhard, Charlotte Myrup, Dana Gerstbacher, Dirk Foell, Eslam Al-Abadi, Flora Mcerlane, Kathryn Cook, Linda Wagner-Weiner, Melissa Elder, L Nandini Moorthy, Paul Dancey, Rae Yeung, Raju Khubchandani, Samundeeswari Deepak, Sirirat Charuvanij, Stacey Tarvin, Susan Shenoi, Tamara Tanner, Kelly Brown, David A Cabral, Archive Investigators Network Within The Pedvas Initiative

Faculty, Staff and Students Publications

Objective: Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are chronic life-threatening vasculitides requiring substantial immunotherapy. Adult trials identified rituximab (RTX) as an alternative to cyclophosphamide (CYC) for remission induction of GPA and MPA. Disease rarity has limited feasibility of similar trials with pediatric patients. We aim to evaluate the relative efficacy and toxicity of CYC and RTX for patients with childhood GPA and MPA through registry-based comparative evaluation.

Methods: From A Registry of Childhood Vasculitis, we identified patients with GPA and MPA who received induction with RTX or CYC. Pediatric Vasculitis Activity Score (PVAS) and Pediatric Vasculitis Damage Index …

Complete, Sustained Resolution Of Pain With Pseudoarthrectomy For Bertolotti Syndrome: A Case Report, Emanuel Narcis Husu, Nirav Parekh, Jeremy I Simon

Faculty, Staff and Students Publications

Background: Bertolotti syndrome, characterized by lumbar pain due to a lumbosacral (LS) transitional vertebra, is a known but still controversial and overlooked pain generator despite an explosion of information on the condition in the last decade. Current management includes plain radiography, advanced imaging, minimally invasive interventions, and LS fusion.

Case report: We present a unique case of a middle-aged man with Castellvi IIa Bertolotti syndrome consisting of a unilateral enlarged, dysplastic L5 transverse process forming a pseudoarticulation (PA) with the ilium and normal anatomy contralaterally. He was diagnosed on a plain radiograph and following a diagnostic injection of the PA, …

Comparison Between Dynamic Models For Predicting Response To Corticosteroids In Alcohol-Associated Hepatitis: A Global Cohort Study, Francisco Idalsoaga, Luis Antonio Díaz, Leonardo Guizzetti, Winston Dunn, Heer Mehta, Jorge Arnold, Gustavo Ayares, Rokhsana Mortuza, Gurpreet Mahli, Alvi H Islam, Shiv K Sarin, Rakhi Maiwall, Wei Zhang, Steve Qian, Douglas Simonetto, Ashwani K Singal, Mohamed A Elfeki, Carolina Ramirez-Cadiz, Joaquín Cabezas, Victor Echavarría, Meritxell Ventura Cots, María Fátima Higuera-De La Tijera, Juan G Abraldes, Mustafa Al-Karaghouli, Prasun K Jalal, Mohamad Ali Ibrahim, Guadalupe García-Tsao, Daniela Goyes, Lubomir Skladaný, Daniel J Havaj, Karolina Sulejova, Svetlana Adamcova Selcanova, Diego Rincón, Vijay H Shah, Patrick S Kamath, Marco Arrese, Ramon Bataller, Juan Pablo Arab

Faculty, Staff and Students Publications

Several dynamic models predict mortality and corticosteroid response in alcohol-associated hepatitis (AH), yet no consensus exists on the most effective model. This study aimed to assess predictive models for corticosteroid response and short-term mortality in severe AH within a global cohort. We conducted a multi-national study of patients with severe AH treated with corticosteroids for at least 7 days, enrolled between 2009 and 2019. Dynamic models-Lille-4, Lille-7, trajectory of serum bilirubin (TSB), and neutrophil-to-lymphocyte ratio (NLR)-were used to estimate 30- and 90-day mortality. Lille-7 demonstrated the highest accuracy for both 30- and 90-day mortality.

Moderate Alcohol-Associated Hepatitis: A Real-World Multicenter Study, Francisco Idalsoaga, Luis Antonio Díaz, Winston Dunn, Heer Mehta, Karen Muñoz, Vicente Caldentey, Jorge Arnold, Gustavo Ayares, Rokhsana Mortuza, Shiv K Sarin, Rakhi Maiwall, Wei Zhang, Steve Qian, Douglas Simonetto, Ashwani K Singal, Mohamed A Elfeki, Carolina Ramirez-Cadiz, Gurpreet Malhi, Adan Ahmed, Hoomam Homsi, Zinia Abid, Joaquín Cabezas, Victor Echavarría, Maria Poca, German Soriano, Berta Cuyas, Meritxell Ventura Cots, María Fátima Higuera-De La Tijera, Maria Ayala-Valverde, Diego Perez, Jaime Gomez, Juan G Abraldes, Mustafa Al-Karaghouli, Prasun K Jalal, Mohamad Ali Ibrahim, Guadalupe García-Tsao, Daniela Goyes, Lubomir Skladaný, Daniel J Havaj, Karolina Sulejova, Svetlana Adamcova Selcanova, Diego Rincón, Kristina R Chacko, Juan C Restrepo, Pamela Yaquich, Luis G Toro, Vijay Shah, Marco Arrese, Patrick S Kamath, Ramon Bataller, Juan Pablo Arab

Faculty, Staff and Students Publications

Background: Severe alcohol-associated hepatitis (sAH) is a well-characterized disease with high short-term mortality. However, there is limited research on those with a "less severe condition" (moderate AH). This study aims to characterize in-depth patients with moderate AH (mAH), including the performance of mortality scoring systems, key prognostic factors, and survival over time.

Methods: A multicenter retrospective cohort study (2009-2019) included patients with mAH (MELD score ≤20 at admission). Cox regression and receiver operating characteristic curves with AUC were used for analysis.

Results: We included 1845 patients with AH (20 centers, 8 countries) between 2009 and 2019. mAH was defined as …

Order And Timing Of Middle Meningeal Artery Embolization As A Perioperative Adjunct To Surgical Evacuation For Chronic Subdural Hematomas: A Multicenter Study, Georgios S Sioutas, Mohamed M Salem, Okkes Kuybu, Mira Salih, Jane Khalife, Kate Carroll, Edward A Duckworth, Dhrumil Vaishnav, Muhammed Amir Essibayi, Alex Nguyen Hoang, Cordell M Baker, Aldo A Mendez Ruiz, Zachary Abecassis, Walid K Salah, Juan F Ruiz Rodriguez, Iris Charcos, Gustavo M Cortez, Sandra Narayanan, Oz Haim, Omar Tanweer, Ricardo Hanel, Peter Kan, Daniel A Tonetti, Raul G Nogueira, Tudor G Jovin, David J Altschul, Michael J Lang, Visish M Srinivasan, Brian T Jankowitz, Ajith J Thomas, Michael R Levitt, Christopher S Ogilvy, Bradley A Gross, Jan-Karl Burkhardt, Ramesh Grandhi

Faculty, Staff and Students Publications

Background

Chronic subdural hematoma (cSDH) is a common neurosurgical condition, and middle meningeal artery embolization (MMAE) has emerged as a minimally invasive adjunct to surgery, but optimal timing remains unclear.

Purpose

To investigate radiographic and clinical outcomes of patients with cSDH undergoing MMAE as an adjunct to surgical evacuation, focusing on order and timing of MMAE relative to surgery.

Materials and Methods

This multicenter, retrospective study included consecutive patients undergoing MMAE adjunct to surgery for cSDH at 10 U.S. centers from September 2018 to September 2023. Clinical and radiographic characteristics and outcomes were examined in MMAE before or after surgery. …

Endothelial Micu1 Protects Against Vascular Inflammation And Atherosclerosis By Inhibiting Mitochondrial Calcium Uptake, Lu Sun, Ruixue Leng, Monan Liu, Meiming Su, Qingze He, Zhidan Zhang, Zhenghong Liu, Zhihua Wang, Hui Jiang, Li Wang, Shuai Guo, Yiming Xu, Yuqing Huo, Clint L Miller, Maciej Banach, Yu Huang, Paul C Evans, Jaroslav Pelisek, Giovanni G Camici, Bradford C Berk, Stefan Offermanns, Junbo Ge, Suowen Xu, Jianping Weng

Faculty, Staff and Students Publications

Mitochondrial dysfunction fuels vascular inflammation and atherosclerosis. Mitochondrial calcium uptake 1 (MICU1) maintains mitochondrial Ca2+ homeostasis. However, the role of MICU1 in vascular inflammation and atherosclerosis remains unknown. Here, we report that endothelial MICU1 prevents vascular inflammation and atherosclerosis by maintaining mitochondrial homeostasis. We observed that vascular inflammation was aggravated in endothelial cell–specific Micu1 knockout mice (Micu1ECKO) and attenuated in endothelial cell–specific Micu1 transgenic mice (Micu1ECTg). Furthermore, hypercholesterolemic Micu1ECKO mice also showed accelerated development of atherosclerosis, while Micu1ECTg mice were protected against atherosclerosis. Mechanistically, MICU1 depletion increased mitochondrial Ca2+ influx, thereby decreasing the expression …

Sialidase Fusion Protein Protects Against Influenza Infection In A Cigarette Smoke-Induced Model Of Copd, Cheng-Yen Chang, Dominique Armstrong, John M Knight, Trevor V Gale, Stephen Hawley, Max Wang, Nancy Chang, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

First- and secondhand smokers are at an increased risk for influenza virus (IFV)-related respiratory failure and death. Despite approved influenza antiviral treatments, there is an unmet need for treatments that can improve outcomes in populations at risk for respiratory failure, including tobacco users with Chronic Obstructive Pulmonary Disease (COPD). Here we show that the sialidase fusion protein, DAS181, reduced viral burden, mitigated inflammation, and attenuated lung function loss, consistent with broad-spectrum anti-influenza responses in a mouse model of COPD and IFV-A infection. Treatment with DAS181 reprogramed the sialic acid-binding immunoglobulin-like lectins (Siglecs) in alveolar macrophages, increased expression of phagocytic marker …

Intestinal Epithelial Serotonin As A Novel Target For Treating Disorders Of Gut-Brain Interaction And Mood, Lin Y Hung, Nuno D Alves, Andrew Del Colle, Ardesheer Talati, Sarah A Najjar, Virginie Bouchard, Virginie Gillet, Yan Tong, Zixing Huang, Kirsteen N Browning, Jialiang Hua, Ying Liu, James O Woodruff, Daniel Juarez, Melissa Medina, Jonathan Posner, Raquel Tonello, Nazli Yalcinkaya, Narek Israelyan, Roey Ringel, Letao Yang, Kam W Leong, Mu Yang, Ji Ying Sze, Tor Savidge, Jay Gingrich, Robert J Shulman, Michael D Gershon, Annie Ouellet, Larissa Takser, Mark S Ansorge, Kara Gross Margolis

Faculty, Staff and Students Publications

Background & aims: Mood disorders and disorders of gut-brain interaction (DGBI) are highly prevalent, commonly comorbid, and lack fully effective therapies. Although selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for these disorders, they may impart adverse effects, including anxiety, anhedonia, dysmotility, and, in children exposed in utero, an increased risk of cognitive, mood, and gastrointestinal disorders. SSRIs act systemically to block the serotonin reuptake transporter and enhance serotonergic signaling in the brain, intestinal epithelium, and enteric neurons. Yet, the compartments that mediate the therapeutic and adverse effects of SSRIs are unknown, as is whether gestational SSRI exposure directly …

Combined Systemic Immunotherapy And Intrathecal Dexamethasone In Febrile Infection Related Epilepsy Syndrome, Kristen S Fisher, Alexander Ankar, Jon Cokley, Eyal Muscal, James J Riviello, Yi-Chen Lai

Faculty, Staff and Students Publications

Febrile infection related epilepsy syndrome (FIRES) is a rare presentation of refractory status epilepticus with immune dysregulation as a potential pathologic mechanism. Despite promising results from second-line immunomodulators, approximately 30% remain refractory to treatment. We describe two children with FIRES who were unable to wean from anesthetic infusions with immunomodulatory treatment and subsequently received concurrent intrathecal dexamethasone and anakinra/tocilizumab as escalation of therapy. Following the initiation of this combined regimen, anesthetic infusions were decreased while maintaining seizure freedom. These cases demonstrate proof of principle that a multi-modal approach may be beneficial and should be considered in the treatment of FIRES.

Postnatal Zika And Dengue Infection And Their Effects On Neurodevelopment Among Children Living In Rural Guatemala, Edwin J Asturias, Amy K Connery, Daniel Olson, Molly M Lamb, Alejandra Paniagua-Avila, Evan J Anderson, Chris Focht, Alison M Colbert, Muktha Natrajan, Jesse J Waggoner, Erin Scherer, D Mirella Calvimontes, Guillermo A Bolaños, Desirée Bauer, Paola Arroyave, Sara Hernández, Maria A Martinez, Aida V Ralda, Neudy Rojop, Edgar E Barrios, Andrea Chacon, Walla Dempsey, Kay M Tomashek, Wendy A Keitel, Hana M El Sahly, Flor M Muñoz

Faculty, Staff and Students Publications

Background: Prenatal Zika virus (ZIKV) infection leads to microcephaly and adverse neurodevelopment. The effects of postnatal ZIKV infection on the developing brain are unknown. We assessed the neurodevelopmental outcomes of children exposed postnatally during the ZIKV epidemic.

Methods: A prospective study enrolled infants 0-3 months of age and their mothers, and children 1.5-3.5 years of age in rural Guatemala from 2017 and were followed for 12 months until 2019. Neurodevelopment was evaluated using the Mullen Scales of Early Learning (MSEL). ZIKV and dengue virus (DENV) infections were identified by polymerase chain reaction (PCR) using active surveillance. Serological analyses, stratified by …

Preferences For Survivorship Education And Delivery Among Latino And Non-Latino Childhood Cancer Survivors And Caregivers, Omar Shakeel, Shiley Aguilar, Alicia Howell, Ashley Ikwuezunma, Olga Taylor, M Fatih Okcu, Ranjan Bista, Jill Hartley, Rodrigo Eraña, Juan Carlos Bernini, Lisa Kahalley, Michael Scheurer, Maria Monica Gramatges

Faculty, Staff and Students Publications

Purpose: To assess survivor and parent perceptions of the long-term survivor visit and preferences regarding accessing health information, survivorship education, and support networks in rural and metropolitan regions of Texas.

Methods: Leveraging the multi-institutional Survivorship and Access to Care for Latinos to Understand Disparities (SALUD) cohort, we administered a 26-item bilingual survey to adult survivors of childhood cancer and parents of younger survivors. Characteristics and responses were compared between survivors vs. parents and Latinos vs. non-Latinos using a t test or Fisher exact test. Odds ratios for the outcomes of interest were calculated with 95% confidence intervals.

Results: We received …