Digital Commons Network^™

Protocol For A Randomized Controlled Trial To Determine If Biomarkers Predict Response To A Pediatric Chronic Pain Symptom Management Program, Rona L Levy, Tasha B Murphy, Margaret M Heitkemper, Miranda A L Van Tilburg, Ann R Mcmeans, Jocelyn Chang, Cynthia Boutte, Katherine Lamparyk, Bruno P Chumpitazi, Robert J Shulman

Faculty, Staff and Students Publications

Background/Objectives: Disorders of gut-brain interaction (DGBI), characterized by chronic abdominal pain and significant disability, affect 15-20% of children and adults and continue into adulthood in ~60% of cases. Costs for adults reach USD 30 billion per year, yet effective management strategies are elusive. Studies support using cognitive behavioral therapy (CBT), but abdominal pain only improves in ~40% of patients. Dietary management (low FODMAP diet; LFD) has also shown promise but it is effective in only a similar percentage of patients. Studies suggest that biologic factors (biomarkers) contribute to CBT response. Similarly, gut microbiome composition appears to influence abdominal pain …

Bile Acid And Microbiome Interactions In The Developing Child, Mary Elizabeth M Tessier, Benjamin L Shneider, Joseph F Petrosino, Geoffrey A Preidis

Faculty, Staff and Students Publications

Interactions between the gut microbiome and bile acids are complex and are linked to outcomes in pediatric liver disease by mechanisms that are incompletely understood. In adults, primary bile acids are synthesized in the liver and secreted into the intestine, where complex communities of gut microbes deconjugate, oxidize, epimerize, and 7α-dehydroxylate bile acids into a diverse array of unconjugated, secondary, allo-, iso-, and oxo-bile acids. In contrast, the infant gut microbiota contains a simple, Bifidobacterium-dominant community that transitions to a more diverse, adult-like community as additional microbes colonize the gut. This microbial succession gradually confers deconjugation, oxidation, epimerization, and 7α-dehydroxylation …

The Small Gtpase Rap1 In Pomc Neurons Regulates Leptin Actions And Glucose Metabolism, Kentaro Kaneko, Weisheng Lu, Yong Xu, Alexei Morozov, Makoto Fukuda

Faculty, Staff and Students Publications

The hypothalamic leptin-proopiomelanocortin (POMC) pathway is critical for regulating metabolism. POMC neurons in the arcuate nucleus respond to leptin and play a pivotal role in mediating energy and glucose balance. However, during diet-induced obesity (DIO), these neurons often develop resistance to exogenous leptin. Recently, the small GTPase Rap1 has been implicated as an inhibitor of neuronal leptin signaling; however, its specific role within POMC neurons remains unexplored. We generated tamoxifen-inducible, POMC neuron-specific Rap1 knockout mice to selectively delete both Rap1a and Rap1b isoforms in POMC neurons. By analyzing these mice through metabolic phenotyping, immunohistochemistry, and biochemical assays, we show that …

Maternal-Fetal Surgery For Myelomeningocele Longitudinal Follow-Up Model: Mitigation Of Care Fragmentation Through Care Coordination And Outcomes Reporting, Jonathan Castillo, Mary M Locastro, Romain Corroenne, Anjali Malhotra, Alexander Van Speybroeck, Grace Lai, Michael A Belfort, Magdalena Sanz Cortes, Heidi Castillo

Faculty, Staff and Students Publications

Purpose

Methods

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Spaceflight Associated Neuro-Ocular Syndrome (Sans) And Its Countermeasures, Tuan Nguyen, Joshua Ong, Tyson Brunstetter, C Robert Gibson, Brandon R Macias, Steven Laurie, Thomas Mader, Alan Hargens, Jay C Buckey, Mimi Lan, Peter Wostyn, Cihan Kadipasaoglu, Scott M Smith, Sara R Zwart, Benjamin J Frankfort, Sarah Aman, Jessica M Scott, Ethan Waisberg, Mouayad Masalkhi, Andrew G Lee

Faculty, Staff and Students Publications

Astronauts can develop a distinct collection of neuro-ophthalmic findings during long duration spaceflight, collectively known as Spaceflight Associated Neuro-ocular Syndrome (SANS). These clinical characteristics include optic disc edema, hyperopic refractive shifts, globe flattening, and chorioretinal folds, which may pose a health risk for future space exploration. Obtaining knowledge of SANS and countermeasures for its prevention is crucial for upcoming crewed space missions and warrants a multidisciplinary approach. This review examines the potential causes and countermeasures of SANS, including space anticipation glasses, lower body negative pressure, venoconstrictive thigh cuffs, impedance threshold devices, translaminar pressure gradient modulation, centrifugation, artificial gravity, pharmaceuticals, and …

Prevalence Of And Risk Factors For Osteoporosis And Fragility Fracture In Adults With Cerebral Palsy: A Systematic Review, Anne Trinh, Ellen Fremion, Shayan Bhathena, Craig F Munns, Prue Morgan, Daniel G Whitney, Bernadette Gillick, Margaret Zacharin, Darcy Fehlings, Amanda J Vincent, Frances Milat

Faculty, Staff and Students Publications

Aim: To systematically review the prevalence and incidence of osteoporosis, osteopenia, low bone mass, and fragility fracture in adults with cerebral palsy (CP), and identify the risk factors for osteoporosis and fracture.

Method: A systematic literature search was performed in the MEDLINE, PubMed, CINAHL, AMED, Cochrane Reviews, EMBASE, and EBM database reviews from inception until May 2024. Search terms covered a combination of keywords for CP, fracture, osteoporosis, incidence and prevalence, and risk factors. Participants were adults with CP aged 18 years and older. JBI critical appraisal instruments were used to assess quality and risk of bias.

Results: Seventeen of …

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 …

Circulating Epstein-Barr Virus Antibody Levels As A Biomarker Of Socioecological Adversity In Amazonian Ecuador, Tyler M Barrett, Melissa A Liebert, Geeta N Eick, Julia G Ridgeway-Diaz, Felicia C Madimenos, Aaron D Blackwell, Tara J Cepon-Robins, Samuel S Urlacher, Lawrence S Sugiyama, J Josh Snodgrass

Faculty, Staff and Students Publications

Objectives: Circulating Epstein-Barr virus antibodies (EBV-Ab) are used as a biomarker of chronic stress in high-income settings, but their relevance in environments with a high burden of infectious disease, nutritional constraints, and limited resources is less clear. We investigated EBV-Ab as a biomarker of adversity in a setting where local ecology and economy may affect immune development differently than in wealthy countries.

Methods: We measured EBV-Ab in finger-prick dried blood spots collected from Indigenous Shuar (n = 433) and non-Indigenous Colonos (n = 84) ranging from < 1 to 87 years old in Amazonian Ecuador. For a subset of adults (≥ 15 years, n = 210), we collected socioeconomic information (income, education, and occupation) and assessed household-level market integration. We determined the most important predictors of EBV-Ab for adults and children using multi-model averaging of linear regression models.

Results: Male children (< 15 years) had lower EBV-Ab than female children (model averaged β [SE]: -0.238 [0.066]). For adults, Shuar had higher EBV-Ab than Colonos (model averaged β [SE]: 0.235 [0.113]), and high systolic blood pressure was an important predictor of elevated EBV-Ab (model averaged β [SE]: 0.088 [0.047]). Individuals who reported unpaid domestic work as their primary occupation had higher EBV-Ab than agricultural workers (model averaged β [SE]: 0.302 [0.113]). Individuals living in houses with more market-sourced infrastructure had lower EBV-Ab (model averaged β [SE]: -0.088 [0.068]).

Conclusions: Circulating EBV-Ab may capture context-specific aspects of socioecological adversity …

Multidisciplinary Care In Body Contouring: An Integrative Approach To Enhancing Outcomes, Jacob Dinis, Sofia C Perez Otero, Diego M Quirarte, Winston R Owens, Sebastian J Winocour

Faculty, Staff and Students Publications

Body contouring procedures have become increasingly common to meet the growing demand for aesthetic surgery, particularly in the context of bariatrics. Massive weight loss (MWL) patients are complex and often require extensive management of comorbidities, malnutrition status, physical debilitation, and psychological sequelae. Patient optimization prior to body contouring surgery in addition to strict postoperative maintenance are crucial to achieve favorable and sustainable outcomes. Surgical candidates should be screened thoroughly, and in the MWL patient population specifically, multidisciplinary care is needed for proper evaluation and support. Notable specialists that routinely contribute in MWL and body contouring patient care include plastic surgeons, …

Nutrition Provision In Pediatric Extracorporeal Membrane Oxygenation: Evidence, Challenges, And Clinical Considerations, Marwa Mansour, Nicole Knebusch, Andrea Ontaneda, Stephanie Vazquez, Jennifer Daughtry, Katri Typpo, Jorge A Coss-Bu

Faculty, Staff and Students Publications

Background/objectives: Nutritional support is a critical yet challenging aspect of care for pediatric patients requiring extracorporeal membrane oxygenation (ECMO). Malnutrition is prevalent in this population and is associated with worse clinical outcomes. This review synthesizes current evidence on nutritional strategies for pediatric ECMO patients, emphasizing assessment methods, feeding routes, challenges, and clinical outcomes.

Methods: A literature review was conducted using PubMed, Scopus, and Web of Science to identify relevant studies published between January 2010 and 2025. Keywords included "pediatric ECMO", "nutrition", "enteral feeding", and "parenteral nutrition". Studies addressing nutritional assessment, enteral and parenteral feeding practices, and their impact on clinical …

Liposomes As Imaging Agents Of Inflammation And Oxidative Stress In Bone Implants, Delia Danila, Patricia S Pardo, R Devesh Kumar Misra, Aladin M Boriek

Faculty, Staff and Students Publications

Liposomes are tiny, spherical vesicles made from cholesterol and natural phospholipids that are promising imaging agents for detecting medical complications. They can carry fluorescent markers or other imaging agents, making them effective for medical imaging. Furthermore, liposomes can target specific cells involved in inflammation, such as macrophages, and accumulate at inflammation sites when injected. Additionally, liposomes can be designed to respond to oxidative stress, which is often associated with bone implant complications. By detecting areas of stress, liposomes provide valuable information about implant health. However, challenges such as rapid clearance from the body, precise targeting, immune reactions, and high production …

The Combined Effect Of High-Intensity Interval Training And Time-Restricted Feeding On The Akt-Igf-1-Mtor Signaling Pathway In The Muscle Tissue Of Type 2 Diabetic Rats, Motahareh Mohebinejad, Fatemeh Kazeminasab, Mahtab Ghanbari Rad, Reza Bagheri, Mazdak Razi, Darryn Willoughby, Fred Dutheil

Faculty, Staff and Students Publications

Background/Objectives: High-intensity interval training (HIIT) and time-restricted feeding (TRF) have shown potential in enhancing glucose metabolism, increasing insulin sensitivity, and promoting muscle health. This study investigates the combined effects of HIIT and TRF on the AKT-IGF-1-mTOR signaling pathway in the muscle tissue of type 2 diabetic (T2D) rats.

Methods: 42 male Wistar rats (4-5 weeks of age) were included in the study. The animals were randomly divided into two groups: 1. Standard diet (SD) non-diabetic (n = 7) and 2. High-fat diet (HFD n = 35) for 4 weeks. T2D was induced by intraperitoneal injection (IP) of streptozotocin (STZ) …

Lipoprotein(A) And Risk Of Incident Atherosclerotic Cardiovascular Disease: Impact Of High-Sensitivity C-Reactive Protein And Risk Variability Among Human Clinical Subgroups, Ron C Hoogeveen, Margaret R Diffenderfer, Elise Lim, Ching-Ti Liu, Hiroaki Ikezaki, Weihua Guan, Michael Y Tsai, Christie M Ballantyne

Faculty, Staff and Students Publications

No abstract provided.

Recent Advances In The Management Of Pediatric Cholestatic Liver Diseases, Krupa R Mysore, Katherine Cheng, Lakshmi Anandini Suri, Rima Fawaz, Alisha M Mavis, Debora Kogan-Liberman, Saeed Mohammad, Sarah A Taylor

Faculty, Staff and Students Publications

Pediatric cholestatic liver diseases are rare conditions that can result from multiple specific underlying etiologies. Among the most common etiologies of pediatric cholestatic liver diseases are biliary atresia, Alagille syndrome (ALGS), and inherited disorders of bile acid transport. These diseases are characterized by episodic or chronic unremitting cholestasis. Due to the chronicity of these conditions, it is imperative to optimize medical management to improve patient quality of life, provide nutritional support, and reduce bile acid toxicity in efforts to slow disease progression. Cholestatic liver diseases remain the leading cause of pediatric liver transplantation, as many underlying disease etiologies have no …

Subacute Neuropathy Post-Liver Transplantation In Zellweger Spectrum Disorder: A Case Report, Clarissa Gonzalez, Madelyn J Cohen, Juhee Hong, Daniel Calame, Kavitha Marri, Sanjiv Harpavat, Michael F Wangler, Krupa Mysore

Faculty, Staff and Students Publications

Peroxisome biogenesis disorders-Zellweger spectrum disorder (PBD-ZSD) is a rare genetic disease caused by mutations in the genes involved in peroxisome biogenesis. PBD-ZSD presentations vary in severity, and treatment of PBD-ZSD remains supportive focused on specific complications. A few reported cases of the use of liver transplantation to treat either neurological symptoms or liver dysfunction and cirrhosis in PBD-ZSD have been published. In this case report, we document the course of a 16-year-old boy diagnosed with PBD-ZSD and a delayed and unexpected neuropathy that developed after undergoing orthotopic liver transplantation (OLT) for which the indication was liver cirrhosis. Following OLT, the …

Postvaccination Immunogenicity Among Pediatric Solid Organ Transplant Recipients, Amy G Feldman, Brenda L Beaty, Jose A Ferrolino, Gabriela Maron, Saira A Ali, Leandra Bitterfeld, Adam Blatt, Mary Alice Boulware, Kathleen M Campbell, Emily Carr, Benhur Cetin, Shelley Chapman, Yeh-Chung Chang, Ryan Cunningham, Ronald H Dallas, Keerti L Dantuluri, Bryanna N Domenick, Noelle H Ebel, Scott Elisofon, Rima Fawaz, Marc Foca, Hayley A Gans, Vani V Gopalareddy, Nitika A Gupta, Katherine Harmann, Jessica Hollenbeck, Anna R Huppler, Catalina Jaramillo, Nagraj Kasi, Nanda Kerkar, Stacee Lerret, Steven J Lobritto, M James Lopez, Alisha Mavis, Sonia Mehra, Sindhu Mohandas, Flor M Munoz, Krupa R Mysore, Nadia Ovchinsky, Kerrigan Perkins, Stacy Postma, Lauren Pratscher, Elizabeth B Rand, Regina K Rowe, Daniel Ruderfer, Danielle Schultz, Katherine Sear, Megan L Sell, Tanvi S Sharma, Janis Stoll, Jerry Turner, Kristen G Valencia Deray, Dominique Villarin, Carly Weaver, Phoebe Wood, Olivia Woodford-Berry, George Yanni, Lara A Danziger-Isakov

Faculty, Staff and Students Publications

This cohort study assesses the protection provided by live attenuated viral vaccines among a pediatric population of solid organ transplant recipients 1 year after vaccination.

Variability In Treatment Of Utis In Children With Genitourinary Anomalies In Children's Hospitals, Catherine S Forster, Alexis C Wood, Stephanie Davis-Rodriguez, Sanyukta Desai, Pearl W Chang, Michael J Tchou, John M Morrison, Rana F Hamdy, Vijaya Vemulakonda, Patrick W Brady, Cynthia Abou Zeid, Sowdhamini S Wallace, Uti In Children With Cakut Study Group

Faculty, Staff and Students Publications

Objective: In children with urinary tract anomalies, febrile urinary tract infections (UTIs) are associated with increased risks of sepsis, hospitalization, and kidney injury. However, the best treatment strategies are unknown. We aimed to describe antibiotic treatment practices and outcomes for UTIs in children with urinary tract anomalies and evaluate whether variability in UTI treatment exists between hospitals.

Methods: We conducted a multicenter retrospective cohort study of children seen in emergency departments (EDs) in 6 free-standing US children's hospitals from January 1, 2017, through December 31, 2018. We included children aged 0-17 years with an anatomic or functional urinary tract anomaly …

Systemic Aging Fuels Heart Failure: Molecular Mechanisms And Therapeutic Avenues, Zhuyubing Fang, Umar Raza, Jia Song, Junyan Lu, Shun Yao, Xiaohong Liu, Wei Zhang, Shujuan Li

Faculty, Staff and Students Publications

Systemic aging influences various physiological processes and contributes to structural and functional decline in cardiac tissue. These alterations include an increased incidence of left ventricular hypertrophy, a decline in left ventricular diastolic function, left atrial dilation, atrial fibrillation, myocardial fibrosis and cardiac amyloidosis, elevating susceptibility to chronic heart failure (HF) in the elderly. Age-related cardiac dysfunction stems from prolonged exposure to genomic, epigenetic, oxidative, autophagic, inflammatory and regenerative stresses, along with the accumulation of senescent cells. Concurrently, age-related structural and functional changes in the vascular system, attributed to endothelial dysfunction, arterial stiffness, impaired angiogenesis, oxidative stress and inflammation, impose additional …

Differential Treatment Effects On Β-Cell Function Using Model-Based Parameters In Type 2 Diabetes: Results From The Glycemia Reduction Approaches In Diabetes: A Comparative Effectiveness Study (Grade), Kristina M Utzschneider, Mark Tripputi, Nicole M Butera, Andrea Mari, Samuel P Rosin, Mary Ann Banerji, Richard M Bergenstal, Necole Brown, Anders L Carlson, Ralph A Defronzo, Michaela R Gramzinski, Tasma Harindhanavudhi, Alexandra Kozedub, William I Sivitz, Michael W Steffes, Ashok Balasubramanyam, Neda Rasouli

Faculty, Staff and Students Publications

Objective: To evaluate how model-based parameters of β-cell function change with glucose-lowering treatment and associate with glycemic deterioration in adults with type 2 diabetes (T2D).

Research design and methods: In the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), β-cell function parameters derived from mathematical modeling of oral glucose tolerance tests were assessed at baseline (N = 4,712) and 1, 3, and 5 years following randomization to insulin glargine, glimepiride, liraglutide, or sitagliptin, added to baseline metformin. Parameters included insulin secretion rate (ISR), glucose sensitivity (insulin response to glucose), rate sensitivity (early insulin response), and potentiation. Linear mixed-effects …

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 …

Most Elderly Patients With Subclinical Hypothyroidism Do Not Need To Be Treated, Risheng Xu, Nicola Abate, Nalini Ram, Kristina Little

Faculty, Staff and Students Publications

Whether subclinical hypothyroidism should be treated in elderly patients (≥ 65 years) is controversial. The authors argue for a personalized, wait-and-see approach rather than universal treatment, pointing out that randomized clinical trials have not shown that levothyroxine treatment makes any difference in terms of hard clinical end points, quality of life, or hypothyroid symptom relief in elderly patients with this condition.

Current Burden Of Steatotic Liver Disease And Fibrosis Among Adults In The United States, 2017-2023, Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Rohit Loomba, Aijaz Ahmed

Faculty, Staff and Students Publications

Background/aims: Multi-society experts proposed the adoption of new terminology, metabolic dysfunctionassociated steatotic liver disease (MASLD) and steatotic liver disease (SLD). We studied the current prevalence of SLD and its subcategories in the US.

Methods: Using the recent National Health and Nutrition Examination Survey from 2017 to 2023, we analyzed data from 12,199 participants (≥18 years) who completed transient elastography. SLD and its subcategories, including MASLD, metabolic and alcohol-related liver disease (MetALD), and alcohol-related liver disease (ALD), were categorized according to consensus nomenclature.

Results: The age-adjusted prevalence of SLD (cut-off: 285 dB/m) was 35.0% (95% confidence interval [CI] 33.4-36.7). Within this …

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 …

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 …

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 …

Insights Into Protection Against Mycobacterium Tuberculosis Infection: Time To Officially Confirm Another Phenotype?, Todia P Setiabudiawan, Philip C Hill, Andrew R Dinardo, Reinout Van Crevel

Faculty, Staff and Students Publications

Immune correlates of protection against infection with Mycobacterium tuberculosis (Mtb) remain elusive. In this issue of the JCI, Dallmann-Sauer and authors demonstrate that lack of tuberculin skin test (TST) and interferon γ release assay (IGRA) conversion among people with HIV despite years-long Mtb exposure is associated with alveolar lymphocytosis, including specific poly-cytotoxic T cells, and M1-type alveolar macrophages with a stronger ex vivo response to the pathogen. Studies in these rare individuals, termed "TB resisters" and in tuberculosis household contacts who are repeatedly IGRA negative in the months after a specific exposure event (known as "early clearers") help elucidate manipulatable …

The Association Between County-Level Social Determinants Of Health And Cardio-Kidney-Metabolic Disease Attributed All-Cause Mortality In The Us: A Cross Sectional Analysis, Antoinette Cotton, Pedro Rvo Salerno, Salil V Deo, Salim S Virani, Khurram Nasir, Ian Neeland, Sanjay Rajagopalan, Naveed Sattar, Sadeer Al-Kindi, Yakov E Elgudin

Faculty, Staff and Students Publications

Background: The American Heart Association recently defined cardio-kidney-metabolic (CKM) syndrome as the intersection between metabolic, renal, and cardiovascular disease. Understanding the contemporary estimates of CKM related mortality in the US is essential for developing targeted public interventions.

Methods: We analyzed state-level and county-level CKM-associated all-cause mortality data (2010-2019) from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER). Median and interquartile (IQR) age-adjusted mortality rates (aaMR) per 100,000 were reported and linked with a multi-component metric for social deprivation: the Social Deprivation Index (SDI: range 0 - 100) grouped as: I: 0 - 25, II: 26 - 50, III: 51 …

Defining The Transcriptional Basis Of Organ-Specific Endothelial Cell Specialization, Joshua D. Wythe, James F. Martin

Faculty, Staff and Students Publications

Blood vessels feature extensive phenotypic and functional differences that help them meet the unique nutritive and energetic demands of the specific organ they reside in. Profiling the chromatin and transcriptional landscape of several organs identified novel gene regulatory networks that determine endothelial cell organ specialization in mammals.

Acute Kidney Injury In Severe Alcohol-Associated Hepatitis Treated With Anakinra Plus Zinc Or Prednisone, Kavish R Patidar, Wanzhu Tu, Thomas G Cotter, Douglas A Simonetto, Amon Asgharpour, Muhammad Y Jan, Qing Tang, Yunpeng Yu, Yang Li, Moyinoluwa Taiwo, Prashanth Thevkar Nagesh, Srinivasan Dasarathy, Patrick S Kamath, Craig J Mcclain, Naga Chalasani, Gyongyi Szabo, Ramon Bataller, Mack Mitchell, Wajahat Z Mehal, Laura E Nagy, Vijay H Shah, Samer Gawrieh, Arun J Sanyal

Faculty, Staff and Students Publications

Background and aims: In a recent trial, patients with severe alcohol-associated hepatitis treated with anakinra plus zinc (A+Z) had lower survival and higher acute kidney injury (AKI) rates versus prednisone (PRED). We characterize the clinical factors and potential mechanisms associated with AKI development in that trial.

Approach and results: Data from 147 participants in a multicenter randomized clinical trial (74 A+Z, 73 PRED) were analyzed. AKI, AKI phenotypes, and kidney injury biomarkers were compared between participants who did/did not develop AKI in the 2 treatment arms. Multivariable competing risk analyses were performed to identify baseline risk factors for incident AKI, …