Medical Specialties Commons^™

Incidence Of Autoimmune Diseases In Children With Atopy Treated With Dupilumab, Stanislaw J Gabryszewski, Kathryn Hirabayashi, Morgan Botdorf, Mitchell Maltenfort, Christopher B Forrest, Theresa W Guilbert, Madeline Schutt, Hiroki Morizono, Gerardo Vazquez Garcia, Anna Cristina Garza-Mayers, Joseph Demetrius Hernandez, Sara Anvari, Suchitra Rao, Jonathan M Spergel

Faculty, Staff and Students Publications

Background: The type 2 inflammation-blocking agent dupilumab has gained traction as an effective treatment of multiple atopic diseases. New-onset autoimmune manifestations have been infrequently reported in dupilumab-treated atopic patients, primarily among adults. Autoimmune outcomes in atopic children on dupilumab are less clear.

Objective: We aimed to determine if dupilumab treatment of atopic children is associated with increased autoimmune or autoinflammatory disease diagnosis risk.

Methods: Using a multi-institutional electronic health record database composed of 10 PEDSnet academic health systems, we performed a retrospective cohort study of children aged 6-17 with atopy (ie, moderate-to-severe atopic dermatitis and/or persistent asthma, as defined by …

Fasting-Based Dietary Interventions In Cancer Patients And Survivors: A Scoping Review, Kuang-Yi Wen, Julianne Freedman, Abenezer Melaku Tafese, William Kevin Kelly, Nicole L Simone

Department of Medical Oncology Faculty Papers

Background: Fasting-based interventions are increasingly investigated as adjuncts to cancer treatment for the potential to reduce therapy-related toxicities, improve metabolic health, and enhance quality of life. However, clinical evidence regarding their efficacy, tolerability, and acceptability remains limited and fragmented. This scoping review aimed to systematically map the current evidence on fasting-based interventions in cancer patients and survivors.

Methods: A literature search was conducted in PubMed, Scopus, Web of Science, and CINAHL up to 10 June 2025. Eligible interventional studies included cancer patients or survivors and evaluated fasting-based interventions, such as time-restricted eating, intermittent fasting, short-term fasting, or fasting-mimicking …

Mdm4 At The Crossroads: Beyond P53 And Mdm2., Dipesh Thapa, Allison St John, Alejandro Parrales, Atul Ranjan, Tomoo Iwakuma

Manuscripts, Articles, Book Chapters and Other Papers

MDM4 (Murine Double Minute 4), also known as MDMX, is a crucial negative regulator of the tumor suppressor p53. MDM4 heterodimerizes with MDM2 to enhance MDM2-mediated ubiquitination and degradation of p53, thereby promoting tumorigenesis. Beyond its canonical role in inhibiting p53 activity, recent studies have revealed diverse p53-independent functions. MDM4 interacts with various proteins, including p73, E2F1, casein kinase 1α, PPARα, and TRIM21 to regulate cell cycle progression, β-catenin-mediated pre-leukemic progression, and ferroptosis independent of p53. In addition, MDM4 functions independently of both p53 and MDM2 by interacting with proteins, such as SMAD family members 3/4, retinoblastoma protein (pRB), p21, …

Craniofacial Differences And Safe Sleep Practices: Findings From A Caregiver Survey At A Children’S Hospital, Cait Vuturo-Brady, Aracelia S. Aldrete, Jesus Gil Inciong, Miccah Seaman, Rianna Leazer

Knowledge and Creativity Expo

Purpose

Many infants with cleft lip and/or palate (CL/P) have airway issues that make supine, flat-surface sleep challenging.¹ Prior studies indicate that alternative positioning may reduce obstructive events,² and early sleep-disordered breathing can affect later development.³  Despite this, caregivers of infants with craniofacial differences rarely receive tailored sleep guidance, and no evidence-based, condition-specific recommendations currently exist.^4,5

Methods

This single-site, cross-sectional study evaluated sleep practices, caregiver education, and barriers to adherence among parents of children (< 3 years) with CL/P treated at CHKD’s Craniofacial Program. Eligible caregivers (n=117) were identified via query of the electronic medical record by CHKD Data Governance and invited to complete an anonymous REDCap survey assessing demographics, sleep environment, counseling, and understanding of safe-sleep recommendations.

Results & Conclusions

Of the 11 caregivers who completed the survey, 91% reported crib sleep, though several also used beds, couches, …

Evaluating Sensory Sensitivities Among Children With Autism Spectrum Disorder In An Adaptive Gymnastics Program, Aicha Kaouss, Bradley Eppinger, Austin Ebbrecht, Kailash Ram, Kaitlin P. Hardy Md

Knowledge and Creativity Expo

Introduction: Children with autism spectrum disorder (ASD) participate in physical activity at lower rates than their neurotypical peers1. Sensory sensitivities, reported in approximately 75–95% of children with ASD, may contribute to this disparity2. Gymnastics environments involve bright lighting and loud noise, which can precipitate sensory overload. The impact of specific sensory features on participation in adaptive gymnastics remains underexplored.

Methods: A cross-sectional study recruited caregivers of children aged 3–12 years with an ASD diagnosis enrolled in the EVMS Adaptive Gymnastics Program. Caregivers completed the Sensory Experiences Questionnaire–Third Edition (SEQ-3)3 and supplemental survey items on Redcap which assessed environmental triggers and …

Thalamic Organization Differentially Contributes To Clinical Conditions In Epilepsy, Qirui Zhang, Sam S. Javidi, Ankeeta Ankeeta, Michael R. Sperling, Zhiqiang Zhang, Joseph I. Tracy

Farber Institute for Neuroscience Faculty Papers

BACKGROUND: The thalamus plays an important role in key clinical conditions of focal temporal lobe epilepsy (TLE), but no investigation has examined whether the same thalamic local and connectome properties shape a patient's status across these different conditions.

METHODS: This retrospective longitudinal MRI study used resting-state fMRI and structural imaging to identify whole-brain focal/regional and connectome-level features associated with six binary clinical conditions of TLE (pre/post-surgery, seizure and neurocognitive outcomes, pathology, seizure subtype, and SOZ lateralization) in 91 patients across two centers (age range: 15-65 years) and 85 matched healthy participants (age range: 18-60 years).

RESULTS: Across conditions, relative to …

Racial And Ethnic Differences In The Clinical Presentation Of Celiac Disease In The United States: A Multi-Institutional Retrospective Analysis, Joy Zhao, John C. Lin, Jason C. Lin, Stephanie M. Moleski

Division of Gastroenterology and Hepatology Faculty Papers

No abstract provided.

Cystic Fibrosis And Sickle Cell Disease Associated With Nonadministration Of Vte Prophylaxis In Hospitalized Adults, Kiera Caparon, Matthew J. Lankiewicz, Jessica Crow, Jennifer C. Yui, John Lindsley, Brandyn D. Lau, Michael B. Streiff, Rakhi P. Naik, Sophie Lanzkron, Lydia H. Pecker, Peggy Kraus, Elliott R. Haut, Jiangxia Wang, Kathryn E. Dane

Cardeza Foundation for Hematologic Research

Cystic fibrosis (CF) and sickle cell disease (SCD) are associated with an increased risk of venous thromboembolism (VTE), and this risk is exacerbated by hospitalization. VTE prophylaxis nonadministration is a VTE risk factor. The objective of this study was to characterize VTE prophylaxis nonadministration among patients with either CF or SCD compared with medically ill patients without CF or SCD. We conducted a single-center retrospective cohort study of hospitalized patients who were prescribed at least 2 doses of pharmacologic VTE prophylaxis. The primary outcome was the proportion of nonadministered VTE prophylaxis doses by cohort. Multivariable logistic regression was used to …

Genome-Wide Crispr Screen Identifies A Cytokine-Enhancer Circuit Driving Hif-2Α Activation In Renal Cancer, Jun Fang, Jeremy M Simon, Tao Wang, Yunpeng Gao, Xianju Bi, Lianxin Hu, Chengheng Liao, Cheng Zhang, Yayoi Adachi, Jin Zhou, Hongyi Liu, Qian Liang, James A Nathan, Ram Mani, James Brugarolas, Qing Zhang

Faculty, Staff and Student Publications

Resistance to HIF-2α inhibitors such as Belzutifan underscores the need to better understand how HIF-2α is transcriptionally regulated in clear cell renal cell carcinoma (ccRCC). Here, we uncover a cytokine-driven enhancer mechanism that sustains HIF-2α expression through the JAK1-STAT3 signaling pathway. Using a genome-wide CRISPR screen in VHL-deficient ccRCC cells, we identified SOCS3 as a key negative regulator of HIF-2α. Mechanistically, loss of SOCS3 activates JAK1-STAT3 signaling, leading to the recruitment of STAT3 to distal enhancers upstream of EPAS1 that physically loop to its promoter to drive HIF-2α transcription. This cytokine-enhancer circuit was recapitulated in ccRCC patient samples and functionally …

Fecal Carbohydrate-Degrading Bacteria Are Associated With Reduced Incidence Of Lower Gastrointestinal Gvhd, Christopher Fan, Tomo Hayase, Chia-Chi Chang, Israel K Glover, Ivonne I Flores, Lauren K Mcdaniel, Miriam R Ortega, Christopher A Sanchez, Rawan K El-Himri, Alexandria N Brown, Jennifer L Karmouch, Mohamed A Jamal, Saira S Ahmed, Taylor M Halsey, Yimei Jin, Wen-Bin Tsai, Rishika Prasad, Altai Enkhbayar, Aqsa Mohammed, Maren Schmiester, Ashish Damania, Nadim J Ajami, Jennifer A Wargo, Christine B Peterson, Gabriela Rondon, Taha Al-Juhaishi, Amin M Alousi, Jeffrey J Molldrem, Richard E Champlin, Elizabeth J Shpall, Eric Martens, Cesar A Arias, Robert R Jenq, Eiko Hayase

Faculty, Staff and Student Publications

Lower gastrointestinal graft-versus-host disease (LGI-GVHD) carries morbidity and mortality for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), with critical contributions from the intestinal microbiome. In a retrospective cohort of metagenomic sequencing of stool from patients with allo-HSCT (N = 90), we found that a reduction in specific Parabacteroides and Bacteroides species around the time of engraftment contributes to LGI-GVHD risk. Given the known diverse carbohydrate-degrading functionality of these bacteria, we investigated gene abundances for carbohydrate-active enzymes (CAZymes) and found that Parabacteroides merdae, P distasonis, and Bacteroides ovatus abundances were significantly correlated with CAZymes in patients who did not develop …

The Epigenetic Effects Of Prenatal Diabetes On The Developing Vascular System- A Gsea Analysis, Daniel I. Telles Orellana

SPARK Symposium Presentations

Prenatal diabetes is a critical medical condition that extensively affects neonatal patients and their families. Numerous previous studies have suggested impairments in vascular development, size, and diversification; however, the molecular and gene regulatory mechanisms underlying these effects remain poorly understood. Understanding these mechanisms is essential for identifying potential therapeutic targets and improving treatment strategies. This study combined experimental zebrafish phenotypic analysis with re-analysis of publicly available RNA-seq data to investigate the effects of elevated glucose on embryonic vascular development. Zebrafish (Danio rerio) embryos were exposed to increasing glucose concentrations (1–3%) during early developmental stages. High glucose exposure showed …

Assessment Of Early Breast Cancer Response To Chemotherapy With Ultrasound Radiomics, Swapnil Dolui, Basak Dogan, Corinne Wessner, Jessica Porembka, Priscilla Machado, Bersu Ozcan, Nisha Unni, Maysa Abu-Khalaf, Flemming Forsberg, Kibo Nam, Kenneth Hoyt

Department of Medical Oncology Faculty Papers

Objective: This prospective study investigated the use of H-scan ultrasound (US) imaging as a novel component of a multiparametric radiomic analysis framework for characterizing human breast cancer response to neoadjuvant chemotherapy (NAC) before and early after treatment initiation. Methods: Thirty breast cancer patients scheduled for NAC were scanned using a clinical US system (Logiq E9, GE HealthCare) equipped with a 9L-D linear array transducer. Radiofrequency (RF) data was obtained at baseline (pre-NAC) and after 10% and 30% of the complete dose of chemotherapy. The RF data was analyzed by a bank of 256 frequency-shifted bandpass filters to form H-scan US …

A Mitochondrial Plasma Proteomic Signature Identifies Metastatic Chromophobe Renal Cell Carcinoma, Clara Steiner, Tiegang Han, Steven Safi, Wafaa Bzeih, Hadi Mansour, Eddy Saad, Jessica F. Williams, Vinay K. Giri, Liliana Ascione, Yehonatan Elon, Adam P. Dicker, Yan Tang, Toni K. Choueiri, Elizabeth P. Henske, Wenxin Xu

Department of Radiation Oncology Faculty Papers

BACKGROUND: Chromophobe renal cell carcinoma (ChRCC) is characterized by the accumulation of abnormal mitochondria, a high rate of mitochondrial DNA (mtDNA) mutations, and altered oxidative metabolism. There are no existing circulating biomarkers to distinguish metastatic ChRCC from clear cell renal cell carcinoma (ccRCC).

METHODS: High-throughput plasma proteomic profiling using the SomaScan platform was performed in 18 ChRCC (including 16 metastatic ChRCC) and 197 metastatic ccRCC patients. Data were harmonized to generate a unified 7K-protein matrix.

RESULTS: Differential expression analysis was performed using limma (version 3.62.2). Of 7272 quantified human plasma proteins, 209 were differentially expressed between ChRCC and ccRCC. Upregulated …

A Retrospective Analysis Of Taxane-Based Chemotherapy In Small Bowel Adenocarcinoma, Mir Lim, Nikhil Grandhi, Preksha Shah, Kanwal Raghav, Victoria Serpas, Maria Pia Morelli, Katrina Pedersen, Aparna Kalyan, Mohamed Salem, Ryan Huey, John Paul Shen, Huamin Wang, Hua Wang, Anjali Vinocha, Jane Thomas, Robert Wolff, Michael J Overman

Faculty, Staff and Student Publications

Background: Small bowel adenocarcinoma (SBA) is molecularly distinct from colorectal and gastric cancers, yet treatment typically parallels colorectal cancer. We evaluated the activity of taxane-based therapy in the largest SBA cohort to date.

Methods: We retrospectively reviewed SBA patients treated with taxane-based chemotherapy at MD Anderson Cancer Center from 1994-2024. Eligible patients had pathologic confirmation, received >1 treatment cycle, and had tumor response evaluation. Survival analyses were analyzed using Kaplan-Meier and Cox proportional hazard models.

Results: Seventy patients were identified. Median age was 57, and 59% were male. Primary sites were duodenum (44%), jejunum (34%), and Ileum (16%). Metastatic sites …

Pediatric Simulation And Emergency Nurse Confidence, Katherine E. Wright

Student Scholarly Projects

Practice Problem: Nurses working in a general emergency department (GED) with a low (3.3%) pediatric patient volume expressed a lack of confidence caring for complex pediatric patients.

PICOT: In general emergency department nurses (P), how does participating in a pediatric simulation event (I), compared to current practice (C), affect nurse confidence scores caring for pediatric patients (O) over 6 weeks (T)?

Evidence: A review of over 17 evidence-based resources found good quality evidence that suggested participating in a simulation event can improve nurse confidence.

Intervention: Over six weeks, GED staff members participated in a pediatric simulation event. The simulation utilized …

Pre-Operative Methicillin-Resistant Staphylococcus Aureus Colonization Increases The Risk Of 90-Day Medical And 2-Year Implant-Related Complications Following Primary Total Shoulder Arthroplasty: A Propensity-Matched Analysis, Muhammad Hamza Ilyas, Tarishi Parmar, Zina Smadi, Viraj A. Deshpande, Akin A. Adio, Joseph A. Abboud, Hafiz F. Kassam

Rothman Institute Papers

BACKGROUND: Pre-operative methicillin-resistant Staphylococcus aureus (MRSA) colonization has been associated with increased risk of post-operative infection and medical complications in lower-extremity arthroplasty; however, its impact on outcomes following total shoulder arthroplasty (TSA) remains poorly understood. This study aims to evaluate the association between MRSA colonization and early medical as well as mid-term implant-related complications after primary TSA.

METHODS: The TriNetX US Research Network was queried to identify primary TSA patients. Propensity score matching (1:1) was performed using demographic characteristics and relevant comorbidities. Ninety-day medical complications, including readmission, emergency department utilization, venous thromboembolism, pneumonia, urinary tract infection, stroke, sepsis, respiratory failure, …

Receptor-Mediated Drug Delivery: Redefining Targeted Drug Conjugates In Oncology, Keon Niles Jafari, Charlene Chai, Shelby Kim, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Targeted drug delivery (TDD), specifically through targeting ligand–drug conjugates, has reshaped oncology by enabling selective delivery of cytotoxic payloads to cancer cells while minimizing uptake by normal tissues. A key approach relies on exploiting overexpressed cell surface receptors (CSRs) to enable selective uptake of drug conjugates via receptor-mediated endocytosis. This review delineates four clinically validated CSRs (HER2, Trop-2, Nectin-4, and SSTR2) with several FDA-approved drug conjugates. Furthermore, emerging CSRs (EGFR, DLL3, and keratin 1) that may support next-generation TDD platforms for cancer treatment are also highlighted. We discuss how CSR type, density on cancer cells, and its mechanism of endocytosis, …

External Fixation Assisted Intramedullary Total Femur Arthroplasty: A Case Report, Matthew Hnatow, Blake Martin, Emma Herrera

School of Medicine Publications

Introduction:Total femur replacement (TFR) is a salvage procedure for patients with multiple failed hip and knee arthroplasties and is associated with high complication rates. Intramedullary TFR has emerged as a technique to preserve critical soft tissue attachments; however, maintaining limb length, alignment, and rotation remains challenging.

Case Presentation: We describe a novel case of intramedullary TFR utilizing external fixation to address these technical challenges. A 64-year-old male with subsidence of a hinged knee tumor prosthesis to the level of the greater trochanter underwent intramedullary TFR. External fixation was applied to the residual femoral and tibial bones to maintain …

Visual-Physiological Concordance And Target Vessel Outcomes: A Μqfr-Based Real-World Cohort Study, Yanfeng Lu, Abdulrahman Alqazzaz, Jasmine Bao, Gary S Mintz, Jiahao Feng, Yong Zhang, Shanshan Gao, Qiang Song, Feifei Ning, Wangge Ma, Haoyu Wu, Yuejiao Wei, Jiaying Li, Ning Guo, Xin Huang

Student Papers, Posters & Projects

BACKGROUND AND OBJECTIVES: Quantitative flow ratio (QFR) offers a non-interventional alternative for evaluating ischemia, yet its concordance with real-world treatment and clinical outcomes remains unclear. This study aimed to assess the alignment between Murray law-based QFR (μQFR) physiological assessment and treatment strategies, evaluate the association between treatment concordance and clinical outcomes, and explore factors influencing concordance.

METHODS: In this retrospective cohort, 242 patients with angiographically intermediate coronary stenosis and μQFR values adjacent to the grey-zone (low: 0.70-0.74; high: 0.86-0.90) were included. Treatment concordance was defined as PCI for low μQFR and medication for high μQFR. The primary endpoint was target …

Multidisciplinary Care In The Management Of Pleomorphic Dermal Sarcoma: A Single-Center Case Series And Review, Jaanvi Mehta, Leena Wardeh, Jayson Suriano, Rishob Dasgupta, Ramsay Hafer, Alexandra Elder, Safiyyah Bhatti, Jason B. Lee, Atrayee B. Mallick, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Epidemiology And Follow-Up Adherence Of Ophthalmic Emergencies: A 10-Year Study At A Tertiary Medical Center In Taiwan, Tsung-Ying Tsai, Chunya Kang, Laura Liu, Nan-Kai Wang, Kuan-Jen Chen, Wei-Chi Wu, Chi-Chun Lai, Sunir J. Garg, Eugene Yu-Chuan Kang, Yih-Shiou Hwang

Wills Eye Hospital Papers

PURPOSE: The purpose of the study was to evaluate factors influencing outpatient follow-up adherence among patients receiving ophthalmology consultations in the emergency department (ED).

MATERIALS AND METHODS: This retrospective cohort study collected data from the Chang Gung Research Database. Patients who received ophthalmology consultations at the ED of Chang Gung Memorial Hospital Linkou Medical Center from January 1, 2010, to December 31, 2019, were included. Patients were divided into two groups based on whether they completed outpatient follow-up within 28 days, a timeframe consistent with our hospital's scheduling policy. Demographics, ED visit timing, triage categories, ophthalmic diagnoses, prior visits, and …

Plant-Based Dietary Patterns Are Associated With Slower Epigenetic Aging, Hyunju Kim, Christina A Castellani, Jiantao Ma, Alexis C Wood, Audrey Ting, Morgan E Grams, Bing Yu, Kelly Ruggles, James S Floyd, Dan E Arking, Casey M Rebholz

Faculty, Staff and Students Publications

Greater adherence to plant-based diets is associated with health benefits. Dietary intake can modify DNA methylation patterns, but it is unknown whether plant-based diets in a largely non-vegetarian population are associated with DNA methylation-based epigenetic aging measures. We examined the associations between 4 different types of plant-based diets indices (PDI) [overall PDI, provegetarian diet, healthy PDI, and unhealthy PDI] and epigenetic aging. We used data from the Atherosclerosis Risk in Communities (ARIC) Study (N=2,810) and National Health and Nutrition Examination Survey (NHANES, N=2,056). PDIs negatively scored higher intake of animal products and positively scored higher intake of all or selected …

Limited English Proficiency, Acculturative Stress, And Quality Of Life Among Korean American Patients With Chronic Hepatitis B, Hee-Soon Juon, Gilbert C. Gee, Julia G. Katcher, Daniel Yang, Katherine Smith, Ann C. Klassen

Department of Medical Oncology Faculty Papers

BACKGROUND: Chronic hepatitis B (CHB) is one of the most widespread liver diseases in the world and disproportionately affects Asian Americans, who are further impacted by the lower quality of life imposed by the infection. Limited English proficiency (LEP) and acculturative stress play an important role in the study of patients with CHB, but the interrelationships of LEP, acculturative stress, and health outcomes are not well studied in this population. This study aims to explore how acculturative stress mediates the relationship between LEP and health outcomes among Korean American patients with CHB.

METHODS: A total of 365 CHB patients completed …

Integration Of Cross-Species Multi-Omics With In Vivo Experimental Validation Identifies Parkinson’S Disease Therapeutic Targets And Novel Risk Factors Within Endolysosomal Pathway Subnetworks, Justin Moore, Leo Rao, Sara Garcia-Bellido, Fangfei Guo, Jorge Botas, Juan Botas

Duncan NRI Faculty and Staff Publications

Parkinson's disease (PD), the most common neurodegenerative movement disorder, imposes a growing healthcare and socioeconomic burden worldwide. A defining hallmark of PD is the accumulation of α-synuclein (αSyn) within intracellular inclusions such as Lewy bodies and Lewy neurites. Genomic studies have identified numerous PD risk factors within the endolysosomal pathway (ELP), an essential cellular system for protein and membrane recycling. Concordantly, recurrent transcriptomic and proteomic alterations in ELP components implicate broad ELP dysfunction as a causal contributor to PD and suggest that additional, uncharacterized ELP genes may cooperate in polygenic disease mechanisms. A promising but underexplored therapeutic concept is that …

Educational Intervention To Improve Awareness Of The Female Athlete Triad Among Division I Athletes, Carly J. Haring, Jonathan Olson Md

Aesculapius Journal (Health Sciences & Medicine)

Introduction: The Female Athlete Triad poses short- and long-term health risks for female athletes through the interrelated components of low energy availability, menstrual dysfunction, and impaired bone health. Despite its prevalence, awareness and education surrounding the Triad remain limited, contributing to delayed recognition and care. The objective of this project was to assess baseline knowledge and comfort discussing Female Athlete Triad–related topics among Division I female athletes and to evaluate the impact of a brief educational intervention on knowledge, attitudes, and help-seeking intentions.

Methods: A community-based educational initiative was conducted in November 2025 among Division I female athletes …

From Screen To Newborn: Making Sense Of Prenatal Genetics In Primary Care, Bob Underwood, Lylach Haizler-Cohen

Pediatrics in Practice: A CME Podcast

This episode dives into the essentials of prenatal genetic testing and its significance for pediatricians. Learn about different types of tests like NIPT and microarrays, and how to interpret results to better care for newborns. Join Dr. Lylach Heisler Cohen, a prenatal genetic testing expert, as she breaks down the complexities of pediatric genetics.

Click here to stream the podcast episode.

Sepsis-Triggered Proteolysis Of Profibrinolytic Annexin A2 Associated With Microvasculopathy-Related Organ Dysfunction, Hana I. Lim, Michael Bender, Huigen Chen, Frances M. West, Julio Lanfranco, Dena Almeida, Katherine A. Hajjar

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

Sepsis is a systemic inflammatory disorder marked by dysregulated inflammation and coagulopathy. Annexin A2 (A2), a profibrinolytic protein, assembles plasminogen and tissue plasminogen activator on cell surfaces, thereby maintaining vascular patency. However, its role in human sepsis has remained poorly defined. We investigated whether A2 undergoes qualitative or quantitative modification during human sepsis with associated end-organ dysfunction. Peripheral blood mononuclear cells and plasma were collected from 65 patients with sepsis and 27 healthy controls. A2 expression and integrity were evaluated with cell surface plasmin generation using immunoblot and fluorometric assays. Both A2 integrity and plasmin generation were significantly reduced in …

Immunotherapy Of Tsa-1.C4 Or In Combination With Bnz Confers Protection Against Trypanosoma Cruzi Infection With A Distinct Cytokine Response, Landy Magaly Pech-Pisté, Victor Dzul-Huchim, Christian Florian Teh-Poot, Fabian Gusovsky, Kathryn Jones, Peter Hotez, Liliana Estefanía Villanueva-Lizama, Maria Elena Bottazzi, Jaime Ortega-Lopez, Julio Vladimir Cruz-Chan

Faculty, Staff and Students Publications

Chagas disease is a poverty-related neglected tropical disease caused by the protozoan Trypanosoma cruzi affecting approximately 6.3 million people, predominantly in the Americas. Approximately 30% of T. cruzi infections progress to chronic cardiomyopathy and 10% of these cases end in death from cardiac failure. The first-line drug Benznidazole (BNZ) require a prolonged treatment regimen and can be highly toxic. Here, we evaluate a therapeutic vaccine in T. cruzi-infected mice, based on the recombinant Trypomastigote Surface Antigen 1 (TSA-1.C4) protein and the emulsified adjuvant E6020, and in combination with a suboptimal dose of BNZ. We observed a reduced burden parasite in …

Fibrinogen-Bmal1 Signaling As A Therapeutic Target To Limit Aortic Dissection By Preserving Vsmc Contractility, Xiaohan Zhong, Dongjie Li, Yuanfei Zhao, Lu Dai, Jinzhang Li, Zhiqi Ji, Bojing Zuo, Hongshan Liu, Haixia Huang, Wei Wang, Haiyang Li, Yuyong Liu, Ming Gong, Xin-Liang Ma, Wenjian Jiang, Meili Wang, Hongjia Zhang

Department of Emergency Medicine Faculty Papers

Aortic dissection (AD) is a life-threatening vascular disease with a high mortality rate. Surgery is essential in the acute phase but carries significant risks, whereas elective surgery during the chronic phase yields better outcomes. However, no pharmacological therapy has been proven effective in slowing AD progression. In our recent pilot clinical study, an association between higher plasma fibrinogen levels and improved clinical outcomes was observed in AD patients, suggesting a potential protective role of fibrinogen. However, direct evidence supporting this hypothesis is lacking. In this study, a population-based analysis of nonsurgically managed patients with acute AD revealed a distinct association: …

Targeting Cardiomyocyte-Derived Extracellular Vesicle Mir-574-5p Protects Against Cognitive Impairment Induced By Ischemia-Reperfusion, Erya Chen, Xiaoyu Zhu, Haiqing Chang, Qi Li, Zhenkun Zhao, Changteng Zhang, Yu Cao, Yajing Wang, Xinliang Ma, Tao Zhu, Shu Zhang, Lu Gan, Jin Liu, Chan Chen

Department of Emergency Medicine Faculty Papers

BACKGROUND:  Acute myocardial ischemia/reperfusion (MI/R) increases risk for cognitive decline, yet the underlying mechanisms mediating heart-brain communication remain poorly understood. Small extracellular vesicles (sEVs) have emerged as novel long-range signaling mediators and may play a critical role.

METHODS: MI/R was induced by transient ligation of the left anterior descending artery. Cognitive performance was assessed using multiple behavioral tests. sEVs derived from cardiomyocytes were labeled to track their distribution and cellular uptake in the brain. Heart and brain tissues were analyzed for microRNAs (miRNAs) expression using bioinformatics, qPCR, and RNAScope. The role of specific miRNAs was investigated through genetic inhibition of …