Medicine and Health Sciences Commons^™

On The Nose: Nasal Neurostimulation As A Technology Countermeasure For Sinonasal Congestion In Astronauts, Timon Ax, Philipp H Zimmermann, Tomas L Bothe, Karen Barchetti, Cintia S De Paiva, Francesc March De Ribot, Slade O Jensen, Thomas J Millar

Faculty, Staff and Students Publications

Human spaceflight subjects the body to numerous and unique challenges. Astronauts frequently report a sense of sinonasal congestion upon entering microgravity for which the exact pathomechanisms are unknown. However, cephalad fluid shift seems to be its primary cause, with CO2 levels and environmental irritants playing ancillary roles. Current management focuses on pharmacotherapy comprising oral and nasal decongestants and antihistamines. These are among the most commonly used treatments in astronauts. With longer and more distant space missions on the horizon, there is a need for efficacious and payload-sparing non-pharmacological interventions. Neurostimulation is a promising countermeasure technology for many ailments on Earth. …

Quality Of Life In Young Adults With Type 1 Diabetes, Marissa N Baudino, Samantha A Carreon, Randi Streisand, Tricia Tang, Sarah Lyons, Siripoom Mckay, Barbara J Anderson, Charles G Minard, Sridevi Devaraj, Ashley M Butler, Marisa E Hilliard

Faculty, Staff and Students Publications

Introduction: Challenges of young adulthood with type 1 diabetes (T1D) include transitioning to adult care, increased T1D self-management responsibilities, and normal developmental transitions. Recognizing patterns of health-related quality of life (HRQOL) across a demographically and clinically broad range of young adults with T1D may help identify who needs additional support as they transfer to adult healthcare. We hypothesized that young adults from specific demographic and clinical groups would report lower HRQOL.

Methods: At baseline of a behavioral RCT (≤2 months after last pediatric T1D clinic visit), 100 young adults (Mage=19.9 ± 1.3, MA1c=8.8 ± 2.0 %) self-reported demographics and HRQOL; …

High Tumor Cd161 Expression Predicts A Survival Advantage And Marks A Th1-Skewed Microenvironment, Briana Amicarella Burns, Manasvi Chandra, Vanaja Konduri, William K Decker

Faculty, Staff and Students Publications

CD8+CD161+ T-cells exhibit augmented memory and cytolytic properties, mediating enhanced immunity in murine tumor models and improved survival in human non-small cell lung cancer. This T-cell subset might serve as a biomarker of positive response to therapy or even be isolated to augment current immunotherapeutic approaches yet limited knowledge of CD161 expression in human cancers restricts practical application. Here we bioinformatically tested the hypothesis that CD161 expression may be associated with positive outcomes in human cancers and investigated mechanisms underlying any observed advantages. Using TCGA-PANCAN dataset, we analyzed expression of CD161 in over 10,000 human tumors, correlating expression levels with …

The Reprogramming Factor Klf4 In Normal And Malignant Blood Cells, H Daniel Lacorazza

Faculty, Staff and Students Publications

The Krüppel-like factor 4 (KLF4) is an evolutionarily conserved zinc finger transcription factor that regulates cellular processes in stem cells, epithelial cells, and immune blood cells by controlling gene expression through genetic, epigenetic, and chromatin remodeling. The landmark 2006 publication identified KLF4 as one of the factors involved in reprogramming differentiated cells into pluripotent stem cells, sparking increased interest in KLF4 research a decade after its discovery, particularly in the fields of stem cell research, epithelial cell biology, endothelial cell function, and tumorigenesis. Over the years, KLF4 has emerged as a key transcription factor in modulating innate and adaptive immunity, …

Diagnostic Delay In Type I Autoimmune Pancreatitis: Clinical, Imaging, Endoscopic And Histologic Predictors Of Timely Diagnosis, Andres Urias Rivera, Travis Josephs, Shilpa Jain, Wasseem Skef, Tara Keihanian, Salmaan Jawaid, Wasif Abidi, Kalpesh Patel, Mohamed O Othman, Fares Ayoub

Faculty, Staff and Students Publications

Background: The diagnosis of autoimmune pancreatitis (AIP) can be challenging due to nonspecific symptoms, low sensitivity of serologic markers, and some overlap in presentation with pancreatic ductal adenocarcinoma (PDAC). We aimed to quantify delays in the diagnosis of AIP and identify factors associated with diagnostic delay.

Methods: This was a single-center retrospective study between 2013 and 2023 of adult patients diagnosed with type 1 AIP based on HISORt criteria. Patients were compared to a randomly selected group of controls with PDAC. Data on clinical presentation, lab results, imaging, procedures, and initial treatment regimen were collected. Timing to diagnosis and predictive …

Editorial: Exploring Klf4’S Role In Immune Cell Function And Disease Progression, H Daniel Lacorazza, Walden Ai

Faculty, Staff and Students Publications

No abstract provided.

Two-Dimensional Speckle Tracking Of The Ascending Aorta: A Novel Approach To Evaluate Arterial Stiffness In Pediatric Patients With Repaired Conotruncal Anomalies Using Echocardiography, Anmol Goyal, Anitha Parthiban, David A White, Daniel Forsha, Doaa Aly

Faculty, Staff and Students Publications

Background: Children with repaired conotruncal abnormalities (CTA) are at risk of progressive aortic dilation and deteriorating aortic elasticity even after surgical correction. Strain imaging, using a 2-dimensional speckle tracking echocardiography (2D-STE), has been used for arterial stiffness assessment, but pediatric data are still lacking. We investigated the feasibility, reproducibility, and clinical value of 2D-STE derived ascending aorta (AAo) stiffness in children with repaired CTA.

Methods: 22 pediatric patients with repaired CTA were included along with 25 age- and sex- matched healthy controls (mean age 10.2 ± 4.5 years). Conventional 2D echocardiographic and 2D-STE assessment of AAo mechanics was performed. M-mode …

Multidisciplinary Approach To Treating Complex Immune Dysregulation Disorders: An Adaptive Model For Institutional Implementation, Lauren A Henderson, Roshini S Abraham, Aisha Ahmed, Lindsey Blount, Scott W Canna, Natalia S Chaimowitz, Shanmuganathan Chandrakasan, Bria Coates, James A Connelly, Megan A Cooper, Christine N Duncan, Anthony French, Melissa Hazen, Michelle L Hermiston, Brian Nolan, Anish Ray, Melissa J Rose, Lisa Forbes Satter, Grant Schulert, Sara Kristen Sexson Tejtel, Tiphanie Vogel, Kelly Walkovich, Matt S Zinter, Edward M Behrens

Faculty, Staff and Students Publications

Patients with immune dysregulation may present with varying combinations of autoimmunity, autoinflammation, immunodeficiency, atopy, lymphoproliferation, and/or malignancy, often with multisystem involvement. Recognizing specific patterns of immune dysregulation, coordinating and interpreting complex diagnostic testing, and choosing initial (often empiric) treatment can be challenging. Centers are increasingly assembling multidisciplinary teams (MDTs) to standardize evaluation and optimize treatment of patients with complex immune dysregulation (immune dysregulation MDTs [immMDTs]). However, published information on the composition and function of immMDTs is sparse, and there is little guidance for those seeking to establish or optimize an immMDT. To inform this review, we assembled a panel of …

Tailor Swiftly: Lessons Learned From A Nationwide Implementation Of An Antimicrobial Stewardship Program For Asymptomatic Bacteriuria, Trenton M Haltom, Sophia Braund, Rogelio Hernandez, Larissa Grigoryan, Barbara W Trautner, Eva Amenta

Faculty, Staff and Students Publications

Objective: Overtreatment of asymptomatic bacteriuria (ASB) is a major cause of antibiotic overuse. We facilitated a nationwide implementation of an ASB antimicrobial stewardship intervention in 41 Veterans Affairs facilities. Twenty-one sites participated in a Virtual Learning Collaborative (VLC) with monthly webinars. We assess what VLC teams learned from one another in these webinars.

Methods: The bi-monthly VLC webinars featured expert presentations and spotlighted 1-2 site teams, asking them to discuss their barriers and facilitators for the intervention. Data come from analyses of descriptive field notes from the webinars and chat transcripts. Field notes were analyzed using the "sort and sift, …

How Gps Communicate The Urgent Suspected Cancer Referral Pathway To Patients: A Qualitative Study Of Gp-Patient Consultations, Jessica Russell, Laura Boswell, Athena Ip, Jenny Harris, Hardeep Singh, Ashley Nd Meyer, Traber D Giardina, Afsana Bhuiya, Katriina L Whitaker, Georgia B Black

Faculty, Staff and Students Publications

Background: The UK National Institute for Health and Care (NICE) recommends that GPs inform patients referred onto the urgent suspected cancer (USC) pathway about what to expect from the service. However, there is a lack of evidence on patient experience and information needs at the point of referral. It is a challenge for GPs to communicate the reasons for referral and provide reassurance.

Aim: To examine how GPs communicate a potential cancer diagnosis and USC referral in practice.

Design & setting: This is a secondary analysis of a dataset of 23 audio-recorded GP-patient consultations, selected from a larger dataset of …

Application Of A Digital Quality Measure For Cancer Diagnosis In Epic Cosmos, Andrew J Zimolzak, Sundas P Khan, Hardeep Singh, Jessica A Davila

Faculty, Staff and Students Publications

Objectives: Missed and delayed cancer diagnoses are common, harmful, and often preventable. We previously validated a digital quality measure (dQM) of emergency presentation (EP) of lung cancer in 2 US health systems. This study aimed to apply the dQM to a new national electronic health record (EHR) database and examine demographic associations.

Materials and methods: We applied the dQM (emergency encounter followed by new lung cancer diagnosis within 30 days) to Epic Cosmos, a deidentified database covering 184 million US patients. We examined dQM associations with sociodemographic factors.

Results: The overall EP rate was 19.6%. EP rate was higher in …

External Validation Of A Novel Cancer-Associated Venous Thromboembolism Risk Assessment Score In A Safety-Net Hospital, Karlynn N Dulberger, Jennifer La, Ang Li, Saran Lotfollahzadeh, Asha Jose, Nhan V Do, Mary T Brophy, J Michael Gaziano, Katya Ravid, Vipul C Chitalia, Nathanael R Fillmore

Faculty, Staff and Students Publications

Background: Cancer-associated thrombosis (CAT) is a leading cause of death in patients diagnosed with cancer. However, pharmacologic thromboprophylaxis use in cancer patients must be carefully evaluated due to a 2-fold increased risk of experiencing a major bleeding event within this population. The electronic health record CAT (EHR-CAT) risk assessment model (RAM) was recently developed, and reports improved performance over the widely used Khorana score. Extensive RAM external validation is crucial to determine accuracy across diverse patient populations prior to clinical utilization.

Objectives: To externally validate EHR-CAT using data from 2103 patients with cancer at the Boston Medical Center (BMC), New …

Baseline Predictors For 28-Day Covid-19 Severity And Mortality Among Hospitalized Patients: Results From The Impacc Study, Jintong Hou, Benjamin Haslund-Gourley, Joann Diray-Arce, Annmarie Hoch, Nadine Rouphael, Patrice M Becker, Alison D Augustine, Al Ozonoff, Leying Guan, Steven H Kleinstein, Bjoern Peters, Elaine Reed, Matt Altman, Charles R Langelier, Holden Maecker, Seunghee Kim, Ruth R Montgomery, Florian Krammer, Michael Wilson, Walter Eckalbar, Steven E Bosinger, Ofer Levy, Hanno Steen, Lindsey B Rosen, Lindsey R Baden, Esther Melamed, Lauren I R Ehrlich, Grace A Mccomsey, Rafick P Sekaly, Joanna Schaenman, Albert C Shaw, David A Hafler, David B Corry, Farrah Kheradmand, Mark A Atkinson, Scott C Brakenridge, Nelson I Agudelo Higuita, Jordan P Metcalf, Catherine L Hough, William B Messer, Bali Pulendran, Kari C Nadeau, Mark M Davis, Ana Fernandez Sesma, Viviana Simon, Monica Kraft, Chris Bime, Carolyn S Calfee, David J Erle, Impacc Network, Lucy F Robinson, Charles B Cairns, Elias K Haddad, Mary Ann Comunale

Faculty, Staff and Students Publications

Introduction: The coronavirus disease 2019 (COVID-19) pandemic threatened public health and placed a significant burden on medical resources. The Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study collected clinical, demographic, blood cytometry, serum receptor-binding domain (RBD) antibody titers, metabolomics, targeted proteomics, nasal metagenomics, Olink, nasal viral load, autoantibody, SARS-CoV-2 antibody titers, and nasal and peripheral blood mononuclear cell (PBMC) transcriptomics data from patients hospitalized with COVID-19. The aim of this study is to select baseline biomarkers and build predictive models for 28-day in-hospital COVID-19 severity and mortality with most predictive variables while prioritizing routinely collected variables.

Methods: We analyzed 1102 …

Evaluation Of Real-World Evidence To Assess Effectiveness Outcomes Of Janus Kinase Inhibitors For Rheumatoid Arthritis: A Systematic Review Of Us Studies, Chandler Gandy, Shadi Bazzazzadehgan, Sebastian Bruera, Yinan Huang

Faculty, Staff and Students Publications

Objective: This review summarized the real-world effectiveness outcomes of Janus kinase inhibitors (JAKi) for rheumatoid arthritis (RA) based on observational studies.

Methods: A systematic review followed PRISMA guidelines, with searches conducted in PubMed, Embase, and CINAHL from each database's inception to June 2, 2023. Studies were included if they evaluated real-world effectiveness outcomes of JAKi for US RA patients. Search terms included "RA", "JAKi", and "real-world". All citations were imported into COVIDENCE platform. Two reviewers independently performed title/abstract screening and full-text eligibility. For each article, study characteristics and effectiveness measures focusing on treatment pattern, clinical response, and patient-reported outcomes (PROs) …

The Utilization Of Microbial Cell-Free Dna Next-Generation Sequencing For The Detection Of Human Herpesvirus-8 In A Quaternary Care Center, Rebecca Berger, Jennifer Jacobe, Fernando H Centeno, Todd Lasco, Mayar Al Mohajer

Faculty, Staff and Students Publications

Background: Human herpesvirus-8 (HHV8) can present with cutaneous or extracutaneous manifestations. While violaceous skin lesions characterize cutaneous Kaposi sarcoma, extracutaneous HHV8 is challenging to diagnose due to nonspecific symptoms.

Objectives: We evaluated the role of microbial cell-free DNA next-generation sequencing (mcfDNA NGS) in diagnosing HHV8-related illness.

Design: Retrospective analysis.

Methods: Between 2017 and 2024, we reviewed the medical charts of 10 immunosuppressed patients at a quaternary care center who had positive HHV8 mcfDNA NGS results.

Results: The clinical and laboratory turnaround times of mcfDNA NGS were 3 and 1 days, respectively (8.5 and 7 days for immunohistochemistry vs 5.5 and …

Impact Of A Cerebrospinal Fluid Diagnostic Stewardship Intervention On Quantity Of Tests, Length Of Stay, Antibiotic Prescriptions, And Cost, Aaron Pathak, Sabra Shay, Todd Lasco, Mayar Al Mohajer

Faculty, Staff and Students Publications

Redundant and low-value cerebrospinal fluid analysis for suspected meningitis can increase costs and antimicrobial use. Our diagnostic stewardship intervention limited available infectious disease cerebrospinal fluid assays to seven common tests, including a multiplex polymerase chain reaction panel. There was no significant difference in the cost of testing or clinical outcomes.

Utility Of Microbial Cell-Free Dna Sequencing In The Diagnosis Of Mycobacterial Infections In A Quaternary Care Center, Fernando H Centeno, Todd Lasco, Ahmed M Hamdi, Mayar Al Mohajer

Faculty, Staff and Students Publications

We examine the performance of microbial cell-free DNA (mcfDNA) next-generation sequencing (NGS) testing on patients admitted to a quaternary care hospital in Houston, Texas. The test was 75.0% sensitive and 97.8% specific for all mycobacterial infections. mcfDNA NGS results led to adjustments in antimicrobial therapy for seven of nine patients with positive results.

Toward Improving Retention In Hiv Care After Pregnancy: Lessons From A Post-Pandemic Cohort In The United States, Alexandra H Latham, Andrea Lugo Morales, Elizabeth Barba Gutierrez, Michael Jochum, Sarah Conrad, Eva H Clark, Kassandra Goytia, Megan Alam, Jessica Gerard, Jennifer Mckinney

Faculty, Staff and Students Publications

Introduction: People living with HIV (PLWH) often experience low rates of retention in HIV care (RIC) and suboptimal viral suppression postpartum. Understanding contemporary barriers to RIC is crucial to identify risk factors for loss to care and thereby improve support during this vulnerable transition. This work aimed to identify factors associated with adequate RIC, defined as two HIV care visits ≥90 days apart in the first year postpartum.

Methods: Electronic records were retrospectively reviewed for PLWH who delivered from 2019 to 2023 and received prenatal care within a single county health system. Variables were collected related to both maternal and …

A Pipeline For Rapid, High-Throughput Imaging And Quantitative Analysis Of Human Intestinal Organoids, Faith M Sawyer, Fabio Stossi, Erika Nachman, Robert A Britton, Michael J Bolt, Michael A Mancini, Mary K Estes, Sarah E Blutt

Faculty, Staff and Students Publications

Human intestinal organoids (HIOs) are a model system for studying human intestinal epithelium. Utilizing HIOs for high-throughput studies remains inefficient, as analyzing their cellular composition and responses to varying experimental conditions requires extensive time and labor. We describe a 96-well plate-based automated pipeline for rapidly imaging and quantifying fluorescent labeling in HIOs using a high-throughput confocal microscope and image analysis software. The pipeline was leveraged to quantify varying levels of cell proliferation among donor HIO lines in response to microbial products. Cytoplasmic fluorescence via antibody labeling was also quantified with the pipeline, enabling measurement of the prevalence of specific cell …

Editorial: Pathogenesis And Clinical Treatment Of Diabetic Nephropathy, Ziyun Xu, Sheng Qiang, Zhaoyong Hu, Haiyong Chen

Faculty, Staff and Students Publications

No abstract provided.

Long-Term Anti-Sars-Cov-2 Antibody Trajectories After Neutralizing Monoclonal Antibody Treatment, Elizabeth S Munroe, Greg A Grandits, Robert C Hyzy, Hallie C Prescott, Thomas W Barrett, Robin L Dewar, Nicole Engen, Anna L Goodman, Timothy J Hatlen, Helene Highbarger, Thomas L Holland, Gareth Hughes, Tomas O Jensen, Muhammad A Khan, Ioannis Kalomenidis, Nayon Kang, Sylvain Laverdure, Prasad Manian, Vidya Menon, Ravi Patel, Srikanth Ramachandruni, Tauseef Rehman, Kathryn Shaw-Saliba, Birgit Thorup Røge, David M Vock, Amy C Weintrob, Barnaby E Young, Anne P Frosch, Strive Network And Therapeutics For Inpatients With Covid-19 (Tico) Study Groups

Faculty, Staff and Students Publications

Background: Neutralizing monoclonal antibodies (nMAbs) have been used to treat COVID-19 and are increasingly being used to treat other infections. However, there is concern that by neutralizing the SARS-CoV-2 virus, nMAbs may decrease the availability of antigens to the immune system, potentially impairing the endogenous polyclonal immune response and decreasing long-term immune protection.

Methods: We compared 28 and 90-day anti-SARS-CoV-2 spike protein neutralization activity and anti-SARS-CoV-2 nucleocapsid response for patients hospitalized with COVID-19 infection randomized to receive nMAbs or placebo in the large platform ACTIV-3/TICO trials. We pooled results from four trials of anti-spike nMAbs. For most tested agents, measurements …

Advancing Narcolepsy Advocacy: Bridging Patient Narratives And Systemic Change, Ahmed Salem Bahammam, Lindsay Jesteadt, Hamza Dhafar, Amir Sharafkhaneh

Faculty, Staff and Students Publications

We introduce the Stigma-to-Structure Advocacy Framework, a novel, evidence-based model designed to transform narcolepsy advocacy by systematically bridging patient narratives with structural change. Narcolepsy remains a profoundly underdiagnosed and misunderstood neurological disorder, with persistent diagnostic delays and pervasive cultural stigma undermining patient well-being and access to care. Despite recent progress in awareness and support, advocacy efforts remain fragmented and insufficiently integrated with health policy, particularly in low- and middle-income countries. This perspective advances a strategic evolution of narcolepsy advocacy through the Stigma-to-Structure Advocacy Framework, which is anchored in three pillars: narrative-driven awareness, clinical system integration, and policy activation. Drawing on …

B-Cell Immune Repertoire Sequencing In Tobacco Cigarette Smoking, Vaping, And Chronic Obstructive Pulmonary Disease In The Copdgene Cohort, Matthew Moll, Zhonghui Xu, Adel Boueiz, Min Hyung Ryu, Edwin K Silverman, Michael H Cho, Craig P Hersh, Maor Sauler, Francesca Polverino, Gregory L Kinney, Jeffrey L Curtis, Laura E Crotty-Alexander, Christopher Vollmers, Peter J Castaldi

Faculty, Staff and Students Publications

Rationale: Cigarette smoking (CS) impairs B-cell function and antibody production, increasing infection risk. The impact of e-cigarette use ('vaping') and combined CS and vaping ('dual-use') on B-cell activity is unclear.

Objective: To examine B-cell receptor sequencing (BCR-seq) profiles associated with CS, vaping, and dual-use.

Methods: BCR-seq was performed on blood RNA samples from 234 participants in the COPDGene study. We assessed multivariable associations of B-cell function measures (immunoglobulin heavy chain (IGH) subclass expression and usage, class-switching, V allele usage, and clonal expansion) with CS, vaping, and dual-use. We adjusted for multiple comparisons using the Benjamini-Hochberg method, identifying significant associations at …