Diseases Commons^™

Retinoid X Receptor As A Mediator Of Post Stroke Recovery By Reversing Age-Associated Phenotypes Of Microglia/Macrophages, Shun-Ming Ting

Dissertations and Theses (Open Access)

After stroke, microglia (MG) and blood-derived macrophages, together (MF), clear dead cells and cellular debris in the infarcted brain through phagocytosis. However, the phagocytic capability of MF declines with age. Age-related changes in MF phenotype also include overactive inflammatory responses to stroke-induced brain injury, altogether resulting in poor recovery after stroke. Retinoid-X-receptor (RXR) is a pleiotropic transcription factor. Our studies suggest that RXRa enhances MF phagocytic functions, reduces inflammatory responses, and improves post-stroke recovery. To establish phenotypes of aging MF, MG were MACS-sorted from the brains of young adults (2-4 months old) and aged (18-20 months old) mice for transcriptomic …

Evaluating The Association Of Influenza Vaccination On Long-Term Covid-19 Symptoms In U.S. Adults, Ratnakar Pingili

Capstone Experience: Master of Public Health

Objective. To evaluate the association of influenza vaccination in the past 12 months with Long COVID effects and clinical and sociodemographic factors.

Methods. Cross-sectional study with data from the 2022 Behavioral Risk Factor Surveillance System (BRFSS), covering 415,132 non-institutionalized U.S. adults with a confirmed COVID-19 diagnosis and influenza vaccination reported within the last 12 months. Logistic regression was conducted between influenza vaccination (exposure) and Long COVID (outcome), controlling for demographic variables, pre-existing health conditions, and socioeconomic status.

Results. Of 120,603 participants, 21.89% reported Long COVID symptoms and 42.04% had received an influenza vaccine. Findings indicate a statistically significant 13% reduction …

Antihypertensive Medications And Risk Of Melanoma And Keratinocyte Carcinomas: A Systematic Review And Meta-Analysis, Olivia G Cohen, Matthew Taylor, Cassandra Mohr, Kevin T Nead, Candice L Hinkston, Sharon H Giordano, Sinead M Langan, David J Margolis, Mackenzie R Wehner

Faculty, Staff and Student Publications

Some antihypertensive medications are photosensitizing. The implications for skin cancer risk remain unclear because results from prior studies are inconsistent and as new evidence is published. We performed a systematic review and meta-analysis to evaluate the association between antihypertensives and common skin cancers (cutaneous squamous cell carcinoma, basal cell carcinoma, and melanoma) and to evaluate dose-response relationships. Forty-four articles met inclusion criteria, and 42 could be meta analyzed. Increased risks were seen for basal cell carcinoma with calcium channel blockers (relative risk [RR] = 1.17, 95% confidence interval [CI] = 1.11-1.22), diuretics (RR = 1.06, 95% CI = 1.03-1.10), and …

Light Scattering By Vitreous Of Humans With Vision Degrading Myodesopsia From Floaters, Alba M Paniagua-Diaz, Justin H Nguyen, Pablo Artal, Wei Gui, J Sebag

Faculty, Staff and Student Publications

PURPOSE: Vision-degrading myodesopsia (VDM) from vitreous floaters significantly degrades vision and impacts visual quality of life (VQOL), but the relationship to light scattering is poorly understood. This study compared in vitro measures of light scatter and transmission in surgically excised human vitreous to preoperative indexes of vitreous structure, visual function, and VQOL.

METHODS: Pure vitreous collected during vitrectomy from 8 patients with VDM had wide-angle straylight measurements and dark-field imaging, performed within 36 hours of vitrectomy. Preoperative VQOL assessment with VFQ-25, contrast sensitivity (CS) measurements with Freiburg acuity contrast testing, and quantitative ultrasonography were compared to light scattering and transmission …

Jak2v617f Reversible Activation Shows Its Essential Requirement In Myeloproliferative Neoplasms, Andrew J Dunbar, Robert L Bowman, Young C Park, Kavi O'Connor, Franco Izzo, Robert M Myers, Abdul Karzai, Zachary Zaroogian, Won Jun Kim, Inés Fernández-Maestre, Michael R Waarts, Abbas Nazir, Wenbin Xiao, Tamara Codilupi, Max Brodsky, Mirko Farina, Louise Cai, Sheng F Cai, Benjamin Wang, Wenbin An, Julie L Yang, Shoron Mowla, Shira E Eisman, Amritha Varshini Hanasoge Somasundara, Jacob L Glass, Tanmay Mishra, Remie Houston, Emily Guzzardi, Anthony R Martinez Benitez, Aaron D Viny, Richard P Koche, Sara C Meyer, Dan A Landau, Ross L Levine

Faculty, Staff and Student Publications

Gain-of-function mutations activating JAK/STAT signaling are seen in the majority of patients with myeloproliferative neoplasms (MPN), most commonly JAK2V617F. Although clinically approved JAK inhibitors improve symptoms and outcomes in MPNs, remissions are rare, and mutant allele burden does not substantively change with chronic therapy. We hypothesized this is due to limitations of current JAK inhibitors to potently and specifically abrogate mutant JAK2 signaling. We therefore developed a conditionally inducible mouse model allowing for sequential activation, and then inactivation, of Jak2V617F from its endogenous locus using a combined Dre-rox/Cre-lox dual-recombinase system. Jak2V617F deletion abrogates MPN features, induces depletion of mutant-specific hematopoietic …

Proteomics For Optimizing Therapy In Acute Myeloid Leukemia: Venetoclax Plus Hypomethylating Agents Versus Conventional Chemotherapy, Eduardo Sabino De Camargo Magalhães, Stefan Edward Hubner, Brandon Douglas Brown, Yihua Qiu, Steven Mitchell Kornblau

Faculty, Staff and Student Publications

The use of Hypomethylating agents combined with Venetoclax (VH) for the treatment of Acute Myeloid Leukemia (AML) has greatly improved outcomes in recent years. However not all patients benefit from the VH regimen and a way to rationally select between VH and Conventional Chemotherapy (CC) for individual AML patients is needed. Here, we developed a proteomic-based triaging strategy using Reverse-phase Protein Arrays (RPPA) to optimize therapy selection. We evaluated the expression of 411 proteins in 810 newly diagnosed adult AML patients, identifying 109 prognostic proteins, that divided into five patient expression profiles, which are useful for optimizing therapy selection. Furthermore, …

Revisiting Feeding Tube Utilization In Oropharynx Cancer: 6-Year Prospective Registry Analysis, Brady J Anderson, Amy C Moreno, Yun Qing, J Jack Lee, Faye M Johnson, Miriam N Lango, Carly E A Barbon, Lavanya Tripuraneni, Ariana Sahli, Vicki Piper, Neil Gross, Clifton D Fuller, Stephen Y Lai, Jeffrey N Myers, Katherine A Hutcheson

Faculty, Staff and Student Publications

OBJECTIVE: Patients treated for oropharyngeal cancer (OPC) have historically demonstrated high feeding tube rates for decreased oral intake and malnutrition. We re-examined feeding tube practices in these patients.

STUDY DESIGN: Retrospective analysis of prospective cohort from 2015 to 2021.

SETTING: Single-institution NCI-Designated Comprehensive Cancer Center.

METHODS: With IRB approval, patients with new oropharyngeal squamous cell cancer or (unknown primary with neck metastasis) were enrolled. Baseline swallowing was assessed via videofluoroscopy and Performance Status Scale for Head and Neck Cancer (PSSHN). G-tubes or nasogastric tubes (NGT) were placed for weight loss before, during, or after treatment. Prophylactic NGT were placed during …

Stat3 Protects Hematopoietic Stem Cells By Preventing Activation Of A Deleterious Autocrine Type-I Interferon Response, Bhakti Patel, Yifan Zhou, Rachel L Babcock, Feiyang Ma, M Anna Zal, Dhiraj Kumar, Yusra B Medik, Laura M Kahn, Josué E Pineda, Elizabeth M Park, Sarah M Schneider, Ximing Tang, Maria Gabriela Raso, Collene R Jeter, Tomasz Zal, Karen Clise-Dwyer, Khandan Keyomarsi, Filippo G Giancotti, Simona Colla, Stephanie S Watowich

Faculty, Staff and Student Publications

Hematopoietic stem and progenitor cells (HSPCs) maintain blood-forming and immune activity, yet intrinsic regulators of HSPCs remain elusive. STAT3 function in HSPCs has been difficult to dissect as Stat3-deficiency in the hematopoietic compartment induces systemic inflammation, which can impact HSPC activity. Here, we developed mixed bone marrow (BM) chimeric mice with inducible Stat3 deletion in 20% of the hematopoietic compartment to avoid systemic inflammation. Stat3-deficient HSPCs were significantly impaired in reconstitution ability following primary or secondary bone marrow transplantation, indicating hematopoietic stem cell (HSC) defects. Single-cell RNA sequencing of Lin-ckit+Sca1+ BM cells (LSKs) revealed aberrant activation of cell cycle, p53, …

Intrabiliary Metastasis Of Colorectal Mucinous Adenocarcinoma Mimicking Choledocholithiasis 18 Years After The Primary Tumor, Sumaya Abdul Ghaffar, David Pfau, Nikhil Madhuripan, Robert Christopher Harmon, Antonio Galvao Neto, Ana Luiza Gleisner

Faculty, Staff and Student Publications

This case report presents a 62-year-old male who had previously undergone curative colectomy and neoadjuvant chemotherapy in 2005 for colorectal cancer. He presented with jaundice, which was initially attributed to choledocholithiasis. After cholecystectomy and repeat ERCPs, hyperbilirubinemia persisted. There was persistent dilation of the right posterior duct on imaging, concerning for biliary stricture, possibly due to cholangiocarcinoma or intraductal papillary neoplasm. During a right posterior hepatectomy, a peripheral liver lesion was found in association with the dilated bile duct. On frozen evaluation, the lesion was found to be invasive adenocarcinoma. The final pathology was compatible with a metastatic mucinous adenocarcinoma …

Pulmonary Endobronchial Hamartoma Presenting With Post-Obstructive Pneumonia, Diane S Habib, Pushan Jani, Bihong Zhao, Elakiya Anjali Jayaraman, Ramesh Kesavan

Faculty, Staff and Student Publications

Pulmonary hamartomas (PH) are rare but are the most common benign tumors found in the lungs. They are slow-growing and are usually found incidentally on chest imaging during the sixth decade of life. Approximately 10% of pulmonary hamartomas are endobronchial. Rarely, pulmonary hamartomas can cause a spectrum of pulmonary symptoms depending on their size and location. We present a case of endobronchial hamartoma causing airway obstruction and recurrent post-obstructive pneumonia.

Multimodal Neurologic Monitoring In Patients Undergoing Extracorporeal Membrane Oxygenation, Khwaja Siddiqui, Muhammad U Hafeez, Ali Ahmad, Syed O Kazmi, Subhasis Chatterjee, Eric Bershad, Mohammad Hirzallah, Chethan Rao, Rahul Damani

Faculty, Staff and Students Publications

Introduction Extracorporeal membrane oxygenation (ECMO) is associated with a high rate of neurologic complications. Multimodal neurologic monitoring (MNM) has the potential for early detection and intervention. We examined the safety and feasibility of noninvasive MNM during ECMO. We hypothesized that survivors and non-survivors would have meaningful differences in transcranial Doppler (TCD) sonography and electroencephalographic (EEG) characteristics, which we aimed to identify. We also investigated adverse neurologic events and attempted to identify differences in EEG and TCD characteristics among patients based on the type of ECMO and the occurrence of these events. Material and methods We performed an observational study on …

Efficacy And Safety Of Endoscopic Submucosal Dissection For Colorectal Dysplasia In Patients With Inflammatory Bowel Disease: A Systematic Review And Meta-Analysis, Talia F Malik, Vaishnavi Sabesan, Babu P Mohan, Asad Ur Rahman, Mohamed O Othman, Peter V Draganov, Gursimran S Kochhar

Faculty, Staff and Students Publications

BACKGROUND/AIMS: In this meta-analysis, we studied the safety and efficacy of endoscopic submucosal dissection (ESD) for colorectal dysplasia in patients with inflammatory bowel disease (IBD).

METHODS: Multiple databases were searched, and studies were retrieved based on pre-specified criteria until October 2022. The outcomes assessed were resection rates, procedural complications, local recurrence, metachronous tumors, and the need for surgery after ESD in IBD. Standard meta-analysis methods were followed using the random-effects model, and I2% was used to assess heterogeneity.

RESULTS: Twelve studies comprising 291 dysplastic lesions in 274 patients were included with a median follow-up of 25 months. The pooled en-bloc …

Impact Of Obesity And Age On Mouse Corneal Innervation At The Epithelial-Stromal Interface, Justin A Courson, Rolando E Rumbaut, Alan R Burns

Faculty, Staff and Students Publications

PURPOSE: The corneal epithelium is the most highly innervated structure in the body. Previously, we reported a novel event whereby stromal axons fuse with basal epithelial cells, limiting nerve penetration into the epithelium. Although corneal-epithelial nerves undergo changes in sensitivity and distribution throughout life and in response to an obesogenic diet, it is unknown if neuronal-epithelial cell fusion is altered. Here, we sought to determine if neuronal-epithelial cell fusion frequency correlates with obesogenic diet consumption and age.

METHODS: Corneas were collected from C57BL/6 mice and evaluated for neuronal-epithelial cell fusion frequency using serial block-face scanning electron microscopy. To assess the …

Chlorthalidone Vs Hydrochlorothiazide For Hypertension Treatment After Myocardial Infarction Or Stroke: A Secondary Analysis Of A Randomized Clinical Trial, Areef Ishani, Cynthia Hau, William C Cushman, Sarah M Leatherman, Robert A Lew, Peter A Glassman, Addison A Taylor, Ryan E Ferguson

Faculty, Staff and Students Publications

IMPORTANCE: Patients with prior myocardial infarction (MI) or stroke have a greater risk of recurrent cardiovascular (CV) events.

OBJECTIVE: To evaluate the association of chlorthalidone (CTD) vs hydrochlorothiazide (HCTZ) with CV outcomes and noncancer deaths in participants with and without prior MI or stroke.

DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified secondary analysis of the Diuretic Comparison Project (DCP), a pragmatic randomized clinical trial conducted within 72 participating Veterans Affairs health care systems from June 2016 to June 2021, in which patients aged 65 years or older with hypertension taking HCTZ at baseline were randomized to continue HCTZ or …

Performance Of A Stool-Based Quantitative Pcr Assay For The Diagnosis Of Tuberculosis In Adolescents And Adults: A Multinational, Prospective Diagnostic Accuracy Study, Alexander Kay, Anca Vasiliu, Lucia Carratala-Castro, Bariki Mtafya, Jose Euberto Mendez Reyes, Nontobeko Maphalala, Shilzia Munguambe, Durbbin Mulengwa, Tara Ness, Belen Saavedra, Jason Bacha, Gugu Maphalala, Rojelio Mejia, Godwin Mtetwa, Sozinho Acacio, Patricia Manjate, Edson Mambuque, Nosisa Shiba, Nokwanda Kota, Mangaliso Ziyane, Nyanda Elias Ntinginya, Christoph Lange, H Lester Kirchner, Andrew R Dinardo, Alberto L Garcia-Basteiro, Anna Maria Mandalakas, Stool4tb Global Partnership

Faculty, Staff and Students Publications

BACKGROUND: Despite increasing availability of rapid molecular tests for the diagnosis of tuberculosis in high-burden settings, many people with tuberculosis are undiagnosed. Reliance on sputum as the primary specimen for tuberculosis diagnostics contributes to this diagnostic gap. We evaluated the diagnostic accuracy and additive yield of a novel stool quantitative PCR (qPCR) assay for the diagnosis of tuberculosis in three countries in Africa with high tuberculosis burdens.

METHODS: We undertook a prospective diagnostic accuracy study in Eswatini, Mozambique, and Tanzania from Sept 21, 2020, to Feb 2, 2023, to compare the diagnostic accuracy for tuberculosis of a novel stool qPCR …

Altered Myocardial Lipid Regulation In Junctophilin-2-Associated Familial Cardiomyopathies, Satadru K Lahiri, Feng Jin, Yue Zhou, Ann P Quick, Carlos F Kramm, Meng C Wang, Xander Ht Wehrens

Faculty, Staff and Students Publications

Myocardial lipid metabolism is critical to normal heart function, whereas altered lipid regulation has been linked to cardiac diseases including cardiomyopathies. Genetic variants in the JPH2 gene can cause hypertrophic cardiomyopathy (HCM) and, in some cases, dilated cardiomyopathy (DCM). In this study, we tested the hypothesis that JPH2 variants identified in patients with HCM and DCM, respectively, cause distinct alterations in myocardial lipid profiles. Echocardiography revealed clinically significant cardiac dysfunction in both knock-in mouse models of cardiomyopathy. Unbiased myocardial lipidomic analysis demonstrated significantly reduced levels of total unsaturated fatty acids, ceramides, and various phospholipids in both mice with HCM and …

Predictors And Impact Of Prolonged Vasoplegia After Continuous-Flow Left Ventricular Assist Device Implantation, Harveen K Lamba, Mary Kim, Meng Li, Andrew B Civitello, Ajith P Nair, Leo Simpson, J Patrick Herlihy, O H Frazier, Joseph G Rogers, Gabriel Loor, Kenneth K Liao, Alexis E Shafii, Subhasis Chatterjee

Faculty, Staff and Students Publications

BACKGROUND: Vasoplegia after cardiac surgery is associated with adverse outcomes. However, the clinical effects of vasoplegia and the significance of its duration after continuous-flow left ventricular assist device (CF-LVAD) implantation are less known.

OBJECTIVES: This study aimed to identify predictors of and outcomes from transient vs prolonged vasoplegia after CF-LVAD implantation.

METHODS: The study was a retrospective review of consecutive patients who underwent CF-LVAD implantation between January 1, 2005, and December 31, 2017. Vasoplegia was defined as the presence of all of the following: mean arterial pressure ≤65 mm Hg, vasopressor (epinephrine, norepinephrine, vasopressin, or dopamine) use for >6 hours …

Clinical Outcomes After Acute Coronary Syndromes Or Revascularization Among People Living With Hiv: A Systematic Review And Meta-Analysis, Mohammed Haji, Michael Capilupi, Michael Kwok, Nouran Ibrahim, Gerald S Bloomfield, Christopher T Longenecker, Maria C Rodriguez-Barradas, Chester N Ashong, Eric Jutkowitz, Tracey H Taveira, Michelle Richard, Jennifer L Sullivan, James L Rudolph, Wen-Chih Wu, Sebhat Erqou

Faculty, Staff and Students Publications

IMPORTANCE: Clinical outcomes after acute coronary syndromes (ACS) or percutaneous coronary interventions (PCIs) in people living with HIV have not been characterized in sufficient detail, and extant data have not been synthesized adequately.

OBJECTIVE: To better characterize clinical outcomes and postdischarge treatment of patients living with HIV after ACS or PCIs compared with patients in an HIV-negative control group.

DATA SOURCES: Ovid MEDLINE, Embase, and Web of Science were searched for all available longitudinal studies of patients living with HIV after ACS or PCIs from inception until August 2023.

STUDY SELECTION: Included studies met the following criteria: patients living with …

Tenapanor As Therapy For Hyperphosphatemia In Maintenance Dialysis Patients: Results From The Optimize Study, Stuart M Sprague, Daniel E Weiner, David P Tietjen, Pablo E Pergola, Steven Fishbane, Geoffrey A Block, Arnold L Silva, Stephen Z Fadem, Robert I Lynn, George Fadda, Lynae Pagliaro, Suling Zhao, Susan Edelstein, David M Spiegel, David P Rosenbaum

Faculty, Staff and Students Publications

KEY POINTS: Tenapanor, a first-in-class local inhibitor of sodium/hydrogen exchanger isoform 3, acts as a phosphate absorption inhibitor by decreasing paracellular phosphate absorption. Tenapanor alone or with phosphate binders achieved

BACKGROUND: OPTIMIZE was a randomized, open-label study evaluating different tenapanor initiation methods. OPTIMIZE evaluated tenapanor alone and in combination with phosphate binders (PBs) to achieve target serum phosphate (P) ≤5.5 mg/dl.

METHODS: Patients with inadequately controlled P receiving maintenance dialysis from 42 US locations who were taking PBs with baseline

RESULTS: By part A end point, 34.4% (

CONCLUSIONS: Tenapanor as monotherapy or in combination with PBs effectively lowered P …

Use Of Topical Methylene Blue To Image Nuclear Morphometry With A Low-Cost Scanning Darkfield Microendoscope, Huayu Hou, Jennifer Carns, Richard A Schwarz, Ann M Gillenwater, Sharmila Anandasabapathy, Rebecca R Richards-Kortum

Faculty, Staff and Students Publications

SIGNIFICANCE: Fiber-optic microendoscopy is a promising approach to noninvasively visualize epithelial nuclear morphometry for early cancer and precancer detection. However, the broader clinical application of this approach is limited by a lack of topical contrast agents available for

AIM: The aim of this study was to evaluate the ability to image nuclear morphometry in vivo with a novel fiber-optic microendoscope used together with topical application of methylene blue (MB), a dye with FDA approval for use in chromoendoscopy in the gastrointestinal tract.

APPROACH: The low-cost, high-resolution microendoscope implements scanning darkfield imaging without complex optomechanical components by leveraging programmable illumination and …

Systematic Evaluation Of Machine Learning-Enhanced Trifocal Iol Power Selection For Axial Myopia Cataract Patients, Danmin Cao, Min Hu, Danlin Zhi, Jianheng Liang, Qian Tan, Qiong Lei, Maoyan Li, Hao Cheng, Li Wang, Weiwei Dai

Faculty, Staff and Students Publications

Purpose: This study aimed to evaluate and optimize intraocular lens (IOL) power selection for cataract patients with high axial myopia receiving trifocal IOLs.

Design: A multi-center, retrospective observational case series was conducted. Patients having an axial length ≥26 mm and undergoing cataract surgery with trifocal IOL implanted were studied.

Methods: Preoperative biometric and postoperative outcome data from 139 eyes were collected to train and test various machine learning (ML) models (support vector machine, linear regression, and stacking regressor) using five-fold cross-validation. The models' performance was further validated externally using data from 48 eyes enrolled from other hospitals. Performance of seven …

Pragmatic Strategies To Address Health Disparities Along The Continuum Of Care In Chronic Liver Disease, Mayur Brahmania, Shari Rogal, Marina Serper, Arpan Patel, David Goldberg, Amit Mathur, Julius Wilder, Jennifer Vittorio, Andrew Yeoman, Nicole E Rich, Mariana Lazo, Ani Kardashian, Sumeet Asrani, Ashley Spann, Nneka Ufere, Manisha Verma, Elizabeth Verna, Dinee Simpson, Jesse D Schold, Russell Rosenblatt, Lisa Mcelroy, Sharad I Wadhwani, Tzu-Hao Lee, Alexandra T Strauss, Raymond T Chung, Ignacio Aiza, Rotonya Carr, Jin Mo Yang, Carla Brady, Brett E Fortune

Faculty, Staff and Students Publications

Racial, ethnic, and socioeconomic disparities exist in the prevalence and natural history of chronic liver disease, access to care, and clinical outcomes. Solutions to improve health equity range widely, from digital health tools to policy changes. The current review outlines the disparities along the chronic liver disease health care continuum from screening and diagnosis to the management of cirrhosis and considerations of pre-liver and post-liver transplantation. Using a health equity research and implementation science framework, we offer pragmatic strategies to address barriers to implementing high-quality equitable care for patients with chronic liver disease.

Herbal And Dietary Supplement Induced Liver Injury Leading To Hepatitis-Associated Severe Aplastic Anemia: A Case Report, Rebecca Mercedes, Sanjiv Harpavat, Paula M Hertel, Ghadir Sasa, Susan Kirk, Kalyani Patel, Krupa R Mysore

Faculty, Staff and Students Publications

Herbal and dietary supplements (HDS) are a common etiology of drug induced liver injury and, specifically, Herbalife® supplements have been implicated. Hepatitis associated aplastic anemia (HAAA) is a rare and potentially fatal complication after acute hepatitis characterized by pancytopenia. While there have been rare cases of HDS leading to HAAA, no cases of Herbalife® induced liver injury leading to HAAA have been reported from this specific HDS. We report a unique case of severe aplastic anemia developing after sub-fulminant liver failure associated with chronic HDS use. This case illustrates the importance of warning the public about HDS as their use …

Immunotherapy Withdrawal By Step-Down To Mesalamine In Pediatric Patients With Ulcerative Colitis, Reka Szigeti, Richard Kellermayer

Faculty, Staff and Students Publications

OBJECTIVE: Parents and pediatric patients with ulcerative colitis (UC) who progressed to systemic immunotherapy are concerned about lifelong risks from such treatments. There is limited knowledge about withdrawal of such agents and step-down (SD) to enteral 5-aminosalicylic acid (mesalamine) before transitioning to adult care.

METHODS: We studied nine pediatric cases with moderate to severe UC who after a median of 2.18 years of clinical remission on systemic immunotherapy stepped down to oral mesalamine treatment.

RESULTS: Average follow-up time from SD was 3.49 years. Five patients (55.5%) had sustained remission (without any flare noted) after SD during follow-up. Sustained clinical remission …

Gut Development Following Insulin-Like Growth Factor-1 Supplementation To Preterm Pigs, Martin Bo Rasmussen, Kristine Holgersen, Stanislava Pankratova, Ole Bæk, Douglas G Burrin, Thomas Thymann, Per Torp Sangild

Faculty, Staff and Students Publications

BACKGROUND: Reduced insulin-like growth factor-1 (IGF-1) levels may contribute to impaired organ development in preterm infants. Using preterm pigs as a model, we hypothesized that IGF-1 supplementation improves health and gut development during the first three weeks of life.

METHODS: First, clinical and organ endpoints were compared between artificially-reared, cesarean-delivered preterm pigs and vaginally-delivered, sow-reared term pigs at 5, 9 and 19 days. Next, preterm pigs were treated with recombinant human IGF-1 for 19 days (2.25 mg/kg/day, systemically).

RESULTS: Relative to term pigs, preterm pigs had lower body weight, fat, bone contents, relative weights of liver and spleen and a …

Improving Adherence To Clinical Practice Guidelines For Managing Gastric Intestinal Metaplasia Among Gastroenterologists At A Us Academic Institution, Jake Jacob, Valentine Millien, Scott Berger, Ruben Hernaez, Gyanprakash A Ketwaroo, Avegail G Flores, Jason K Hou, Maria E Jarbrink-Sehgal, Natalia I Khalaf, Daniel G Rosen, Hashem B El-Serag, Mimi C Tan

Faculty, Staff and Students Publications

BACKGROUND: Clinical guidelines reserve endoscopic surveillance after a gastric intestinal metaplasia (GIM) diagnosis for high-risk patients. However, it is unclear how closely guidelines are followed in clinical practice. We examined the effectiveness of a standardized protocol for the management of GIM among gastroenterologists at a US hospital.

METHODS: This was a preintervention and postintervention study, which included developing a protocol and education of gastroenterologists on GIM management. For the preintervention study, 50 patients with GIM were randomly selected from a histopathology database at the Houston VA Hospital between January 2016 and December 2019. For the postintervention study, we assessed change …

Sars-Cov-2 Viral Load In The Nasopharynx At Time Of First Infection Among Unvaccinated Individuals: A Secondary Cross-Protocol Analysis Of 4 Randomized Trials, Leigh H Fisher, Jia Jin Kee, Albert Liu, Claudia M Espinosa, April K Randhawa, James Ludwig, Craig A Magaret, Samuel T Robinson, Peter B Gilbert, Ollivier Hyrien, James G Kublin, Nadine Rouphael, Ann R Falsey, Magdalena E Sobieszczyk, Hana M El Sahly, Beatriz Grinsztejn, Glenda E Gray, Karen L Kotloff, Cynthia L Gay, Brett Leav, Ian Hirsch, Frank Struyf, Lisa M Dunkle, Kathleen M Neuzil, Lawrence Corey, Yunda Huang, Paul A Goepfert, Stephen R Walsh, Lindsey R Baden, Holly Janes, Covid-19 Prevention Network (Covpn)

Faculty, Staff and Students Publications

IMPORTANCE: SARS-CoV-2 viral load (VL) in the nasopharynx is difficult to quantify and standardize across settings, but it may inform transmission potential and disease severity.

OBJECTIVE: To characterize VL at COVID-19 diagnosis among previously uninfected and unvaccinated individuals by evaluating the association of demographic and clinical characteristics, viral variant, and trial with VL, as well as the ability of VL to predict severe disease.

DESIGN, SETTING, AND PARTICIPANTS: This secondary cross-protocol analysis used individual-level data from placebo recipients from 4 harmonized, phase 3 COVID-19 vaccine efficacy trials sponsored by Moderna, AstraZeneca, Janssen, and Novavax. Participants were SARS-CoV-2 negative at baseline …

Retrospective Analysis Of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome In Paediatric Patients Undergoing Hematopoietic Cell Transplantation -A Multicentre Study, Dristhi Ragoonanan, Hisham Abdel-Azim, Aditya Sharma, Saleh Bhar, Jennifer Mcarthur, Renee Madden, April Rahrig, Rajinder Bajwa, Jian Wang, Victoria Sun, Mariah Wright, Rebekah Lassiter, Basirat Shoberu, Jitesh Kawedia, Sajad Jawad Khazal, Kris Michael Mahadeo, Pediatric Acute Lung Injury And Sepsis Investigators (Palisi) Network

Faculty, Staff and Students Publications

BACKGROUND: Sinusoidal obstruction syndrome is a potentially fatal complication following hematopoietic cell transplantation, high-intensity chemotherapies and increasingly seen with calicheamicin based leukemia therapies. Paediatric specific European Society for Blood and Marrow Transplantation (pEBMT) diagnostic criteria have demonstrated benefit in single center studies compared to historic criteria. Yet, the extent to which they have been universally implemented remains unclear.

METHODS: We conducted a retrospective multi-centre study to examine the potential impact of the Baltimore, modified Seattle and pEBMT criteria on the incidence, severity, and outcomes of sinusoidal obstruction syndrome among paediatric hematopoietic cell transplantation patients.

FINDINGS: The incidence of sinusoidal obstruction …

Age-Related Differences In The Mouse Corneal Epithelial Transcriptome And Their Impact On Corneal Wound Healing, Anmar Abu-Romman, Kaitlin K Scholand, Gowthaman Govindarajan, Zhiyuan Yu, Sonali Pal-Ghosh, Mary A Stepp, Cintia S De Paiva

Faculty, Staff and Students Publications

PURPOSE: Aging is a risk factor for dry eye. We sought to identify changes in the aged mouse corneal epithelial transcriptome and determine how age affects corneal sensitivity, re-epithelialization, and barrier reformation after corneal debridement.

METHODS: Corneal epithelium of female C57BL/6J (B6) mice of different ages (2, 12, 18, and 24 months) was collected, RNA extracted, and bulk RNA sequencing performed. Cornea sensitivity was measured with an esthesiometer in 2- to 3-month-old, 12- to 13-month-old, 18- to 19-month-old, and 22- to 25-month-old female and male mice. The 2-month-old and 18-month-old female and male mice underwent unilateral corneal debridement using a …

Piezo1 Regulates Meningeal Lymphatic Vessel Drainage And Alleviates Excessive Csf Accumulation, Dongwon Choi, Eunkyung Park, Joshua Choi, Renhao Lu, Jin Suh Yu, Chiyoon Kim, Luping Zhao, James Yu, Brandon Nakashima, Sunju Lee, Dhruv Singhal, Joshua P Scallan, Bin Zhou, Chester J Koh, Esak Lee, Young-Kwon Hong

Faculty, Staff and Students Publications

Piezo1 regulates multiple aspects of the vascular system by converting mechanical signals generated by fluid flow into biological processes. Here, we find that Piezo1 is necessary for the proper development and function of meningeal lymphatic vessels and that activating Piezo1 through transgenic overexpression or treatment with the chemical agonist Yoda1 is sufficient to increase cerebrospinal fluid (CSF) outflow by improving lymphatic absorption and transport. The abnormal accumulation of CSF, which often leads to hydrocephalus and ventriculomegaly, currently lacks effective treatments. We discovered that meningeal lymphatics in mouse models of Down syndrome were incompletely developed and abnormally formed. Selective overexpression of …