Diseases Commons^™

Integrating Explainable Machine Learning And Transcriptomics Data Reveals Cell-Type Specific Immune Signatures Underlying Macular Degeneration, Khang Ma, Hosei Nakajima, Nipa Basak, Arko Barman, Rinki Ratnapriya

Faculty, Staff and Students Publications

Genome-wide association studies (GWAS) have established key role of immune dysfunction in Age-related Macular Degeneration (AMD), though the precise role of immune cells remains unclear. Here, we develop an explainable machine-learning pipeline (ML) using transcriptome data of 453 donor retinas, identifying 81 genes distinguishing AMD from controls (AUC-ROC of 0.80, CI 0.70–0.92). Most of these genes were enriched in their expression within retinal glial cells, particularly microglia and astrocytes. Their role in AMD was further strengthened by cellular deconvolution, which identified distinct differences in microglia and astrocytes between normal and AMD. We corroborated these findings using independent single-cell data, where …

Case Report On Acute Hemorrhagic Acute Disseminated Encephalomyelitis (Adem) Following Parvovirus B19 Infection In An Immunocompetent Child, Akash Dnyandeo Sarkate, Sushma Save, Alpana Kondekar, Raja Rajan

Digital Journal of Clinical Medicine

Acute disseminated encephalomyelitis (ADEM) is a rare, immune-mediated demyelinating disorder of the central nervous system, often triggered by viral infections. Parvovirus B19 has been implicated in various haematological and neurological manifestations; however, its association with acute hemorrhagic ADEM remains rare. Here, we report a case of a 5-year-old male immunocompetent child who developed ADEM following parvovirus B19 infection, emphasising the rarity of such presentations and the importance of early recognition and management.

Tumor Microenvironment Governs The Prognostic Landscape Of Immunotherapy For Head And Neck Squamous Cell Carcinoma: A Computational Model-Guided Analysis, Priyan Bhattacharya, Alban J Linnenbach, Andrew P. South, Ubaldo E. Martinez-Outshoorn, Joseph M. Curry, Jennifer M. Johnson, Larry A. Harshyne, Mỹ G. Mahoney, Adam J. Luginbuhl, Rajanikanth Vadigepalli

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Immune checkpoint inhibition (ICI) has emerged as a critical treatment strategy for squamous cell carcinoma of the head and neck (HNSCC) that halts the immune escape of the tumor cells. Increasing evidence suggests that the onset, progression, and lack of/no response of HNSCC to ICI are emergent properties arising from the interactions within the tumor microenvironment (TME). Deciphering how the diversity of cellular and molecular interactions leads to distinct HNSCC TME subtypes subsequently governing the ICI response remains largely unexplored. We developed a cellular-molecular model of the HNSCC TME that incorporates multiple cell types, cellular states, and transitions, and molecularly …

A Novel Cardiomyopathy Phenotype Linked To A Chd7 Missense Variant, In Young Park, Chih-Wei Hsu, Karim Bouazoune, Christina E Espindola, Madeline Hannah Mclaughlin Armond, Cristian Coarfa, Sandra L Grimm, James F Martin, Donna M Martin, Cheryl Lyn Walker

Center for Medical Ethics and Health Policy Staff Publications

Loss of function in the chromatin remodeler CHD7 causes CHARGE syndrome, characterized by variable penetrance and diverse abnormalities. However, establishing genotype-phenotype correlations has been challenging, as most CHD7 inactivating mutations are null alleles. Through CHD7 missense variant analysis at potential phosphorylation sites, we identified T730 (T720 in mice) as a critical residue associated with pathogenesis. Using a CHD7 T730 missense variant (Chd7T720A) and a frameshift null allele (Chd7fs) in a mouse model, we found that Chd7fs/fs mice were non-viable, while Chd7fs/+ mice exhibited haploinsufficiency-related circling behavior. Notably, Chd7fs/T720A mice died before postnatal …

Association Of Estimated Plasma Volume Status With Invasive Hemodynamics And All-Cause Mortality In Patients With Liver Cirrhosis, Esteban Kosak Lopez, Phuuwadith Wattanachayakul, Jose Manuel Martinez Manzano, Andrew Geller, Simone Jarrett, John Malin, Raul Leguizamon, Tara John, Rasha Khan, Ian Mclaren, Alexander Prendergast, Kevin Lo, Zurab Azmaiparashvili

Einstein Health Papers

BACKGROUND: Estimated plasma volume status (ePVS) correlates with intravascular congestion and prognosis in patients with heart failure. The ePVS relationship with invasive hemodynamic profiling and clinical outcomes in patients with liver cirrhosis (LC) remains unclear.

METHODS: This single-center retrospective cohort study included LC patients who underwent right heart catheterization (RHC) between 2018 and 2023. Estimated plasma volume status (ePVS) was calculated using the Strauss-derived Duarte formula, with patients classified into high (> 5.5%) and low-ePVS (≤ 5.5%) groups. Cox-multivariable analysis was used to determine if ePVS was associated with all-cause mortality within 1 year post-RHC among transplant-free patients.

RESULTS: Of …

Insights On Human Papillomavirus Among Medical Students And Professionals, Fathima Thansiha, Amogha Shree, Rashmi S

Digital Journal of Clinical Medicine

Background: As per World Health Organization, in 2022, 660000 women were diagnosed with cervical cancer worldwide and 350000 women died from the disease. Sexual behaviour is the major risk factor and exposure to Human Papillomavirus has been established as a causative agent in 70-80% of the cases for development of cervical cancer. Most infections with HPV resolve spontaneously and cause no symptoms, persistent infection can cause cervical cancer in women. Effective primary (HPV vaccination) and secondary prevention approaches (screening and treating precancerous lesions) will prevent most cervical cancer cases. Thus, study was conducted with the objective of assessing the knowledge …

Measles, Mumps, Rubella Immunization And The Resurgence Of Measles In America, Peter J Hotez

Faculty, Staff and Students Publications

No abstract provided.

Fracture Patterns In Craniofacial Gunshot Wounds: A Seven-Year Experience, Gabriela G Cruz, Sameer H Siddiqui, David Z Allen, Kunal R Shetty, Sean P Mckee, Brady J Anderson, Mark Knackstedt, W Katherine Kao, Tang Ho

Faculty, Staff and Student Publications

Objective: To characterize facial fracture patterns and understand predictors of surgical repair and LOS with the objective of assisting providers in managing and understanding these complex injuries.

Study design: This is a retrospective cohort chart review study.

Methods: A retrospective review was conducted for patients admitted with gunshot wounds (GSWs) to the head, neck, or face between January 2013 and March 2020 at a level one trauma tertiary care hospital. Univariate and multivariate analysis were performed to identify associations with surgical repair and LOS.

Results: Of the 578 patients with head, neck, or facial GSWs, 204 survived and sustained facial …

Association Between Timing Of Angiotensin Ii Administration And Outcomes In Vasoplegia After Cardiac Surgery, Travis J Miles, Michael T Guinn, Orlando R Suero, Todd K Rosengart, Marc R Moon, Joseph S Coselli, Ravi K Ghanta, Subhasis Chatterjee

Faculty, Staff and Students Publications

Objective: Vasoplegic shock after cardiopulmonary bypass (CPB) is a highly morbid condition. The novel vasopressor angiotensin II is increasingly being used for catecholamine-resistant vasoplegia. Although early intervention with adjunctive therapies such as methylene blue can improve outcomes of vasoplegia, the optimal timing for escalation with angiotensin II is unknown.

Methods: Pharmacologic data were extracted from electronic health records for patients who underwent surgery with CPB during 2017-2022. Patients were identified who received angiotensin II intraoperatively or postoperatively (ie, early or late). Multivariable logistic regression was used to determine the risk-adjusted effects of earlier angiotensin II administration on postoperative major adverse …

Clinical Interrogation Of Tp53 Aberrations And Its Impact On Survival In Patients With Myeloid Neoplasms, Jayastu Senapati, Sanam Loghavi, Guillermo Garcia-Manero, Guillin Tang, Tapan Kadia, Nicholas J Short, Hussein A Abbas, Naszrin Arani, Courtney D Dinardo, Gautam Borthakur, Naveen Pemmaraju, Betul Oran, Elizabeth Shpall, Uday Popat, Richard Champlin, Sherry Pierce, Sankalp Arora, Ghayas Issa, Musa Yilmaz, Keyur Patel, Koichi Takahashi, Guillermo Montalban-Bravo, Danielle Hammond, Fadi G Haddad, Farhad Ravandi, Hagop M Kantarjian, Naval G Daver

Faculty, Staff and Student Publications

In myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) with TP53 aberrations, dissecting the interaction amongst patient, disease and treatment factors are important for therapeutic decisions and prognostication. This retrospective analysis included patients with newly diagnosed MDS (>5% blasts) and AML with TP53 mutation(s) treated at MD Anderson Cancer Center. We factored patient age, TP53 aberration burden, therapy intensity and use of venetoclax in the AML subgroup, and allogeneic hematopoietic stem cell transplantation (HSCT) to interrogate outcomes. TP53 was annotated as high-risk (TP53HR) if >1 mutation, one mutation plus allelic deletion or a single mutation with variant allele frequency …

Neovascular Pruning By Ido1 Inhibitors Can Potentiate Immunogenic Cytotoxicity Of Ischemia-Targeted Agents To Synergistically Enhance Anti-Pd-1 Responsiveness, Shih-Chun Shen, Souvik Dey, James B. Duhadaway, Erika Sutanto-Ward, Maurice T. Hampton, Serguei V. Kozlov, George C. Prendergast, Alexander J. Muller

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Strategies for deploying indoleamine 2,3-dioxygenase 1 (IDO1)-targeted therapies for use against cancer have focused on IDO1's role in promoting peripheral immune tolerance that shields tumors from effector T cells. However, preclinical investigation of both primary and metastatic tumor development in the lungs has uncovered a previously unappreciated role for IDO1 in directing a counterregulatory response to interferon (IFN)-γ that realigns the local inflammatory environment to promote tumor neovascularization. Understanding how to therapeutically leverage the ability of IDO1 inhibitors to subvert inflammatory neovascularization within the tumor microenvironment has potential ramifications for future clinical development of these compounds.

METHODS: Pulmonary metastases …

Post-Recovery Viral Shedding Shapes Wastewater-Based Epidemiological Inferences, Tin Phan, Samantha Brozak, Bruce Pell, Stanca M Ciupe, Ruian Ke, Ruy M Ribeiro, Anna Gitter, Kristina D Mena, Alan S Perelson, Yang Kuang, Fuqing Wu

Faculty, Staff and Student Publications

Background: The prolonged viral shedding from the gastrointestinal tract is well documented for numerous pathogens, including SARS-CoV-2. However, the impact of prolonged viral shedding on epidemiological inferences using wastewater data is not yet fully understood.

Methods: To gain a better understanding of this phenomenon at the population level, we extended a wastewater-based modeling framework that integrates viral shedding dynamics, viral load data in wastewater, case report data, and an epidemic model.

Results: Our results indicate that as an outbreak progresses, the viral load from recovered individuals gradually becomes predominant, surpassing that from the infectious population. This phenomenon leads to a …

Characterization Of Immunogenicity Of Hiv Mrna Vaccine In Humanized Mice, Omoyeni Precious Adejare

Biotechnology Theses

Human Immunodeficiency Virus (HIV) remains a leading global cause of mortality. Despite decades of research, a definitive cure or an effective vaccine for HIV infection has yet to be discovered. The major target for HIV vaccine development is the envelope (Env) trimeric protein that is responsible for host cell attachment and fusion. This comprises gp120 and the transmembrane gp41. Gp140, a truncated form of gp160(full envelope trimer) lacks the transmembrane and cytoplasmic domains of gp41, closely mimics the native HIV envelope has been shown to enhance the induction of broadly neutralizing antibodies (BnAbs) when used as protein vaccine in previous …

From M. Chelonae To M. Immunogenum: A Rare Case Of Dual Nontuberculous Mycobacterial Infection, Ifeanyi Kingsley Uche, Nathalia Simonetti, Andrea Murina

School of Medicine Faculty Publications

No abstract provided.

Reducing Surgery For Pediatric Posttonsillectomy Hemorrhage Using Tranexamic Acid: A Quality Improvement Initiative, Laura A. Petrauskas, Janavi Sethurathnam, Ansley J. Kunnath, Rahul K. Sharma, John Ceremsak, Ryan H. Belcher, James D. Phillips, Jay A. Werkhaven, Amy S. Whigham, Lyndy J. Wilcox, Christopher T. Wootten, Frank W. Virgin, Jason S. Park

School of Medicine Faculty Publications

Objective: Evaluate the use of tranexamic acid (TXA) and observation as a management option for pediatric patients presenting with posttonsillectomy hemorrhage (PTH). Study Design: Retrospective analysis of a prospectively implemented quality improvement initiative with a historical control comparison group. Setting: Tertiary children's hospital. Methods: Patients < 18 years of age who underwent adenotonsillectomy (AT) and returned to the Emergency Department for PTH were included. Patients who were stable without large volume or active bleeding were given intravenous TXA and admitted for overnight observation. Data were compared in a before-and-after analysis: preprotocol (April 2022 to March 2023) versus postprotocol (April 2023 to March 2024). For cost-effectiveness analysis, we analyzed aggregated claims data from a commercial claims database. Results: Preprotocol 1800 adenotonsillectomies were performed, and 40 procedures were performed for control of hemorrhage (2.2 per 100 AT). Postprotocol 2356 adenotonsillectomies were performed, and 30 procedures were performed to control hemorrhage (1.3 per 100 AT) showing a significant reduction in return to the operating room (relative risk [RR] = 0.59, 95% confidence interval [CI] [0.358, 0.916], P-value.020). There were no reported adverse events attributable to TXA. An estimated 21 surgeries were avoided, and 26 additional patients were observed in the hospital during the postprotocol period, for an estimated net cost savings of $174,970. Conclusion: The implementation of a standardized TXA protocol significantly reduced the need for return to the operating room for PTH in pediatric patients, without complications and with net cost savings to the health care system.

Imaging Hallmarks Of Idiopathic Intracranial Hypertension And Insights Into Pathogenesis, Albalooshy Basimah, Scott Faro, Hsiangkuo Yuan, Kiran Talekar, Prabath Mondel, Enchao Qiu, Joga Chaganti

Department of Radiology Faculty Papers

Idiopathic Intracranial hypertension (IIH), also referred to as pseudotumor cerebri, is a term used to describe increased intracranial pressure in the absence of a known identifiable secondary cause. Despite advancements of neuroimaging techniques, imaging of the pathological underpinnings in the diagnosis of IIH has been limited. Although the causation of IIH has been ascribed to increased Cerebrospinal Fluid production and disordered drainage through the dural sinuses, new evidence shows that the glymphatic system which is an alternate pathway of drainage is likely to play a pivotal role. In this review, we address the pathophysiological underpinnings in the causation of IIH …

Intersection Of Alcohol Use, Pain Symptoms, And Negative Affect In Total Knee Arthroplasty Patients And People With Hiv, Taylor Fitzpatrick-Schmidt, Vinod Dasa, Claudia Leonardi, Tekeda F. Ferguson, David A. Welsh, Patricia E. Molina, Martin J.J. Ronis, Scott Edwards

School of Medicine Faculty Publications

Alcohol is a well-known analgesic, although excessive alcohol use can lead to hyperalgesia and heightened negative affect. This cross-sectional study examined associations between alcohol use, self-reported pain, and negative affective symptoms in two distinct cohorts of patients vulnerable to chronic pain: individuals undergoing total knee arthroplasty (TKA) surgery and a cohort of people with HIV (PWH). Participants were enrolled in two clinical studies: a retrospective study of patients undergoing TKA and a longitudinal study of PWH, the New Orleans Alcohol Use in HIV (NOAH) cohort. Based on the Alcohol Use Disorders Identification Test – Consumption (AUDIT-C) score, participants in both …

Pcsk-9 Inhibitors Treatment: The Cardiovascular Disparity, Julia Lees, Seana-Pierre Williams, Tahir Razzaq, Michael B. Roberts

The Journal of Integrated Primary Care

Introduction: According to the Center for Disease Control and Prevention (CDC) and American Heart Association (AHA), cardiovascular disease is the leading cause of death in the United States. This phenomenon disproportionally affects the African American population, who have a 31% higher mortality rate than non-Hispanic Caucasian individuals. A retrospective review of PCSK-9 medication use, specifically in a patient population that had minimal representation in the large, landmark clinical trials, can lead to better understanding about the therapeutic potential in cardiovascular disease reduction and patient outcomes attributed to medication use. Education regarding this novel drug class, medication access and patient support, …

Sickle Cell Mice Exhibit Elevated Plasma Bilirubin And Altered Intracranial Cerebral Blood Velocities That Are Exacerbated By Hypoxia-Reoxygenation, Francisco J. Nunez, Ashraf M. Mohieldin, Amy Y. Pan, Sean P. Palecek, Rahima Zennadi, Ramani Ramchandran, Kevin R. Rarick, Surya M. Nauli

Pharmacy Faculty Articles and Research

Sickle cell disease (SCD) is a genetic disorder characterized by sickle red blood cells (RBCs). Sickle RBCs cause cerebral vasculopathies including vaso-occlusive events, leading to ischemia-reperfusion injury and hypoxic tissue environment. To date, the physiological blood flow velocities in cerebral vessels of preclinical SCD models has not been evaluated under hypoxic-reoxygenation. In our study, we used transcranial ultrasound techniques to measure abnormal blood flow velocities in the internal carotid (ICA) and middle cerebral arteries (MCA) of transgenic sickle cell mice (SS) challenged with hypoxia-reoxygenation. Our study showed that SS mice that underwent hypoxic stress exhibited lower relative mean velocities in …

Safety And Efficacy Of A Mesenchymal Stem Cell Secretome Therapy (Kpi-012) For Persistent Corneal Epithelial Defects: A Phase 1b Trial, Valeria Sánchez Huerta, Hugo Quiroz-Mercado, Enrique O Graue-Hernández, Alejandro Navas, Spencer Alford, Darius Kharabi, Stephen Pflugfelder

Faculty, Staff and Students Publications

Background: Persistent corneal epithelial defect (PCED) is a condition often refractory to conventional treatments. KPI-012 is a topical mesenchymal stem cell secretome therapy under investigation for PCED management.

Objective: To assess the safety, tolerability, and corneal wound healing efficacy of KPI-012 in a phase 1b, proof-of-concept, open-label, single-arm clinical trial.

Methods: The safety profile and tolerability of topical self-administered KPI-012 therapy (twice daily, 1-week duration) were first evaluated in an initial safety cohort of participants with pre-existing permanent vision loss and no active corneal disease (n = 3). The safety profile and efficacy of KPI-012 were then assessed in participants …

Ovarian Cancer G Protein-Coupled Receptor-1 Signaling Bias Dictates Anti-Contractile Effect Of Benzodiazepines On Airway Smooth Muscle, Dominic R. Villalba, Arun K. Jannu, Elham Javed, Isha Dandekar, Ruping Wang, Deepak A. Deshpande, Steven S. An, Reynold A. Panettieri, Dale D. Tang, Raymond B. Penn, Ajay P. Nayak

Center for Translational Medicine Faculty Papers

BACKGROUND: We recently reported that the ovarian cancer G protein-coupled receptor-1 (OGR1) can be pharmacologically biased with specific benzodiazepines to couple with distinct heterotrimeric G proteins in human airway smooth muscle (ASM) cells. Lorazepam stimulated both G

METHODS: Models of histamine (His) -stimulated contraction included imaging of ex vivo human precision cut lung slices (hPCLS) and Magnetic Twisting Cytometry (MTC) analysis of human ASM cell stiffness. To explore mechanisms of regulation, we examined effects on myosin light chain (pMLC) phosphorylation and PKA activity in primary human ASM cultures, as well as actin cytoskeleton integrity as defined by changes in the …

Genetic, Transcriptomic, And Epigenomic Insights Into Sjögren's Disease: An Integrative Network Investigation And Immune Diseases Comparison, Nitesh Enduru, Astrid M Manuel, Zhongming Zhao

Faculty, Staff and Student Publications

Sjögren's disease (SjD) is a systemic autoimmune disorder primarily causing dry eyes and mouth. It frequently overlaps with other autoimmune diseases (AIDs), including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, the genetic basis of SjD remains underexplored, limiting our understanding of its connections to other immune-mediated conditions. In this study, we aimed to identify gene networks associated with SjD through the integration of genetic, transcriptomic, and epigenomic data. We further compared the genetic factors of SjD with other immune-mediated diseases. We analyzed genome-wide association studies (GWAS) summary statistics, DNA methylation, and transcriptomic data using our in-house network-based methods, …

Identification And Preclinical Assessment Of Novel Therapeutic Modalities In Environmental Exposure-Induced Lung Disease, Aaron D. Schwab

Theses & Dissertations

Environmental lung diseases are preventable respiratory conditions either caused or made worse by inhaled environmental exposures. Contemporarily, environmental lung diseases are most associated with workplace exposures given specific occupational processes aerosolize inflammatory agents that can be inhaled at high concentrations. Although a considerable amount is known regarding immunoglobulin (Ig)E-mediated responses to environmental exposures, little is known about non-IgE mediated respiratory conditions resulting from lipopolysaccharide (LPS)-enriched organic dust exposure(s). Chronic respiratory diseases such as asthma, hypersensitivity pneumonitis, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis have all been identified as environmental lung diseases caused or exacerbated by such environmental dusts. Therapeutic …

New First Trimester Circulating Angiogenic Biomarkers In Predicting Early-Onset And Late-Onset Fetal Growth Restriction: A Case-Control Study, Xiaoyi Bai, Wei Li, Wenjing Ding, Oi Ka Chan, Maran Bo Wah Leung, So Ling Lau, Daljit Singh Sahota, Chi Chiu Wang, Tak Yeung Leung

Faculty, Staff and Students Publications

Background: First trimester prediction of fetal growth restriction (FGR) remain suboptimal. We aimed to search for new circulating angiogenic biomarkers for improvement.

Methods: This case-control study compared 73 singleton pregnancies with early or late-onset FGR based on Delphi consensus and 73 matched normal controls. Their maternal serum samples stored during 11-13 weeks were retrieved for measurement of 36 angiogenic biomarkers by MILLIPLEX® human angiogenesis magnetic bead panels. Those biomarkers that showed significant differences between the study groups were further analysed with receiver operating characteristic (ROC) curve.

Results: In the early-onset FGR group, log10MoM of soluble neuropilin-1 (sNRP-1: 0.08 ± 0.11 …

Exploring Cisd1 As A Multifaceted Biomarker In Cancer: Implications For Diagnosis, Prognosis, And Immunotherapeutic Response, Caiyue Li, Zhipin Liang, Gabrielle Vontz, Connor Kent, Wenbo Ma, Lei Liu, Riya Dahal, Jovanny Zabaleta, Guoshuai Cai, Jia Zhou, Huangen Ding, Qiang Shen

School of Graduate Studies Faculty Publications

CISD1, an outer mitochondrial membrane iron-sulfur cluster protein, regulates intracellular iron levels, oxidative stress, and mitochondrial dynamics, playing critical roles in cellular bioenergetics and redox homeostasis. Although CISD1 has been identified as a prognostic biomarker in specific cancers, its broader implications in tumorigenesis, cancer progression, and immunotherapy remain unclear. Given the heterogeneity of cancer and the need for robust biomarkers across cancers, this study conducts the first comprehensive pan-cancer analysis of CISD1 by evaluating its roles in cancer and treatment. We obtained and analyzed data from databases including TCGA, GTEx, THPA, GEPIA2.0, SangerBox, cBioPortal, TIMER2.0, CAMOIP, DAVID, SRPLOT, and TISIDB. …

A Cluster Randomized Trial Of A Multicomponent Clinical Care Pathway (Mccp) To Improve Masld Diagnosis And Management In Primary Care: Study Protocol, Kyler M Godwin, Larissa Grigoryan, Aaron P Thrift, Hao Duong, Fasiha Kanwal, Traber Giardina, Himabindu Kadiyala, Andrew Zimolzak, Kavish R Patidar, Hashem B El-Serag

Faculty, Staff and Students Publications

Background: Metabolic dysfunction associated steatotic liver disease (MASLD) is the most common chronic liver disorder in the world. Most patients with MASLD are undiagnosed, untreated and unreferred. Treatment depends on diagnosis and accurate staging of fibrosis risk, and therefore screening at the primary care setting coupled with consistent, timely, evidence-based, widely accessible, and testable management processes is critical. Randomized controlled trials of methods for screening, diagnosis, severity stratification, and referral are lacking. We previously validated the MASLD clinical care pathway (MCCP), a multistep algorithmic process geared to support primary care settings in screening, diagnosis, risk stratification, and suggested referral and …

Circrna-Based Antimir Therapy: A Novel Approach To Hypertension Treatment, Vahideh Tarhriz, Kamran Hosseini, Leila Abkhooie, Eric Lazartigues

School of Medicine Faculty Publications

The increasing recognition of the types and functions of non-coding RNAs has opened new avenues for their use as novel therapeutic strategies in the treatment of chronic diseases such as hypertension. While most preclinical and clinical studies on hypertension focus on prognosis and treatment, there are still no specific therapeutic approaches for primary and essential hypertension. Modest efficacy and reduced long-term adherence to treatment underscore the need for novel, mechanism-based strategies to address the underlying molecular mechanisms. AntimiRs, as synthetic RNA molecules, and circular RNAs (circRNAs), as naturally occurring RNA species that function as microRNA sponges, could play a crucial …

Reexploring The Stress Trial: Subgroup Postoperative Outcomes Following Methylprednisolone For Infant Heart Surgery, Sudeep D Sunthankar, Kevin D Hill, Jeffrey P Jacobs, H Scott Baldwin, Marshall L Jacobs, Jennifer S Li, Eric M Graham, Ashraf M Resheidat, Venugopal Amula, Mark S Bleiweis, Eric L Wald, Pirooz Eghtesady, John P Scott, Brett R Anderson, Michael F Swartz, Alexis Benscoter, William Ravekes, Prince J Kannankeril

Faculty, Staff and Students Publications

Objective Assess the association between intraoperative methylprednisolone and specific postoperative outcomes among subgroups undergoing infant heart surgery.

Design: Subpopulation analyses of The Steroids to Reduce Systemic Inflammation after Infant Heart Surgery trial, a double-blind randomized placebo-controlled trial.

Setting: 24 congenital heart centers.

Patients: Infants (< 1 year old) undergoing heart surgery with cardiopulmonary bypass. Patients stratified by Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery (STAT) Mortality Category, age, gestational age, and presence of chromosomal or syndromic diagnosis (CSD).

Interventions: Methylprednisolone (30 mg/kg) versus placebo administered into cardiopulmonary bypass pump-priming fluid.

Measurements and main results: Outcomes included death, heart transplantation, mechanical circulatory support, reinterventions, and hospital length of stay. Ranked composite outcome (death, transplant, or one of 13 major complications) was compared between placebo and methylprednisolone for each subgroup using the win ratio. Methylprednisolone …

Efficacy And Safety Of Larotrectinib In Patients With Trk Fusion Gastrointestinal Cancer, Changsong Qi, Lin Shen, Thierry Andre, Hyun Cheol Chung, Timothy L Cannon, Elena Garralda, Antoine Italiano, Damian T Rieke, Tianshu Liu, Domnita-Ileana Burcoveanu, Natascha Neu, Chiara E Mussi, Rui-Hua Xu, David S Hong, Alexander Drilon, Jordan Berlin

Faculty, Staff and Student Publications

Background: Larotrectinib is the first-in-class, highly selective TRK inhibitor with demonstrated efficacy in various TRK fusion solid tumours. We report the efficacy and safety of larotrectinib in patients with TRK fusion gastrointestinal (GI) cancer.

Methods: Patients with TRK fusion GI cancer from NAVIGATE (NCT02576431) were included. Response was independent review committee (IRC)-assessed per RECIST v1.1.

Results: As of July 2023, 44 patients were enrolled. Tumour types included colorectal (CRC; n = 26), pancreatic (n = 7), cholangiocarcinoma (n = 4), gastric (n = 3), and one each of appendiceal, duodenal, oesophageal and hepatic cancers. Of the 26 patients …

Low Dose Aspirin Is Associated With Improved 30-And 92-Day Outcomes In Patients With Acute Pancreatitis: A Multinational Multicenter Analysis, Do Han Kim Md, Donghyun Ko Md, Pedro Palacios Argueta Md, Wilhelm S. Basegoda Md, Jose A. Porres, Frank J. Lukens Md, Paul T. Kroner Md

Posters

Currently, no medications are known to formally treat or prevent acute pancreatitis (AP). Significant attention has been devoted to aspirin (ASA), with rodent models showing that it is associated with decreased inflammatory cytokine levels and protects against acinar cell necrosis. Current human studies, which are limited to retrospective inpatient outcomes only on the index hospitalization for AP, do suggest that patients on ASA have improved outcomes. The aim of our study was to explore de 30- and 90- day outcomes of patients with AP on long-term ASA use.