Diseases Commons^™

Interpretable Mechanistic And Machine Learning Models For Pre-Dicting Cardiac Remodeling From Biochemical And Biomechanical Features, Anamul Haque

All Dissertations

Biochemical and biomechanical signals drive cardiac remodeling, resulting in altered heart physiology and the precursor for several cardiac diseases, the leading cause of death for most racial groups in the USA. Reversing cardiac remodeling requires medication and device-assisted treatment such as Cardiac Resynchronization Therapy (CRT), but current interventions produce highly variable responses from patient to patient. Mechanistic modeling and Machine learning (ML) approaches have the functionality to aid diagnosis and therapy selection using various input features. Moreover, 'Interpretable' machine learning methods have helped make machine learning models fairer and more suited for clinical application. The overarching objective of this doctoral …

Biological Age Mediates The Effects Of Perceived Neighborhood Problems On Heart Failure Risk Among Black Persons, Ganga Bey, James Pike, Priya Palta, Anthony Zannas, Qian Xiao, Shelly-Ann Love, Gerardo Heiss

Faculty, Staff and Student Publications

OBJECTIVE: We assessed whether biological age, measured by the epigenetic clock GrimAge, mediates the association of objective and subjective neighborhood disadvantage with incident HF among Black persons.

METHODS: Participants were 1448 self-reported Black adults (mean age (standard deviation, SD) = 64.3 (5.5)) dually enrolled in two community-based cohorts in Jackson, Mississippi, the ARIC and JHS cohorts, who were free of HF as of January 1, 2000. Incident HF events leading to hospitalization through December 31, 2017, were classified using ICD-9 discharge codes of HF. Multilevel age- and sex-adjusted Cox causal mediation models were used to examine whether biological age (at …

Alignment Between 24-H Light-Dark And Activity-Rest Rhythms Is Associated With Diabetes And Glucose Metabolism In A Nationally Representative Sample Of American Adults, Qian Xiao, John Durbin, Cici Bauer, Chris Ho Ching Yeung, Mariana G Figueiro

Faculty, Staff and Student Publications

OBJECTIVE: The alignment between environmental stimuli (e.g., dark, light) and behavior cycles (e.g., rest, activity) is an essential feature of the circadian timing system, a key contributor to metabolic health. However, no previous studies have investigated light-activity alignment in relation to glycemic control in human populations.

RESEARCH DESIGN AND METHODS: The analysis included ∼7,000 adults (aged 20-80 years) from the National Health and Nutrition Examination Survey (NHANES) (2011-2014) with actigraphy-measured, multiday, 24-h activity and light data. We used phasor analysis to derive phasor magnitude and phasor angle, which measures coupling strength and phase difference between the activity-rest and light-dark cycles, …

Transferability Of Tsetse Habitat Models Between Different Regions In Kenya And Rwanda, Stella Gachoki, Anton Vrieling, Thomas A. Groen, Andrew Skidmore, Daniel Masiga

All Peer-Reviewed Publications

Accurate and reliable information on the distribution of tsetse habitats is crucial for the effective management of African Trypanosomiasis in sub-Saharan Africa. However, conducting large-scale surveillance of tsetse flies to develop distribution maps is impractical due to vast areas infested and limited resources available. To address this challenge, we evaluated the applicability of tsetse habitat models developed in the intensively sampled Shimba Hills National Reserve in Kenya for both the wet and the dry season, to two other regions in Kenya (Ruma National Park and Nguruman Conservancy) and one region in Rwanda (Akagera National Park). The models utilized satellite-based estimates …

Pathomic Features Reveal Immune And Molecular Evolution From Lung Preneoplasia To Invasive Adenocarcinoma, Pingjun Chen, Frank R Rojas, Xin Hu, Alejandra Serrano, Bo Zhu, Hong Chen, Lingzhi Hong, Rukhmini Bandyoyadhyay, Muhammad Aminu, Neda Kalhor, J Jack Lee, Siba El Hussein, Joseph D Khoury, Harvey I Pass, Andre L Moreira, Vamsidhar Velcheti, Daniel H Sterman, Junya Fukuoka, Kazuhiro Tabata, Dan Su, Lisha Ying, Don L Gibbons, John V Heymach, Ignacio I Wistuba, Junya Fujimoto, Luisa M Solis Soto, Jianjun Zhang, Jia Wu

Faculty, Staff and Student Publications

Recent statistics on lung cancer, including the steady decline of advanced diseases and the dramatically increasing detection of early-stage diseases and indeterminate pulmonary nodules, mark the significance of a comprehensive understanding of early lung carcinogenesis. Lung adenocarcinoma (ADC) is the most common histologic subtype of lung cancer, and atypical adenomatous hyperplasia is the only recognized preneoplasia to ADC, which may progress to adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and eventually to invasive ADC. Although molecular evolution during early lung carcinogenesis has been explored in recent years, the progress has been significantly hindered, largely due to insufficient materials …

Shift From Older- To Newer-Generation Antiseizure Medications In People With Acute Ischemic Stroke In Australia: A Population-Based Study, Stella Jung-Hyun Kim, Stephen Wood, Clara Marquina, Emma Foster, J Simon Bell, Jenni Ilomäki

Faculty, Staff and Student Publications

OBJECTIVE: To investigate the trends in antiseizure medications (ASMs) use following ischemic stroke and to examine factors associated with use of newer- and older-generation ASMs.

METHODS: A retrospective cohort study was conducted using state-wide linked health datasets. Patients who were hospitalized with a first-ever ischemic stroke between 2013 and 2017 and were dispensed ASM within 12 months from discharge were included. Logistic regression was used to examine the predictors of receiving newer-generation ASMs. Generalized linear modeling was used to identify factors associated with ASM use after ischemic stroke.

RESULTS: Of 19 601 people hospitalized with a first-ever ischemic stroke, 989 …

Evaluation Of The Quality Of Thyroidectomy-Related Posts On A Video-Based Social Media Platform, Yun J Kim, Matthew Lin, Ryan J Davis, Oluwatobiloba Ayo-Ajibola, Daniel Kwon, Kevin Hur

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate the quality of thyroidectomy-related posts on TikTok, the fastest-growing social media platform worldwide.

METHODS: Videos posted from April 2020 to September 2022 were queried on TikTok using the search terms "thyroidsurgery," "thyroidectomy," and "thyroidremoval." Two reviewers recorded thematic, demographic, and performance data of these posts. The DISCERN instrument was used to evaluate the quality and reliability of the information contained in the videos. Descriptive statistics were used to characterize post-submitter demographics and video content. Simple and multiple linear regression analyses were used to evaluate the association between DISCERN scores and video characteristics. Univariate analysis of variance was …

Comparative Study Between Antegrade Flexible Ureteroscopy And Reterograde Intrarenal Surgery In The Management Of Impacted Upper Ureteric Stones 15 Cm Or Larger, Ahmed Mohey, Ahmed A Abdelfattah, Ahmed E Mohammed, Abdelmoniem Marzouk, Amr S El-Dakhakhny

Faculty, Staff and Student Publications

OBJECTIVE: To prospectively investigate the safety and efficacy of antegrade flexible ureteroscopy (FURS) with the following criteria (supine, ultrasonic guided puncture through lower calyx with 14 fr tract, tubeless) versus retrograde intrarenal surgery (RIRS) in the management of large impacted upper ureteric stones ≥ 1.5 cm.

PATIENTS AND METHODS: This study recruited 61 patients with single large impacted upper ureteric stone of ≥ 1.5 cm. The patients were randomly allocated to two groups. Group A, included 31 patients who treated by antegrade FURS, all patients were put in supine modified galadako Valdivia position and the renal access is reached by …

Incidence, Risk Assessment And Prevention Of Sudden Cardiac Death In Cardiomyopathies, Marija Polovina, Carsten Tschöpe, Giuseppe Rosano, Marco Metra, Filippo Crea, Wilfried Mullens, Johann Bauersachs, Karen Sliwa, Rudolf A De Boer, Dimitrios Farmakis, Thomas Thum, Domenico Corrado, Antoni Bayes-Genis, Biykem Bozkurt, Gerasimos Filippatos, Andre Keren, Hadi Skouri, Brenda Moura, Maurizio Volterrani, Magdy Abdelhamid, Milika Ašanin, Gordana Krljanac, Milenko Tomić, Gianluigi Savarese, Marianna Adamo, Yuri Lopatin, Ovidiu Chioncel, Andrew J S Coats, Petar M Seferović

Faculty, Staff and Students Publications

Cardiomyopathies are a significant contributor to cardiovascular morbidity and mortality, mainly due to the development of heart failure and increased risk of sudden cardiac death (SCD). Despite improvement in survival with contemporary treatment, SCD remains an important cause of mortality in cardiomyopathies. It occurs at a rate ranging between 0.15% and 0.7% per year (depending on the cardiomyopathy), which significantly surpasses SCD incidence in the age- and sex-matched general population. The risk of SCD is affected by multiple factors including the aetiology, genetic basis, age, sex, physical exertion, the extent of myocardial disease severity, conduction system abnormalities, and electrical instability, …

Impact Of Routine Urine Cultures On Antibiotic Usage In Those Undergoing A Routine Annual Spinal Cord Injury Evaluation, Sarah May, Annette Walder, Casey Hines-Munson, Ivy Poon, S Ann Holmes, Charlesnika T Evans, Barbara W Trautner, Felicia Skelton

Faculty, Staff and Students Publications

OBJECTIVE: The Veterans Health Administration (VHA), the largest single provider of spinal cord injury and disorder (SCI/D) care in the United States, currently mandates that every patient receives a screening urine culture during the annual evaluation, a yearly comprehensive history and physical examination. This testing has shown in a small subset of patients to overidentify asymptomatic bacteriuria that is then inappropriately treated with antibiotics. The objective of the current analysis was to assess the association of the annual evaluation on urine testing and antibiotic treatment in a national sample of Veterans with SCI/D.

DESIGN/METHOD: A retrospective cohort study using national …

Clinical Exome Sequencing Efficacy And Phenotypic Expansions Involving Anomalous Pulmonary Venous Return, Emily A Huth, Xiaonan Zhao, Nichole Owen, Pamela N Luna, Ida Vogel, Inger L H Dorf, Shelagh Joss, Jill Clayton-Smith, Michael J Parker, Jacoba J Louw, Marc Gewillig, Jeroen Breckpot, Alison Kraus, Erina Sasaki, Usha Kini, Trent Burgess, Tiong Y Tan, Ruth Armstrong, Katherine Neas, Giovanni B Ferrero, Alfredo Brusco, Wihelmina S Kerstjens-Frederikse, Julia Rankin, Lindsey R Helvaty, Benjamin J Landis, Gabrielle C Geddes, Kim L Mcbride, Stephanie M Ware, Chad A Shaw, Seema R Lalani, Jill A Rosenfeld, Daryl A Scott

Faculty, Staff and Students Publications

Anomalous pulmonary venous return (APVR) frequently occurs with other congenital heart defects (CHDs) or extra-cardiac anomalies. While some genetic causes have been identified, the optimal approach to genetic testing in individuals with APVR remains uncertain, and the etiology of most cases of APVR is unclear. Here, we analyzed molecular data from 49 individuals to determine the diagnostic yield of clinical exome sequencing (ES) for non-isolated APVR. A definitive or probable diagnosis was made for 8 of those individuals yielding a diagnostic efficacy rate of 16.3%. We then analyzed molecular data from 62 individuals with APVR accrued from three databases to …

Empagliflozin In Patients Admitted To Hospital With Covid-19 (Recovery): A Randomised, Controlled, Open-Label, Platform Trial, Recovery Collaborative Group

Faculty, Staff and Student Publications

BACKGROUND: Empagliflozin has been proposed as a treatment for COVID-19 on the basis of its anti-inflammatory, metabolic, and haemodynamic effects. The RECOVERY trial aimed to assess its safety and efficacy in patients admitted to hospital with COVID-19.

METHODS: In the randomised, controlled, open-label RECOVERY trial, several possible treatments are compared with usual care in patients hospitalised with COVID-19. In this analysis, we assess eligible and consenting adults who were randomly allocated in a 1:1 ratio to either usual standard of care alone or usual standard of care plus oral empagliflozin 10 mg once daily for 28 days or until discharge …

Teen Pregnancy Involvement Among African, Caribbean And Black Adolescent Boys And Girls: A Scoping Review, Andrea Vacirca, Titia A L Sulzer, Thomas Mesnard, Aidin Baghbani-Oskouei, Laura Ocasio, Thanila A Macedo, Hence J M Verhagen, Robert Rhee, Gustavo S Oderich

Faculty, Staff and Student Publications

We describe a case of an abdominal aortic aneurysm (AAA) and angulated proximal neck treated with a Gore Excluder conformable endoprosthesis and show relevant technical pitfalls in the deployment of the graft main body. An 82-year-old man presented with a 71-mm asymptomatic AAA with an angulated infrarenal proximal neck (75°) and was referred to our unit. The patient was treated with a 26-mm Gore Excluder conformable device, which was deployed slightly above the renal arteries after precatheterization of the lowest renal artery. The graft was then repositioned with support of the introducer sheath and a stiff guide wire. The proximal …

Influence Of Treatment Intensity And Medical Comorbidities In Older Adults With Peripheral T Cell Lymphoma, Max J Gordon, Zhigang Duan, Hui Zhao, Loretta Nastoupil, Samuel Ng, Alexey V Danilov, Swaminathan Iyer, Sharon H Giordano

Faculty, Staff and Student Publications

We conducted a population-based study of patients >65 years, diagnosed 2008-2017, with peripheral T-cell lymphoma (PTCL) using SEER-Medicare. Associations between PTCL subtype, treatment regimen, comorbidity, and mortality were assessed using the Kaplan-Meier method and multivariable Cox regression. Amongst the 2,546 patients, the median age was 77 years (interquartile range, 71-83). 5-year overall survival (OS) ranged from 22.2% to 37.3% depending on PTCL subtype. The most common frontline regimen was cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). 5-year OS rate was 47.0% for patients treated with etoposide + CHOP (N = 67; CHOEP), 33.7% for those treated with CHOP (N …

Clinico-Genomic Profiling Of Conventional And Dedifferentiated Chondrosarcomas Reveals Tp53 Mutation To Be Associated With Worse Outcomes, Ryan A Denu, Richard K Yang, Alexander J Lazar, Shalin S Patel, Valerae O Lewis, Jason Roszik, J Andrew Livingston, Wei-Lien Wang, Kenna R Shaw, Ravin Ratan, Maria A Zarzour, Justin Bird, Shaan Raza, Kadir C Akdemir, Jordi Rodon Ahnert, Vivek Subbiah, Shreyaskumar Patel, Anthony P Conley

Faculty, Staff and Student Publications

PURPOSE: Chondrosarcomas are the most common primary bone tumor in adults. Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are prevalent. We aimed to assess the clinico-genomic properties of IDH mutant versus IDH wild-type (WT) chondrosarcomas as well as alterations in other genes.

EXPERIMENTAL DESIGN: We included 93 patients with conventional and dedifferentiated chondrosarcoma for which there were available clinical next-generation sequencing data. Clinical and genomic data were extracted and compared between IDH mutant and IDH WT chondrosarcomas and between TP53 mutant and TP53 WT chondrosarcomas.

RESULTS: IDH1 and IDH2 mutations are prevalent in chondrosarcoma (50.5%), more common in chondrosarcomas arising …

Identifying The Optimal Deep Learning Architecture And Parameters For Automatic Beam Aperture Definition In 3d Radiotherapy, Skylar S Gay, Kelly D Kisling, Brian M Anderson, Lifei Zhang, Dong Joo Rhee, Callistus Nguyen, Tucker Netherton, Jinzhong Yang, Kristy Brock, Anuja Jhingran, Hannah Simonds, Ann Klopp, Beth M Beadle, Laurence E Court, Carlos E Cardenas

Faculty, Staff and Student Publications

PURPOSE: Two-dimensional radiotherapy is often used to treat cervical cancer in low- and middle-income countries, but treatment planning can be challenging and time-consuming. Neural networks offer the potential to greatly decrease planning time through automation, but the impact of the wide range of hyperparameters to be set during training on model accuracy has not been exhaustively investigated. In the current study, we evaluated the effect of several convolutional neural network architectures and hyperparameters on 2D radiotherapy treatment field delineation.

METHODS: Six commonly used deep learning architectures were trained to delineate four-field box apertures on digitally reconstructed radiographs for cervical cancer …

Steroid Receptor Coactivator-2 Drives Epithelial Reprogramming That Enables Murine Embryo Implantation, Vineet K Maurya, Maria M Szwarc, David M Lonard, Ramakrishna Kommagani, San Pin Wu, Bert W O'Malley, Francesco J Demayo, John P Lydon

Faculty, Staff and Students Publications

Although we have shown that steroid receptor coactivator-2 (SRC-2), a member of the p160/SRC family of transcriptional coregulators, is essential for decidualization of both human and murine endometrial stromal cells, SRC-2’s role in the earlier stages of the implantation process have not been adequately addressed. Using a conditional SRC-2 knockout mouse (SRC-2 ^d/d) in timed natural pregnancy studies, we show that endometrial SRC-2 is required for embryo attachment and adherence to the luminal epithelium. Implantation failure is associated with the persistent expression of Mucin 1 and E-cadherin on the apical surface and basolateral adherens junctions of the SRC-2 …

Tumor-Infiltrating Normal B Cells Revealed By Immunoglobulin Repertoire Clonotype Analysis Are Highly Prognostic And Crucial For Antitumor Immune Responses In Dlbcl, Zijun Y Xu-Monette, Yong Li, Thomas Snyder, Tiantian Yu, Tingxun Lu, Alexandar Tzankov, Carlo Visco, Govind Bhagat, Wenbin Qian, Karen Dybkaer, April Chiu, Wayne Tam, Youli Zu, Eric D Hsi, Fredrick B Hagemeister, Yingjun Wang, Heounjeong Go, Maurilio Ponzoni, Andrés J M Ferreri, Michael B Møller, Benjamin M Parsons, Xiangshan Fan, J Han Van Krieken, Miguel A Piris, Jane N Winter, Qingyan Au, Ilan Kirsch, Mingzhi Zhang, John Shaughnessy, Bing Xu, Ken H Young

Faculty, Staff and Students Publications

PURPOSE: Tumor-infiltrating B lymphocytes (TIL-B) have demonstrated prognostic and predictive significance in solid cancers. In this study, we aimed to distinguish TIL-Bs from malignant B-cells in diffuse large B-cell lymphoma (DLBCL) and determine the clinical and biological significance.

EXPERIMENTAL DESIGN: A total of 269 patients with de novo DLBCL from the International DLBCL R-CHOP Consortium Program were studied. Ultra-deep sequencing of the immunoglobulin genes was performed to determine B-cell clonotypes. The frequencies and numbers of TIL-B clonotypes in individual repertoires were correlated with patient survival, gene expression profiling (GEP) data, and frequencies of DLBCL-infiltrating immune cells quantified by fluorescent multiplex …

The Evolving Role Of Vericiguat In Patients With Chronic Heart Failure, Ross M. Dies, Corrie N. Jackson, Chelsi J. Flanagan, Evan S. Sinnathamby, Noah J. Spillers, Pooja Potharaju, Naina Singh, Giustino Varrassi, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Heart failure (HF) is a chronic and progressive clinical disorder characterized by an inability to pump sufficient blood to meet metabolic demands. It poses a substantial global healthcare burden, leading to high morbidity, mortality, and economic impact. Current treatments for HF include lifestyle modifications, guideline-directed medical therapies (GDMT), and device interventions, but the need for novel therapeutic approaches remains significant. The introduction of vericiguat, a soluble guanylate cyclase stimulator, has shown promise in improving outcomes for heart failure patients. Vericiguat addresses the underlying pathophysiological mechanisms of heart failure by augmenting the cyclic guanosine monophosphate (cGMP) pathway, leading to enhanced cardiac …

Chimeric Antigen Receptor T Cells In Hodgkin And T-Cell Lymphomas, Ibrahim N Muhsen, Laquisa C Hill, Carlos A Ramos

Faculty, Staff and Students Publications

The authors review the current use of chimeric antigen receptor (CAR)-transduced T cells (CAR-T) in Hodgkin lymphoma (HL) and T-cell lymphomas (TCL) and discuss the data on CD30-targeting CAR-T cells, which seem to be safe and effective in HL. In addition, the authors examine the use of CAR-T cells targeting CD30, CD5, or CD7 in TCL, while highlighting the unique challenges of their use in this subset of lymphomas. Furthermore, the authors present future directions and ongoing trials investigating the use of CAR-T cells in TCL and HL.

Unexpected Hepatic Manifestations Of Rheumatoid Arthritis, Ankur Patel, Christo Mathew, Lucas Mcgowan, Sarah Bohac, Andrew Caruso, Scott Larson

Faculty, Staff and Students Publications

Rheumatoid arthritis is an inflammatory condition typically affecting joint spaces. However, extra-articular manifestations are common including vascular and gastrointestinal tract involvement. This disease may also manifest as nodules, although these are typically found in the extremities and are very rarely seen in the liver. When a patient presents with liver nodules, an extensive work-up is typically completed to determine infectious, inflammatory, or malignant etiologies. We report hepatic findings of rheumatoid arthritis during an extensive inpatient investigation of liver lesions.

Whole-Genome Sequencing Uncovers Two Loci For Coronary Artery Calcification And Identifies Arse As A Regulator Of Vascular Calcification, Paul S De Vries, Matthew P Conomos, Kuldeep Singh, Christopher J Nicholson, Deepti Jain, Natalie R Hasbani, Wanlin Jiang, Sujin Lee, Christian L Lino Cardenas, Sharon M Lutz, Doris Wong, Xiuqing Guo, Jie Yao, Erica P Young, Catherine Tcheandjieu, Austin T Hilliard, Joshua C Bis, Lawrence F Bielak, Michael R Brown, Shaila Musharoff, Shoa L Clarke, James G Terry, Nicholette D Palmer, Lisa R Yanek, Huichun Xu, Nancy Heard-Costa, Jennifer Wessel, Margaret Sunitha Selvaraj, Rebecca H Li, Xiao Sun, Adam W Turner, Adrienne M Stilp, Alyna Khan, Anne B Newman, Asif Rasheed, Barry I Freedman, Brian G Kral, Caitlin P Mchugh, Chani Hodonsky, Danish Saleheen, David M Herrington, David R Jacobs, Deborah A Nickerson, Eric Boerwinkle, Fei Fei Wang, Gerardo Heiss, Goo Jun, Greg L Kinney, Haakon H Sigurslid, Harshavardhan Doddapaneni, Ira M Hall, Isabela M Bensenor, Jai Broome, James D Crapo, James G Wilson, Jennifer A Smith, John Blangero, Jose D Vargas, Jose Verdezoto Mosquera, Joshua D Smith, Karine A Viaud-Martinez, Kathleen A Ryan, Kendra A Young, Kent D Taylor, Leslie A Lange, Leslie S Emery, Marcio S Bittencourt, Matthew J Budoff, May E Montasser, Miao Yu, Michael C Mahaney, Mohammed S Mahamdeh, Myriam Fornage, Nora Franceschini, Paulo A Lotufo, Pradeep Natarajan, Quenna Wong, Rasika A Mathias, Richard A Gibbs, Ron Do, Roxana Mehran, Russell P Tracy, Ryan W Kim, Sarah C Nelson, Scott M Damrauer, Sharon L R Kardia, Stephen S Rich, Valentin Fuster, Valerio Napolioni, Wei Zhao, Wenjie Tian, Xianyong Yin, Yuan-I Min, Alisa K Manning, Gina Peloso, Tanika N Kelly, Christopher J O'Donnell, Alanna C Morrison, Joanne E Curran, Warren M Zapol, Donald W Bowden, Lewis C Becker, Adolfo Correa, Braxton D Mitchell, Bruce M Psaty, John Jeffrey Carr, Alexandre C Pereira, Themistocles L Assimes, Nathan O Stitziel, John E Hokanson, Cecelia A Laurie, Jerome I Rotter, Ramachandran S Vasan, Wendy S Post, Patricia A Peyser, Clint L Miller, Rajeev Malhotra

Faculty, Staff and Student Publications

Coronary artery calcification (CAC) is a measure of atherosclerosis and a well-established predictor of coronary artery disease (CAD) events. Here we describe a genome-wide association study (GWAS) of CAC in 22,400 participants from multiple ancestral groups. We confirmed associations with four known loci and identified two additional loci associated with CAC (ARSE and MMP16), with evidence of significant associations in replication analyses for both novel loci. Functional assays of ARSE and MMP16 in human vascular smooth muscle cells (VSMCs) demonstrate that ARSE is a promoter of VSMC calcification and VSMC phenotype switching from a contractile to a calcifying …

Relative Hepatotoxocity, Carcinogenicity, And Toxicogenomics Of Select Dehydropyrrolizidine Alkaloids In Mice, Michael J. Clayton

All Graduate Theses and Dissertations, Fall 2023 to Present

Dehydropyrrolizidine alkaloids are arguably the most important plant derived toxins in terms of impact on human and animal health. Dehydropyrrolizidine alkaloids are a large group of chemically related compounds found in 3% of flowering plants worldwide. Human exposure occurs from ingestion of herbal products including teas supplements or contaminated grain. Animals are exposed through contaminated feed or grazing. There are at least 350 identified toxic PAs, from more than 6,000 plants. The toxins primarily cause liver damage, but some are proven to cause cancer. Indidvidual dehydropyrrolizidine alkaloids vary in their toxic effects. Riddelliine is the only dehydropyrrolizidine alkaloid with extensive …

Surgical Techniques/Case Videos-Complex Aortic Case: Top Tips (Taaar), Joseph Stapleton Coselli

Faculty, Staff and Students Publications

This complex case study describes the surgical approach for a patient with chronic aortic dissection and multiple comorbidities. The patient had multiple previous surgeries, including aortic repair. The surgical approach involved a thoracoabdominal aortic aneurysm repair with left heart bypass, spinal fluid drainage, selective visceral perfusion, and protection of the surviving kidney. A Dacron tube graft was used to replace the damaged area.

Thoracoabdominal Aortic Aneurysm: A Journey Through The Distal Aorta, Joseph Stapleton Coselli

Faculty, Staff and Students Publications

The field of surgical aortic repair has advanced significantly over time, transitioning from aneurysm ligation to homografts, then to Dacron grafts, and now endovascular procedures. With new endovascular technologies emerging, they are likely to dominate the field of aortic surgery, but surgeons must exercise caution and not abandon their open-surgery skills. Open repair of thoracoabdominal aortic aneurysm surgery continues to be a durable operation. As the field continues to evolve, further research is needed to advance this complex surgical endeavor.

Serum Biomarkers Of Nociceptive And Neuropathic Pain In Chronic Pancreatitis, Jami L Saloman, Yan Li, Kimberly Stello, Wenhao Li, Shuang Li, Anna Evans Phillips, Kristen Hall, Evan L Fogel, Santhi Swaroop Vege, Liang Li, Dana K Andersen, William E Fisher, Christopher E Forsmark, Phil A Hart, Stephen J Pandol, Walter G Park, Mark D Topazian, Stephen K Van Den Eeden, Jose Serrano, Darwin L Conwell, Dhiraj Yadav, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to CP-related pain, which makes successful treatment difficult. The identification of biomarkers for subtypes of pain could provide viable targets for nonopioid interventions and the development of mechanistic approaches to pain management in CP. Nineteen inflammation- and nociception-associated proteins were measured in serum collected from 358 subjects with definite CP enrolled in PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, a prospective observational study of pancreatitis in US adult subjects. First, serum levels of putative biomarkers were …

Risk Stratification Model For Hepatocellular Cancer In Patients With Cirrhosis, Fasiha Kanwal, Saira Khaderi, Amit G Singal, Jorge A Marrero, Sumeet K Asrani, Christopher I Amos, Aaron P Thrift, Jennifer R Kramer, Xian Yu, Yumei Cao, Michelle Luster, Abeer Al-Sarraj, Jing Ning, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: The available risk stratification indices for hepatocellular cancer (HCC) have limited applicability. We developed and externally validated an HCC risk stratification index in U.S. cohorts of patients with cirrhosis.

METHODS: We used data from 2 prospective U.S. cohorts to develop the risk index. Patients with cirrhosis were enrolled from 8 centers and followed until development of HCC, death, or December 31, 2021. We identified an optimal set of predictors with the highest discriminatory ability (C-index) for HCC. The predictors were refit using competing risk regression and its predictive performance was evaluated using the area under the receiver-operating …

Low-Dose Aspirin For Primary Prevention Of Cardiovascular Events Comparing East Asians With Westerners: A Meta-Analysis, Rock Bum Kim, Ang Li, Ki-Soo Park, Yune-Sik Kang, Jang-Rak Kim, Eliano P Navarese, Diana A Gorog, Udaya S Tantry, Paul A Gurbel, Jin Yong Hwang, Oh-Young Kwon, Young-Hoon Jeong

Faculty, Staff and Students Publications

BACKGROUND: East Asians have shown different risk profiles for both thrombophilia and bleeding than Western counterparts.

OBJECTIVES: The authors sought to evaluate the effect of low-dose aspirin for primary prevention between these populations.

METHODS: We searched randomized clinical trials (RCTs) for intervention with low-dose aspirin (≤100 mg once daily) in participants without symptomatic cardiovascular disease until December 31, 2021. The number of events between the arms was extracted for analysis. Pooled risk ratios (RRs) and risk differences (RDs) were analyzed in each population. Outcomes included a major adverse cardiovascular event (MACE), cardiovascular death, myocardial infarction, stroke, and major bleeding (intracranial …

Safety Of Prehospital Intravenous Bolus Dose Nitroglycerin In Patients With Acute Pulmonary Edema: A 4-Year Review, Casey Patrick, Louis Fornage, Brad Ward, Michael Wells, Kevin Crocker, Kelly Rogers Keene, Sara Andrabi, Robert Dickson

Faculty, Staff and Students Publications

BACKGROUND: Intravenous nitrates are a primary therapy for hypertensive congestive heart failure (CHF) with acute pulmonary edema (APE) in the hospital setting. Historically, sublingual nitrates are the mainstay of emergency medical services (EMS) pharmacologic therapy for these patients. We aimed to evaluate the safety of prehospital bolus dose intravenous nitroglycerin in patients with APE.

METHODS: This is a retrospective evaluation of EMS data between March 15, 2018, and March 15, 2022, where CHF with APE was suspected and bolus-dose intravenous nitroglycerin was administered. Protocol inclusion criteria were hypertension (systolic blood pressure [SBP] >160 mmHg) and acute respiratory distress, with a …

Association Between Physical Activity And Reduced Mortality In Inoperable Lung Cancer, Vinicius Cavalheri, Isis Grigoletto, Joanne Mcveigh, David Manners, Terry Boyle, Carolyn J. Peddle-Mcintyre, Rajesh Thomas, Jeanie Leong, Samantha Bowyer, Kirsten Mooney, Leon Straker, Daniel A. Galvão

Research outputs 2022 to 2026

We examined device-measured physical activity (PA) and sedentary behaviour at the time of diagnosis in people with inoperable lung cancer and investigated their associations with 12-month mortality. The people with inoperable lung cancer wore an accelerometer for seven days prior to the treatment commencement. The analysed PA/sedentary behaviour variables included light-intensity PA, moderate-to-vigorous-intensity PA (MVPA), step count, the total time spent sedentary, and the usual sedentary bout duration. The data on the disease stage, clinical covariates and 12-month mortality were extracted from medical records. Cox regression models were used to estimate the association between the PA measures and 12-month mortality, …