Diseases Commons^™

Registry Of Aortic Diseases To Model Adverse Events And Progression (Roadmap) In Uncomplicated Type B Aortic Dissection: Study Design And Rationale, Domenico Mastrodicasa, Martin J Willemink, Valery L Turner, Virginia Hinostroza, Marina Codari, Kate Hanneman, Maral Ouzounian, Daniel Ocazionez Trujillo, Rana O Afifi, Sandeep Hedgire, Nicholas S Burris, Bo Yang, Joan M Lacomis, Thomas G Gleason, Davide Pacini, Gianluca Folesani, Luigi Lovato, Ricarda Hinzpeter, Hatem Alkadhi, Arthur E Stillman, Edward P Chen, Sander M J Van Kuijk, Geert W H Schurink, Anna M Sailer, Kathrin Bäumler, D Craig Miller, Michael P Fischbein, Dominik Fleischmann

Faculty, Staff and Student Publications

PURPOSE: To describe the design and methodological approach of a multicenter, retrospective study to externally validate a clinical and imaging-based model for predicting the risk of late adverse events in patients with initially uncomplicated type B aortic dissection (uTBAD).

MATERIALS AND METHODS: The Registry of Aortic Diseases to Model Adverse Events and Progression (ROADMAP) is a collaboration between 10 academic aortic centers in North America and Europe. Two centers have previously developed and internally validated a recently developed risk prediction model. Clinical and imaging data from eight ROADMAP centers will be used for external validation. Patients with uTBAD who survived …

Rapid Cooling Is A Safe Technique In Patients Undergoing Circulatory Arrest For Aortic Repair, Holly N Smith, Akiko Tanaka, Max Chehadi, Harleen K Sandhu, Charles C Miller, Hazim J Safi, Anthony L Estrera

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate our institutional experience with rapid cooling for hypothermic circulatory arrest in proximal aortic repair.

METHODS: We retrospectively reviewed data from 2171 patients who underwent proximal aortic surgery requiring hypothermic circulatory arrest between 1991 and 2020. Cooling times were divided into quartiles and clinical outcome event rates were compared across quartiles using contingency table methods. Incremental effect of cooling time was assessed in the context of other perfusion time variables using multiple logistic regression analysis.

RESULTS: Median age was 61 years (interquartile range, 49-70 years) and 34.1% of patients were women. The procedure was emergent in 33.5% of …

Association Of Apremilast With Vascular Inflammation And Cardiometabolic Function In Patients With Psoriasis: The Vip-A Phase 4, Open-Label, Nonrandomized Clinical Trial, Joel M Gelfand, Daniel B Shin, April W Armstrong, Stephen K Tyring, Andrew Blauvelt, Scott Gottlieb, Benjamin N Lockshin, Robert E Kalb, Robert Fitzsimmons, Justin Rodante, Philip Parel, Grigory A Manyak, Laurel Mendelsohn, Megan H Noe, Maryte Papadopoulos, Maha N Syed, Thomas J Werner, Joy Wan, Martin P Playford, Abass Alavi, Nehal N Mehta

Faculty, Staff and Student Publications

IMPORTANCE: Psoriasis is an inflammatory condition associated with metabolic and cardiovascular disease. Apremilast, a phosphodiesterase 4 inhibitor, is commonly used for psoriasis and can cause weight loss.

OBJECTIVE: To determine the association between apremilast and aortic vascular inflammation as assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), cardiometabolic markers (primary outcomes at week 16), and abdominal fat composition.

DESIGN, SETTING, AND PARTICIPANTS: A single-arm, open-label, interventional, nonrandomized clinical trial in which the imaging and laboratory outcomes were measured by an investigator who was blinded to time was conducted between April 11, 2017, and August 17, 2021, at 7 dermatology sites …

Accuracy And Safety Of Scout Dose Resin Yttrium-90 Microspheres For Radioembolization Therapy Treatment Planning: A Prospective Single-Arm Clinical Trial, Nima Kokabi, Linzi A Webster, Mohammad Elsayed, Jeffrey M Switchenko, Bernard Chen, David Brandon, James Galt, Ila Sethi, Mircea Cristescu, S Cheenu Kappadath, David M Schuster

Faculty, Staff and Student Publications

PURPOSE: To compare the accuracy and safety of 0.56 GBq resin yttrium-90 (

MATERIALS AND METHODS: This prospective single-arm clinical trial (Clinicaltrials.gov: NCT04172714) recruited patients with HCC. Patients underwent same-day mapping with MAA and scout

RESULTS: Thirty patients were treated using 19 segmental and 14 nonsegmental (ie, 2 contiguous segments or nonsegmental) therapies. MAA had weak LSF, moderate TNR, and moderate TD linear correlation with Rx

CONCLUSIONS: Compared with MAA, scout

Airway Mucus Dysfunction In Covid-19, Burton F Dickey, Jichao Chen, R Stokes Peebles

Faculty, Staff and Student Publications

No abstract provided.

A Pilot Survey: Retention In Pain Medicine Among Fellowship Trained Anesthesiologists, Sarang S Koushik, Kelly Leap, Kenneth Seier, Kay See Tan, Naum Shaparin, Alan D Kaye, Omar Viswanath, Grant H Chen

Faculty, Staff and Student Publications

BACKGROUND: We aim to explore the factors related to job satisfaction among pain physicians and identify the reasons why individuals minimize or stop practicing outpatient pain medicine.

OBJECTIVES/STUDY DESIGN: This is a survey-based study with the primary goal to identify factors determining job satisfaction and dissatisfaction among pain medicine fellowship graduates who continue to practice and those who are no longer practicing interventional pain. A secondary goal is to elucidate reasons for anesthesiologists trained in pain medicine to leave pain medicine, despite an additional year of training, and to work as general anesthesiologists.

METHODS: In this study, all 114 pain …

Association Of Hematologic Response And Assay Sensitivity On The Prognostic Impact Of Measurable Residual Disease In Acute Myeloid Leukemia: A Systematic Review And Meta-Analysis, Nicholas J Short, Chenqi Fu, Donald A Berry, Roland B Walter, Sylvie D Freeman, Christopher S Hourigan, Xuelin Huang, Graciela Nogueras Gonzalez, Hyunsoo Hwang, Xinyue Qi, Hagop Kantarjian, Shouhao Zhou, Farhad Ravandi

Faculty, Staff and Student Publications

Measurable residual disease (MRD) is associated with relapse and survival in acute myeloid leukemia (AML). We aimed to quantify the impact of MRD on outcomes across clinical contexts, including its association with hematologic response and MRD assay sensitivity. We performed systematic literature review and meta-analysis of 48 studies that reported the association between MRD and overall survival (OS) or disease-free survival (DFS) in AML and provided information on the MRD threshold used and the hematologic response of the study population. Among studies limited to patients in complete remission (CR), the estimated 5-year OS for the MRD-negative and MRD-positive groups was …

Assessment Of Disease Severity And Quality Of Life In Patients With Atopic Dermatitis From South Korea, Sang Wook Son, Ji Hyun Lee, Jiyoung Ahn, Sung Eun Chang, Eung Ho Choi, Tae Young Han, Yong Hyun Jang, Hye One Kim, Moon-Bum Kim, You Chan Kim, Hyun Chang Ko, Joo Yeon Ko, Sang Eun Lee, Yang Won Lee, Bark-Lynn Lew, Chan Ho Na, Chang Ook Park, Chun Wook Park, Kui Young Park, Kun Park, Young Lip Park, Joo Young Roh, Young-Joon Seo, Min Kyung Shin, Sujin Lee, Sang Hyun Cho

Faculty, Staff and Student Publications

BACKGROUND: Data illustrating the impact of atopic dermatitis (AD) on lives of adults with AD in South Korea are limited.

OBJECTIVE: To assess the AD disease severity and its impact on quality of life (QoL) in patients with AD from South Korea.

METHODS: Patients with AD utilizing the specialist dermatology services of major hospitals in South Korea were assessed for disease severity using Eczema Area and Severity Index (EASI) score, for QoL using Dermatology Life Quality Index (DLQI) (for QoL), and for comorbidities and treatment experience via retrospective review of 12-month medical records. Clinical and sociodemographic characteristics were also measured. …

Massive Macroglossia, A Rare Side Effect Of Covid-19: Clinical, Histologic, And Genomic Findings In Covid-19-Positive Versus Covid-19-Negative Patients, Victoria A Mañón, David Chubb, Laura S Farach, Rachid Karam, Mary C Farach-Carson, Nadarajah Vigneswaran, Karan Saluja, Simon Young, Mark Wong, James C Melville

Faculty, Staff and Student Publications

PURPOSE: The primary purpose of this study is to identify if there is an underlying genetic predisposition for COVID-related macroglossia and if this susceptibility is higher among individuals of African heritage. Secondary objectives include determining if genetic testing of COVID-infected patients who are intubated and prone could identify patients with higher susceptibility to the development of macroglossia.

METHODS: A retrospective chart review was completed for each patient, and prospectively, genetic and histopathologic analyses were completed. Whole-exome sequencing was completed on two patients; immunohistochemistry was completed on the COVID-positive tissue samples.

RESULTS: Histopathology of the COVID-positive patient revealed significant peri-lymphocytic infiltrate, …

Allergic Sensitization Pattern In The Korean Dermatologic Patients, Yujin Han, Yu Ri Woo, Hei Sung Kim, Jeong Deuk Lee, Sookhee Choi, Jeesuk Yu, Sang Hyun Cho

Faculty, Staff and Student Publications

BACKGROUND: Avoiding causative allergens is important for controlling the clinical course of allergic diseases. Allergen sensitization is influenced by many factors including the environment and lifestyle. The socioeconomic development, climate, and lifestyle changes have increased the prevalence of allergic diseases worldwide. However, there is little information about changes in the trend of the common allergens over time.

OBJECTIVE: This study was aimed at identifying the trends of the common allergens in Korea over a 10-year period based on the results of the multiple allergosorbent test chemiluminescent assay (MAST-CLA).

METHODS: We retrospectively reviewed the medical records of 5,760 patients aged ≥18 …

Transcriptomic Profiling Of Trypanosoma Congolense Mouthpart Parasites From Naturally Infected Flies, Sara Silva Pereira, Kawira Mathenge, Daniel Masiga, Andrew Jackson

All Peer-Reviewed Publications

Background: Animal African trypanosomiasis, or nagana, is a veterinary disease caused by African trypanosomes transmitted by tsetse flies. In Africa, Trypanosoma congolense is one of the most pathogenic and prevalent causes of nagana in livestock, resulting in high animal morbidity and mortality and extensive production losses. In the tsetse fly, parasites colonise the midgut and eventually reach the mouthparts, from where they can be transmitted as the fly feeds on vertebrate hosts such as cattle. Despite the extreme importance of mouthpart-form parasites for disease transmission, very few global expression profile studies have been conducted in these parasite forms. Methods: Here, …

Mdm2 Antagonist Improves Therapeutic Activity Of Azacitidine In Myelodysplastic Syndromes And Chronic Myelomonocytic Leukemia, Yue Wei, Hong Zheng, Pamela Pennington Lockyer, Faezeh Darbaniyan, Ziyi Li, Rashmi Kanagal-Shamanna, Kelly A Soltysiak, Hui Yang, Irene Ganan-Gomez, Guillermo Montalban-Bravo, Kelly S Chien, Kim-Anh Do, Naval Daver, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

Failure of hypomethylation agent (HMA) treatments is an important issue in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Recent studies indicated that function of wildtype TP53 positively impacts outcome of HMA treatments. We investigated the combination of the HMA azacitidine (AZA) with DS-3032b and DS-5272, novel antagonists of the TP53 negative regulator MDM2, in cellular and animal models of MDS and CMML. In TP53 wildtype myeloid cell line, combinational effects of DS-3032b or DS-5272 with AZA were observed. In Tet2-knockout mouse model of MDS and CMML, DS-5272 and AZA combination ameliorated disease-like phenotype. RNA-Seq analysis in mouse bone …

Endovascular Repair Of Aortic Arch Graft Pseudoaneurysm Using A Duct Occluder Device With Onlay Fusion Guidance, Guilherme B Barbosa Lima, Laura Ocasio, Emanuel R Tenorio, Marina Dias-Neto, Thanila A Macedo, Gustavo S Oderich

Faculty, Staff and Student Publications

Aortic arch pseudoaneurysms can be caused by previous surgery, infection, or trauma. In select patients with small tears and no evidence of infection, local repair can be performed using an open or endovascular technique.1 Open surgical repeat surgery has increased risks and endovascular repair has been especially appealing for the elderly, higher risk patients, and patients with multiple prior procedures.2 We have reported the use of a ductal occluder device in a patient with a large aortic arch pseudoaneurysm.3 Our patient has provided written informed consent for the report of his case details and imaging studies.

Study Protocol Cover-All: Clinical Impact Of A Volumetric Image Method For Confirming Tumour Coverage With Ablation On Patients With Malignant Liver Lesions, Yuan-Mao Lin, Iwan Paolucci, Brian M Anderson, Caleb S O'Connor, Bastien Rigaud, Maria Briones-Dimayuga, Kyle A Jones, Kristy K Brock, Bryan M Fellman, Bruno C Odisio

Faculty, Staff and Student Publications

Purpose: This study aims to evaluate the intra-procedural use of a novel ablation confirmation (AC) method, consisting of biomechanical deformable image registration incorporating AI-based auto-segmentation, and its impact on tumor coverage by quantitative three-dimensional minimal ablative margin (MAM) CT-generated assessment.

Materials and methods: This single-center, randomized, phase II, intent-to-treat trial is enrolling 100 subjects with primary and secondary liver tumors (≤ 3 tumors, 1-5 cm in diameter) undergoing microwave or radiofrequency ablation with a goal of achieving ≥ 5 mm MAM. For the experimental arm, the proposed novel AC method is utilized for ablation applicator(s) placement verification and MAM assessment. …

Development Of A Distributed International Patient Data Registry For Hairy Cell Leukemia, Leslie A Andritsos, Mirela Anghelina, Jasmine Neal, James S Blachly, Puneet Mathur, Omkar Lele, Claire Dearden, Sunil Iyengar, Matthew Cross, Clive S Zent, Kerry A Rogers, Narendranath Epperla, Gerard Lozanski, Christopher C Oakes, Eric Kraut, Amy S Ruppert, Qiuhong Zhao, Seema A Bhat, Francesco Forconi, Versha Banerji, Sasanka Handunnetti, Constantine S Tam, John F Seymour, Monica Else, Robert J Kreitman, Alan Saven, Timothy Call, Sameer A Parikh, Farhad Ravandi, James B Johnston, Enrico Tiacci, Xavier Troussard, Martin S Tallman, Sascha Dietrich, Tamar Tadmor, Alessandro Gozzetti, Pier Luigi Zinzani, Tadeusz Robak, Graeme Quest, Judit Demeter, Kanti Rai, Soledad A Fernandez, Michael Grever

Faculty, Staff and Student Publications

Hairy cell leukemia (HCL) is a rare lymphoproliferative disorder, comprising only 2% of all leukemias. The Hairy Cell Leukemia Foundation (HCLF) has developed a patient data registry to enable investigators to better study the clinical features, treatment outcomes, and complications of patients with HCL. This system utilizes a centralized registry architecture. Patients are enrolled at HCL Centers of Excellence (COE) or via a web-based portal. All data are de-identified, which reduces regulatory burden and increases opportunities for data access and re-use. To date, 579 patients have been enrolled in the registry. Efforts are underway to engage additional COE's to expand …

Neoadjuvant Chemotherapy Is Associated With Altered Immune Cell Infiltration And An Anti-Tumorigenic Microenvironment In Resected Pancreatic Cancer, Andressa Dias Costa, Sara A Väyrynen, Akhil Chawla, Jinming Zhang, Juha P Väyrynen, Mai Chan Lau, Hannah L Williams, Chen Yuan, Vicente Morales-Oyarvide, Dalia Elganainy, Harshabad Singh, James M Cleary, Kimberly Perez, Kimmie Ng, William Freed-Pastor, Joseph D Mancias, Stephanie K Dougan, Jiping Wang, Douglas A Rubinson, Richard F Dunne, Margaret M Kozak, Lauren Brais, Emma Reilly, Thomas Clancy, David C Linehan, Daniel T Chang, Aram F Hezel, Albert C Koong, Andrew J Aguirre, Brian M Wolpin, Jonathan A Nowak

Faculty, Staff and Student Publications

PURPOSE: Neoadjuvant chemotherapy is increasingly administered to patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC), yet its impact on the tumor immune microenvironment is incompletely understood.

DESIGN: We employed quantitative, spatially resolved multiplex immunofluorescence and digital image analysis to identify T-cell subpopulations, macrophage polarization states, and myeloid cell subpopulations in a multi-institution cohort of up-front resected primary tumors (n = 299) and in a comparative set of resected tumors after FOLFIRINOX-based neoadjuvant therapy (n = 36) or up-front surgery (n = 30). Multivariable-adjusted Cox proportional hazards models were used to evaluate associations between the immune microenvironment and patient …

Radiomics In Abdominopelvic Solid-Organ Oncologic Imaging: Current Status, Xiaoyang Liu, Mohamed G Elbanan, Antonio Luna, Masoom A Haider, Andrew D Smith, Carl F Sabottke, Bradley M Spieler, Baris Turkbey, David Fuentes, Ahmed Moawad, Serageldin Kamel, Natally Horvat, Khaled M Elsayes

Faculty, Staff and Student Publications

Radiomics is the process of extraction of high-throughput quantitative imaging features from medical images. These features represent noninvasive quantitative biomarkers that go beyond the traditional imaging features visible to the human eye. This article first reviews the steps of the radiomics pipeline, including image acquisition, ROI selection and image segmentation, image preprocessing, feature extraction, feature selection, and model development and application. Current evidence for the application of radiomics in abdominopelvic solid-organ cancers is then reviewed. Applications including diagnosis, subtype determination, treatment response assessment, and outcome prediction are explored within the context of hepatobiliary and pancreatic cancer, renal cell carcinoma, prostate …

Mediterranean-Style Diet And Exercise Improve Parameters For Management And Prevention Of Type 2 Diabetes Mellitus, Stefani Ann Derrick

Master's Theses

Type 2 diabetes mellitus (T2DM) is a chronic condition recognized as the inability to maintain glucose homeostasis, typically presenting with insulin resistance and systemic inflammation. With the prevalence of T2DM and major risk factors such as prediabetes and obesity increasing each year, there is a crucial need to identify strategies for the management and prevention of this condition. Addressing lifestyle-related risk factors through consumption of a well-balanced, nutritious diet and maintaining regular moderate- to high-intensity physical activity may provide a strategy for improving glycemic control, improving metrics of body composition, and decreasing the inflammatory response associated with metabolic dysregulation. Twenty-two …

A Study Of Heart Disease Diagnosis Using Machine Learning And Data Mining, Intisar Ahmed

Electronic Theses, Projects, and Dissertations

Heart disease is the leading cause of death for people around the world today. Diagnosis for various forms of heart disease can be detected with numerous medical tests, however, predicting heart disease without such tests is very difficult. Machine learning can help process medical big data and provide hidden knowledge which otherwise would not be possible with the naked eye. The aim of this project is to explore how machine learning algorithms can be used in predicting heart disease by building an optimized model. The research questions are; 1) What Machine learning algorithms are used in the diagnosis of heart …

Discovery And Systematic Characterization Of Risk Variants And Genes For Coronary Artery Disease In Over A Million Participants, Krishna G Aragam, Tao Jiang, Anuj Goel, Stavroula Kanoni, Brooke N Wolford, Deepak S Atri, Elle M Weeks, Minxian Wang, George Hindy, Wei Zhou, Christopher Grace, Carolina Roselli, Nicholas A Marston, Frederick K Kamanu, Ida Surakka, Loreto Muñoz Venegas, Paul Sherliker, Satoshi Koyama, Kazuyoshi Ishigaki, Bjørn O Åsvold, Michael R Brown, Ben Brumpton, Paul S De Vries, Olga Giannakopoulou, Panagiota Giardoglou, Daniel F Gudbjartsson, Ulrich Güldener, Syed M Ijlal Haider, Anna Helgadottir, Maysson Ibrahim, Adnan Kastrati, Thorsten Kessler, Theodosios Kyriakou, Tomasz Konopka, Ling Li, Lijiang Ma, Thomas Meitinger, Sören Mucha, Matthias Munz, Federico Murgia, Jonas B Nielsen, Markus M Nöthen, Shichao Pang, Tobias Reinberger, Gavin Schnitzler, Damian Smedley, Gudmar Thorleifsson, Moritz Von Scheidt, Jacob C Ulirsch, Biobank Japan, Epic-Cvd, David O Arnar, Noël P Burtt, Maria C Costanzo, Jason Flannick, Kaoru Ito, Dong-Keun Jang, Yoichiro Kamatani, Amit V Khera, Issei Komuro, Iftikhar J Kullo, Luca A Lotta, Christopher P Nelson, Robert Roberts, Gudmundur Thorgeirsson, Unnur Thorsteinsdottir, Thomas R Webb, Aris Baras, Johan L M Björkegren, Eric Boerwinkle, George Dedoussis, Hilma Holm, Kristian Hveem, Olle Melander, Alanna C Morrison, Marju Orho-Melander, Loukianos S Rallidis, Arno Ruusalepp, Marc S Sabatine, Kari Stefansson, Pierre Zalloua, Patrick T Ellinor, Martin Farrall, John Danesh, Christian T Ruff, Hilary K Finucane, Jemma C Hopewell, Robert Clarke, Rajat M Gupta, Jeanette Erdmann, Nilesh J Samani, Heribert Schunkert, Hugh Watkins, Cristen J Willer, Panos Deloukas, Sekar Kathiresan, Adam S Butterworth, Cardiogramplusc4d Consortium

Faculty, Staff and Student Publications

The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci. We prioritized likely causal variants using functionally informed fine-mapping, yielding 42 associations with less than five variants in the 95% credible set. Similarity-based clustering suggested roles for early developmental processes, cell cycle signaling and vascular cell migration and proliferation in …

Dawn-To-Dusk Dry Fasting Induces Anti-Atherosclerotic, Anti-Inflammatory, And Anti-Tumorigenic Proteome In Peripheral Blood Mononuclear Cells In Subjects With Metabolic Syndrome, Ayse L Mindikoglu, Jihwan Park, Antone R Opekun, Mustafa M Abdulsada, Zoe R Wilhelm, Prasun K Jalal, Sridevi Devaraj, Sung Yun Jung

Faculty, Staff and Students Publications

BACKGROUND: Metabolic syndrome characterized by abdominal obesity, high blood pressure, elevated fasting glucose and triglyceride levels and low high-density lipoprotein cholesterol level is associated with pro-inflammatory state, increased risk for atherosclerosis, and multiple cancers. Our previous results on subjects with metabolic syndrome showed that 4-week dawn-to-dusk (sunset) dry fasting resulted in significant changes in the serum proteome and improvement in several metabolic risk factors. Peripheral blood mononuclear cells (PBMC) proteomics is a powerful tool that can provide mechanistic insights into how dawn-to-dusk dry fasting affects protein expression in metabolic pathways at cellular level. In this study, we determined whether dawn-to-dusk …

Comprehensive Genetic Analysis Of The Human Lipidome Identifies Loci Associated With Lipid Homeostasis With Links To Coronary Artery Disease, Gemma Cadby, Corey Giles, Phillip E. Melton, Kevin Huynh, Natalie A. Mellett, Thy Duong, Anh Nguyen, Michelle Cinel, Alex Smith, Gavriel Olshansky, Tingting Wang, Marta Brozynska, Mike Inouye, Nina S. Mccarthy, Amir Ariff, Joseph Hung, Jennie Hui, John Beilby, Marie Pierre Dubé, Gerald F. Watts, Sonia Shah, Naomi R. Wray, Wei Ling Florence Lim, Pratishtha Chatterjee, Ian Martins, Simon M. Laws, Tenielle Porter, Michael Vacher, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, Kevin Taddei, Matthias Arnold, Gabi Kastenmüller, Kwangsik Nho, Andrew J. Saykin, Xianlin Han, Rima Kaddurah-Daouk, Ralph N. Martins, John Blangero, Peter J. Meikle, Eric K. Moses

Research outputs 2022 to 2026

We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were …

Vascular Endothelial Growth Factor And The Risk Of Venous Thromboembolism: A Genetic Correlation And Two-Sample Mendelian Randomization Study, Qiaoyun Zhang, Xiaoyu Zhang, Jie Zhang, Biyan Wang, Qiuyue Tian, Xiaoni Meng, Jinxia Zhang, Mengyang Jiang, Yiqiang Zhang, Deqiang Zheng, Lijuan Wu, Wei Wang, Baoguo Wang, Youxin Wang

Research outputs 2022 to 2026

Background: The relationship between vascular endothelial growth factor (VEGF) and the risk of venous thromboembolism (VTE) has always been one of the concerns in the medical field. However, the causal inferences from published observational studies on this issue may be affected by confounders or reverse causality. We performed a two-sample bidirectional Mendelian randomization (MR) to infer the associations between VEGF and VTE. Methods: Summary statistics from genome-wide association studies (GWAS) for VEGF and VTE were obtained from published meta-analysis studies and the FinnGen consortium, respectively. Independent genetic variables significantly associated with exposure were selected as instrumental variables. Linkage disequilibrium score …

Combined Evaluation Of Arterial Stiffness, Glycemic Control And Hypertension For Macrovascular Complications In Type 2 Diabetes, Zhiyuan Wu, Siqi Yu, Haiping Zhang, Zheng Guo, Yulu Zheng, Zongkai Xu, Zhiwei Li, Xiangtong Liu, Xia Li, Shuo Chen, Jingbo Zhang, Lixin Tao, Xiuhua Guo

Research outputs 2022 to 2026

Background: Arterial stiffness, glycemic control and blood pressure are risk factors of macrovascular complications in type 2 diabetes. This study aimed to investigate the combined association of arterial stiffness, glycemic control and hypertension status with the occurrence of diabetic macrovascular complication. Methods: A total of 1870 patients of diabetes were enrolled from Beijing Health Management Cohort between 2008 and 2018 as baseline, and then followed for macrovascular complication onset. We proposed a composite risk score (0 – 4) by arterial stiffness severity, pool glycemic control and hypertension status. Cox model was used to estimate the hazard ratio (HR) and 95 …

Current Insights On The Use Of Insulin And The Potential Use Of Insulin Mimetics In Targeting Insulin Signalling In Alzheimer’S Disease, Amy Woodfield, Tatiana Gonzales, Erik Helmerhorst, Simon Laws, Philip Newsholme, Tenielle Porter, Giuseppe Verdile

Research outputs 2022 to 2026

Alzheimer’s disease (AD) and type 2 diabetes (T2D) are chronic diseases that share several pathological mechanisms, including insulin resistance and impaired insulin signalling. Their shared features have prompted the evaluation of the drugs used to manage diabetes for the treatment of AD. Insulin delivery itself has been utilized, with promising effects, in improving cognition and reducing AD related neuropathology. The most recent clinical trial involving intranasal insulin reported no slowing of cognitive decline; however, several factors may have impacted the trial outcomes. Long-acting and rapid-acting insulin analogues have also been evaluated within the context of AD with a lack of …

Genetic Liability Between Covid-19 And Heart Failure: Evidence From A Bidirectional Mendelian Randomization Study, Huachen Wang, Zheng Guo, Yulu Zheng, Bing Chen

Research outputs 2022 to 2026

Background: Previous studies have observed inconsistent associations between coronavirus disease 2019 (COVID-19) and heart failure (HF), but these studies were prone to bias based on reverse causality and residual confounding factors. We aimed to investigate genetic liability between COVID-19 and heart failure using a bidirectional Mendelian randomization study. Methods: The causal relationship between COVID-19 (including COVID-19, hospitalized COVID-19 compared with the general population, and severe COVID-19) and HF are determined by using a bidirectional Mendelian randomization analysis. We drew on summary statistics from the largest HF genome-wide association study (GWAS) meta-analysis on individuals of European ancestry, which included 47,309 HF …

Assessment Of A Polygenic Hazard Score For The Onset Of Pre-Clinical Alzheimer’S Disease, Michael Vacher, Vincent Doré, Tenielle Porter, Lidija Milicic, Victor L. Villemagne, Pierrick Bourgeat, Sam C. Burnham, Timothy Cox, Colin L. Masters, Christopher C. Rowe, Jurgen Fripp, James D. Doecke, Simon M. Laws

Research outputs 2022 to 2026

Background: With a growing number of loci associated with late-onset (sporadic) Alzheimer’s disease (AD), the polygenic contribution to AD is now well established. The development of polygenic risk score approaches have shown promising results for identifying individuals at higher risk of developing AD, thereby facilitating the development of preventative and therapeutic strategies. A polygenic hazard score (PHS) has been proposed to quantify age-specific genetic risk for AD. In this study, we assessed the predictive power and transferability of this PHS in an independent cohort, to support its clinical utility. Results: Using genotype and imaging data from 780 individuals enrolled in …

Association Of Visceral Adiposity Index With Incident Nephropathy And Retinopathy: A Cohort Study In The Diabetic Population, Zhiyuan Wu, Siqi Yu, Xiaoping Kang, Yue Liu, Zongkai Xu, Zhiwei Li, Jinqi Wang, Xinlei Miao, Xiangtong Liu, Xia Li, Jingbo Zhang, Wei Wang, Lixin Tao, Xiuhua Guo

Research outputs 2022 to 2026

Background: The association between visceral adiposity index (VAI) and diabetic complications has been reported in cross-sectional studies, while the effect of VAI on complication development remains unclear. This study aims to evaluate the longitudinal association of VAI and Chinese VAI (CVAI) with the incidence of diabetic nephropathy and retinopathy using a Chinese cohort. Methods: A total of 8 948 participants with type 2 diabetes from Beijing Health Management Cohort were enrolled during 2013–2014, and followed until December 31, 2019. Nephropathy was confirmed by urine albumin/creatinine ratio and estimated glomerular filtration rate; retinopathy was diagnosed using fundus photograph. Results: The mean …

Optimization Of Clostridium Septicum Antigen Production And Evaluation Of Vaccine Administration Parameters For A Candidate Bacterin-Toxoid To Prevent Dermatitis In Commercial Turkeys, Aaron Forga

Graduate Theses and Dissertations

The objective of this thesis was to optimize the hemolytic activity of two isolates of Clostridium septicum to evaluate if hemolytic titer of C. septicum antigen at time of formalin inactivation corresponded to increased serum antibody titer to the C. septicum alpha-toxin of turkeys immunized with an experimental formalin inactivated bacterin-toxoid vaccine. Chapter 1 provides a brief overview of the thesis. Chapter 2 consists of a literature review focused on clostridial dermatitis, specifically C. septicum-associated dermatitis (cellulitis) that affects commercial turkeys. Chapter 3 outlines our attempts to optimize an experimental autogenous bacterin-toxoid vaccine as a potential strategy to mitigate clostridial …

Distinctive Kidney Function Trajectories Following Left Ventricular Assist Device Implantation, Carl P Walther, Julia S Benoit, Harveen K Lamba, Andrew B Civitello, Kevin F Erickson, Nandan K Mondal, Kenneth K Liao, Sankar D Navaneethan

Faculty, Staff and Students Publications

BACKGROUND: The aim of this study was to assess for distinct kidney function trajectories following left ventricular assist device (LVAD) placement. Cohort studies of LVAD recipients demonstrate that kidney function tends to increase early after LVAD placement, followed by decline and limited sustained improvement. Inter-individual differences in kidney function response may be obscured.

METHODS: We identified continuous flow LVAD implantations in US adults (2016-2017) from INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). Primary outcomes were estimated glomerular filtration rate (eGFR) trajectories pre-implantation to ∼12 months. Latent class mixed models were applied to primary and validation samples. Clinical differences among …