Medical Specialties Commons^™

Long-Term Continuous Glucose Monitor Use In Very Young Children With Type 1 Diabetes: One-Year Results From The Sence Study, Michelle A Van Name, Lauren G Kanapka, Linda A Dimeglio, Kellee M Miller, Anastasia Albanese-O'Neill, Persis Commissariat, Sarah D Corathers, Kara R Harrington, Marisa E Hilliard, Barbara J Anderson, Jennifer C Kelley, Lori M Laffel, Sarah A Macleish, Brandon M Nathan, William V Tamborlane, R Paul Wadwa, Steven M Willi, Kristen M Williams, Kupper A Wintergerst, Stephanie Woerner, Jenise C Wong, Daniel J Desalvo

Faculty, Staff and Students Publications

OBJECTIVES: Achieving optimal glycemic outcomes in young children with type 1 diabetes (T1D) is challenging. This study examined the durability of continuous glucose monitoring (CGM) coupled with a family behavioral intervention (FBI) to improve glycemia.

STUDY DESIGN: This one-year study included an initial 26-week randomized controlled trial of CGM with FBI (CGM+FBI) and CGM alone (Standard-CGM) compared with blood glucose monitoring (BGM), followed by a 26-week extension phase wherein the BGM Group received the CGM+FBI (BGM-Crossover) and both original CGM groups continued this technology.

RESULTS: Time in range (70-180 mg/dL) did not improve with …

Defining The Full Spectrum Of Pediatric Firearm Injury And Death In The United States: It Is Even Worse Than We Think, Bindi J Naik-Mathuria, Cary M Cain, Elizabeth A Alore, Liang Chen, Lisa A Pompeii

Faculty, Staff and Students Publications

OBJECTIVE: To characterize the full spectrum of pediatric firearm injury in the United States by describing fatal and nonfatal injury data epidemiology, vulnerable populations, and temporal trends.

BACKGROUND: Firearm injury is the leading cause of death in children and adolescents in the United States. Nonfatal injury is critical to fully define the problem, yet accurate data at the national level are lacking.

METHODS: A cross-sectional study combining national firearm injury data from the Centers for Disease Control (fatal) and the National Trauma Data Bank (nonfatal) between 2008 and 2019 for ages 0 to 17 years. Data were analyzed using descriptive …

Multiple Primary Lung Cancers: Treatment Outcomes After Stereotactic Body Radiotherapy (Sbrt), Gyujae Choi, George Chen, Weiyuan Mai, Albert Chen, Angela Zhu

Faculty, Staff and Students Publications

PURPOSE/OBJECTIVES: Patients with lung cancer sometimes present with multiple primary lung cancers (MPLCs), either simultaneously (synchronous) or after treatment of an initial lesion (metachronous). Although open surgery remains a treatment mainstay for patients with stage I-II non-small-cell lung cancer (NSCLC), stereotactic body radiation therapy (SBRT) is an acceptable alternative for patients who are medically unfit for or who refuse surgery. In this study, we retrospectively examine the outcome among patients with early-stage MPLCs treated at our institution with SBRT.

MATERIALS/METHODS: Patients at our institution receiving SBRT for MPLC between June 2011 and March 2020 were reviewed retrospectively. Prior to undergoing …

Readmissions After Surgical Aortic Valve Replacement: Influence Of Prosthesis Type, Christopher B Sylvester, Christopher T Ryan, William C Frankel, Rodrigo Zea-Vera, Qianzi Zhang, Matthew J Wall, Marc R Moon, Joseph S Coselli, Todd K Rosengart, Subhasis Chatterjee, Ravi K Ghanta

Faculty, Staff and Students Publications

INTRODUCTION: Prosthesis choice during aortic valve replacement (AVR) weighs lifelong anticoagulation with mechanical valves (M-AVR) against structural valve degeneration in bioprosthetic valves (B-AVR).

METHODS: The Nationwide Readmissions Database was queried to identify patients who underwent isolated surgical AVR between January 1, 2016 and December 31, 2018, stratifying by prothesis type. Propensity score matching was used to compare risk-adjusted outcomes. Readmission at 1 y was estimated with Kaplan-Meier (KM) analysis.

RESULTS: Patients (n = 109,744) who underwent AVR (90,574 B-AVR and 19,170 M-AVR) were included. B-AVR patients were older (median 68 versus 57 y; P < 0.001) and had more comorbidities (mean Elixhauser score: 11.8 versus 10.7; P < 0.001) compared to M-AVR patients. After matching (n = 36,951), there was no difference in age (58 versus 57 y; P = 0.6) and Elixhauser score (11.0 versus 10.8; P = 0.3). B-AVR patients had similar in-hospital mortality (2.3% versus 2.3%; P = 0.9) and cost (mean: $50,958 versus $51,200; P = 0.4) compared with M-AVR patients. However, B-AVR patients had shorter length of stay (8.3 versus 8.7 d; P < 0.001) and fewer readmissions at 30 d (10.3% versus 12.6%; P < 0.001) and 90 d (14.8% versus 17.8%; P < 0.001), and 1 y (P < 0.001, KM analysis). Patients undergoing B-AVR were less likely to be readmitted for bleeding or coagulopathy (5.7% versus 9.9%; P < 0.001) and effusions (9.1% versus 11.9%; P < 0.001).

CONCLUSIONS: B-AVR patients had similar early …

Association Between Antibiotic Prophylaxis Before Cystectomy Or Stent Removal And Infection Complications: A Systematic Review, Luca Antonelli, Kirby Sebro, Abdelilah Lahmar, Peter C Black, Saum Ghodoussipour, Jill M Hamilton-Reeves, Jay Shah, Jensen Bente Thoft, Seth Paul Lerner, Carlos Llorente, Ilaria Lucca, Mark A Preston, Sarah P Psutka, John P Sfakianos, Susanne Vahr Lauridsen, Stephen B Williams, James Catto, Hooman Djaladat, Wassim Kassouf, Katherine Loftus, Siamak Daneshmand, Christian D Fankhauser

Faculty, Staff and Students Publications

Context: Patients undergoing radical cystectomy frequently suffer from infectious complications, including urinary tract infections (UTIs) and surgical site infections (SSIs) leading to emergency department visits, hospital readmission, and added cost.

Objective: To summarize the literature regarding perioperative antibiotic prophylaxis, ureteric stent usage, and prevalence of infectious complications after cystectomy.

Evidence acquisition: A systematic review of PubMed/Medline, EMBASE, Cochrane Library, and reference lists was conducted.

Evidence synthesis: We identified 20 reports including a total of 55 306 patients. The median rates of any infection, UTIs, SSIs, and bacteremia were 40%, 20%, 11%, and 6%, respectively. Perioperative antibiotic prophylaxis differed substantially between …

Affinity-Based Electrochemical Sensors For Biomolecular Detection In Whole Blood, Elizabeth C Wilkirson, Kavya L Singampalli, Jiran Li, Desh Deepak Dixit, Xue Jiang, Diego H Gonzalez, Peter B Lillehoj

Faculty, Staff and Students Publications

The detection and/or quantification of biomarkers in blood is important for the early detection, diagnosis, and treatment of a variety of diseases and medical conditions. Among the different types of sensors for detecting molecular biomarkers, such as proteins, nucleic acids, and small-molecule drugs, affinity-based electrochemical sensors offer the advantages of high analytical sensitivity and specificity, fast detection times, simple operation, and portability. However, biomolecular detection in whole blood is challenging due to its highly complex matrix, necessitating sample purification (i.e., centrifugation), which involves the use of bulky, expensive equipment and tedious sample-handling procedures. To address these challenges, various strategies have …

Realizing The Promise Of Dolutegravir In Effectively Treating Children And Adolescents Living With Hiv In Real-World Settings In 6 Countries In Eastern And Southern Africa, Jason Michael Bacha, Sandile Dlamini, Florence Anabwani, Judith Gwimile, Jacqueline Balungi Kanywa, John Farirai, Menard Bvumbwe, Mabene Tsotako, Teresa Steffy, Diane Nguyen, Jose Euberto Mendez-Reyes, Peter Elyanu, Heather Haq

Faculty, Staff and Students Publications

BACKGROUND: Despite encouraging results from clinical trials and in high-income countries, large-scale data on the effectiveness and safety of dolutegravir (DTG) in children and adolescents living with HIV (CALHIV) are lacking in low- and middle-income countries (LMICs).

METHODS: Retrospective analysis was performed among CALHIV 0-19 years old and weighing greater than or equal to 20 kg who received DTG from 2017 to 2020 at sites in Botswana, Eswatini, Lesotho, Malawi, Tanzania and Uganda to determine effectiveness, safety and predictors of viral load suppression (VLS) among CALHIV using DTG, including through single drug substitutions (SDS).

RESULTS: Among 9419 CALHIV using DTG, …

Characterization Of Atrial And Ventricular Remodeling In An Improved Minimally Invasive Mouse Model Of Transverse Aortic Constriction, Jose Alberto Navarro-Garcia, Satadru K Lahiri, Yuriana Aguilar-Sanchez, Anilkumar K Reddy, Xander H T Wehrens

Faculty, Staff and Students Publications

INTRODUCTION: Heart failure (HF) is the leading cause of death worldwide. Most large and small animal disease models of HF are based on surgical procedures. A common surgical technique to induce HF is transverse aortic constriction (TAC), which induces pressure overload. The conventional TAC (cTAC) procedure is a highly invasive surgery that is associated with severe inflammation and excessive perioperative deaths.

AIM: To establish an improved, minimally invasive TAC (mTAC) procedure that does not require thoracotomy.

METHODS AND RESULTS: Following anesthesia, mice were intubated, and a small incision was made at the neck and chest. After cutting the sternum about …

Geospatial Distribution Of Obsessive-Compulsive Disorder Specialists: Understanding Access As A Function Of Distance, Insurance Status, And Neighborhood Socioeconomic Status, Abiodun O Oluyomi, Sophie C Schneider, Catherine Christian, Juan M Alvarez, Orri Smárason, Wayne K Goodman, Eric A Storch

Faculty, Staff and Students Publications

Obsessive-compulsive disorder is an impairing psychiatric condition affecting 1-2% of adults and youth. Cognitive-behavioral therapy with exposure and response prevention (CBT) is an efficacious intervention but requires specialty training and access is often limited. While certain factors are associated with treatment access, one key barrier that has not been explored is the geographic availability of OCD treatment providers. Using integrated geographically-referenced data, we examined the geographic distribution of OCD CBT specialty providers across the state of Texas, with particular attention to the relationship to neighborhood socioeconomic disadvantage, insurance status, and rural versus urban status. We found that specialist providers are …

Burden Of High-Risk Phenotype Of Heavy Alcohol Consumption Among Obese Us Population: Results From National Health And Nutrition Examination Survey, 1999–2020, Syed Ahsan Raza, Itunu O Sokale, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: The phenotype of combined heavy alcohol consumption and obesity has the potential to pose as a considerable health burden in the U.S. No studies using nationally representative data in the U.S. have reported their secular joint prevalence trends. We estimated the prevalence and examined the joint trends of heavy alcohol use and obesity over time among adult U.S. men and women in different age groups and according to race/ethnicity.

METHODS: Using data from 10 cycles of the U.S. National Health and Nutrition Examination Survey (NHANES) from 1999 to 2020, we examined secular trends in the combined phenotype of heavy …

Actionable Solutions To Achieve Health Equity In Chronic Liver Disease, Patricia D Jones, Jennifer C Lai, Jasmohan S Bajaj, Fasiha Kanwal

Faculty, Staff and Students Publications

There are well-described racial and ethnic disparities in the burden of chronic liver diseases. Hispanic persons are at highest risk for developing nonalcoholic fatty liver disease, the fastest growing cause of liver disease. Hepatitis B disproportionately affects persons of Asian or African descent. The highest rates of hepatitis C occur in American Indian and Alaskan Native populations. In addition to disparities in disease burden, there are also marked racial and ethnic disparities in access to treatments, including liver transplantation. Disparities also exist by gender and geography, especially in alcohol-related liver disease. To achieve health equity, we must address the root …

Closure Of Refractory Gastrocutaneous Fistula With Endoscopically Guided Percutaneous Suturing With The Use Of Miniature Biopsy Forceps, Rogelio Garcia, Juan D Gomez Cifuentes, Fuad Aloor, Tara Keihanian, Marvin Ryou, Wasif M Abidi

Faculty, Staff and Students Publications

A PEG tube is an ideal option for enteral nutrition in patients with impaired swallowing or for nutrition optimization. After PEG tube removal, the tract usually closes spontaneously. However, persistent gastrocutaneous fistula (GCF) is a rare but well-known adverse event of long-term PEG tube use.¹ Despite the evolution of endoscopic techniques over the last decade, such as over-the-scope clips (OTSCs), endoscopic suturing, and biosynthetic glue plaque, the management of GCF remains challenging.2, 3, 4, 5, 6 Although endoscopic suturing results in full-thickness closure of the gastric wall, persistent leakage from the cutaneous site may …

Machine Learning For Ecg Diagnosis And Risk Stratification Of Occlusion Myocardial Infarction, Salah S Al-Zaiti, Christian Martin-Gill, Jessica K Zègre-Hemsey, Zeineb Bouzid, Ziad Faramand, Mohammad O Alrawashdeh, Richard E Gregg, Stephanie Helman, Nathan T Riek, Karina Kraevsky-Phillips, Gilles Clermont, Murat Akcakaya, Susan M Sereika, Peter Van Dam, Stephen W Smith, Yochai Birnbaum, Samir Saba, Ervin Sejdic, Clifton W Callaway

Faculty, Staff and Students Publications

Patients with occlusion myocardial infarction (OMI) and no ST-elevation on presenting electrocardiogram (ECG) are increasing in numbers. These patients have a poor prognosis and would benefit from immediate reperfusion therapy, but, currently, there are no accurate tools to identify them during initial triage. Here we report, to our knowledge, the first observational cohort study to develop machine learning models for the ECG diagnosis of OMI. Using 7,313 consecutive patients from multiple clinical sites, we derived and externally validated an intelligent model that outperformed practicing clinicians and other widely used commercial interpretation systems, substantially boosting both precision and sensitivity. Our derived …

Suitability Of Double-Stranded Dna As A Molecular Standard For The Validation Of Analytical Ultracentrifugation Instruments, Maduni Ranasinghe, Jonathan M Fogg, Daniel J Catanese, Lynn Zechiedrich, Borries Demeler

Faculty, Staff and Students Publications

To address the current lack of validated molecular standards for analytical ultracentrifugation (AUC), we investigated the suitability of double-stranded DNA molecules. We compared the hydrodynamic properties of linear and circular DNA as a function of temperature. Negatively supercoiled, nicked, and linearized 333 and 339 bp minicircles were studied. We quantified the hydrodynamic properties of these DNAs at five different temperatures, ranging from 4 to 37 °C. To enhance the precision of our measurements, each sample was globally fitted over triplicates and five rotor speeds. The exceptional stability of DNA allowed each sample to be sedimented repeatedly over the course of …

Ywhae Loss Of Function Causes A Rare Neurodevelopmental Disease With Brain Abnormalities In Human And Mouse, Anne-Sophie Denommé-Pichon, Stephan C Collins, Ange-Line Bruel, Anna Mikhaleva, Christel Wagner, Valerie E Vancollie, Quentin Thomas, Martin Chevarin, Mathys Weber, Carlos E Prada, Alexis Overs, María Palomares-Bralo, Fernando Santos-Simarro, Marta Pacio-Míguez, Tiffany Busa, Eric Legius, Carlos A Bacino, Jill A Rosenfeld, Gwenaël Le Guyader, Matthieu Egloff, Xavier Le Guillou, Maria Antonietta Mencarelli, Alessandra Renieri, Salvatore Grosso, Jonathan Levy, Blandine Dozières, Isabelle Desguerre, Antonio Vitobello, Yannis Duffourd, Christopher J Lelliott, Christel Thauvin-Robinet, Christophe Philippe, Laurence Faivre, Binnaz Yalcin

Faculty, Staff and Students Publications

Purpose: Miller-Dieker syndrome is caused by a multiple gene deletion, including PAFAH1B1 and YWHAE. Although deletion of PAFAH1B1 causes lissencephaly unambiguously, deletion of YWHAE alone has not clearly been linked to a human disorder.

Methods: Cases with YWHAE variants were collected through international data sharing networks. To address the specific impact of YWHAE loss of function, we phenotyped a mouse knockout of Ywhae.

Results: We report a series of 10 individuals with heterozygous loss-of-function YWHAE variants (3 single-nucleotide variants and 7 deletions < 1 Mb encompassing YWHAE but not PAFAH1B1), including 8 new cases and 2 follow-ups, added with 5 cases (copy number variants) from literature review. Although, until now, only 1 intragenic deletion has been described in YWHAE, we report 4 new variants specifically in YWHAE (3 splice variants and 1 intragenic deletion). The most frequent manifestations are developmental delay, delayed speech, seizures, and brain malformations, including corpus callosum hypoplasia, delayed myelination, and ventricular dilatation. Individuals with variants affecting YWHAE alone have milder features than those with larger deletions. Neuroanatomical studies in Ywhae-/- mice revealed brain structural defects, including thin cerebral cortex, corpus callosum dysgenesis, and hydrocephalus paralleling those seen in humans.

Conclusion: This study further demonstrates that YWHAE loss-of-function variants cause a neurodevelopmental disease with brain abnormalities.

A Crispr/Cas9-Engineered Mouse Carrying A Conditional Knockout Allele For The Early Growth Response-1 Transcription Factor, Vineet K Maurya, Yan Ying, Denise G Lanza, Jason D Heaney, John P Lydon

Faculty, Staff and Students Publications

Early growth response 1 (EGR1) mediates transcriptional programs that are indispensable for cell division, differentiation and apoptosis in numerous physiologies and pathophysiologies. Whole-body EGR1 knockouts in mice (Egr1KO) have advanced our understanding of EGR1 function in an in vivo context. To extend the utility of the mouse to investigate EGR1 responses in a tissue- and/or cell-type-specific manner, we generated a mouse model in which exon 2 of the mouse Egr1 gene is floxed by CRISPR/Cas9 engineering. The floxed Egr1 alleles (Egr1f/f) are designed to enable spatiotemporal control of Cre-mediated EGR1 ablation in the …

Unravelling Spatial Gene Associations With Seagal: A Python Package For Spatial Transcriptomics Data Analysis And Visualization, Linhua Wang, Chaozhong Liu, Yang Gao, Xiang H-F Zhang, Zhandong Liu

Faculty, Staff and Students Publications

SUMMARY: In the era where transcriptome profiling moves toward single-cell and spatial resolutions, the traditional co-expression analysis lacks the power to fully utilize such rich information to unravel spatial gene associations. Here, we present a Python package called Spatial Enrichment Analysis of Gene Associations using L-index (SEAGAL) to detect and visualize spatial gene correlations at both single-gene and gene-set levels. Our package takes spatial transcriptomics datasets with gene expression and the aligned spatial coordinates as input. It allows for analyzing and visualizing genes' spatial correlations and cell types' colocalization within the precise spatial context. The output could be visualized as …

Predictors Of Self-Reported General Health Status In People Experiencing Homelessness With Serious Mental Illness, Landon Presnall, Robert Suchting, Gaybrielle Hicks, Jane Hamilton

Faculty, Staff and Student Publications

PURPOSE: The growing homeless population in the U.S.A. is disproportionately impacted by poor mental and physical health status, including a higher incidence of acute and chronic health problems, increased hospitalizations, and premature mortality compared to the general population. This study examined the association between demographic, social, and clinical factors and perceptions of general health status among the homeless population during admission to an integrated behavioral health treatment program.

METHODS: The study sample included 331 adults experiencing homelessness with a serious mental illness or co-occurring disorder. Participants were enrolled in services at a day program for unsheltered homeless adults, a residential …

Genome-Wide Association Analyses Define Pathogenic Signaling Pathways And Prioritize Drug Targets For Iga Nephropathy, Krzysztof Kiryluk, Elena Sanchez-Rodriguez, Xu-Jie Zhou, Francesca Zanoni, Lili Liu, Nikol Mladkova, Atlas Khan, Maddalena Marasa, Jun Y Zhang, Olivia Balderes, Simone Sanna-Cherchi, Andrew S Bomback, Pietro A Canetta, Gerald B Appel, Jai Radhakrishnan, Hernan Trimarchi, Ben Sprangers, Daniel C Cattran, Heather Reich, York Pei, Pietro Ravani, Kresimir Galesic, Dita Maixnerova, Vladimir Tesar, Benedicte Stengel, Marie Metzger, Guillaume Canaud, Nicolas Maillard, Francois Berthoux, Laureline Berthelot, Evangeline Pillebout, Renato Monteiro, Raoul Nelson, Robert J Wyatt, William Smoyer, John Mahan, Al-Akash Samhar, Guillermo Hidalgo, Alejandro Quiroga, Patricia Weng, Raji Sreedharan, David Selewski, Keefe Davis, Mahmoud Kallash, Tetyana L Vasylyeva, Michelle Rheault, Aftab Chishti, Daniel Ranch, Scott E Wenderfer, Dmitry Samsonov, Donna J Claes, Oleh Akchurin, Dimitrios Goumenos, Maria Stangou, Judit Nagy, Tibor Kovacs, Enrico Fiaccadori, Antonio Amoroso, Cristina Barlassina, Daniele Cusi, Lucia Del Vecchio, Giovanni Giorgio Battaglia, Monica Bodria, Emanuela Boer, Luisa Bono, Giuliano Boscutti, Gianluca Caridi, Francesca Lugani, Gianmarco Ghiggeri, Rosanna Coppo, Licia Peruzzi, Vittoria Esposito, Ciro Esposito, Sandro Feriozzi, Rosaria Polci, Giovanni Frasca, Marco Galliani, Maurizio Garozzo, Adele Mitrotti, Loreto Gesualdo, Simona Granata, Gianluigi Zaza, Francesco Londrino, Riccardo Magistroni, Isabella Pisani, Andrea Magnano, Carmelita Marcantoni, Piergiorgio Messa, Renzo Mignani, Antonello Pani, Claudio Ponticelli, Dario Roccatello, Maurizio Salvadori, Erica Salvi, Domenico Santoro, Guido Gembillo, Silvana Savoldi, Donatella Spotti, Pasquale Zamboli, Claudia Izzi, Federico Alberici, Elisa Delbarba, Michał Florczak, Natalia Krata, Krzysztof Mucha, Leszek Pączek, Stanisław Niemczyk, Barbara Moszczuk, Malgorzata Pańczyk-Tomaszewska, Malgorzata Mizerska-Wasiak, Agnieszka Perkowska-Ptasińska, Teresa Bączkowska, Magdalena Durlik, Krzysztof Pawlaczyk, Przemyslaw Sikora, Marcin Zaniew, Dorota Kaminska, Magdalena Krajewska, Izabella Kuzmiuk-Glembin, Zbigniew Heleniak, Barbara Bullo-Piontecka, Tomasz Liberek, Alicja Dębska-Slizien, Tomasz Hryszko, Anna Materna-Kiryluk, Monika Miklaszewska, Maria Szczepańska, Katarzyna Dyga, Edyta Machura, Katarzyna Siniewicz-Luzeńczyk, Monika Pawlak-Bratkowska, Marcin Tkaczyk, Dariusz Runowski, Norbert Kwella, Dorota Drożdż, Ireneusz Habura, Florian Kronenberg, Larisa Prikhodina, David Van Heel, Bertrand Fontaine, Chris Cotsapas, Cisca Wijmenga, Andre Franke, Vito Annese, Peter K Gregersen, Sreeja Parameswaran, Matthew Weirauch, Leah Kottyan, John B Harley, Hitoshi Suzuki, Ichiei Narita, Shin Goto, Hajeong Lee, Dong Ki Kim, Yon Su Kim, Jin-Ho Park, Belong Cho, Murim Choi, Ans Van Wijk, Ana Huerta, Elisabet Ars, Jose Ballarin, Sigrid Lundberg, Bruno Vogt, Laila-Yasmin Mani, Yasar Caliskan, Jonathan Barratt, Thilini Abeygunaratne, Philip A Kalra, Daniel P Gale, Ulf Panzer, Thomas Rauen, Jürgen Floege, Pascal Schlosser, Arif B Ekici, Kai-Uwe Eckardt, Nan Chen, Jingyuan Xie, Richard P Lifton, Ruth J F Loos, Eimear E Kenny, Iuliana Ionita-Laza, Anna Köttgen, Bruce A Julian, Jan Novak, Francesco Scolari, Hong Zhang, Ali G Gharavi

Faculty, Staff and Students Publications

IgA nephropathy (IgAN) is a progressive form of kidney disease defined by glomerular deposition of IgA. Here we performed a genome-wide association study of 10,146 kidney-biopsy-diagnosed IgAN cases and 28,751 controls across 17 international cohorts. We defined 30 genome-wide significant risk loci explaining 11% of disease risk. A total of 16 loci were new, including TNFSF4/TNFSF18, REL, CD28, PF4V1, LY86, LYN, ANXA3, TNFSF8/TNFSF15, REEP3, ZMIZ1, OVOL1/RELA, ETS1, IGH, IRF8, TNFRSF13B and FCAR. The risk loci were enriched in gene orthologs causing abnormal IgA levels when genetically manipulated in mice. We also observed a positive genetic correlation between IgAN and serum …

Outersphere Approach To Increasing The Persistance Of Oxygen-Sensitive Europium(Ii)-Containing Contrast Agents For Magnetic Resonance Imaging With Perfluorocarbon Nanoemulsions Toward Imaging Of Hypoxia, Jacob C Lutter, Andrea L Batchev, Caitlyn J Ortiz, Alexander G Sertage, Jonathan Romero, S A Amali S Subasinghe, Steen E Pedersen, Md Abul Hassan Samee, Robia G Pautler, Matthew J Allen

Faculty, Staff and Students Publications

Radiographic mapping of hypoxia is needed to study a wide range of diseases. Complexes of EuII are a promising class of molecules to fit this need, but they are generally limited by their rapid oxidation rates in vivo. Here, a perfluorocarbon-nanoemulsion perfused with N2, forms an interface with aqueous layers to hinder oxidation of a new perfluorocarbon-soluble complex of EuII. Conversion of the perfluorocarbon solution of EuII into nanoemulsions results in observable differences between reduced and oxidized forms by MRI both in vitro and in vivo. Oxidation in vivo occurrs over a period of ~30 min compared to <5 min for a comparable EuII-containing complex without nanoparticle interfaces. These results represent a critical step toward delivery of EuII-containing complexes in vivo for the study of hypoxia.

Safety Endpoints With Vadadustat Versus Darbepoetin Alfa In Patients With Non- Dialysis-Dependent Ckd: A Post Hoc Regional Analysis Of The Pro2tect Randomized Clinical Trial Of Esa-Treated Patients, Patrick S Parfrey, Steven K Burke, Glenn M Chertow, Kai-Uwe Eckardt, Alan G Jardine, Eldrin F Lewis, Wenli Luo, Kunihiro Matsushita, Peter A Mccullough, Todd Minga, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: In the PRO

STUDY DESIGN: Phase 3, global, open-label, randomized, active-controlled clinical trial.

SETTING & PARTICIPANTS: A total of 1,725 erythropoiesis-stimulating agent (ESA)-treated patients with anemia and NDD-CKD.

INTERVENTION: 1:1 randomization to receive vadadustat or darbepoetin alfa.

OUTCOMES: The primary safety end point was the time to first MACE.

RESULTS: At baseline, patients in Europe (n=444) were primarily treated with darbepoetin alfa, showed higher proportions on low ESA doses (/kg/wk epoetin alfa equivalents) with a hemoglobin concentration of ≥10 g/dL compared with patients in the US (n=665) and non-US/non-Europe (n=614) regions. The MACE rates per 100 person-years …

Accuracy Of Artificial Intelligence In Estimating Best-Corrected Visual Acuity From Fundus Photographs In Eyes With Diabetic Macular Edema, William Paul, Philippe Burlina, Rohita Mocharla, Neil Joshi, Zhuolin Li, Sophie Gu, Onnisa Nanegrungsunk, Kira Lin, Susan B Bressler, Cindy X Cai, Jun Kong, T Y Alvin Liu, Hadi Moini, Weiming Du, Fouad Amer, Karen Chu, Robert Vitti, Farshid Sepehrband, Neil M Bressler

Faculty, Staff and Students Publications

IMPORTANCE: Best-corrected visual acuity (BCVA) is a measure used to manage diabetic macular edema (DME), sometimes suggesting development of DME or consideration of initiating, repeating, withholding, or resuming treatment with anti-vascular endothelial growth factor. Using artificial intelligence (AI) to estimate BCVA from fundus images could help clinicians manage DME by reducing the personnel needed for refraction, the time presently required for assessing BCVA, or even the number of office visits if imaged remotely.

OBJECTIVE: To evaluate the potential application of AI techniques for estimating BCVA from fundus photographs with and without ancillary information.

DESIGN, SETTING, AND PARTICIPANTS: Deidentified color fundus …

Treatment Of Cervical Dystonia With Botox (Onabotulinumtoxina): Development, Insights, And Impact, Joseph Jankovic, Joseph Tsui, Mitchell F Brin

Faculty, Staff and Students Publications

Cervical dystonia (CD), the most common focal dystonia encountered in neurologic practice, is a chronic disorder in which the muscles of the neck involuntarily contract and cause abnormal postures and movements of the head, neck, and shoulders. Treatment of CD prior to botulinum toxin was unsatisfactory, as existing therapies often did not improve symptoms. The use of botulinum toxin for CD grew out of its success in treating blepharospasm, another type of focal dystonia. On the basis of results from a double-blind, placebo-controlled trial, onabotulinumtoxinA was approved in 2000 in the US for the treatment of CD in adults in …

Discriminating Mild Traumatic Brain Injury And Posttraumatic Stress Disorder Using Latent Neuroimaging And Neuropsychological Profiles In Active-Duty Military Service Members, Nicola L De Souza, Carrie Esopenko, Yuane Jia, J Scott Parrott, Tricia L Merkley, Emily L Dennis, Frank G Hillary, Carmen Velez, Douglas B Cooper, Jan E Kennedy, Jeffrey D Lewis, Gerald E York, Deleene S Menefee, Stephen R Mccauley, Amy O Bowles, Elisabeth A Wilde, David F Tate

Faculty, Staff and Students Publications

OBJECTIVE: Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) commonly occur among military Service Members and Veterans and have heterogenous, but also overlapping symptom presentations, which often complicate the diagnoses of underlying impairments and development of effective treatment plans. Thus, we sought to examine whether the combination of whole brain gray matter (GM) and white matter (WM) structural measures with neuropsychological performance can aid in the classification of military personnel with mTBI and PTSD.

METHODS: Active-Duty US Service Members ( n = 156; 87.8% male) with a history of mTBI, PTSD, combined mTBI+PTSD, or orthopedic injury completed a …

Allogeneic, Off-The-Shelf, Sars-Cov-2-Specific T Cells (Alvr109) For The Treatment Of Covid-19 In High-Risk Patients, Spyridoula Vasileiou, Laquisa Hill, Manik Kuvalekar, Aster G Workineh, Ayumi Watanabe, Yovana Velazquez, Suhasini Lulla, Kimberly Mooney, Natalia Lapteva, Bambi J Grilley, Helen E Heslop, Cliona M Rooney, Malcolm K Brenner, Todd N Eagar, George Carrum, Kevin A Grimes, Ann M Leen, Premal Lulla

Faculty, Staff and Students Publications

Defects in T-cell immunity to SARS-CoV-2 have been linked to an increased risk of severe COVID-19 (even after vaccination), persistent viral shedding and the emergence of more virulent viral variants. To address this T-cell deficit, we sought to prepare and cryopreserve banks of virus-specific T cells, which would be available as a partially HLA-matched, off-the-shelf product for immediate therapeutic use. By interrogating the peripheral blood of healthy convalescent donors, we identified immunodominant and protective T-cell target antigens, and generated and characterized polyclonal virus-specific T-cell lines with activity against multiple clinically important SARS-CoV-2 variants (including 'delta' and 'omicron'). The feasibility of …

Proteomic Analysis Identifies Circulating Proteins Associated With Plasma Amyloid-Β And Incident Dementia, Adrienne Tin, Kevin J Sullivan, Keenan A Walker, Jan Bressler, Rajesh Talluri, Bing Yu, Jeanette Simino, Valborg Gudmundsdottir, Valur Emilsson, Lori L Jennings, Lenore Launer, Hao Mei, Eric Boerwinkle, B Gwen Windham, Rebecca Gottesman, Vilmundur Gudnason, Josef Coresh, Myriam Fornage, Thomas H Mosley

Faculty, Staff and Student Publications

BACKGROUND: Plasma amyloid-β (Aβ) (Aβ

METHODS: We analyzed the association of these 3 plasma Aβ measures with 4638 circulating proteins among a subset of the participants of the Atherosclerosis Risk in Communities (ARIC) study (midlife:

RESULTS: At midlife, of the 296 Aβ-associated proteins, 8 were associated with incident dementia from midlife and late life in the ARIC study, and NPPB, IBSP, and THBS2 were replicated in the AGES-Reykjavik Study. At late life, of the 34 Aβ-associated proteins, none were associated with incident dementia at midlife, and kidney function explained 10%, 12%, and 0.2% of the variance of Aβ

CONCLUSIONS: This …

Safety Endpoints With Vadadustat Versus Darbepoetin Alfa In Patients With Non-Dialysis-Dependent Ckd: A Post Hoc Regional Analysis Of The Pro, Wolfgang C Winkelmayer, Susan Arnold, Steven K Burke, Glenn M Chertow, Kai-Uwe Eckardt, Alan G Jardine, Eldrin F Lewis, Wenli Luo, Kunihiro Matsushita, Peter A Mccullough, Todd Minga, Patrick S Parfrey

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: Prespecified analyses of the PRO

STUDY DESIGN: Phase 3, global, open-label, randomized, active-controlled clinical trial.

SETTING AND PARTICIPANTS: Erythropoiesis-stimulating agent-untreated patients with anemia and NDD-CKD.

INTERVENTION: Eligible patients were randomized 1:1 to receive vadadustat or darbepoetin alfa.

OUTCOMES: The primary safety end point was time to first MACE. Secondary safety end points included time to first expanded MACE (MACE plus hospitalization for heart failure or thromboembolic event, excluding vascular access thrombosis).

RESULTS: In the non-US/non-Europe region, there was a higher proportion of patients with baseline estimated glomerular filtration rate (eGFR) level of ≤10 mL/min/1.73 m

LIMITATIONS: Different …

Extracellular Vesicle-Packaged Ilk From Mesothelial Cells Promotes Fibroblast Activation In Peritoneal Fibrosis, Qiang Huang, Yuxiang Sun, Long Peng, Juan Sun, Zixin Sha, Hongchun Lin, Yongjie Li, Canming Li, Huiqun Li, Hongli Shang, Yanxu Chen, Xianrui Dou, Zhaoyong Hu, Zengchun Ye, Hui Peng

Faculty, Staff and Students Publications

Progressive peritoneal fibrosis and the loss of peritoneal function often emerged in patients undergoing long-term peritoneal dialysis (PD), resulting in PD therapy failure. Varieties of cell-cell communications among peritoneal cells play a significant role in peritoneal fibrogenesis. Extracellular vesicles (EVs) have been confirmed to involve in intercellular communication by transmitting proteins, nucleic acids or lipids. However, their roles and functional mechanisms in peritoneal fibrosis remain to be determined. Using integrative analysis of EV proteomics and single-cell RNA sequencing, we characterized the EVs isolated from PD patient's effluent and revealed that mesothelial cells are the main source of EVs in PD …

On-Campus Mental Health Service Use Among College Students With Autism: A Case Study Applying The Andersen Behavioral Model Of Health Services Use, Estella C. Lilyquist

Electronic Theses and Dissertations

The unique set of impairments and limitations presented by students with autism spectrum disorder (ASD) make the accessing of campus-based nonacademic resources more difficult and complicated than their typically developed peers. Each year, the rate of students entering college with disabilities continues to grow, but their mental well-being is relatively poor. The purpose of this qualitative case study was to apply the conceptual framework of the Andersen behavioral model of health services use (ABMHSU) to the experiences of college students with ASD to understand and predict their utilization of campus-provided mental health resources. The participants were seven college students with …

Enhancement Of Tki Sensitivity In Lung Adenocarcinoma Through M6a-Dependent Translational Repression Of Wnt Signaling By Circ-Fbxw7, Kai Li, Zi Yang Peng, Rui Wang, Xiang Li, Ning Du, Da Peng Liu, Jia Zhang, Yun Feng Zhang, Lei Ma, Ye Sun, Shou Ching Tang, Hong Ren, Yi Ping Yang, Xin Sun

School of Medicine Faculty Publications

Background: Tyrosine kinase inhibitors (TKIs) that specifically target mutational points in the EGFR gene have significantly reduced suffering and provided greater relief to patients with lung adenocarcinoma (LUAD). The third-generation EGFR-TKI, Osimertinib, has been successfully employed in clinical treatments to overcome resistance to both original and acquired T790M and L858R mutational points. Nevertheless, the issue of treatment failure response has emerged as an insurmountable problem. Methods: By employing a combination of multiple and integrated approaches, we successfully identified a distinct population within the tumor group that plays a significant role in carcinogenesis, resistance, and recurrence. Our research suggests that addressing …