Medical Specialties Commons^™

Atrial Cardiomyocyte-Restricted Cleavage Of Gasdermin D Promotes Atrial Arrhythmogenesis, Yue Yuan, Pascal Martsch, Xiaohui Chen, Enrique Martinez, Luge Li, Jia Song, Theresa Poppenborg, Florian Bruns, Jong Hwan Kim, Markus Kamler, James F Martin, Issam Abu-Taha, Dobromir Dobrev, Na Li

Faculty, Staff and Students Publications

Background and aims: Enhanced inflammatory signalling causally contributes to atrial fibrillation (AF) development. Gasdermin D (GSDMD) is an important downstream effector of several inflammasome pathways. However, the role of GSDMD, particularly the cleaved N-terminal (NT)-GSDMD, in non-immune cells remains elusive. This study aimed to elucidate the function of NT-GSDMD in atrial cardiomyocytes (ACMs) and determine its contribution to atrial arrhythmogenesis.

Methods: Human atrial appendages were used to assess the protein levels and localization. A modified adeno-associated virus 9 was employed to establish ACM-restricted overexpression of NT-GSDMD in mice.

Results: The cleavage of GSDMD was enhanced in ACMs of AF patients. …

The Burden Of Steatotic Liver Disease Before And During The Covid-19 Pandemic: Correspondence To Editorial On “Current Burden Of Steatotic Liver Disease And Fibrosis Among Adults In The United States, 2017–2023”, Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Rohit Loomba, Aijaz Ahmed

Faculty, Staff and Students Publications

No abstract provided.

Soluble Mesothelin-Related Peptide As A Prognosticator In Pleural Mesothelioma Patients Receiving Checkpoint Immunotherapy, Sonali Mitra, Hee-Jin Jang, Allen Kuncheria, Sung Wook Kang, Jong Min Choi, Ji Seon Shim, Claire Lee, Priyanka Ranchod, Peter Jindra, Maheshwari Ramineni, Meera Patel, R Taylor Ripley, Shawn S Groth, Shanda H Blackmon, Bryan M Burt, Hyun-Sung Lee

Faculty, Staff and Students Publications

Background: Immune checkpoint therapy (ICT) has significantly impacted the treatment of malignant pleural mesothelioma (MPM). Despite some promising results from combination therapies, nearly half of MPM patients do not benefit, underscoring the urgent need for reliable predictive biomarkers. This study assesses the prognostic value of serum soluble mesothelin-related peptide (SMRP) and PD-L1 levels in MPM patients receiving ICT.

Methods: We conducted a retrospective analysis of 125 MPM patients treated with ICT by measuring pre-ICT serum levels of SMRP and PD-L1. We also examined the correlation of these serum levels with tumor mRNA expressions of mesothelin and PD-L1. Both univariable and …

Sialidase Fusion Protein Protects Against Influenza Infection In A Cigarette Smoke-Induced Model Of Copd, Cheng-Yen Chang, Dominique Armstrong, John M Knight, Trevor V Gale, Stephen Hawley, Max Wang, Nancy Chang, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

First- and secondhand smokers are at an increased risk for influenza virus (IFV)-related respiratory failure and death. Despite approved influenza antiviral treatments, there is an unmet need for treatments that can improve outcomes in populations at risk for respiratory failure, including tobacco users with Chronic Obstructive Pulmonary Disease (COPD). Here we show that the sialidase fusion protein, DAS181, reduced viral burden, mitigated inflammation, and attenuated lung function loss, consistent with broad-spectrum anti-influenza responses in a mouse model of COPD and IFV-A infection. Treatment with DAS181 reprogramed the sialic acid-binding immunoglobulin-like lectins (Siglecs) in alveolar macrophages, increased expression of phagocytic marker …

Insights Into Protection Against Mycobacterium Tuberculosis Infection: Time To Officially Confirm Another Phenotype?, Todia P Setiabudiawan, Philip C Hill, Andrew R Dinardo, Reinout Van Crevel

Faculty, Staff and Students Publications

Immune correlates of protection against infection with Mycobacterium tuberculosis (Mtb) remain elusive. In this issue of the JCI, Dallmann-Sauer and authors demonstrate that lack of tuberculin skin test (TST) and interferon γ release assay (IGRA) conversion among people with HIV despite years-long Mtb exposure is associated with alveolar lymphocytosis, including specific poly-cytotoxic T cells, and M1-type alveolar macrophages with a stronger ex vivo response to the pathogen. Studies in these rare individuals, termed "TB resisters" and in tuberculosis household contacts who are repeatedly IGRA negative in the months after a specific exposure event (known as "early clearers") help elucidate manipulatable …

Rapid Diagnostic Sequencing Of Stool Dna Using Targeted Nanopore Sequencing In Patients With A Pulmonary Tuberculosis Diagnosis, Tara Ness, Nontobeko Maphalala, Wethusonkhe Khumalo, Doctor Sibandze, Abigail Seeger, Maia Madison, Anca Vasiliu, Durbin Mulengwa, Clement Gascua, Mangaliso Ziyane, Sindisiwe Dlamini, Gugu Maphalala, Eric Bortz, Alexander Kay, Christoph Lange, Viola Dreyer, Tanja Niemann, Stefan Niemann, Andrew Dinardo, Anna Mandalakas, Stool4tb Global Partnership

Faculty, Staff and Students Publications

Background: Approximately 1.25 million individuals died of tuberculosis in 2023, in part due to ineffective treatment. In patients with paucibacillary tuberculosis, microbiologic confirmation and drug resistance testing via respiratory specimens is challenging; hence, stool samples are increasingly used for microbiologic confirmation. Targeted next-generation sequencing (tNGS) of stool DNA may improve detection of drug-resistant (DR) tuberculosis, helping patients receive appropriate treatments.

Methods: We assessed the ability of a nanopore tNGS approach using stool to detect drug resistance in a prospective, nested cohort of consecutive participants in Eswatini with pulmonary tuberculosis confirmed via sputum culture or sputum GeneXpert Ultra from 2020 to …

Unveiling Racial Disparities In Prostate Cancer Using An Integrative Genomic And Transcriptomic Analysis, Abdalla Elbialy, Akshay Sood, Shang-Jui Wang, Peng Wang, Ahmed Fadiel, Anil V Parwani, Steven Huang, Gennady Shvets, Nagireddy Putluri, Jenny Li, Xuefeng Liu

Faculty, Staff and Students Publications

Prostate cancer exhibits significant racial disparities, with African American (AA) individuals showing ∼64% higher incidence and 2.3 times greater mortality rates compared to their Caucasian (CA) counterparts. Understanding the complex interplay of genetic, environmental, lifestyle, socioeconomic, and healthcare access factors is crucial for developing effective interventions to reduce this disproportionate burden.

This study aims to uncover the genetic and transcriptomic differences driving these disparities through a comprehensive analysis using RNA sequencing (RNA-seq) and exome sequencing of prostate cancer tissues from both Black and White patients.

Our transcriptomics analysis revealed enhanced activity in pathways linked to immune response and cellular interactions …

Warm-Ischemia And Cold Storage Induced Modulation Of Ferroptosis Observed In Human Hearts Donated After Circulatory Death And Brain Death, Shiyi Li, Katherine V Nordick, Abdussalam E Elsenousi, Rishav Bhattacharya, Randall P Kirby, Adel M Hassan, Camila Hochman-Mendez, Todd K Rosengart, Kenneth K Liao, Nandan K Mondal

Faculty, Staff and Students Publications

We investigated ferroptosis, a type of programmed cell death mechanism, in human hearts donated after brain death (DBD) and those donated after circulatory death (DCD), focusing on warm ischemia time (WIT) and cold storage. A total of 24 hearts were procured, with six from the DBD group and 18 from the DCD group. The DCD group was divided into three subgroups, each containing six hearts, based on different WITs of 20, 40, and 60 min. All procured hearts were placed in cold storage for up to 6 h. Left ventricular biopsies were performed at 0, 2, 4, and 6 h. …

Playbook Workflow Builder: Interactive Construction Of Bioinformatics Workflows, Daniel J B Clarke, John Erol Evangelista, Zhuorui Xie, Giacomo B Marino, Anna I Byrd, Mano R Maurya, Sumana Srinivasan, Keyang Yu, Varduhi Petrosyan, Matthew E Roth, Miroslav Milinkov, Charles Hadley King, Jeet Kiran Vora, Jonathon Keeney, Christopher Nemarich, William Khan, Alexander Lachmann, Nasheath Ahmed, Alexandra Agris, Juncheng Pan, Srinivasan Ramachandran, Eoin Fahy, Emmanuel Esquivel, Aleksandar Mihajlovic, Bosko Jevtic, Vuk Milinovic, Sean Kim, Patrick Mcneely, Tianyi Wang, Eric Wenger, Miguel A Brown, Alexander Sickler, Yuankun Zhu, Sherry L Jenkins, Philip D Blood, Deanne M Taylor, Adam C Resnick, Raja Mazumder, Aleksandar Milosavljevic, Shankar Subramaniam, Avi Ma'ayan

Faculty, Staff and Students Publications

The Playbook Workflow Builder (PWB) is a web-based platform to dynamically construct and execute bioinformatics workflows by utilizing a growing network of input datasets, semantically annotated API endpoints, and data visualization tools contributed by an ecosystem of collaborators. Via a user-friendly user interface, workflows can be constructed from contributed building-blocks without technical expertise. The output of each step of the workflow is added into reports containing textual descriptions, figures, tables, and references. To construct workflows, users can click on cards that represent each step in a workflow, or construct workflows via a chat interface that is assisted by a large …

Time Tracking And Comparison Of Genetic Counseling Tasks In Inpatient And Outpatient Settings, Alexandra Osborne, Emily Magness Bland, Callie Diamonstein, Kristen Fishler

Faculty, Staff and Students Publications

Genetic counselors (GCs) practice in critical care settings. Some GCs have full-time inpatient roles, while most GCs who see inpatients do so as needed or on a rotating schedule in addition to seeing patients in an outpatient setting. Few studies have tracked and compared the amount of time it takes GCs to perform tasks in the inpatient and outpatient settings. Genetic counselors were invited to participate in this study via the National Society of Genetic Counselors research listserv. Participants completed an online survey asking how their role is structured and what types of support are available to them while seeing …

Primary Prevention Of Cardiovascular Disease In Asia: Challenges: A Narrative Review, Mayank Dalakoti, Norman H Y Lin, Jonathan Yap, Aaysha Cader, Prajapati Dipanker, Derek Lee, Raja Ezman Raja Shariff, Lucky Cuenza, Satoshi Honda, Vorn Malis, Haowen Jiang, Anish Hirachan, Misato Chimura, Tee Joo Yeo, Khung Keong Yeo, Jack Wei Chieh Tan, Jasper Tromp, Poay Huan Loh, Nicholas W S Chew, Scott Wong, Ching-Hui Sia, Benjamin Y Q Tan, Sofian Johar, Gregory Y H Lip, Eugene Yang, Salim S Virani, Steven Hageman, Hueiming Liu, Emanuele Di Angelantonio, Prabhakaran Dorairaj, Angela S Koh, Calvin Chin, Wael Al Mahmeed, Mark Y Chan, Roger Foo

Faculty, Staff and Students Publications

Importance: Asia is home to 60% of the world's population, including the world's 2 most populous countries, India (1.1B) and China (1.2B). With cardiovascular disease burden and mortality increasing, the role of preventive cardiology is increasingly important.

Observations: The challenges in addressing the cardiovascular disease burden in Asia include unique cardiometabolic features of the different populations, heterogeneity of risk factors among Asian countries, differing levels of health literacy and socioeconomic status, suboptimal infrastructure to support preventive care especially in the primary care sector, high out-of-pocket costs, and environmental pollution.

Conclusions: Asia is a large continent that comprises diverse populations with …

The Association Between County-Level Social Determinants Of Health And Cardio-Kidney-Metabolic Disease Attributed All-Cause Mortality In The Us: A Cross Sectional Analysis, Antoinette Cotton, Pedro Rvo Salerno, Salil V Deo, Salim S Virani, Khurram Nasir, Ian Neeland, Sanjay Rajagopalan, Naveed Sattar, Sadeer Al-Kindi, Yakov E Elgudin

Faculty, Staff and Students Publications

Background: The American Heart Association recently defined cardio-kidney-metabolic (CKM) syndrome as the intersection between metabolic, renal, and cardiovascular disease. Understanding the contemporary estimates of CKM related mortality in the US is essential for developing targeted public interventions.

Methods: We analyzed state-level and county-level CKM-associated all-cause mortality data (2010-2019) from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER). Median and interquartile (IQR) age-adjusted mortality rates (aaMR) per 100,000 were reported and linked with a multi-component metric for social deprivation: the Social Deprivation Index (SDI: range 0 - 100) grouped as: I: 0 - 25, II: 26 - 50, III: 51 …

Telehealth Is Effective In The Evaluation Of Individuals With Undiagnosed Rare Disorders: An Undiagnosed Diseases Network Study, Queenie K-G Tan, Allyn Mcconkie-Rosell, Rachel Mahoney, Rebecca C Spillmann, Kelly Schoch, Sirisak Chanprasert, Maria T Acosta, Camilo Toro, Jill A Rosenfeld, James P Orengo, Daryl A Scott, Jorge L Granadillo, Kathleen Sisco, Daniel J Wegner, Mustafa Tekin, Stephanie Bivona, Léshon Peart, Lance Rodan, Devon Bonner, Matthew T Wheeler, Jonathan A Bernstein, Maura Ruzhnikov, Undiagnosed Diseases Network, David R Adams, Fuki M Hisama, Vandana Shashi

Faculty, Staff and Students Publications

Patients with undiagnosed and/or rare disorders frequently manifest dysmorphic and neurological features. There is a lack of information on the effectiveness of telehealth in the evaluation of these disorders. We thus compared an unassisted virtual physical examination (PE) with an in-person PE in undiagnosed individuals and also assessed participant telehealth satisfaction. Twenty-six individuals enrolled in the Undiagnosed Diseases Network study underwent an in-home synchronous virtual PE, and a subsequent in-person PE, by the same clinician. The participants completed surveys on telehealth usability and provider empathy. On PE, general appearance and craniofacial features showed near perfect agreement (κ = 0.81-1.00) between …

Most Elderly Patients With Subclinical Hypothyroidism Do Not Need To Be Treated, Risheng Xu, Nicola Abate, Nalini Ram, Kristina Little

Faculty, Staff and Students Publications

Whether subclinical hypothyroidism should be treated in elderly patients (≥ 65 years) is controversial. The authors argue for a personalized, wait-and-see approach rather than universal treatment, pointing out that randomized clinical trials have not shown that levothyroxine treatment makes any difference in terms of hard clinical end points, quality of life, or hypothyroid symptom relief in elderly patients with this condition.

Career Choices For Graduates Of Combined Medicine-Pediatrics Residency Programs: A Multi-Year Survey, Anoop Agrawal, Michael Aronica, Michael Kisielewski, Benjamin Doolittle

Faculty, Staff and Students Publications

Background: Combined medicine-pediatrics training was formally established in 1967 by the American Board of Pediatrics and the American Board of Internal Medicine. More than 8000 physicians have completed dual training. Their career choices are not well-described.

Objective: To describe career choices among graduates of combined medicine-pediatrics training programs.

Methods: Nationally representative research surveys conducted each winter from 2017 to 2023 of combined medicine-pediatrics (Med-Peds) residency program directors (PDs), whose programs were (1) of continued accreditation status with the Accreditation Council for Graduate Medical Education (N = 77 to 80) and (2) members of the Medicine Pediatrics Program Directors Association. One …

Tardive Dyskinesia Versus Tardive Syndrome What Is In A Name?, Karen Frei, Alicia Scott, Stanley N Caroff, Joseph Jankovic, William Ondo, Leslie Citrome, Robert Hauser, Joseph H Friedman, Roongroj Bhidayasiri, Martha Sajatovic, Dennis Alters, Jonathan Meyer, Stuart Factor, E K Tan, G Remington, Ira Glick, Hubert Fernandez, Cynthia Comella, John Kane, Joseph Mcevoy, Delwyn Miller, Clement C Zai, J P Lindenmayer, Richard Trosch, Daniel D Truong

Faculty, Staff and Students Publications

No abstract provided.

Foraging Animals Use Dynamic Bayesian Updating To Model Meta-Uncertainty In Environment Representations, James Webb, Paul Steffan, Benjamin Y Hayden, Daeyeol Lee, Caleb Kemere, Matthew Mcginley

Faculty, Staff and Students Publications

Foraging theory predicts animal behavior in many contexts. In patch-based foraging behaviors, the marginal value theorem (MVT) gives the optimal strategy for deterministic environments whose parameters are fully known to the forager. In natural settings, environmental parameters exhibit variability and are only partially known to the animal based on its experience, creating uncertainty. Models of uncertainty in foraging are well established. However, natural environments also exhibit unpredicted changes in their statistics. As a result, animals must ascertain whether the currently observed quality of the environment is consistent with their internal models, or whether something has changed, creating meta-uncertainty. Behavioral strategies …

Neurd Offers Automated Proofreading And Feature Extraction For Connectomics, Brendan Celii, Stelios Papadopoulos, Zhuokun Ding, Paul G Fahey, Eric Wang, Christos Papadopoulos, Alexander B Kunin, Saumil Patel, J Alexander Bae, Agnes L Bodor, Derrick Brittain, Joann Buchanan, Daniel J Bumbarger, Manuel A Castro, Erick Cobos, Sven Dorkenwald, Leila Elabbady, Akhilesh Halageri, Zhen Jia, Chris Jordan, Dan Kapner, Nico Kemnitz, Sam Kinn, Kisuk Lee, Kai Li, Ran Lu, Thomas Macrina, Gayathri Mahalingam, Eric Mitchell, Shanka Subhra Mondal, Shang Mu, Barak Nehoran, Sergiy Popovych, Casey M Schneider-Mizell, William Silversmith, Marc Takeno, Russel Torres, Nicholas L Turner, William Wong, Jingpeng Wu, Szi-Chieh Yu, Wenjing Yin, Daniel Xenes, Lindsey M Kitchell, Patricia K Rivlin, Victoria A Rose, Caitlyn A Bishop, Brock Wester, Emmanouil Froudarakis, Edgar Y Walker, Fabian Sinz, H Sebastian Seung, Forrest Collman, Nuno Maçarico Da Costa, R Clay Reid, Xaq Pitkow, Andreas S Tolias, Jacob Reimer

Faculty, Staff and Students Publications

We are in the era of millimetre-scale electron microscopy volumes collected at nanometre resolution1,2. Dense reconstruction of cellular compartments in these electron microscopy volumes has been enabled by recent advances in machine learning3–6. Automated segmentation methods produce exceptionally accurate reconstructions of cells, but post hoc proofreading is still required to generate large connectomes that are free of merge and split errors. The elaborate 3D meshes of neurons in these volumes contain detailed morphological information at multiple scales, from the diameter, shape and branching patterns of axons and dendrites, down to the fine-scale …

Foundation Model Of Neural Activity Predicts Response To New Stimulus Types, Eric Y Wang, Paul G Fahey, Zhuokun Ding, Stelios Papadopoulos, Kayla Ponder, Marissa A Weis, Andersen Chang, Taliah Muhammad, Saumil Patel, Zhiwei Ding, Dat Tran, Jiakun Fu, Casey M Schneider-Mizell, Microns Consortium, R Clay Reid, Forrest Collman, Nuno Maçarico Da Costa, Katrin Franke, Alexander S Ecker, Jacob Reimer, Xaq Pitkow, Fabian H Sinz, Andreas S Tolias

Faculty, Staff and Students Publications

The complexity of neural circuits makes it challenging to decipher the brain’s algorithms of intelligence. Recent breakthroughs in deep learning have produced models that accurately simulate brain activity, enhancing our understanding of the brain’s computational objectives and neural coding. However, it is difficult for such models to generalize beyond their training distribution, limiting their utility. The emergence of foundation models1 trained on vast datasets has introduced a new artificial intelligence paradigm with remarkable generalization capabilities. Here we collected large amounts of neural activity from visual cortices of multiple mice and trained a foundation model to accurately predict neuronal responses …

Functional Connectomics Reveals General Wiring Rule In Mouse Visual Cortex, Zhuokun Ding, Paul G Fahey, Stelios Papadopoulos, Eric Y Wang, Brendan Celii, Christos Papadopoulos, Andersen Chang, Alexander B Kunin, Dat Tran, Jiakun Fu, Zhiwei Ding, Saumil Patel, Lydia Ntanavara, Rachel Froebe, Kayla Ponder, Taliah Muhammad, J Alexander Bae, Agnes L Bodor, Derrick Brittain, Joann Buchanan, Daniel J Bumbarger, Manuel A Castro, Erick Cobos, Sven Dorkenwald, Leila Elabbady, Akhilesh Halageri, Zhen Jia, Chris Jordan, Dan Kapner, Nico Kemnitz, Sam Kinn, Kisuk Lee, Kai Li, Ran Lu, Thomas Macrina, Gayathri Mahalingam, Eric Mitchell, Shanka Subhra Mondal, Shang Mu, Barak Nehoran, Sergiy Popovych, Casey M Schneider-Mizell, William Silversmith, Marc Takeno, Russel Torres, Nicholas L Turner, William Wong, Jingpeng Wu, Wenjing Yin, Szi-Chieh Yu, Dimitri Yatsenko, Emmanouil Froudarakis, Fabian Sinz, Krešimir Josić, Robert Rosenbaum, H Sebastian Seung, Forrest Collman, Nuno Maçarico Da Costa, R Clay Reid, Edgar Y Walker, Xaq Pitkow, Jacob Reimer, Andreas S Tolias

Faculty, Staff and Students Publications

Understanding the relationship between circuit connectivity and function is crucial for uncovering how the brain computes. In mouse primary visual cortex, excitatory neurons with similar response properties are more likely to be synaptically connected1–8; however, broader connectivity rules remain unknown. Here we leverage the millimetre-scale MICrONS dataset to analyse synaptic connectivity and functional properties of neurons across cortical layers and areas. Our results reveal that neurons with similar response properties are preferentially connected within and across layers and areas—including feedback connections—supporting the universality of ‘like-to-like’ connectivity across the visual hierarchy. Using a validated digital twin model, …

Predictors And Outcomes Of First Pass Efficacy In Posterior Circulation Strokes: Insights From Star Collaboration, Muhammad U Hafeez, Muhammed A Essibayi, Daniel Raper, Omar Tanweer, Mithun Sattur, Sami Al-Kasab, Joshua Burks, Robert Townsend, Diana Alsbrook, Travis Dumont, Min S Park, Nitin Goyal, Adam S Arthur, Ilko Maier, Justin Mascitelli, Robert Starke, Stacey Wolfe, Kyle Fargen, Alejandro Spiotta, Peter T Kan

Faculty, Staff and Students Publications

Background: First-pass efficacy (FPE) has been established as an important predictor of favorable functional outcomes after endovascular thrombectomy (ET) in anterior circulation strokes. In this retrospective cohort study, we investigate predictors and clinical outcomes of FPE in posterior circulation strokes (pcAIS).

Methods: The Stroke Thrombectomy and Aneurysm Registry database was used to identify pcAIS patients who achieved FPE. Their baseline characteristics and outcomes were compared with the non-FPE group. The primary outcome was a 90-day modified Rankin Scale (mRS) of 0-3. Univariate (UVA) and multivariate (MVA) analyses were done to evaluate predictors of FPE. Safety outcomes included distal emboli, vessel …

Key Decision-Making Factors In Pediatric Microtia Repair, Maya Guhan, Grace Anand, Yi-Chun Liu

Faculty, Staff and Students Publications

No abstract provided.

Obesity And Outcomes After Elective Thoracoabdominal Aortic Aneurysm Repair, Sanford Zeigler, Kyle W Blackburn, Ahmad Tabatabaeishoorijeh, Veronica A Glover, Susan Y Green, Marc R Moon, Scott A Lemaire, Joseph S Coselli

Faculty, Staff and Students Publications

Objective: Obesity can complicate surgical repair, but its relationship to outcomes after open thoracoabdominal aortic aneurysm (TAAA) repair remains uncertain. Therefore, we examined whether obesity is associated with greater operative risk after elective TAAA repair.

Methods: We retrospectively evaluated data from 2517 open, elective, single-practice TAAA repairs (from 1986 to 2023) and compared patients without obesity or underweight (body mass index [BMI] 18.6-29.9; n = 1977) with patients with obesity (BMI ≥30; n = 540 [21.5%]). Multivariable logistic regression modeling identified predictors of operative mortality in patients with obesity. We created propensity-matched cohorts (n = 540 pairs) and compared their …

Clinical Decision-Making About Immunosuppressive Treatment In Focal Segmental Glomerulosclerosis., Brooke Blazius, Jonathan P. Troost, Jeffrey B. Kopp, Rulan S. Parekh, Brenda Gillespie, Isabelle Ayoub, Mahmoud Kallash, Rasheed Gbadegesin, Pietro A. Canetta, Tarak Srivastava, Tracy E. Hunley, Katherine E. Twombley, Yonatan A. Peleg, Larry A. Greenbaum, Aftab S. Chishti, Carla M. Nester, Amy K. Mottl, Susan L. Hogan, Virginie Royal, Vivette D. D'Agati, Kimberly J. Reidy, Krzysztof Mucha, Julia Steinke, Simone Sanna-Cherchi, David T. Selewski, Dhruti P. Chen, C John Sperati, Ronald J. Falk, Howard Trachtman, Jason M. Kidd, Cure Glomerulonephropathy (Curegn) Study Consortium

Manuscripts, Articles, Book Chapters and Other Papers

RATIONALE & OBJECTIVE: Focal segmental glomerulosclerosis (FSGS) is a heterogeneous disorder with a high risk of progression to kidney failure. There are no approved therapies for FSGS, and futility of treatment is poorly defined. The Cure Glomerulonephropathy (CureGN) study offers the opportunity to describe the characteristics of participants who started immunosuppressive therapy (IST), never received IST, or in whom this treatment was discontinued.

STUDY DESIGN: An observational cohort.

SETTINGS & PARTICIPANTS: Participants enrolled in CureGN with FSGS and surveyed nephrologists.

INTERVENTIONS: The clinical and laboratory data from participants with FSGS who were enrolled in the CureGN observational cohort were reviewed …

Differential Impacts On Proteoglycan Expression In The Response To Lens Wounding In Reparative And Pro-Fibrotic Microenvironments, Janice L Walker, A. Sue Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Ex vivo lens epithelial explant cultures created through a technique that mimics cataract surgery provided an ideal model with which to compare the impacts on proteoglycan expression in the response to wounding in both reparative promoting and pro-fibrotic microenvironments. On their native basement membrane capsule the injured lens epithelium undergoes regenerative repair, with the wound closing within a few days. Their migration across the wound area is led by a population of activated lens resident immune cells. The same leader cell population also directs the wounded epithelium to migrate off the outside edges of the lens explant across the surrounding …

Gastroesophageal Reflux And Gastrointestinal Symptoms After Metabolic And Bariatric Surgery In Adolescents: An 8-Year Follow-Up Analysis, John B Rode, Suhail A Zeineddin, Jane C Khoury, Todd M Jenkins, Stephanie R Sisley, Anita P Courcoulas, Justin R Ryder, Marc P Michalsky, Thomas H Inge

Children’s Nutrition Research Center Staff Publications

Importance: Vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) are the most commonly performed metabolic and bariatric surgery (MBS) procedures in adolescents and adults. Despite their safety and effectiveness, there is concern over postoperative gastrointestinal symptoms (GIS), especially gastroesophageal reflux symptoms (GERS), in those undergoing VSG.

Objective: To evaluate the long-term prevalence of GIS in adolescents who underwent RYGB or VSG.

Design, setting, and participants: This is a prospective, multicenter, observational cohort study at five academic referral centers in the United States. Patients were enrolled from February 28, 2007, through December 30, 2011. The analysis included 228 adolescents: 161 …

Quality-Of-Care Measures For Cardio-Oncology: An Ic-Os And Acc Cardio-Oncology Leadership Council Perspective, Vijay U Rao, Anita Deswal, Daniel Lenihan, Susan Dent, Teresa Lopez-Fernandez, Alexander R Lyon, Ana Barac, Nicolas Palaskas, Ming Hui Chen, Hector R Villarraga, Diego Sadler, Courtney M Campbell, Kerry Skurka, Matt J Wagner, Matthias Totzeck, Kathryn J Ruddy, Paul Heidenreich, Randal Thomas, Daniel Addison, Sarju Ganatra, Richard Cheng, David Reeves, Arjun K Ghosh, Joerg Herrmann

Children’s Nutrition Research Center Staff Publications

This document serves as a perspective on quality assessments in the discipline of cardio-oncology. We aim to define the current landscape, identify needs for quality and outcome improvements, and propose a roadmap for establishing viable metrics to improve patient care. Specifically, this document: 1) addresses the current lack of measurable high-quality metrics in cardio-oncology and their implications; 2) highlights needs and topic-specific barriers; 3) illustrates the process and application of a measurable quality metric; and 4) provides a framework to demonstrate measurable value for the growing population of patients with cancer and cardiovascular diseases.

Demographic Clinical Trial Diversity Assessment Methods: Use Of Real-World Data, Hua Chen, Nnadozie Emechebe, Sudeep Karve, Leon Raskin, Jailene Leal, Ning Cheng, Wendy Sebby, Kim Ribeiro, Samuel Crawford

Children’s Nutrition Research Center Staff Publications

Diversity in clinical trials is defined by the inclusion of clinical trial participants from various demographic groups that are representative of the broader population impacted by a disease state. Diversity in clinical trials is critical in identifying potential differences in safety and efficacy of treatments across races, ethnicities, ages, sexes, or other variables. In the United States, clinical trial diversity is often benchmarked against US Census data, which may limit the representativeness of patient demographics in clinical trials. Disease-specific, demographic estimates from real-world data (RWD) can facilitate benchmarking of clinical trials, support trial enrollment and the development of trial diversity …

Suppression Of Hypothalamic Oestrogenic Signal Sustains Hyperprolactinemia And Metabolic Adaptation In Lactating Mice, Meng Yu, Bing Feng, Jonathan C Bean, Qianru Zhao, Yongjie Yang, Hailan Liu, Yongxiang Li, Benjamin P Eappen, Hesong Liu, Longlong Tu, Kristine M Conde, Mengjie Wang, Xi Chen, Na Yin, Darah Ave Threat, Nathan Xu, Junying Han, Peiyu Gao, Yi Zhu, Darryl L Hadsell, Yang He, Pingwen Xu, Yanlin He, Chunmei Wang

Faculty, Staff and Students Publications

17β-oestradiol (E2) inhibits overeating and promotes brown adipose tissue (BAT) thermogenesis, whereas prolactin (PRL) does the opposite. During lactation, the simultaneous decline in E2 and surge in PRL contribute to maternal metabolic adaptations, including hyperphagia and suppressed BAT thermogenesis. However, the underlying neuroendocrine mechanisms remain unclear. Here, we find that oestrogen receptor alpha (ERα)-expressing neurons in the medial basal hypothalamus (MBH), specifically the arcuate nucleus of the hypothalamus and the ventrolateral subdivision of the ventromedial hypothalamus (vlVMH), are suppressed during lactation. Deletion of ERα from MBH neurons in virgin female mice induces metabolic phenotypes characteristic of lactation, including hyperprolactinemia, hyperphagia …

Acute Kidney Injury In Severe Alcohol-Associated Hepatitis Treated With Anakinra Plus Zinc Or Prednisone, Kavish R Patidar, Wanzhu Tu, Thomas G Cotter, Douglas A Simonetto, Amon Asgharpour, Muhammad Y Jan, Qing Tang, Yunpeng Yu, Yang Li, Moyinoluwa Taiwo, Prashanth Thevkar Nagesh, Srinivasan Dasarathy, Patrick S Kamath, Craig J Mcclain, Naga Chalasani, Gyongyi Szabo, Ramon Bataller, Mack Mitchell, Wajahat Z Mehal, Laura E Nagy, Vijay H Shah, Samer Gawrieh, Arun J Sanyal

Faculty, Staff and Students Publications

Background and aims: In a recent trial, patients with severe alcohol-associated hepatitis treated with anakinra plus zinc (A+Z) had lower survival and higher acute kidney injury (AKI) rates versus prednisone (PRED). We characterize the clinical factors and potential mechanisms associated with AKI development in that trial.

Approach and results: Data from 147 participants in a multicenter randomized clinical trial (74 A+Z, 73 PRED) were analyzed. AKI, AKI phenotypes, and kidney injury biomarkers were compared between participants who did/did not develop AKI in the 2 treatment arms. Multivariable competing risk analyses were performed to identify baseline risk factors for incident AKI, …