Critical Care Commons^™

Early Immune Factors Associated With The Development Of Post-Acute Sequelae Of Sars-Cov-2 Infection In Hospitalized And Non-Hospitalized Individuals, Jacqueline M Leung, Michelle J Wu, Pouya Kheradpour, Chen Chen, Katherine A Drake, Gary Tong, Vanessa K Ridaura, Howard C Zisser, William A Conrad, Natalia Hudson, Jared Allen, Christopher Welberry, Celine Parsy-Kowalska, Isabel Macdonald, Victor F Tapson, James N Moy, Christopher R Defilippi, Ivan O Rosas, Mujeeb Basit, Jerry A Krishnan, Sairam Parthasarathy, Bellur S Prabhakar, Mirella Salvatore, Charles C Kim

Faculty, Staff and Students Publications

BACKGROUND: Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to post-acute sequelae of SARS-CoV-2 (PASC) that can persist for weeks to years following initial viral infection. Clinical manifestations of PASC are heterogeneous and often involve multiple organs. While many hypotheses have been made on the mechanisms of PASC and its associated symptoms, the acute biological drivers of PASC are still unknown.

METHODS: We enrolled 494 patients with COVID-19 at their initial presentation to a hospital or clinic and followed them longitudinally to determine their development of PASC. From 341 patients, we conducted multi-omic profiling on peripheral blood …

Anesthetic Management Of A Patient With Renal Cell Carcinoma-Associated Venous Thrombosis And Massive Transfusion, Gary Zhang, Ryan Palacios, Jamal Hasoon, Christopher L Robinson, Anvinh Nguyen

Faculty, Staff and Students Publications

A 53-year-old male with a history of multiple deep venous thromboses (DVTs) underwent a right open radical nephrectomy with inferior vena cava (IVC) thrombectomy in the context of renal cell carcinoma (RCC)-associated venous thrombosis. Imaging and renal biopsy revealed a diagnosis of RCC with non-occlusive thrombosis of the left renal vein and occlusive thrombosis of the infrarenal IVC. The major risks of concern for the procedure included thrombus embolization from surgical manipulation and massive bleeding. Intraoperatively, the patient experienced significant hemorrhage requiring massive transfusion protocol. The purpose of this case report is to emphasize the importance of multidisciplinary involvement, intraoperative …

How To Peer Review A Neurology Education Manuscript, Daniel G Di Luca, Steven M Lazar, Preeta Gupta, Marie Charmaine S Lukban, Cole Crowson, Dara V F Albert, Jeremy J Moeller, Andres Fernandez, Andrew M Southerland, Zachary London

Faculty, Staff and Students Publications

Peer review is an essential process in scientific research, ensuring the comprehensiveness, accuracy, and suitability of manuscripts for publication. Neurology education research differs from biomedical clinical research in several ways. These differences encompass specific paradigms, the use of theoretical frameworks, and different methodological approaches. Despite the high number of studies and journal publications on neurology education, there is a dearth of resources and guidance on how to perform a formal review on this specific literature. This article aims to review the distinctive features of neurology education from clinical research while proposing an organizational framework and model for performing peer reviews …

Interventricular Septal Hematoma Complicating Left Branch Bundle Lead Implantation: Treatment By Covered Stent, César Del Castillo, Jorge Van-Grieken, Marco Coello, Carlos Torres-Herrera, Barbara Clericus, Daniel Requena, Arnulfo Begazo, Franco Appiani, Boris Kuzmicic, Paola Varleta

Faculty, Staff and Students Publications

We present a female patient with heart failure with reduced ejection fraction who underwent left bundle branch cardiac resynchronization therapy. Left bundle branch lead implantation was complicated with septal branch perforation causing an iatrogenic coronary fistula complicated by septal hematoma formation and development of shock. Occlusion by covered stents was successfully achieved.

Corrigendum To “Phenotypes Of Disease Severity In A Cohort Of Hospitalized Covid-19 Patients: Results From The Impacc Study” [Ebiomedicine 83 (2022) 104208], Al Ozonoff, Joanna Schaenman, Naresh Doni Jayavelu, Carly E Milliren, Carolyn S Calfee, Charles B Cairns, Monica Kraft, Lindsey R Baden, Albert C Shaw, Florian Krammer, Harm Van Bakel, Denise A Esserman, Shanshan Liu, Ana Fernandez Sesma, Viviana Simon, David A Hafler, Ruth R Montgomery, Steven H Kleinstein, Ofer Levy, Chris Bime, Elias K Haddad, David J Erle, Bali Pulendran, Kari C Nadeau, Mark M Davis, Catherine L Hough, William B Messer, Nelson I Agudelo Higuita, Jordan P Metcalf, Mark A Atkinson, Scott C Brakenridge, David Corry, Farrah Kheradmand, Lauren I R Ehrlich, Esther Melamed, Grace A Mccomsey, Rafick Sekaly, Joann Diray-Arce, Bjoern Peters, Alison D Augustine, Elaine F Reed, Matthew C Altman, Patrice M Becker, Nadine Rouphael, Impacc Study Group Members

Faculty, Staff and Students Publications

No abstract provided.

Resuscitative Endovascular Balloon Occlusion Of The Aorta And Resuscitative Thoracotomy Are Associated With Similar Outcomes In Traumatic Cardiac Arrest, Ezra Y Koh, Erin E Fox, Charles E Wade, Thomas M Scalea, Charles J Fox, Ernest E Moore, Bryan C Morse, Kenji Inaba, Eileen M Bulger, David E Meyer

Faculty, Staff and Student Publications

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive alternative to resuscitative thoracotomy (RT) for patients with hemorrhagic shock. However, the potential benefits of this approach remain subject of debate. The aim of this study was to compare the outcomes of REBOA and RT for traumatic cardiac arrest.

Methods: A planned secondary analysis of the United States Department of Defense-funded Emergent Truncal Hemorrhage Control study was performed. Between 2017 and 2018, a prospective observational study of noncompressible torso hemorrhage was conducted at six Level I trauma centers. Patients were dichotomized by REBOA or RT, and baseline …

Contemporary Use Of Coronary Physiology In Cardiology, Ayman Elbadawi, Ramy Sedhom, Mohamed Ghoweba, Abdelazeem Mohamed Etewa, Waleed Kayani, Faisal Rahman

Faculty, Staff and Students Publications

Coronary angiography has a limited ability to predict the functional significance of intermediate coronary lesions. Hence, physiological assessment of coronary lesions, via fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR), has been introduced to determine their functional significance. An accumulating body of evidence has consolidated the role of physiology-guided revascularization, particularly among patients with stable ischemic heart disease. The use of FFR or iFR to guide decision-making in patients with stable ischemic heart disease and intermediate coronary lesions received a class I recommendation from major societal guidelines. Nevertheless, the role of coronary physiology testing is less clear among certain …

Job Characteristics That Enrich Clinician-Educators’ Career: A Theory-Informed Exploratory Survey, M Hossein Tcharmtchi, Shelley Kumar, Jennifer Rama, Brian Rissmiller, Danny Castro, Satid Thammasitboon

Faculty, Staff and Students Publications

Clinician educators (CEs) play a vital role in helping academic institutions achieve the missions of patient care, education and research. The driving forces that motivate pediatric CEs in professional growth and personal satisfaction remain unexplored. An exploratory survey research to investigate the job characteristics and factors that motivate CEs to pursue professional growth with personal satisfaction. Using the Job Characteristics Model (JCM) as a framework, we developed a 22-item survey comprised of the JCM derived Job Diagnostic Survey, Global Job Satisfaction scales and demographics. We collected data from January 2020 to March 2020 from self-identified pediatric CEs (with and without …

Metabolic Dysfunction, Triglyceride-Glucose Index, And Risk Of Severe Asthma Exacerbation, Kristen A Staggers, Charles Minard, Michelle Byers, Drew A Helmer, Tianshi David Wu

Faculty, Staff and Students Publications

BACKGROUND: Metabolic conditions may worsen asthma. There is a need to define a composite biomarker of metabolic dysfunction that has relevance to asthma outcomes.

OBJECTIVE: To determine the association of the triglyceride-glucose index (TyG), a biomarker of metabolic syndrome and insulin resistance, with risk of severe asthma exacerbation.

METHODS: A 5-year retrospective cohort of patients with asthma receiving health care from the US Veterans Health Administration from January 1, 2015, to December 31, 2019, was constructed. Fasting TyG values were extracted. Patients were followed for a severe asthma exacerbation, defined as an asthma-related corticosteroid prescription fill or an emergency encounter …

Tlr7 Promotes Smoke-Induced Experimental Lung Damage Through The Activity Of Mast Cell Tryptase, Gang Liu, Tatt Jhong Haw, Malcolm R Starkey, Ashleigh M Philp, Stelios Pavlidis, Christina Nalkurthi, Prema M Nair, Henry M Gomez, Irwan Hanish, Alan Cy Hsu, Elinor Hortle, Sophie Pickles, Joselyn Rojas-Quintero, Raul San Jose Estepar, Jacqueline E Marshall, Richard Y Kim, Adam M Collison, Joerg Mattes, Sobia Idrees, Alen Faiz, Nicole G Hansbro, Ryutaro Fukui, Yusuke Murakami, Hong Sheng Cheng, Nguan Soon Tan, Sanjay H Chotirmall, Jay C Horvat, Paul S Foster, Brian Gg Oliver, Francesca Polverino, Antonio Ieni, Francesco Monaco, Gaetano Caramori, Sukhwinder S Sohal, Ken R Bracke, Peter A Wark, Ian M Adcock, Kensuke Miyake, Don D Sin, Philip M Hansbro

Faculty, Staff and Students Publications

Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when wild-type mice are treated with the mast cell stabilizer, cromolyn. Furthermore, therapeutic treatment with anti-TLR7 monoclonal antibody suppresses CS-induced emphysema, experimental COPD and accumulation of pulmonary mast cells in mice. …

Plasma Metabolomics And Quantitative Interstitial Abnormalities In Ever-Smokers, Bina Choi, Raúl San José Estépar, Suneeta Godbole, Jeffrey L Curtis, Jennifer M Wang, Rubén San José Estépar, Ivan O Rosas, Jared R Mayers, Brian D Hobbs, Craig P Hersh, Samuel Y Ash, Meilan K Han, Russell P Bowler, Kathleen A Stringer, George R Washko, Wassim W Labaki

Faculty, Staff and Students Publications

BACKGROUND: Quantitative interstitial abnormalities (QIA) are an automated computed tomography (CT) finding of early parenchymal lung disease, associated with worse lung function, reduced exercise capacity, increased respiratory symptoms, and death. The metabolomic perturbations associated with QIA are not well known. We sought to identify plasma metabolites associated with QIA in smokers. We also sought to identify shared and differentiating metabolomics features between QIA and emphysema, another smoking-related advanced radiographic abnormality.

METHODS: In 928 former and current smokers in the Genetic Epidemiology of COPD cohort, we measured QIA and emphysema using an automated local density histogram method and generated metabolite profiles …

Sex And Gender In Copd And Asthma, Joan B Soriano, Francesca Polverino

Faculty, Staff and Students Publications

No abstract provided.

Does Chronic Obstructive Pulmonary Disease Originate From Different Cell Types?, Yohannes Tesfaigzi, Jeffrey L Curtis, Irina Petrache, Francesca Polverino, Farrah Kheradmand, Ian M Adcock, Stephen I Rennard

Faculty, Staff and Students Publications

The onset of chronic obstructive pulmonary disease (COPD) is heterogeneous, and current approaches to define distinct disease phenotypes are lacking. In addition to clinical methodologies, subtyping COPD has also been challenged by the reliance on human lung samples from late-stage diseases. Different COPD phenotypes may be initiated from the susceptibility of different cell types to cigarette smoke, environmental pollution, and infections at early stages that ultimately converge at later stages in airway remodeling and destruction of the alveoli when the disease is diagnosed. This perspective provides discussion points on how studies to date define different cell types of the lung …

A Case Report Of Anesthesia-Induced Diffuse Alveolar Hemorrhage Presenting To The Emergency Department, Daniel Yiu, Christopher Stephens, Jacquelyn Mccullough, Lesley Osborn

Faculty, Staff and Student Publications

Introduction: The inhaled anesthetic sevoflurane is an uncommon etiology of diffuse alveolar hemorrhage (DAH). As DAH typically presents in the inpatient, postoperative setting, it has been infrequently reported in the anesthesiology literature and, to our knowledge, has not been reported in the emergency medicine literature to date.

Case report: We describe the presentation of a young, healthy male in respiratory distress to a busy urban emergency department (ED) after an outpatient surgical procedure. We highlight the etiology of post-anesthesia DAH and the acute management of this rare diagnosis in the ED.

Conclusion: With outpatient surgical centers becoming an increasingly popular …

Hidroadenocarcinoma Mimicking Epidermal Inclusion Cyst Of The Palm, Connor L Zale, Sean Kelly, Kevin Krul

Faculty, Staff and Student Publications

Hidradenocarcinoma is a rare malignant tumor of sweat glands of the skin that has been reported several times in the hand. We report a case of hidradenocarcinoma of the palm in a 55-year-old woman that presented as a painless volar hand mass. A staged rotational forearm flap was used after resection.

Vertebro-Vertebral Fistula Occlusion Using A Woven Endobridgetm-Device, Rasmus Holmboe Dahl, Mohammad Ghasemi-Rad, Vagn Eskesen, Susanne Christiansen Frevert, Christine Sølling, Goetz Benndorf

Faculty, Staff and Students Publications

Vertebro-vertebral fistulas (VVFs) are vascular lesions that may develop after trauma or spontaneously in association with connective tissue disorders. We present a rare case of a post-traumatic VVF in a young patient presenting with a painless swelling and a bruit in her left upper neck. Digital subtraction angiography showed an arteriovenous fistula between the left vertebral artery (VA) and the vertebral venous plexus with significant steal phenomenon. Endovascular therapy was performed using a Woven EndoBridgeTM (WEB)-device combined with coils that allowed preservation of the VA. The patient fully recovered from her symptoms and follow-up imaging showed stable occlusion. In conclusion, …

Inflammatory Activity Of Epithelial Stem Cell Variants From Cystic Fibrosis Lungs Is Not Resolved By Cftr Modulators, Shan Wang, Suchan Niroula, Ashley Hoffman, Melika Khorrami, Melina Khorrami, Feng Yuan, Grace N Gasser, Soon Choi, Bovey Liu, Justin Li, Mark L Metersky, Matthew Vincent, Christopher P Crum, Richard C Boucher, Harry Karmouty-Quintana, Howard J Huang, Ajay Sheshadri, Burton F Dickey, Kalpaj R Parekh, John F Engelhardt, Frank D Mckeon, Wa Xian

Faculty, Staff and Student Publications

Rationale

CFTR (cystic fibrosis transmembrane conductance regulator) modulator drugs restore function to mutant channels in patients with cystic fibrosis (CF) and lead to improvements in body mass index and lung function. Although it is anticipated that early childhood treatment with CFTR modulators will significantly delay or even prevent the onset of advanced lung disease, lung neutrophils and inflammatory cytokines remain high in patients with CF with established lung disease despite modulator therapy, underscoring the need to identify and ultimately target the sources of this inflammation in CF lungs.

Objectives

To determine whether CF lungs, like chronic obstructive pulmonary disease (COPD) …

Improving Outcomes For Infants After Cardiopulmonary Bypass Surgery For Congenital Heart Disease: A Commentary On Recent Randomized Controlled Trials, Luregn J Schlapbach, Kristen S Gibbons, Warwick Butt, Prince J Kannankeril, Jennifer S Li, Kevin D Hill

Faculty, Staff and Students Publications

The recent NITRIC and STRESS trials demonstrate opportunities to perform pragmatic large randomized trials in congenital heart disease. We discuss lessons learnt from these trials which can inform future trial design and conduct in the field of pediatric heart surgery.

A Myeloid Program Associated With Covid-19 Severity Is Decreased By Therapeutic Blockade Of Il-6 Signaling, Jason A Hackney, Haridha Shivram, Jason Vander Heiden, Chris Overall, Luz Orozco, Xia Gao, Eugene Kim, Nathan West, Aditi Qamra, Diana Chang, Arindam Chakrabarti, David F Choy, Alexis J Combes, Tristan Courau, Gabriela K Fragiadakis, Arjun Arkal Rao, Arja Ray, Jessica Tsui, Kenneth Hu, Nicholas F Kuhn, Matthew F Krummel, David J Erle, Kirsten Kangelaris, Aartik Sarma, Zoe Lyon, Carolyn S Calfee, Prescott G Woodruff, Rajani Ghale, Eran Mick, Ashley Byrne, Beth Shoshana Zha, Charles Langelier, Carolyn M Hendrickson, Monique G P Van Der Wijst, George C Hartoularos, Tianna Grant, Raymund Bueno, David S Lee, John R Greenland, Yang Sun, Richard Perez, Anton Ogorodnikov, Alyssa Ward, Chun Jimmie Ye, Thiru Ramalingam, Jacqueline M Mcbride, Fang Cai, Anastasia Teterina, Min Bao, Larry Tsai, Ivan O Rosas, Aviv Regev, Sharookh B Kapadia, Rebecca N Bauer, Carrie M Rosenberger

Faculty, Staff and Students Publications

Altered myeloid inflammation and lymphopenia are hallmarks of severe infections. We identified the upregulated EN-RAGE gene program in airway and blood myeloid cells from patients with acute lung injury from SARS-CoV-2 or other causes across 7 cohorts. This program was associated with greater clinical severity and predicted future mechanical ventilation and death. EN-RAGEhi myeloid cells express features consistent with suppressor cell functionality, including low HLA-DR and high PD-L1. Sustained EN-RAGE program expression in airway and blood myeloid cells correlated with clinical severity and increasing expression of T cell dysfunction markers. IL-6 upregulated many EN-RAGE program genes in monocytes in vitro. …

Revisiting Asthma Obstructive Sleep Apnea Overlap: Current Knowledge And Future Needs, Damini Saxena, Ikuyo Imayama, Muhammad Adrish

Faculty, Staff and Students Publications

Asthma and obstructive sleep apnea are highly prevalent conditions with a high cost burden. In addition to shared risk factors, existing data suggest a bidirectional relationship between asthma and OSA, where each condition can impact the other. Patients with asthma often complain of sleep fragmentation, nocturnal asthma symptoms, daytime sleepiness, and snoring. The prevalence of OSA increases with asthma severity, as evidenced by multiple large studies. Asthma may lower the threshold for arousal in OSA, resulting in the hypopnea with arousal phenotype. Epidemiologic studies in adults have shown that OSA is associated with worse asthma severity, increased frequency of exacerbation, …

Peripheral Levels Of The Brain-Derived Neurotrophic Factor In Coronary Artery Disease: A Systematic Review And Meta-Analysis, Parnian Shobeiri, Amir Hossein Behnoush, Amirmohammad Khalaji, Antonio Lucio Teixeira, Nima Rezaei

Faculty, Staff and Student Publications

BACKGROUND: Among its functions, brain-derived neurotrophic factor (BDNF) regulates endothelial and macrophage activation, possibly playing a role in atherosclerotic plaque pathophysiology. Given contradicting reports, this study sought to investigate whether blood levels of BDNF differed between patients with coronary heart disease (CHD) and controls.

METHODS: We explored PubMed, Embase, Web of Science, and Cochrane Library for studies comparing BDNF blood levels in patients with CHD and controls. Random-effect meta-analysis was conducted to calculate the standardized mean differences (SMD) and 95% confidence intervals (CI). The Newcastle-Ottawa scale was used to evaluate the quality of included articles, and statistical analyses were conducted …

Obesity Paradox Or Hypoxia Preconditioning: How Obstructive Sleep Apnea Modifies The Obesity-Mi Relationship, Amir Sharafkhaneh, Ritwick Agrawal, Vijay Nambi, Ahmed Bahammam, Javad Razjouyan

Faculty, Staff and Students Publications

OBJECTIVES: The objective of this study was to evaluate the interaction between obesity and obstructive sleep apnea on acute MI in hospital mortality.

METHODS: This retrospective cohort study utilized Veterans Health Administration data from years 1999-2020. Participants were categorized according to their body mass index (BMI) to non-obese (BMI

RESULTS: Among 72,036 veterans with acute-MI hospitalization, individuals with obesity and obstructive sleep apnea (OB-SA) had the lowest in-hospital mortality rate (1.0%) compared to those without obesity and obstructive sleep apnea (nOB-nSA, 2.8%), with obesity but without obstructive sleep apnea (OB-nSA, 2.4%), and with obesity and obstructive sleep apnea (nOB-SA, 1.4%). …

The Pre-Adaptation Of A Stroke-Specific Self-Management Program Among Older Adults, Timothy Reistetter, Kimberly Hreha, Julianna M Dean, Monique R Pappadis, Rachel R Deer, Chih-Ying Li, Ickpyo Hong, Annalisa Na, Sara Nowakowski, Hashem M Shaltoni, Suresh K Bhavnani

Faculty, Staff and Students Publications

Objectives:

Managing multimorbidity as aging stroke patients is complex; standard self-management programs necessitate adaptations. We used visual analytics to examine complex relationships among aging stroke survivors’ comorbidities. These findings informed pre-adaptation of a component of the Chronic Disease Self-Management Program.

Methods:

Secondary analysis of 2013–2014 Medicare claims with stroke as an index condition, hospital readmission within 90 days (n=42,938), and 72 comorbidities. Visual analytics identified patient subgroups and co-occurring comorbidities. Guided by the framework for reporting adaptations and modifications to evidence-based interventions (FRAME), an interdisciplinary team developed vignettes that highlighted multimorbidity to customize the self-management program.

Results:

There were five …

Molecular Insights Using Spatial Transcriptomics Of The Distal Lung In Congenital Diaphragmatic Hernia, Krithika Lingappan, Oluyinka O Olutoye, Abiud Cantu, Manuel Eliezer Cantu Gutierrez, Nahir Cortes-Santiago, J D Hammond, Jamie Gilley, Joselyn Rojas Quintero, Hui Li, Francesca Polverino, Jason P Gleghorn, Sundeep G Keswani

Faculty, Staff and Students Publications

Abnormal pulmonary vascular development and function in congenital diaphragmatic hernia (CDH) is a significant factor leading to pulmonary hypertension. The lung is a very heterogenous organ and has marked cellular diversity that is differentially responsive to injury and therapeutic agents. Spatial transcriptomics provides the unmatched capability of discerning the differences in the transcriptional signature of these distinct cell subpopulations in the lung with regional specificity. We hypothesized that the distal lung parenchyma (selected as a region of interest) would show a distinct transcriptomic profile in the CDH lung compared with control (normal lung). We subjected lung sections obtained from male …

Updates On The Immune Cell Basis Of Hepatic Ischemia-Reperfusion Injury, Mi Jeong Heo, Ji Ho Suh, Kyle L Poulsen, Cynthia Ju, Kang Ho Kim

Faculty, Staff and Student Publications

Liver ischemia-reperfusion injury (IRI) is the main cause of organ dysfunction and failure after liver surgeries including organ transplantation. The mechanism of liver IRI is complex and numerous signals are involved but cellular metabolic disturbances, oxidative stress, and inflammation are considered the major contributors to liver IRI. In addition, the activation of inflammatory signals exacerbates liver IRI by recruiting macrophages, dendritic cells, and neutrophils, and activating NK cells, NKT cells, and cytotoxic T cells. Technological advances enable us to understand the role of specific immune cells during liver IRI. Accordingly, therapeutic strategies to prevent or treat liver IRI have been …

Cocaine Use Disorder Effects On Blood Oxytocin Levels And Oxtr Dna Methylation, Manassés Soares Souza, Breno Sanvicente-Vieira, Aline Zaparte, Talita Baptista, Maria Aparecida Nagai, Flávia Rotea Mangone, Ana Carolina Pavanelli, Thiago Wendt Viola, Rodrigo Grassi-Oliveira

School of Medicine Faculty Publications

Substance use disorders have been associated with alterations in the oxytocinergic system, but few studies have investigated both the peptide and epigenetic mechanisms potentially implicated in the regulation of oxytocin receptor. In this study, we compared plasma oxytocin and blood DNA methylation in the OXTR gene between people with and without cocaine use disorder (CUD). We measured the oxytocin levels of 51 people with CUD during acute abstinence and of 30 healthy controls using an enzyme immunoassay. The levels of DNA methylation in four CpG sites at exon III of the OXTR gene were evaluated in a subsample using pyrosequencing. …

Transcriptomic And Proteomic Assessment Of Tocilizumab Response In A Randomized Controlled Trial Of Patients Hospitalized With Covid-19, Haridha Shivram, Jason A Hackney, Carrie M Rosenberger, Anastasia Teterina, Aditi Qamra, Olusegun Onabajo, Jacqueline Mcbride, Fang Cai, Min Bao, Larry Tsai, Aviv Regev, Ivan O Rosas, Rebecca N Bauer

Faculty, Staff and Students Publications

High interleukin (IL)-6 levels are associated with greater COVID-19 severity. IL-6 receptor blockade by tocilizumab (anti-IL6R; Actemra) is used globally for the treatment of severe COVID-19, yet a molecular understanding of the therapeutic benefit remains unclear. We characterized the immune profile and identified cellular and molecular pathways modified by tocilizumab in peripheral blood samples from patients enrolled in the COVACTA study, a phase 3, randomized, double-blind, placebo-controlled trial of the efficacy and safety of tocilizumab in hospitalized patients with severe COVID-19. We identified markers of inflammation, lymphopenia, myeloid dysregulation, and organ injury that predict disease severity and clinical outcomes. Proteomic …

Shp2 Promotes Sarcoidosis Severity By Inhibiting Skp2-Targeted Ubiquitination Of Tbet In Cd8+ T Cells, Sherly I Celada, Clarice X Lim, Alexandre F Carisey, Scott A Ochsner, Carlos F Arce Deza, Praveen Rexie, Fernando Poli De Frias, Rafael Cardenas-Castillo, Francesca Polverino, Markus Hengstschläger, Konstantin Tsoyi, Neil J Mckenna, Farrah Kheradmand, Thomas Weichhart, Ivan O Rosas, Luc Van Kaer, Lindsay J Celada

Faculty, Staff and Students Publications

Sarcoidosis is an interstitial lung disease (ILD) characterized by IFNγ and TBET dysregulation. Although one-third of patients progress from granulomatous inflammation to severe lung damage, the molecular mechanisms underlying this process remain unclear. Here, we report that pharmacological inhibition of phosphorylated SH2 containing protein tyrosine phosphatase-2 (pSHP2), a facilitator of aberrant IFNγ levels, decreases large granuloma formation and macrophage infiltration in the lungs of mice with sarcoidosis-like disease. Positive treatment outcomes were dependent on the effective enhancement of TBET ubiquitination within CD8+ T cells. Mechanistically, our findings identified a previously unknown post-translational modification (PTM) pathway in which the E3 F-box …

The Impact Of Covid-19 On Carotid-Femoral Pulse Wave Velocity: A Systematic Review And Meta-Analysis, Iwona Jannasz, Michal Pruc, Mansur Rahnama-Hezavah, Tomasz Targowski, Robert Olszewski, Stepan Feduniw, Karolina Petryka, Lukasz Szarpak

Faculty, Staff and Students Publications

COVID-19 is a complex multisystemic disease that can result in long-term complications and, in severe cases, death. This study investigated the effect of COVID-19 on carotid–femoral pulse wave velocity (cfPWV) as a measurement to evaluate its impact on arterial stiffness and might help predict COVID-19-related cardiovascular (CV) complications. PubMed, Web of Science, Embase, and the Cochrane Library were searched for relevant studies, and meta-analysis was performed. The study protocol was registered in PROSPERO (nr. CRD42023434326). The Newcastle–Ottawa Quality Scale was used to evaluate the quality of the included studies. Nine studies reported cfPWV among COVID-19 patients and control groups. The …

Understanding Ip3r Channels: From Structural Underpinnings To Ligand-Dependent Conformational Landscape, Mariah R Baker, Guizhen Fan, Vikas Arige, David I Yule, Irina I Serysheva

Faculty, Staff and Student Publications

Inositol 1,4,5-trisphosphate receptors (IP3Rs) are ubiquitously expressed large-conductance Ca2+-permeable channels predominantly localized to the endoplasmic reticulum (ER) membranes of virtually all eukaryotic cell types. IP3Rs work as Ca2+ signaling hubs through which diverse extracellular stimuli and intracellular inputs are processed and then integrated to result in delivery of Ca2+ from the ER lumen to generate cytosolic Ca2+ signals with precise temporal and spatial properties. IP3R-mediated Ca2+ signals control a vast repertoire of cellular functions ranging from gene transcription and secretion to the more enigmatic brain activities such as learning and memory. IP3Rs open and release Ca2+ when they bind both …