Critical Care Commons^™

A Novel Humanized Chi3l1 Blocking Antibody Attenuates Acetaminophen-Induced Liver Injury In Mice, Leike Li, Yankai Wen, Daniel Wrapp, Jongmin Jeong, Peng Zhao, Wei Xiong, Constance Lynn Atkins, Zhao Shan, Deng Hui, Jason S Mclellan, Ningyan Zhang, Cynthia Ju, Zhiqiang An

Faculty, Staff and Student Publications

Acetaminophen (APAP) overdose is a leading cause of acute liver injury in the USA. The chitinase 3-like-1 (Chi3l1) protein contributes to APAP-induced liver injury (AILI) by promoting hepatic platelet recruitment. Here, we report the development of a Chi3l1-targeting antibody as a potential therapy for AILI. By immunizing a rabbit successively with the human and mouse Chi3l1 proteins, we isolated cross-reactive monoclonal antibodies (mAbs) from single memory B cells. One of the human and mouse Chi3l1 cross-reactive mAbs was humanized and characterized in both

The Rising Tide Of Revisional Surgery: Tracking Changes In Index Cases Among Bariatric-Accredited Fellowships, Lincoln N Strickland, Erika Y Faraoni, Wei Ruan, Xiaoyi Yuan, Holger K Eltzschig, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense desmoplastic stroma that impedes drug delivery, reduces parenchymal blood flow, and suppresses the anti-tumor immune response. The extracellular matrix and abundance of stromal cells result in severe hypoxia within the tumor microenvironment (TME), and emerging publications evaluating PDAC tumorigenesis have shown the adenosine signaling pathway promotes an immunosuppressive TME and contributes to the overall low survival rate. Hypoxia increases many elements of the adenosine signaling pathway, resulting in higher adenosine levels in the TME, further contributing to immune suppression. Extracellular adenosine signals through 4 adenosine receptors (Adora1, Adora2a, Adora2b, Adora3). Of …

Cytological Diagnosis Of Pilomatrixoma And Its Diagnostic Pitfalls, Sabina Khan, Inara Abeer, Musharraf Husain, Sujata Jetley

Faculty, Staff and Student Publications

BACKGROUND: Pilomatrixoma (PMX) is a relatively uncommon benign cutaneous neoplasm arising from skin adnexa. It presents as a subcutaneous asymptomatic nodule mostly in the head and neck region and is frequently misdiagnosed by the clinicians. Although easily diagnosed on histopathology, the cytologic features of PMX are less distinctive, depending on the stage and evolution of disease and may mimic other benign or even malignant lesions.

AIM: To study the cyto-morphological features of this uncommon neoplasm and identify its potential diagnostic pitfalls on fine needle aspiration cytology (FNAC).

MATERIAL AND METHODS: Archival records of histopathologically diagnosed Pilomatrixoma were analyzed during study …

Henry Gas Solubility Optimization Double Machine Learning Classifier For Neurosurgical Patients, Diana T Mosa, Amena Mahmoud, John Zaki, Shaymaa E Sorour, Shaker El-Sappagh, Tamer Abuhmed

Faculty, Staff and Student Publications

This study aims to predict head trauma outcome for Neurosurgical patients in children, adults, and elderly people. As Machine Learning (ML) algorithms are helpful in healthcare field, a comparative study of various ML techniques is developed. Several algorithms are utilized such as k-nearest neighbor, Random Forest (RF), C4.5, Artificial Neural Network, and Support Vector Machine (SVM). Their performance is assessed using anonymous patients' data. Then, a proposed double classifier based on Henry Gas Solubility Optimization (HGSO) is developed with Aquila optimizer (AQO). It is implemented for feature selection to classify patients' outcome status into four states. Those are mortality, morbidity, …

Contribution Of Metabolic Cell Swelling On Microcirculatory Perfusion In Septic Shock, Charles E. Payne

Theses and Dissertations

Sepsis, a systemic immunological response that leads to organ-dysfunction, the development of septic shock, and death has mortality rate of 15-25%. A subset of sepsis, septic shock, has an in-hospital mortality rate of 30-50%. Sepsis and its treatment are the most expensive healthcare problem in the United States with the US Agency for Healthcare Research and Quality estimating annual costs over $20 billion. Hypoxia experienced in septic shock induces metabolic cell and tissue swelling leading to further microcirculatory dysfunction and poor tissue perfusion. Reversing metabolic cell swelling corrects these perfusion defects. Two models were used in rats to induce septic …

Cerebrospinal Fluid Biomarkers Provide Evidence For Kidney-Brain Axis Involvement In Cerebral Malaria Pathogenesis, Andrea L Conroy, Dibyadyuti Datta, Robert O Opoka, Anthony Batte, Paul Bangirana, Adnan Gopinadhan, Kagan A Mellencamp, Ayse Akcan-Arikan, Richard Idro, Chandy C John

Faculty, Staff and Students Publications

INTRODUCTION: Cerebral malaria is one of the most severe manifestations of malaria and is a leading cause of acquired neurodisability in African children. Recent studies suggest acute kidney injury (AKI) is a risk factor for brain injury in cerebral malaria. The present study evaluates potential mechanisms of brain injury in cerebral malaria by evaluating changes in cerebrospinal fluid measures of brain injury with respect to severe malaria complications. Specifically, we attempt to delineate mechanisms of injury focusing on blood-brain-barrier integrity and acute metabolic changes that may underlie kidney-brain crosstalk in severe malaria.

METHODS: We evaluated 30 cerebrospinal fluid (CSF) markers …

Characterization Of Propofol Use For Non-Procedural Sedation In A Pediatric Intensive Care Unit, Jenna Wood Bartlett, Brooke N Curry, Matthew A Musick, Megan Mckee Moore

Faculty, Staff and Students Publications

OBJECTIVE: Given the limited literature describing propofol use in pediatric patients, this study aimed to describe the dosing and duration of propofol infusions for non-procedural sedation in the pediatric intensive care unit (PICU). The secondary objectives were to describe the change in concomitant sedative requirements from the 24-hour period before propofol initiation to the 24-hour period after discontinuation of propofol and to review the frequency of adverse events.

METHODS: This retrospective descriptive cohort study evaluated children 1 month to less than 18 years old who received a continuous infusion of propofol for non-procedural sedation in the PICU between May 2018 …

Rapid Response Events With Multiple Triggers Are Associated With Poor Outcomes In Children, Erin M Kritz, Jenilea K Thomas, Nawara S Alawa, Elit B Hadad, Danielle M Guffey, Aarti C Bavare

Faculty, Staff and Students Publications

OBJECTIVE: We describe the characteristics and outcomes of pediatric rapid response team (RRT) events within a single institution, categorized by reason for RRT activation (RRT triggers). We hypothesized that events with multiple triggers are associated with worse outcomes.

PATIENTS AND METHODS: Retrospective 3-year study at a high-volume tertiary academic pediatric hospital. We included all patients with index RRT events during the study period.

RESULTS: Association of patient and RRT event characteristics with outcomes including transfers to ICU, need for advanced cardiopulmonary support, ICU and hospital length of stay (LOS), and mortality were studied. We reviewed 2,267 RRT events from 2,088 …

Case Report: Selexipag In Pediatric Pulmonary Hypertension: Initiation, Transition, And Titration, Jenna M Faircloth, Neelam D Bhatt, Corey A Chartan, Ryan D Coleman, Natalie Villafranco, Fadel E Ruiz, Raysa Morales-Demori, Elise Whalen, Erin Ely, Rozmeen Fombin, Nidhy P Varghese

Faculty, Staff and Students Publications

Selexipag, a selective prostacyclin receptor agonist, is approved for treating pulmonary arterial hypertension in WHO Group 1 adult patients. Compared to parenteral prostacyclin formulations, selexipag offers a significant improvement in patient’s and caregiver’s quality of life because of its oral formulation, frequency of administration, and mechanism of action. Although experience in the pediatric population is limited and selexipag is not FDA-approved for use in the pediatric pulmonary hypertension population, many US pediatric centers are expanding the use of this therapy to this younger population. We report our institution's experience in the use of selexipag to treat pulmonary hypertension in children …

Characteristics Of Type 2 Diabetes In Female And Male Youth, Beatriz Castillo Rodriguez, Marcela Astudillo, Mustafa Tosur, Ahmad Rafaey, Siripoom Mckay, Fida Bacha, Ashok Balasubramanyam, Maria J Redondo

Faculty, Staff and Students Publications

The incidence of type 2 diabetes in children is rising and carries a worse prognosis than in adults. The influence of sex on pediatric type 2 diabetes outcomes has not been well investigated. We studied 715 youth with type 2 diabetes diagnosed at a median age of 13.7 years and compared sex differences in demographic, clinical, and laboratory characteristics within the first year of diagnosis. Females diagnosed with type 2 diabetes were younger and at a higher stage of pubertal development than males, yet presented with lower A1Cs, a lower prevalence of diabetic ketoacidosis, and higher HDL cholesterol levels.

Acute Thrombotic Thrombocytopenic Purpura: Rare And Life-Threatening Side Effect Of Recent Bnt-162b2 Covid-19 Vaccination, Jay Patel, Muhammad Umair Jahngir, Ahmad Abdulzahir, Ismael Rodriguez

HCA Healthcare Journal of Medicine

Thrombotic thrombocytopenic purpura (TTP) is a rare, potentially life-threatening disorder characterized by uncontrolled and spontaneous clot formation throughout the body. Known secondary causes of TTP include malignancy, bone marrow transplantation, pregnancy, various medications, and HIV infection. TTP in the setting of COVID-19 vaccination is rare and not well reported. Reported cases have been confined primarily to the AstraZeneca and Johnson and Johnson COVID-19 Vaccines. TTP in the setting of Pfizer BNT-162b2 vaccination has only recently been reported. We present a patient with no obvious risk factors for TTP who presented with acute altered mental status and was found to have …

Ratio Of Vascular Pedicle Width And Thoracic Diameter To Differentiate Cardiogenic And Non-Cardiogenic Pulmonary Edema, Rahmi Afifi, Achmad Fachri, Amir Sjarifuddin Madjid, Joedo Prihartono, Marcel Prasetyo, Andreas Christian

Makara Journal of Health Research

Background: Excess intravascular volume evaluation is essential in the intensive care unit (ICU); however, clinical information to differentiate cardiogenic and non-cardiogenic pulmonary edema has been proven ineffective. Thus, this study aimed to distinguish cardiogenic from non-cardiogenic pulmonary edema using the ratio of vascular pedicle width (VPW) to thoracic diameter (VPTR).

Methods: This cross-sectional study was conducted based on secondary data from chest radiographs of 100 patients with clinical symptoms of pulmonary edema in the ICU from January 2013 to December 2015. Cardiogenic and non-cardiogenic pulmonary edema were distinguished using VPW and cardiothoracic ratio measurements (CTR). VPTR was measured …

Hif1a-Dependent Induction Of Alveolar Epithelial Pfkfb3 Dampens Acute Lung Injury, Christine U Vohwinkel, Nana Burns, Ethan Coit, Xiaoyi Yuan, Eszter K Vladar, Christina Sul, Eric P Schmidt, Peter Carmeliet, Kurt Stenmark, Eva S Nozik, Rubin M Tuder, Holger K Eltzschig

Faculty, Staff and Student Publications

Acute lung injury (ALI) is a severe form of lung inflammation causing acute respiratory distress syndrome in patients. ALI pathogenesis is closely linked to uncontrolled alveolar inflammation. We hypothesize that specific enzymes of the glycolytic pathway could function as key regulators of alveolar inflammation. Therefore, we screened isolated alveolar epithelia from mice exposed to ALI induced by injurious ventilation to assess their metabolic responses. These studies pointed us toward a selective role for isoform 3 of the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3). Pharmacologic inhibition or genetic deletion of Pfkfb3 in alveolar epithelia (Pfkfb3loxP/loxP SPC-ER-Cre+ mice) was associated with profound increases in ALI during …

Investigating The Effectiveness Of Prehospital Recognition And Administration Of Intravenous Antibiotics In Septic Patients, Laura Keane, Ian Peterson

Physician Assistant Capstones, 2020-current

Objective: To compare the 30-day mortality rate of suspected sepsis patients who received prehospital (Emergency Medical Services- EMS) antibiotic administration in an ambulance as compared to antibiotic administration in the hospital. Design: Systematic literature review. Methods: Research was conducted in PubMed and Google Scholar with the search terms: sepsis, antibiotics, prehospital, EMS, ambulance. The 3 articles selected were chosen after removing articles not from a randomized control trial, no antibiotic administration, and not a free article. Results: From our meta-analysis of the three studies, we concluded that providing antibiotics before arriving at the hospital for patients with suspected septic infections. …

Sunsetting Excessive Chest X-Rays In An Intensive Care Unit: A Quality Improvement Project, Cassandra Sweet

Doctors of Nursing Practice (DNP) Final Projects, 2020-current

In the cardiovascular service line at an academic medical center in the southeastern United States, obtaining daily chest x-rays still occurred despite evidence that it is unnecessary and possibly even harmful. This quality improvement project was implemented in a 24-bed Cardiovascular Intensive Care Unit and 20-bed acute care unit, together considered to be the cardiac service line. Using the implementation framework of the Model for Improvement and Plan/Do/Study/Act, a guideline that outlines appropriate times to obtain a chest x-ray based on the American College of Radiology’s appropriateness criteria was created. Daily chest x-rays were eliminated and replaced with an on-demand …

Characterization Of Pulmonary Vascular Remodeling And Microrna-126-Targets In Copd-Pulmonary Hypertension, Khushboo Goel, Nicholas Egersdorf, Amar Gill, Danting Cao, Scott D Collum, Soma S Jyothula, Howard J Huang, Maor Sauler, Patty J Lee, Susan Majka, Harry Karmouty-Quintana, Irina Petrache

Faculty, Staff and Student Publications

BACKGROUND: Despite causing increased morbidity and mortality, pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) patients (COPD-PH) lacks treatment, due to incomplete understanding of its pathogenesis. Hypertrophy of pulmonary arterial walls and pruning of the microvasculature with loss of capillary beds are known features of pulmonary vascular remodeling in COPD. The remodeling features of pulmonary medium- and smaller vessels in COPD-PH lungs are less well described and may be linked to maladaptation of endothelial cells to chronic cigarette smoking (CS). MicroRNA-126 (miR126), a master regulator of endothelial cell fate, has divergent functions that are vessel-size specific, supporting the survival …

Trib3 Mediates Fibroblast Activation And Fibrosis Though Interaction With Atf4 In Ipf, Lan Wang, Wenyu Zhao, Cong Xia, Zhongzheng Li, Weiming Zhao, Kai Xu, Ningdan Wang, Hui Lian, Ivan O Rosas, Guoying Yu

Faculty, Staff and Students Publications

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by fibroblast activation, excessive deposition of extracellular matrix, and progressive scarring; the pathogenesis remains elusive. The present study explored the role of Tribbles pseudokinase 3 (TRIB3), a well-known stress and metabolic sensor, in IPF. TRIB3 is down-regulated in the lungs of IPF patients in comparison to control subjects. Deficiency of TRIB3 markedly inhibited A549 epithelial cells’ proliferation and migration, significantly reducing wound healing. Conversely, overexpression of TRIB3 promoted A549 cell proliferation and transmigration while it inhibited its apoptosis. Meanwhile, overexpressed TRIB3 inhibited fibroblast activation and decreased ECM …

Unfavorable Social Determinants Of Health Are Associated With Higher Burden Of Financial Toxicity Among Patients With Atherosclerotic Cardiovascular Disease In The Us: Findings From The National Health Interview Survey, Javier Valero-Elizondo, Zulqarnain Javed, Rohan Khera, Mauricio E. Tano, Ramzi Dudum, Isaac Acquah, Adnan A. Hyder, Julia Andrieni, Garima Sharma, Salim S. Virani

Office of the Provost

Background: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of financial toxicity, defined as excess financial strain from healthcare, in the US. Identifying factors that put patients at greatest risk can help inform more targeted and cost-effective interventions. Specific social determinants of health (SDOH) such as income are associated with a higher risk of experiencing financial toxicity from healthcare, however, the associations between more comprehensive measures of cumulative social disadvantage and financial toxicity from healthcare are poorly understood.
Methods: Using the National Health Interview Survey (2013-17), we assessed patients with self-reported ASCVD. We identified 34 discrete SDOH items, across 6 …

A Unified Model Of Age-Related Cardiovascular Disease, Michael Fossel, Joe Bean, Nina Khera, Mikhail G Kolonin

Faculty, Staff and Student Publications

Despite progress in biomedical technologies, cardiovascular disease remains the main cause of mortality. This is at least in part because current clinical interventions do not adequately take into account aging as a driver and are hence aimed at suboptimal targets. To achieve progress, consideration needs to be given to the role of cell aging in disease pathogenesis. We propose a model unifying the fundamental processes underlying most age-associated cardiovascular pathologies. According to this model, cell aging, leading to cell senescence, is responsible for tissue changes leading to age-related cardiovascular disease. This process, occurring due to telomerase inactivation and telomere attrition, …

Nursing Considerations For Post-Traumatic Amnesia After A Traumatic Brain Injury, Hannah Grant

Senior Honors Theses

A period known as post-traumatic amnesia (PTA) often follows a traumatic brain injury (TBI). PTA is characterized by anterograde and retrograde amnesia, confusion, disorientation, and agitation. The duration and severity of PTA is a key indicator of the long-term prognosis after a TBI, so proper assessment and nursing care of a PTA patient is crucial. TBIs range from mild to severe, but primarily affect the fronto-temporal lobes. In PTA, both neural lesions and white matter damage within the parahippocampal region can cause PTA. A nurse must perform a thorough assessment of a TBI patient, but, since PTA is a key …