Critical Care Commons^™

Plasma Extracellular Vesicle Proteins As Promising Noninvasive Biomarkers For Diagnosis Of Idiopathic Pulmonary Fibrosis, Raju S R Adduri, Kai Cai, Karen Velasco-Alzate, Ravikiran Vasireddy, Jeffrey W Miller, Sergio Poli De Frías, Fernando Poli De Frías, Yasushi Horimasu, Hiroshi Iwamoto, Noboru Hattori, Yingze Zhang, Kevin F Gibson, Anoop K Pal, Zhe Chen, Daniela Nicastro, Li Li, Sujith Cherian, Lynette M Sholl, Sreerama Shetty, Harrison Ndetan, Anthony H Maeda, Maria A Planchart Ferretto, Gary M Hunninghake, David A Schwartz, Daniel J Kass, Ivan O Rosas, Nagarjun V Konduru

Faculty, Staff and Students Publications

High-resolution computed tomography (HRCT) imaging is critical for diagnostic evaluation of Idiopathic Pulmonary Fibrosis (IPF). However, several other interstitial lung diseases (ILDs) often exhibit radiologic pattern similar to IPF on HRCT making the diagnosis of the disease difficult. Therefore, biomarkers that distinguish IPF from other ILDs can be a valuable aid in diagnosis. Using mass spectrometry, we performed proteomic analysis of plasma extracellular vesicles (EVs) in patients diagnosed with IPF, chronic hypersensitivity pneumonitis, nonspecific interstitial pneumonitis, and healthy subjects. A five-protein signature was identified by lasso regression and was validated in an independent cohort using ELISA. The five-protein signature derived …

Calculating Differences In Surrogate Lung Perfusion Measurements Between Smokers And Nonsmokers As A Biomarker To Assess Their Potentials For Developing Chronic Obstructive Pulmonary Disease, A Prakash, A Nowacki, Y K. Liu, J Cisneros-Paz, Girish Nair, E Castillo

Conference Presentation Abstracts

Purpose: COPD (chronic obstructive pulmonary disease) is a collection of lung diseases that complicates breathing and causes irreversible lung damage. Given that it is a progressive disease, early detection is crucial for managing its symptoms. We recently developed a method for calculating pulmonary blood mass change (PBMC) apparent on paired inhale/exhale non-contrast computed tomography (CT) scans as a quantitative surrogate for lung perfusion. Our long term objective is to develop a PBMC biomarker for predicting COPD progression. As a first step, we hypothesize that PBMC is significantly lower for non-COPD smokers versus non-COPD non-smokers. Methods: CT scans from 77 healthy …

Difficult Or Impossible Facemask Ventilation In Children With Difficult Tracheal Intubation: A Retrospective Analysis Of The Pedi Registry, Annery G Garcia-Marcinkiewicz, Lisa K Lee, Bishr Haydar, John E Fiadjoe, Clyde T Matava, Pete G Kovatsis, James Peyton, Mary L Stein, Raymond Park, Brad M Taicher, Thomas W Templeton

Faculty, Staff and Student Publications

BACKGROUND: Difficult facemask ventilation is perilous in children whose tracheas are difficult to intubate. We hypothesised that certain physical characteristics and anaesthetic factors are associated with difficult mask ventilation in paediatric patients who also had difficult tracheal intubation.

METHODS: We queried a multicentre registry for children who experienced "difficult" or "impossible" facemask ventilation. Patient and case factors known before mask ventilation attempt were included for consideration in this regularised multivariable regression analysis. Incidence of complications, and frequency and efficacy of rescue placement of a supraglottic airway device were also tabulated. Changes in quality of mask ventilation after injection of a …

Thiazolidinedione Use And Retinal Fluid In The Comparison Of Age-Related Macular Degeneration Treatments Trials, Jason Q Core, Peiying Hua, Ebenezer Daniel, Juan E Grunwald, Glenn Jaffe, Maureen G Maguire, Gui-Shuang Ying, Comparison Of Age-Related Macular Degeneration Treatments Trials (Catt) Research Group

Faculty, Staff and Student Publications

BACKGROUND: Thiazolidinediones, commonly used antidiabetic medications, have been associated with an increased risk of development of diabetic macular oedema and increased vascular endothelial cell permeability. Macular neovascularisation in age-related macular degeneration (AMD) and associated fluid leakage may be influenced by thiazolidinediones. This study aims to determine the association between thiazolidinedione usage and retinal morphological outcomes or visual acuity (VA) in patients treated with bevacizumab or ranibizumab for neovascular AMD (nAMD).

METHODS: Secondary analysis of data from the Comparison of Age-related Macular Degeneration Treatments Trials. Participant self-reported diabetes status and thiazolidinedione usage at baseline. VA, intraretinal, subretinal and subretinal pigment epithelium …

Immunometabolism At The Heart Of Cardiovascular Disease, Matthew Deberge, Rajesh Chaudhary, Samantha Schroth, Edward B Thorp

Faculty, Staff and Student Publications

Immune cell function among the myocardium, now more than ever, is appreciated to regulate cardiac function and pathophysiology. This is the case for both innate immunity, which includes neutrophils, monocytes, dendritic cells, and macrophages, as well as adaptive immunity, which includes T cells and B cells. This function is fueled by cell-intrinsic shifts in metabolism, such as glycolysis and oxidative phosphorylation, as well as metabolite availability, which originates from the surrounding extracellular milieu and varies during ischemia and metabolic syndrome. Immune cell crosstalk with cardiac parenchymal cells, such as cardiomyocytes and fibroblasts, is also regulated by complex cellular metabolic circuits. …

Ndufs4 Regulates Cristae Remodeling In Diabetic Kidney Disease, Koki Mise, Jianyin Long, Daniel L Galvan, Zengchun Ye, Guizhen Fan, Irina I Serysheva, Travis I Moore, Jun Wada, Paul T Schumacker, Benny H Chang, Farhad R Danesh

Faculty, Staff and Student Publications

The mitochondrial electron transport chain (ETC) is a highly adaptive process to meet metabolic demands of the cell, and its dysregulation has been associated with diverse clinical pathologies. However, the role and nature of impaired ETC in kidney diseases remains poorly understood. Here, we generated diabetic mice with podocyte-specific overexpression of Ndufs4, an accessory subunit of mitochondrial complex I, as a model to investigate the role of ETC integrity in diabetic kidney disease (DKD). We find that these conditional mice exhibit significant improvements in cristae morphology, mitochondrial dynamics, and albuminuria. By coupling proximity labeling with super-resolution imaging, we also identify …

Anesthetic Considerations For Cardiac Tamponade After Internal Jugular Central Line Placement During Trauma Resuscitation: A Case Report, Kevin M Chen, Jamal Hasoon, Anvinh Nguyen

Faculty, Staff and Students Publications

Numerous complications are associated with central venous catheters. Among them, cardiac tamponade is a rare but well-documented catastrophic complication. A 22-year-old healthy male presented with Code 1 trauma resulting from gunshot wounds in the abdomen. Upon examination, he was found to have a large pericardial fluid collection, a large right supraclavicular hematoma, and significant amount of bilateral pleural effusions secondary to extraluminal placement of the right internal jugular central line during resuscitation. After repairing the internal jugular injury and draining the pericardial fluid, the patient was transferred from the intensive care unit to the regular hospital floor. However, 15 days …

Timing Of Invasive Mechanical Ventilation And Death In Critically Ill Adults With Covid-19: A Multicenter Cohort Study., Adam Green, Jean-Sebastien Rachoin, Christa Schorr, Phil Dellinger, Jonathan D Casey, Isabel Park, Shruti Gupta, Rebecca M Baron, Shahzad Shaefi, Krystal Hunter, David E Leaf

Cooper Medical School of Rowan University Departmental Research

PURPOSE: To investigate if the timing of initiation of invasive mechanical ventilation (IMV) for critically ill patients with COVID-19 is associated with mortality.

MATERIALS AND METHODS: The data for this study were derived from a multicenter cohort study of critically ill adults with COVID-19 admitted to ICUs at 68 hospitals across the US from March 1 to July 1, 2020. We examined the association between early (ICU days 1-2) versus late (ICU days 3-7) initiation of IMV and time-to-death. Patients were followed until the first of hospital discharge, death, or 90 days. We adjusted for confounding using a multivariable Cox …

Randomized Intervention And Outpatient Follow-Up Lowers 30-D Readmissions For Patients With Hepatic Encephalopathy, Decompensated Cirrhosis, Antoinette Pusateri, Kevin Litzenberg, Claire Griffiths, Caitlin Hayes, Bipul Gnyawali, Michelle Manious, Sean G Kelly, Lanla F Conteh, Sajid Jalil, Haikady N Nagaraja, Khalid Mumtaz

Faculty, Staff and Student Publications

BACKGROUND: We previously reported national 30-d readmission rates of 27% in patients with decompensated cirrhosis (DC).

AIM: To study prospective interventions to reduce early readmissions in DC at our tertiary center.

METHODS: Adults with DC admitted July 2019 to December 2020 were enrolled and randomized into the intervention (INT) or standard of care (SOC) arms. Weekly phone calls for a month were completed. In the INT arm, case managers ensured outpatient follow-up, paracentesis, and medication compliance. Thirty-day readmission rates and reasons were compared.

RESULTS: Calculated sample size was not achieved due to coronavirus disease 2019; 240 patients were randomized into …

Detrimental Effects Of Pcsk9 Loss-Of-Function In The Pediatric Host Response To Sepsis Are Mediated Through Independent Influence On Angiopoietin-1., Mihir R. Atreya, Natalie Z. Cvijanovich, Julie C. Fitzgerald, Scott L. Weiss, Michael T. Bigham, Parag N. Jain, Adam J. Schwarz, Riad Lutfi, Jeffrey Nowak, Geoffrey L. Allen, Neal J. Thomas, Jocelyn R. Grunwell, Torrey Baines, Michael Quasney, Bereketeab Haileselassie, Matthew N. Alder, Patrick Lahni, Scarlett Ripberger, Adesuwa Ekunwe, Kyle R. Campbell, Keith R. Walley, Stephen W. Standage

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Sepsis is associated with significant mortality. Yet, there are no efficacious therapies beyond antibiotics. PCSK9 loss-of-function (LOF) and inhibition, through enhanced low-density lipoprotein receptor (LDLR) mediated endotoxin clearance, holds promise as a potential therapeutic approach among adults. In contrast, we have previously demonstrated higher mortality in the juvenile host. Given the potential pleiotropic effects of PCSK9 on the endothelium, beyond canonical effects on serum lipoproteins, both of which may influence sepsis outcomes, we sought to test the influence of PCSK9 LOF genotype on endothelial dysfunction.

METHODS: Secondary analyses of a prospective observational cohort of pediatric septic shock. Genetic variants …

Sodium-Glucose Cotransporter 2 Inhibitors To Decrease The Uric Acid Concentration-A Novel Mechanism Of Action, Anna Kochanowska, Przemysław Rusztyn, Karolina Szczerkowska, Stanisław Surma, Aleksandra Gąsecka, Miłosz J Jaguszewski, Łukasz Szarpak, Krzysztof J Filipiak

Faculty, Staff and Students Publications

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are glucose-lowering agents whose positive impact on cardiovascular risk has been described extensively. Not only do they influence lipid profile, blood pressure, atherosclerosis risk, hemoglobin level, and insulin resistance, but they also reduce cardiovascular events, all-cause mortality, and hospitalization rates. Some of these effects may be due to their impact on serum uric acid (SUA) concentration. Findings from nine meta-analyses showed that, indeed, SGLT2is significantly reduce SUA. The data on the drug- and dose-dependency of this effect were inconclusive. Several factors alternating the beneficial effects of SGLT2is on SUA, such as glycated hemoglobin concentration (HbA1c), …

Blm Overexpression As A Predictive Biomarker For Chk1 Inhibitor Response In Parp Inhibitor-Resistant Brca-Mutant Ovarian Cancer, Nitasha Gupta, Tzu-Ting Huang, Jayakumar R Nair, Daniel An, Grant Zurcher, Erika J Lampert, Ann Mccoy, Ashley Cimino-Mathews, Elizabeth M Swisher, Marc R Radke, Christina M Lockwood, Jonathan B Reichel, Chih-Yuan Chiang, Kelli M Wilson, Ken Chih-Chien Cheng, Darryl Nousome, Jung-Min Lee

Faculty, Staff and Student Publications

Poly(ADP-ribose) polymerase inhibitors (PARPis) have changed the treatment paradigm in breast cancer gene (BRCA)–mutant high-grade serous ovarian carcinoma (HGSC). However, most patients eventually develop resistance to PARPis, highlighting an unmet need for improved therapeutic strategies. Using high-throughput drug screens, we identified ataxia telangiectasia and rad3-related protein/checkpoint kinase 1 (CHK1) pathway inhibitors as cytotoxic and further validated the activity of the CHK1 inhibitor (CHK1i) prexasertib in PARPi-sensitive and -resistant BRCA-mutant HGSC cells and xenograft mouse models. CHK1i monotherapy induced DNA damage, apoptosis, and tumor size reduction. We then conducted a phase 2 study (NCT02203513) of prexasertib …

Comparative Outcomes Of Interventions For Femoropopliteal Chronic Total Occlusion Versus Non-Chronic Total Occlusion Lesions From The Multicenter Xlpad Registry, Shirling Tsai, Yulun Liu, Lawrence Hoang, Michael Vu, Hua Lu, Bala Ramanan, David Fernandez Vazquez, Zachary Rosol, Sameh Sayfo, Mohamad Amer Alaiti, Panagiotis Koutakis, Emmanouil S Brilakis, Mehdi H Shishehbor, Subhash Banerjee

Faculty, Staff and Student Publications

Background Endovascular intervention of femoropopliteal chronic total occlusions (CTOs) is technically more complex. However, there is lack of comparative analysis between CTO and non-CTO femoropopliteal interventions. Methods and Results We report procedural details and outcomes of patients treated for femoropopliteal CTO and non-CTO lesions in the XLPAD (Excellence in Peripheral Artery Disease) registry (NCT01904851) between 2006 and 2019. Primary outcomes were procedural success and 1-year major adverse limb events, a composite of all-cause death, target limb revascularization, or major amputation. Analysis included 2895 patients (CTO: n=1516 patients; non-CTO: n=1379 patients) with 3658 lesions (CTO: n=1998 lesions; non-CTO: n=1660 lesions). Conventional …

High-Resolution Transcriptomic And Epigenetic Profiling Identifies Novel Regulators Of Copd, Uwe Schwartz, Maria Llamazares Prada, Stephanie T Pohl, Mandy Richter, Raluca Tamas, Michael Schuler, Corinna Keller, Vedrana Mijosek, Thomas Muley, Marc A Schneider, Karsten Quast, Joschka Hey, Claus P Heußel, Arne Warth, Hauke Winter, Özdemirhan Serçin, Harry Karmouty-Quintana, Soma Sk Jyothula, Manish K Patel, Felix Herth, Ina Koch, Giuseppe Petrosino, Alexandru Titimeaua, Balca R Mardin, Dieter Weichenhan, Tomasz P Jurkowski, Charles D Imbusch, Benedikt Brors, Vladimir Benes, Birgit Jung, David Wyatt, Heiko F Stahl, Christoph Plass, Renata Z Jurkowska

Faculty, Staff and Student Publications

Patients with chronic obstructive pulmonary disease (COPD) are still waiting for curative treatments. Considering its environmental cause, we hypothesized that COPD will be associated with altered epigenetic signaling in lung cells. We generated genome-wide DNA methylation maps at single CpG resolution of primary human lung fibroblasts (HLFs) across COPD stages. We show that the epigenetic landscape is changed early in COPD, with DNA methylation changes occurring predominantly in regulatory regions. RNA sequencing of matched fibroblasts demonstrated dysregulation of genes involved in proliferation, DNA repair, and extracellular matrix organization. Data integration identified 110 candidate regulators of disease phenotypes that were linked …

Rare Event Of Intraoral Kinking Of Endotracheal Tube Upon Prone Positioning In A Patient Undergoing Posterior Fossa Surgery, Sonali Turki, Amiya K. Barik, Amit Sharma, Abhishek Arya

International Journal of Health and Allied Sciences

Prone position is commonly employed for many surgical procedures including neurosurgeries, spine surgeries, urological procedures, and in refractory ARDS patients. An endotracheal tube is a conduit to provide a secured airway to the patient. But in case of any equipment failure, it can cause catastrophic events. Intra-oral kinking is a rarer event. It can pose a major troubleshooting standstill owing to the inaccessible view of the kinked portion and the rarity of its occurrence to cross the clinician’s mind in the emergency scenario. We thus report this as the first such case of intraoral kinking against the soft palate in …

Reducing The Environmental Impact Of Surgery On A Global Scale: Systematic Review And Co-Prioritization With Healthcare Workers In 132 Countries, National Institute For Health And Care Research Global Health Research Unit On Global Surgery

Faculty, Staff and Student Publications

BACKGROUND: Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres.

METHODS: This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their …

Tenofovir Induced Hypokalaemia - A Case Report, Ankisha Gupta, Kiran P. K, Rajendra Prasad S

Digital Journal of Clinical Medicine

Tenofovir, an important medication for HIV/AIDS, carries the risk of hypokalemia in patients receiving treatment. Factors such as dietary deficits, vomiting, or diarrhea further increase this risk. Tenofovir acts as a mitochondrial toxin by inhibiting the DNA polymerase gamma enzyme, crucial for mitochondrial DNA replication. Consequently, ATP generation is depleted through the aerobic pathway, leading to dysfunction in the proximal tubule. This dysfunction manifests as renal acidosis type 2, which involves reduced bicarbonate excretion by the proximal tubule, resulting in renal bicarbonate wasting and decreased serum bicarbonate levels. Consequently, the lumen of the distal nephron becomes negatively charged, leading to …

Targeting Neddylation And Sumoylation In Chemoresistant Triple Negative Breast Cancer, Wei Ruan, Jiwen Li, Seungwon Choi, Xinxin Ma, Yafen Liang, Ragini Nair, Xiaoyi Yuan, Tingting W Mills, Holger K Eltzschig

Faculty, Staff and Student Publications

Previous studies implicate extracellular adenosine signaling in attenuating myocardial ischemia and reperfusion injury (IRI). This extracellular adenosine signaling is terminated by its uptake into cells by equilibrative nucleoside transporters (ENTs). Thus, we hypothesized that targeting ENTs would function to increase cardiac adenosine signaling and concomitant cardioprotection against IRI. Mice were exposed to myocardial ischemia and reperfusion injury. Myocardial injury was attenuated in mice treated with the nonspecific ENT inhibitor dipyridamole. A comparison of mice with global Ent1 or Ent2 deletion showed cardioprotection only in Ent1-/- mice. Moreover, studies with tissue-specific Ent deletion revealed that mice with myocyte-specific Ent1 deletion (Ent1loxP/loxP …

Hyperthermic Extracorporeal Applied Tumor Therapy (Heatt®) In Advanced Unresponsive Cancer, Joseph B. Zwischenberger, Peyton Skaggs, Katherine Breetz, Jan Winetz, Roger Vertrees

Journal of Shock and Hemodynamics

Hyperthermia has been utilized for cancer therapy, including metastatic cancer, for decades with isolated success. Previous research has indicated that the elevated temperature of 42°C induces cell death, apoptosis, or senescence of responsive cancers, providing a mechanism for tumor destruction and management. Veno-venous perfusion-induced systemic hyperthermia (V-V PISH) may be the key to improving advanced tumor responsiveness to previously failed chemotherapy and/or radiation as combination therapy. The most recent iteration of V-V PISH, Hyperthermic Extracorporeal Applied Tumor Therapy (HEATT®), provides homogeneous heating of all tissues with electrolyte and pH control and continues to prove safe and effective. The utilization of …

Implementation Of A Virtual Interprofessional Icu Learning Collaborative: Successes, Challenges, And Initial Reactions From The Structured Team- Based Optimal Patient-Centered Care For Virus Covid-19 Collaborators, Simon Zec, Nika Zorko Garbajs, Yue Dong, Ognjen Gajic, Christina Kordik, Lori Harmon, Marija Bogojevic, Romil Singh, Yuqiang Sun, Vikas Bansal, Linh Vu, Kelly Cawcutt, John M. Litell, Sarah Redmond, Elly Fitzpatrick, Kirstin J. Kooda, Michelle Biehl, Neha S. Dangayach, Viren Kaul, June M. Chae, Aaron Leppin, Mathew Siuba, Rahul Kashyap, Allan J. Walkey, Alexander S. Niven

Jefferson Hospital Staff Papers and Presentations

IMPORTANCE: Initial Society of Critical Care Medicine Discovery Viral Infection and Respiratory illness Universal Study (VIRUS) Registry analysis suggested that improvements in critical care processes offered the greatest modifiable opportunity to improve critically ill COVID-19 patient outcomes. OBJECTIVES: The Structured Team-based Optimal Patient-Centered Care for Virus COVID-19 ICU Collaborative was created to identify and speed implementation of best evidence based COVID-19 practices. DESIGN, SETTING, AND PARTICIPANTS: This 6-month project included volunteer interprofessional teams from VIRUS Registry sites, who received online training on the Checklist for Early Recognition and Treatment of Acute Illness and iNjury approach, a structured and systematic method …

Fluid Overload Precedes And Masks Cryptic Kidney Injury In Pediatric Acute Respiratory Distress Syndrome, Celeste G Dixon, Sameer Thadani, Julie C Fitzgerald, Ayse Akcan-Arikan, Nadir Yehya

Faculty, Staff and Students Publications

OBJECTIVES: Given the complex interrelatedness of fluid overload (FO), creatinine, acute kidney injury (AKI), and clinical outcomes, the association of AKI with poor outcomes in critically ill children may be underestimated due to definitions used. We aimed to disentangle these temporal relationships in a large cohort of children with acute respiratory distress syndrome (ARDS).

DESIGN: Retrospective cohort study.

SETTING: Quaternary care PICU.

PATIENTS: Seven hundred twenty intubated children with ARDS between 2011 and 2019.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Daily fluid balance, urine output (UOP), and creatinine for days 1-7 of ARDS were retrospectively abstracted. A subset of patients …

Prognostic Value Of Severe Acute Respiratory Syndrome Coronavirus-2 Viral Load And Antibodies In Patients Hospitalized With Covid-19, Rebecca N Bauer, Anastasia Teterina, Haridha Shivram, Jacqueline Mcbride, Carrie M Rosenberger, Fang Cai, Min Bao, Larry Tsai, Oliver Gordon, Ivan T Lee, Jeffrey J Wallin, Danielle Porter, Kavita Juneja, Gregory Camus, Ivan O Rosas, Steffen Wildum

Faculty, Staff and Students Publications

Observational studies have identified the potential prognostic value for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load and anti-SARS-CoV-2 antibodies in coronavirus disease 2019 (COVID-19). However, viral load in nasopharyngeal (NP) swabs produced inconsistent results in prognostic analyses, and the prognostic value of viral load or antibodies has not been confirmed in large clinical trials. COVACTA and REMDACTA were double-blind, randomized, controlled trials with a combined enrollment of 1078 patients hospitalized with COVID-19 treated with tocilizumab or placebo in COVACTA or tocilizumab plus remdesivir or placebo plus remdesivir in REMDACTA. We assessed the potential prognostic value of NP and serum …

Quantifying Disease Progression In Copd Patients By Forecasting Pft Scores Using Extracted Features From Non-Contrast Ct, A T. Luong, C J. Herrera, E Young, Y K. Liu, A Nowacki, J Cisneros-Paz, Girish Nair, E Castillo

Conference Presentation Abstracts

Purpose: Currently there is no validated method for quantifying risk of disease progression in chronic obstructive pulmonary disease (COPD). We aim to address this by predicting whether a patient will worsen using a machine learning model trained on basic patient information, current pulmonary function values, FEV1 and FVC, and extracted features from a non-contrast CT scan. Disease severity is characterized by these pulmonary function values, and by extension disease progression can be determined by the change in these values between future timepoints. Methods: XGBoost, a popular classification library that utilizes gradient boosted trees, was used to define an ensemble model …

Quantifying Disease Progression In Copd Patients By Forecasting Pft Scores Using Extracted Features From Non-Contrast Ct, A T. Luong, C J. Herrera, E Young, Y K. Liu, A Nowacki, J Cisneros-Paz, Girish Nair, E Castillo

Conference Presentation Abstracts

Purpose: Currently there is no validated method for quantifying risk of disease progression in chronic obstructive pulmonary disease (COPD). We aim to address this by predicting whether a patient will worsen using a machine learning model trained on basic patient information, current pulmonary function values, FEV1 and FVC, and extracted features from a non-contrast CT scan. Disease severity is characterized by these pulmonary function values, and by extension disease progression can be determined by the change in these values between future timepoints. Methods: XGBoost, a popular classification library that utilizes gradient boosted trees, was used to define an ensemble model …

Aryl Hydrocarbon Receptor Maintains Hepatic Mitochondrial Homeostasis In Mice, Mi Jeong Heo, Ji Ho Suh, Sung Ho Lee, Kyle L Poulsen, Yu A An, Bhagavatula Moorthy, Sean M Hartig, David D Moore, Kang Ho Kim

Faculty, Staff and Student Publications

OBJECTIVE: Mitophagy removes damaged mitochondria to maintain cellular homeostasis. Aryl hydrocarbon receptor (AhR) expression in the liver plays a crucial role in supporting normal liver functions, but its impact on mitochondrial function is unclear. Here, we identified a new role of AhR in the regulation of mitophagy to control hepatic energy homeostasis.

METHODS: In this study, we utilized primary hepatocytes from AhR knockout (KO) mice and AhR knockdown AML12 hepatocytes. An endogenous AhR ligand, kynurenine (Kyn), was used to activate AhR in AML12 hepatocytes. Mitochondrial function and mitophagy process were comprehensively assessed by MitoSOX and mt-Keima fluorescence imaging, Seahorse XF-based …

Real-World Safety Of Neurohormonal Antagonist Initiation Among Older Adults Following A Heart Failure Hospitalization, Parag Goyal, Andrew R Zullo, Barbara Gladders, Chukwuma Onyebeke, Min Ji Kwak, Larry A Allen, Emily B Levitan, Monika M Safford, Lauren Gilstrap

Faculty, Staff and Student Publications

AIMS: To optimize guideline-directed medical therapy for heart failure, patients may require the initiation of multiple neurohormonal antagonists (NHAs) during and following hospitalization. The safety of this approach for older adults is not well established.

METHODS AND RESULTS: We conducted an observational cohort study of 207 223 Medicare beneficiaries discharged home following a hospitalization for heart failure with reduced ejection fraction (HFrEF) (2008-2015). We performed Cox proportional hazards regression to examine the association between the count of NHAs initiated within 90 days of hospital discharge (as a time-varying exposure) and all-cause mortality, all-cause rehospitalization, and fall-related adverse events over the …

Factors, Enablers And Challenges For Covid-19 Vaccine Development, Jean-Louis Excler, Melanie Saville, Lois Privor-Dumm, Sarah Gilbert, Peter J Hotez, Didi Thompson, Salim Abdool-Karim, Jerome H Kim

Faculty, Staff and Students Publications

The COVID-19 pandemic triggered a sense of vulnerability and urgency that led to concerted actions by governments, funders, regulators and industry to overcome traditional challenges for the development of vaccine candidates and to reach authorisation. Unprecedented financial investments, massive demand, accelerated clinical development and regulatory reviews were among the key factors that contributed to accelerating the development and approval of COVID-19 vaccines. The rapid development of COVID-19 vaccines benefited of previous scientific innovations such as mRNA and recombinant vectors and proteins. This has created a new era of vaccinology, with powerful platform technologies and a new model for vaccine development. …

Vaccine Access, Equity And Justice: Covid-19 Vaccines And Vaccination, Lois Privor-Dumm, Jean-Louis Excler, Sarah Gilbert, Salim S Abdool Karim, Peter J Hotez, Didi Thompson, Jerome H Kim

Faculty, Staff and Students Publications

Although significant progress has been made in achieving goals for COVID-19 vaccine access, the quest for equity and justice remains an unfinished agenda. Vaccine nationalism has prompted calls for new approaches to achieve equitable access and justice not only for vaccines but also for vaccination. This includes ensuring country and community participation in global discussions and that local needs to strengthen health systems, address issues related to social determinants of health, build trust and leverage acceptance to vaccines, are addressed. Regional vaccine technology and manufacturing hubs are promising approaches to address access challenges and must be integrated with efforts to …

The Vitamin D Serum Levels In Pregnant Women Affected By Covid-19: A Systematic Review And Meta-Analysis, Luiza Szarpak, Stepan Feduniw, Michal Pruc, Michal Ciebiera, Basar Cander, Mansur Rahnama-Hezavah, Łukasz Szarpak

Faculty, Staff and Students Publications

Vitamin D can modulate immune responses, and its deficiency is linked to increased autoimmunity and susceptibility to infection. In the general population, it has been observed that serum vitamin D levels are connected with the risk of COVID-19 and its severity. Our study aims to examine reported findings on the effect of vitamin D serum levels on infection of COVID-19 during pregnancy. PubMed, Web of Science, Embase, and Cochrane Library were searched for relevant studies. Serum vitamin D serum levels in COVID-19-positive and COVID-19-negative pregnant women were 24.61 ± 20.86 ng/mL and 24.12 ± 17.33 ng/mL, respectively. In mild vs. …

Ca2+ Efflux Facilitated By Co-Transport Of Inorganic Phosphate Anion In The H+/Ca2+ Antiporter Yfke, Wei Niu, Wenchang Zhou, Shuo Lu, Trung Vu, Vasanthi Jayaraman, José D Faraldo-Gómez, Lei Zheng

Faculty, Staff and Student Publications

Ca2+ is an important signaling messenger. In microorganisms, fungi, and plants, H+/Ca2+ antiporters (CAX) are known to play key roles in the homeostasis of intracellular Ca2+ by catalyzing its efflux across the cell membrane. Here, we reveal that the bacterial CAX homolog YfkE transports Ca2+ in two distinct modes: a low-flux H+/Ca2+ exchange mode and a high-flux mode in which Ca2+ and phosphate ions are co-transported (1:1) in exchange for H+. Coupling with phosphate greatly accelerates the Ca2+ efflux activity of YfkE. Our studies reveal that Ca2+ and phosphate bind to adjacent sites in a central translocation pathway and lead …