Critical Care Commons^™

Ceftaroline Pharmacokinetics On Ecmo, A Pediatric Case Report., Kathryn Pavia, Ashton Bellamy, Alaina Burns, Allison Scott, Ethan A. Poweleit

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: In-vitro studies suggest that patients on extracorporeal membrane oxygenation (ECMO) may struggle to achieve therapeutic ceftaroline exposure to treat infections due to antibiotic sequestration within the ECMO oxygenator; however, there are no published data regarding ceftaroline concentrations from patients supported by ECMO.

PATIENT PRESENTATION: Here we present an analysis of ceftaroline pharmacokinetics in a 5-y-old patient supported on ECMO due to influenza-associated necrotizing pneumonia.

RESULTS: A total of nine concentrations were analyzed, including three concentrations prior to cannulation and six on ECMO. ECMO cannulation was associated with a relatively small change in the volume of distribution (0.17 L/kg to …

Posaconazole Target Attainment In Critically Ill Children: A 15-Year Single-Center Retrospective Analysis., Kathryn Pavia, Addison M. Pritchett Ms, Jennifer Goldman

Manuscripts, Articles, Book Chapters and Other Papers

Posaconazole is a triazole antifungal agent used for prophylaxis and treatment of invasive fungal diseases. Posaconazole has high inter-individual variability in dose-exposure relationship and benefits from therapeutic drug monitoring (TDM). Adult studies report particularly high rates of subtherapeutic exposure among intensive care unit (ICU) patients related to changes in physiology during critical illness. The rates of subtherapeutic posaconazole exposure among critically ill children in ICU's are unknown. This single-center retrospective analysis at a large freestanding children's hospital used TDM results from 2010 to 2025 obtained while patients were undergoing care in a pediatric ICU. Therapeutic targets were ≥ 1.0 mg/L …

Leveraging Administrative Health Data To Capture Rare Adverse Drug Reactions: Identifying Pediatric Patients With Trimethoprim-Sulfamethoxazole Acute Respiratory Distress Syndrome., Keith Feldman, Jenna Miller, Katherine Doane, Laura Loftis, James W. Antoon, Kevin J. Downes, Jennifer Goldman

Manuscripts, Articles, Book Chapters and Other Papers

Rare adverse drug reactions (ADRs) are underrecognized and underreported in the electronic medical record (EMR). These events often require clinical review, making systematic identification challenging. The study aim was to develop an approach to prioritize identification and validation of a rare ADR to trimethoprim-sulfamethoxazole causing acute respiratory distress syndrome (TMP-SMX ARDS) across medical institutions. We developed a clinical phenotype based on 2 local TMP-SMX ARDS cases mapped to standardized elements of a national comparative healthcare database (PHIS). We validated identification of TMP-SMX ARDS at scale across medical institutions. A set of scoring criteria was created to prioritize cases and generate …

State And Regional Variation In Access To Pediatric Extracorporeal Membrane Oxygenation., Allan M. Joseph, Andrew J. Lautz, Carlie N. Myers, Ranjit S. Chima, Juan P. Gurria, Shafee Salloum, Wendy Hasson, Matthew P. Malone, Jenna Miller, Reanna Smith, Maya L. Dewan

Manuscripts, Articles, Book Chapters and Other Papers

Extracorporeal membrane oxygenation (ECMO) is only available in specialized medical centers. We conducted a geospatial analysis and found state- and region-level variation in the supply of ECMO centers, and the number of children who had access to ECMO. These findings may help target areas for the development of new ECMO programs.

Cytokine-Based Strategies To Improve Prognostic Enrichment Of Pediatric Ards., E Scott Halstead, Todd M. Umstead, Zissis C. Chroneos, Cainan Riccio-Baum, S Rameeza Allie, Daniel J. Mckeone, Debbie Spear, Ryan A. Nofziger, Ronald C. Sanders, Danielle Ahn, Jasmine C. Dowell, Asdis Finnsdottir Wagner, Neal J. Thomas, Prithvi Sendi, W Joshua Frazier, Courtney M. Rowan, Parag N. Jain, Dalia A. Bashir, Stuart H. Friess, Brian M. Varisco, Jocelyn Grunwell, Aline B. Maddux, Stephen T. Famularo, Nadir Yehya

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Hyper-inflammation is common to multiple critical care syndromes, including acute respiratory distress syndrome (ARDS) and sepsis, and is associated with worse outcomes. A signature of hyper-inflammatory ARDS has been described in adults using IL-6, TNFR1, and bicarbonate, and has prognostic utility. We investigated the application of this traditional parsimonious signature to pediatric ARDS patients and tested whether we could improve prognostic enrichment using other cytokines.

METHODS: We leveraged a prospective multicenter cohort study of 500 children with ARDS (Linking Endotypes and Outcomes in Pediatric Acute Respiratory Distress Syndrome [LEOPARDS]; NCT04113434) study. Plasma samples were obtained within 24 h of …

Z Variant Heterozygosity In Alpha-1 Antitrypsin Deficiency: Disease Risk And Treatment Implications, Craig P. Hersh, Jeffrey H. Teckman, Pavel Strnad, Aaron Hakim, Tomás P. Carroll, Ian P. Hall, Auyon J. Ghosh, Igor Barjaktarevic, Noel G. Mcelvaney, Joseph E. Kaserman, David A. Lomas, Charlie Strange, M Bradley Drummond, Stephen I. Rennard, Kathi E. Hanna, Virginia C. Clark, Monica P. Goldklang, Peg Iverson, Andrew A. Wilson

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Individuals heterozygous for alpha-1 antitrypsin deficiency (AATD) have one copy of the normal "M" allele and one copy of an abnormal allele ("Z", "S", or another variant) in the SERPINA1 gene. Historically, evidence has been lacking to support the concept that heterozygotes are at increased risk for liver and/or lung complications compared to individuals homozygous for the M allele. However, growing evidence suggests that inheritance of a single Z allele increases the risk of disease in some individuals. The Alpha-1 Foundation convened a workshop on October 27, 2023, in Bethesda, Maryland that included stakeholders from the research, pharmaceutical, and …

Bayesian Reanalysis Of Early Remdesivir For The Treatment Of Covid-19 In Outpatients With High Risk Of Progression To Severe Disease, Mazin Abdelghany, Fang Yu, Stephen I. Rennard, Yeongjin Gwon

Journal Articles: Pulmonary & Critical Care Med

BACKGROUND: Though Bayesian methods are flexible, intuitive, and readily incorporated into clinical decision-making, with particular utility when prior information is available, they remain underutilized in the analysis of clinical trials.

METHODS: In PINETREE, a Phase 3 randomized controlled trial (RCT) of remdesivir (RDV) for the treatment of outpatients with COVID-19 at high risk of severe disease, the primary outcome of COVID-19-related hospitalization or all-cause death was reanalyzed using a range of reference and data-driven priors. Posterior probability distributions were used to calculate the probability that the estimated hazard ratio (HR) was below a range of clinically meaningful specified thresholds and …

External Multicenter Validation Of The Esah Score For Predicting Outcomes After Subarachnoid Hemorrhage, Natália Vasconcellos De Oliveira Souza, Rohan Sharma, Otavio Frederico De Toledo, Ingrid Pereira Marques, Salvador F. Gutierrez-Aguirre, Lara-Velazquez Montserrat, Eric Sauvageau, Naval Neeraj, Amin Aghaebrahim, Feres Chaddad Neto, Ricardo A. Hanel, Gisele Sampaio Silva, William David Freeman

Jefferson Hospital Staff Papers and Presentations

Reliable assessment of prognosis after aneurysmal subarachnoid hemorrhage (SAH) is essential to inform clinical decision-making and prevent premature assumptions of poor outcome. The enhanced SAH (eSAH) score combines three routinely available variables-age, Glasgow Coma Scale (GCS), and subarachnoid hemorrhage blood volume (SAHV)-to provide an objective framework for early outcome stratification. SAHV is estimated using the ABC/2-derived ellipsoid method applied across five major cisternal compartments on non-contrast CT. While the eSAH score has shown promise in initial derivation studies, its external performance and calibration have not yet been validated across diverse healthcare settings. We conducted a retrospective cohort study using consecutive …

Frequency, Duration, And Cost Of Pulmonary Exacerbations Among Patients With Bronchiectasis, Maitreyee Mohanty, Claudia Leiras, Haiyan Sun, Reina Rau, John Fastenau, Joseph Feliciano, Sunjay R Devarajan

Faculty, Staff and Students Publications

Background: In administrative claims database studies of bronchiectasis, pulmonary exacerbations are usually defined using a fixed period for their start and end, which prevents assessment of exacerbation duration and thereby limits assessment of exacerbation characteristics. Here, we applied a novel cost-based algorithm to characterize exacerbations.

Methods: This cohort study used the Merative MarketScan Commercial Claims and Encounters database, 1-Jan-2016 to 31-Dec-2022. Patients ≥18 years with bronchiectasis (≥2 outpatient or ≥1 inpatient claim with bronchiectasis; no cystic fibrosis) had 12 months of continuous enrollment before (baseline) and ≥12 months after (follow-up) index (first bronchiectasis claim). Cost-based exacerbations were identified by compound …

Perioperative Nutrition In Pediatric Patients With Congenital Heart Disease And Heart Failure., Jaime Silva-Gburek, Kelsey May, Bailey Walvoord, Catalina Lozano, Jorge A. Coss-Bu

Manuscripts, Articles, Book Chapters and Other Papers

Optimal nutritional therapy is important for infants and children with perioperative congenital heart disease and heart failure. Medical providers face physiological and metabolic challenges when administering enteral and parenteral nutrition to these patients. Complications related to enteral nutrition can increase morbidity and mortality, although outcomes are improved in those cases in which caloric and nutrient administration can be achieved. Consensus regarding feeding strategies and timing of nutritive care is lacking. This narrative review aims to summarize, analyze and discuss the most recent literature on nutritional therapy in perioperative congenital heart disease, heart failure and pediatric patients requiring mechanical circulatory support …

Ultra-Low-Field Portable Magnetic Resonance Imaging Feasibility And Safety In Pediatric And Neonatal Extracorporeal Membrane Oxygenation: A Single-Center Year-Long Experience., Jessica S. Wallisch, Asdis Finnsdottir Wagner, John M. Daniel Iv, Allison Taber, Maura Sien, Sarah Foster, Nathan S. Artz, Timothy Zinkus, Hung-Wen Yeh, Jose A. Pineda, Patrick M. Kochanek, Sherwin S. Chan

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Despite improving outcomes, extracorporeal membrane oxygenation (ECMO) remains associated with high rates of acute brain injury, impacting survival and outcomes. Clinical imaging modalities, including computed tomography and standard-field magnetic resonance imaging (≥1.5 Tesla), have either limited early detection of ischemic-type injuries or are incompatible with ECMO, causing diagnostic delays. A Food and Drug Administration-cleared ultra-low-field portable magnetic resonance imaging (pMRI; 0.064 Tesla) has shown promise in acute brain injury detection and use with MRI-unsafe equipment, but pediatric ECMO data are limited.

METHODS: This institutional review board-approved, single-center study was conducted at a quaternary children's hospital. Neonatal and pediatric patients …

Global Trends And Forecast Of Cardiovascular Diseases, Cancer, And Shared Risk Factors: Insights From The Gbd 2021, Chieh Y Koo, Bryan Chong, Jayanth Jayabaskaran, Srinithy Nagarajan, Silingga M Jauhari, Yiming Chen, Li L Tan, Anurag Mehta, Muhammad S Khan, Mark Muthiah, Derek Hausenloy, A M Richards, Dennis T Ko, Christian D Mallen, Eric A Secemsky, Mark Y Chan, Paaladinesh Thavendiranathan, Nicholas W S Chew, Mamas A Mamas

Faculty, Staff and Students Publications

Background: Cardiovascular disease (CVD) and cancer share multiple risk factors and are the leading causes of morbidity and death worldwide. This study aims to examine historical and projected trends of the combined CVD-cancer global estimates and their shared risk factors.

Methods: Death and disability-adjusted life years (DALYs) associated with CVDs, cancers, and their risk factors were obtained from the GBD (Global Burden of Disease) 2021 study. Historical estimates from 1990 to 2021 and forecast data from 2025 to 2050 were examined across age groups, regions, sociodemographic index, and sex.

Results: In 2021, CVD-cancer resulted in age-standardized DALY rates of 8009 …

Centrally Inserted Central Catheter Placement Using A Novel, Handheld, Image-Guided, Robotic Device: Results Of Initial Feasibility Trial In Patients, James P Herlihy, William E Cohn, Adrian Ebner

Faculty, Staff and Students Publications

Background: Central venous access devices (CVADs) are an essential and widely used tool for the treatment of the critically ill, patients undergoing major surgery, and for many patients requiring hemodialysis. Automation of centrally inserted central catheters (CICCs) could potentially make CVAD placement safer, more effective, and more accessible. A new device that uses ultrasound image-guided, robotic needle placement, in addition to traditional Seldinger technique, to place a CICC is described.

Objective: The device was used in a small, first-in-human, trial for placing non-tunneled hemodialysis catheters (NTHDCs), in order to determine feasibility of clinical use.

Methods: Consecutive patients requiring a NTHDC, …

Cyp1b1 Mediates Cigarette Smoke-Induced Lipid Accumulation In Alveolar Type 2 Cells, Yin Zhu, Siddhika Gamare, Francesca Polverino, Caroline A Owen, Payaningal R Somanath, Xiaoyun Wang, Duo Zhang

Faculty, Staff and Students Publications

Alterations in lipid profiles have been shown in patients with chronic obstructive pulmonary disease (COPD), but the underlying molecular mechanisms remain unclear. In this study, we aimed to investigate the role of cytochrome P450 family-1 subfamily B member 1 (CYP1B1) in cigarette smoke (CS)-induced lipid accumulation in alveolar type II epithelial (AT2) cells. We observed a steady increase in CYP1B1 protein levels in AT2 cells from COPD patients. Additionally, CS exposure induced CYP1B1 expression in AT2 cells of murine lungs. In vitro, treatment with cigarette smoke extract (CSE) not only upregulated CYP1B1 expression but also triggered lipid accumulation in AT2-like …

Β-Catenin Functions As A Molecular Adapter For Disordered Cbaf Interactions, Yuen San Chan, Qinyu Gao, Sarah A Robinson, Wenzhi Wang, Ruzena Filandrova, Lisa-Maria Weinhold, Mario Loeza Cabrera, Miao Zhang, Chandra Shekar R Ambati, Antonio M Lerario, Nagireddy Putluri, Katja Kiseljak-Vassiliades, Margaret E Wierman, Mouhammed Amir Habra, Gary D Hammer, Vaclav Veverka, Katerina Cermakova, H Courtney Hodges

Faculty, Staff and Students Publications

BAF (SWI/SNF) chromatin remodelers engage binding partners to generate site-specific DNA accessibility. However, the basis for interaction between BAF and divergent binding partners has remained unclear. Here, we tested the hypothesis that scaffold proteins augment BAF's binding repertoire by examining β-catenin (CTNNB1) and steroidogenic factor 1 (SF-1, NR5A1), a transcription factor central to steroid production in human cells. BAF inhibition rapidly opposed SF-1/β-catenin enhancer occupancy, impairing SF-1 target activation and SF-1/β-catenin autoregulation. These effects arise due to β-catenin's role as a molecular adapter between SF-1 and an intrinsically disordered region (IDR) of the canonical BAF (cBAF) subunit ARID1A. In contrast …

Mechano-Signal Transduction Pathways Of The Diaphragmatic Muscle And Role Of Cytoskeleton, Junaith S Mohamed, Patricia S Pardo, Aladin M Boriek

Faculty, Staff and Students Publications

Mechanotransduction, also referred to as mechano-signal transduction, is a biophysical process wherein cells perceive and respond to mechanical stimuli by converting them into biochemical signals that initiate specific cellular responses. This mechanism is fundamental to the development and growth, and proper functioning of mechanically active tissues, such as the diaphragm-a respiratory muscle vital for breathing in mammals. In vivo, the diaphragm is subjected to transdiaphragmatic pressure, and therefore, its muscle fibers are subjected to mechanical forces not only in the direction of the muscle fibers but also in the direction transverse to the fibers. Previous research conducted in our laboratory …

Sensing The Stiffness: Cellular Mechano-Sensing At The Implant Interface, Patricia S Pardo, Delia Danila, Raja Devesh Kumar Misra, Aladin M Boriek

Faculty, Staff and Students Publications

In this perspective, we highlight the relevance of the FA-Hippo signaling pathway and its regulation of the Yes-associated protein (YAP) and the transcriptional coactivator with a PDZ-binding domain (TAZ) as main players in the process of implants integration. The modulation and responses of YAP/TAZ triggered by substrate and ECM stiffness are of particular interest in the construction of materials used for medical implants. YAP/TAZ nuclear localization and activity respond to the substrate stiffness by several mechanisms that involve the canonical and non-canonical Hippo signaling and independently of the Hippo cascade. YAP/TAZ regulate the expression of genes involved in several mechanisms …

Assessment Of Functioning Using The Whodas 20 Among People With Myasthenia Gravis-Associated Disability: A Nationwide Follow-Up Study, Jia-Pei Hong, Chih-Hong Lee, Chien Tai Hong, Lung Chan, Chen-Chih Chung, Prangthip Charoenpong, Hou-Chang Chiu, Tsan-Hon Liou

Faculty, Staff and Students Publications

Background: Advancements in treatment have increased the life expectancy of patients with Myasthenia Gravis (MG), yet the understanding of functional changes in these individuals remains limited. In our study, we explored the functional abilities of individuals with MG using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0).

Methods: This observational study analyzed data from 286 patients with MG, acquired from the Data Bank of Persons with Disabilities (TDPD) in Taiwan between July 11, 2012, and December 31, 2021. Participants were diagnosed with MG after the acute phase. The functional disability outcome was assessed using the WHODAS 2.0. Due …

Figo Position Statement: Gamete Donations, Laurie Henry, Aris Antsaklis, Dov Feldberg, Jaideep Malhotra, Suchitra Pandit, Carlos Salazar, Alex Vidaeff, Rafal Zadykowicz, M Louise Hull, Nikhil Purandare

Faculty, Staff and Students Publications

Gamete donation has become a crucial part of Assisted Reproductive Technologies (ARTs), providing hope to individuals, including those who may have no other option for parenthood. This process comes with a wide range of ethical, medical, and legal challenges that need to be carefully addressed to protect the well-being and rights of all parties involved: donors, recipients, and offspring. Navigating these complexities requires strict ethical standards, robust regulatory frameworks, and international collaboration. By standardizing these, the field of gamete donation can continue to develop while ensuring that all parties are well informed and safeguarded. This paper explores the ethical concerns …

Military Inhalational Exposures Outside The Theater Of Conflict And Chronic Respiratory Symptoms, Reza Hosseini, Eric Garshick, Martin D Slade, Andrew Timmons, Anna M Korpak, Nicholas L Smith, Karen S Nakayama, Coleen P Baird, Paul Ciminera, Farrah Kheradmand, Vincent S Fan, Jaime E Hart, Petros Koutrakis, Ware Glenn Kuschner, Octavian C Ioachimescu, Michael Jerrett, Philippe R Montgrain, Susan P Proctor, Christine H Wendt, Cherry Wongtrakool, Emily S Wan, Paul D Blanc, Carrie A Redlich

Faculty, Staff and Students Publications

Importance: Deployment to Afghanistan and Southwest Asia has been associated with adverse respiratory health outcomes. However, the impact of inhalational exposures (eg, vapor, dust, gas, fumes), which are known correlates of reduced lung function and future chronic lung disease, during military service time outside this deployment period has not been assessed.

Objective: To assess military inhalational exposures during nonwartime routine activities and their associations with chronic respiratory symptoms.

Design, setting, and participants: This cross-sectional study used data from the US Department of Veterans Affairs Service and Health Among Deployed Veterans study. US veterans who served between October 7, 2001, and …

Best Practices For A Competency-Based Curriculum In Critical Care Ultrasonography For Fellows, Paru Patrawalla, Frances West, Navitha Ramesh, Paul Mayo, Amik Sodhi

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

New guidelines from the Accreditation Council on Graduate Medical Education for critical care ultrasound (CCUS) training went into effect on July 1, 2024, for critical care medicine and combined pulmonary and critical care medicine fellows. Fellowship programs will need to ensure that their fellows demonstrate competence in skills that are essential to CCUS, which currently encompasses applications in basic cardiac, lung/pleural, abdominal, and vascular ultrasonography (US). This may be a challenge for fellowship programs that have nascent CCUS curricula and limited faculty expertise. In this Perspective, we share expert and evidence-based recommendations on how to implement a competency-based curriculum in …

Protein Biomarkers Of Interstitial Lung Abnormalities In Relatives Of Patients With Pulmonary Fibrosis, Jonathan A Rose, Mark P Steele, Esteban J Kosak Lopez, Gisli Thor Axelsson, Andrea G Galecio Chao, Alan Waich, Katie Regan, Swati Gulati, Anthony H Maeda, Sharmin Sultana, Claire Cutting, Ann-Marcia C Tukpah, Andrew J Synn, Mary B Rice, Hilary J Goldberg, Joyce S Lee, David A Lynch, Rachel K Putman, Hiroto Hatabu, Benjamin A Raby, David A Schwartz, Ivan O Rosas, Gary M Hunninghake

Faculty, Staff and Students Publications

Rationale: First-degree relatives of patients with pulmonary fibrosis (referred to here as relatives) are at high risk for interstitial lung abnormalities (ILA), highlighting the need for biomarkers for risk prediction. We aimed to identify blood proteins associated with and predictive of ILA among relatives of patients with pulmonary fibrosis.

Methods: Relatives enrolled in two independent cohorts had protein levels measured using an aptamer-based proteomic platform. ILA were assessed with computed tomography scans as per Fleischner Society recommendations. Protein associations with ILA were assessed using regression. Significant proteins were used with clinical variables to detect ILA.

Results: Of 237 relatives from …

The Perk/Atf4 Pathway Is Required For Metabolic Reprogramming And Progressive Lung Fibrosis, Jyotsana Pandey, Jennifer L Larson-Casey, Mallikarjun H Patil, Chao He, Nisarat Pinthong, A Brent Carter

Faculty, Staff and Students Publications

Asbestosis is a prototypical type of fibrosis that is progressive and does not resolve. ER stress is increased in multiple cell types that contribute to fibrosis; however, the mechanism(s) by which ER stress in lung macrophages contributes to fibrosis is poorly understood. Here, we show that ER stress resulted in protein kinase RNA-like ER kinase (PERK; Eif2ak3) activation in humans with asbestosis. Similar results were seen in asbestos-injured mice. Mice harboring a conditional deletion of Eif2ak3 were protected from fibrosis. Lung macrophages from asbestosis individuals had evidence of metabolic reprogramming to fatty acid oxidation (FAO). Eif2ak3fl/fl mice had increased oxygen …

Let-7 Restrains An Epigenetic Circuit In At2 Cells To Prevent Fibrogenic Intermediates In Pulmonary Fibrosis, Matthew J Seasock, Md Shafiquzzaman, Maria E Ruiz-Echartea, Rupa S Kanchi, Brandon T Tran, Lukas M Simon, Matthew D Meyer, Phillip A Erice, Shivani L Lotlikar, Stephanie C Wenlock, Scott A Ochsner, Anton Enright, Alex F Carisey, Freddy Romero, Ivan O Rosas, Katherine Y King, Neil J Mckenna, Cristian Coarfa, Antony Rodriguez

Faculty, Staff and Students Publications

MicroRNA-mediated post-transcriptional regulation of lung alveolar type 2 (AT2) and AT1 cell differentiation remains understudied. Here, we demonstrate that the let-7 miRNA family plays a homeostatic role in AT2 quiescence by preventing the uncontrolled accumulation of AT2 transitional cells and promoting AT1 differentiation. Using mouse and organoid models, we show that genetic ablation of let-7a1/let-7f1/let-7d cluster (let-7afd) in AT2 cells prevents AT1 differentiation and leads to KRT8 transitional cell accumulation in progressive pulmonary fibrosis. Integration of AGO2-eCLIP with RNA-sequencing identified direct let-7 targets within an oncogene feed-forward regulatory network, including BACH1/EZH2/MYC, which drives an aberrant fibrotic cascade. Additional CUT&RUN-sequencing analyses …

Early Nintedanib Deployment In Covid-19 Interstitial Lung Disease (Endcov-I): Study Protocol Of A Randomised, Double-Blind, Placebo-Controlled Trial, Valeria Santibanez, Aditi Mathur, Jigna Zatakia, Nicole Ng, Michele Cohen, Emilia Bagiella, Stacey-Ann Brown, Ivan O Rosas, Nina M Patel, Amy Olson, Peide Li, Maria Padilla

Faculty, Staff and Students Publications

Introduction: In December 2019, the novel SARS-CoV-2 triggered a global pneumonia outbreak, leading to millions of deaths worldwide. A subset of survivors faces increased morbidity and mortality, particularly due to subacute lung injury evolving to chronic fibrosing interstitial lung disease. While nintedanib, a tyrosine-kinase inhibitor, shows promise in treating progressive fibrotic lung disease, limited randomised trial data exists for post-COVID-19-induced lung injury. We hypothesise that treatment with nintedanib may attenuate advancement to the fibrotic stages, offering a potential avenue for improving outcomes in this specific patient subset.

Methods and analysis: We describe the design of a multicentre, randomised, double-blind, placebo-controlled …

A Review Of Gut Failure As A Cause And Consequence Of Critical Illness, Danielle E. Soranno, Craig M. Coopersmith, Jessica F. Brinkworth, Faith N. F. Factora, Julia H. Muntean, Monty G. Mythen, Jacob Raphael, Andrew D. Shaw, Vidula Vachharajani, Jeannette S. Messer

Department of Anesthesiology Faculty Papers

In critical illness, all elements of gut function are perturbed. Dysbiosis develops as the gut microbial community loses taxonomic diversity and new virulence factors appear. Intestinal permeability increases, allowing for translocation of bacteria and/or bacterial products. Epithelial function is altered at a cellular level and homeostasis of the epithelial monolayer is compromised by increased intestinal epithelial cell death and decreased proliferation. Gut immunity is impaired with simultaneous activation of maladaptive pro- and anti-inflammatory signals leading to both tissue damage and susceptibility to infections. Additionally, splanchnic vasoconstriction leads to decreased blood flow with local ischemic changes. Together, these interrelated elements of …

Acute-On-Chronic Liver Failure (Aclf): The ‘Kyoto Consensus’-Steps From Asia, Ashok Choudhury, Anand V Kulkarni, Vinod Arora, A S Soin, Abdul Kadir Dokmeci, Abhijeet Chowdhury, Abraham Koshy, Ajay Duseja, Ajay Kumar, Ajay Kumar Mishra, Ajay Kumar Patwa, Ajit Sood, Akash Roy, Akash Shukla, Albert Chan, Aleksander Krag, Amar Mukund, Ameet Mandot, Amit Goel, Amna Subhan Butt, Amrish Sahney, Ananta Shrestha, Andrés Cárdenas, Angelo Di Giorgio, Anil Arora, Anil Chandra Anand, Anil Dhawan, Ankur Jindal, Anoop Saraya, Anshu Srivastava, Anupam Kumar, Apichat Kaewdech, Apurva Pande, Archana Rastogi, Arun Valsan, Ashish Goel, Ashish Kumar, Ashwani K Singal, Atsushi Tanaka, Audrey Coilly, Ayaskanta Singh, Babu Lal Meena, Barath Jagadisan, Barjesh Chander Sharma, Bikrant Bihari Lal, C E Eapen, Cesar Yaghi, Chandan Kumar Kedarisetty, Chang Wook Kim, Charles Panackel, Chen Yu, Chetan R Kalal, Chhagan Bihari, Chien Hao Huang, Chitranshu Vasishtha, Christian Jansen, Christian Strassburg, Chun Yen Lin, Constantine J Karvellas, Cosmas Rinaldi Adithya Lesmana, Cyriac Abby Philips, Debbie Shawcross, Dharmesh Kapoor, Dhiraj Agrawal, Diana Alcantara Payawal, Dibya Lochan Praharaj, Dinesh Jothimani, Do Seon Song, Dong Joon Kim, Dong-Sik Kim, Duan Zhongping, Fazal Karim, Francois Durand, Gamal E Shiha, Gennaro D'Amico, George K Lau, Girish Kumar Pati, Graciela Elia Castro Narro, Guan-Huei Lee, Gupse Adali, Guru Prasad Dhakal, Gyongyi Szabo, H C Lin, Hai Li, Hari Kumar Nair, Harshad Devarbhavi, Harshvardhan Tevethia, Hasmik Ghazinian, Hemamala Ilango, Hong Ling Yu, Irsan Hasan, J Fernandez, Jacob George, Jaideep Behari, James Fung, Jasmohan Bajaj, Jaya Benjamin, Jennifer C Lai, Jidong Jia, Jin Hua Hu, Jin Jun Chen, Jin Lin Hou, Jin Mo Yang, Johannes Chang, Jonel Trebicka, Jörg C Kalf, Jose D Sollano, Joy Varghese, Juan Pablo Arab, Jun Li, K Rajender Reddy, Kaiser Raja, Kalpana Panda, Kamal Kajal, Karan Kumar, Kaushal Madan, Kemal Fariz Kalista, Kessarin Thanapirom, Khin Maung Win, Ki Tae Suk, Krishnadas Devadas, Laurentius A Lesmana, Lubna Kamani, Madhumita Premkumar, Madunil A Niriella, Mamun Al Mahtab, Man Fung Yuen, Manal Hel Sayed, Manasa Alla, Manav Wadhawan, Manoj Kumar Sharma, Manoj Sahu, Manya Prasad, Mark Dhinesh Muthiah, Martin Schulz, Meenu Bajpai, Mettu Srinivas Reddy, Michael Praktiknjo, Ming Lung Yu, Mithra Prasad, Mithun Sharma, Mohamed Elbasiony, Mohammed Eslam, Mohd Golam Azam, Mohd Rela, Moreshwar S Desai, Mukul Vij, Nadim Mahmud, Narendra Singh Choudhary, Navin Kumar Marannan, Necati Ormeci, Neeraj Saraf, Nipun Verma, Nobuaki Nakayama, Norifumi Kawada, Oidov Baatarkhuu, Omesh Goyal, Osamu Yokosuka, P N Rao, Paolo Angeli, Pathik Parikh, Patrick S Kamath, Paul J Thuluvath, Philipp Lingohr, Piyush Ranjan, Prashant Bhangui, Pravin Rathi, Puja Sakhuja, Puneet Puri, Qin Ning, R K Dhiman, Rahul Kumar, Rajan Vijayaraghavan, Rajeev Khanna, Rakhi Maiwall, Ravi Mohanka, Richard Moreau, Rino Alvani Gani, Rohit Loomba, Rohit Mehtani, Ruveena Bhavani Rajaram, S S Hamid, Sachin Palnitkar, Sadhna Lal, Sagnik Biswas, Sakkarin Chirapongsathorn, Samagra Agarwal, Sanjeev Sachdeva, Sanjiv Saigal, Santhosh E Kumar, Sargsyan Violeta, Satender Pal Singh, Satoshi Mochida, Saurabh Mukewar, Seema Alam, Seng Gee Lim, Shahinul Alam, Shalimar, Shantan Venishetty, Shikha S Sundaram, Shiran Shetty, Shobna Bhatia, Shweta A Singh, Shyam Kottilil, Simone Strasser, S M Shasthry, Soe Thiha Maung, Soek Siam Tan, Sombat Treeprasertsuk, Sonal Asthana, Steffen Manekeller, Subhash Gupta, Subrat Kumar Acharya, Sudhamshu K C, Sudhir Maharshi, Sumeet Asrani, Sunil Dadhich, Sunil Taneja, Suprabhat Giri, Surender Singh, Tao Chen, Tarana Gupta, Tatsuo Kanda, Tawesak Tanwandee, Teerha Piratvishuth, Ulrich Spengler, V G Mohan Prasad, Vandana Midha, Venera Rakhmetova, Vicente Arroyo, Vikrant Sood, Vinay Kumar Br, Vincent Wai-Sun Wong, Viniyendra Pamecha, Virendra Singh, Vishwa Mohan Dayal, Vivek A Saraswat, Wray Kim, Wasim Jafri, Wenyi Gu, Wong Yu Jun, Xiaolong Qi, Yogesh K Chawla, Yoon Jun Kim, Yu Shi, Zaigham Abbas, Guresh Kumar, Shuichiro Shiina, Lai Wei, Masao Omata, Shiv Kumar Sarin, Apasl-Aclf Research Consortium (Aarc) For Apasl-Aclf Working Party

Faculty, Staff and Students Publications

Acute-on-chronic liver failure (ACLF) is a condition associated with high mortality in the absence of liver transplantation. There have been various definitions proposed worldwide. The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set in 2004 on ACLF was published in 2009, and the "APASL ACLF Research Consortium (AARC)" was formed in 2012. The AARC database has prospectively collected nearly 10,500 cases of ACLF from various countries in the Asia-Pacific region. This database has been instrumental in developing the AARC score and grade of ACLF, the concept of the …

Oxidative Stress Promotes Lipid-Laden Macrophage Formation Via Cyp1b1, Yin Zhu, Saugata Dutta, Yohan Han, Dooyoung Choi, Francesca Polverino, Caroline A Owen, Payaningal R Somanath, Xiaoyun Wang, Duo Zhang

Faculty, Staff and Students Publications

Emerging evidence suggests that lipid-laden macrophages (LLM) participate in lung damage in various clinical conditions. However, the mechanisms involved in LLM formation are not fully understood. In this study, we aimed to investigate the link between reactive oxygen species (ROS) and LLM formation. We found that ROS triggered by cigarette smoke extract (CSE) or H2O2 significantly promoted LLM formation. Given the key role of ROS in LLM formation, we further demonstrated that LLM formation is induced by various ROS-producing stimuli, including bacteria, oxidized low-density lipoprotein (OxLDL), hyperoxia, and E-cigarette vapor extract (EVE). Meanwhile, cytochrome P450 family-1 subfamily B member 1 …

Research Progress And Clinical Translation Potential Of Coronary Atherosclerosis Diagnostic Markers From A Genomic Perspective, Hanxiang Liu, Yuchen Zhang, Yueyan Zhao, Yuzhen Li, Xiaofeng Zhang, Lingyu Bao, Rongkai Yan, Yixin Yang, Huixian Zhou, Jinming Zhang, Siyuan Song

Children’s Nutrition Research Center Staff Publications

Objective: Coronary atherosclerosis (CAD) is characterized by arterial intima lipid deposition, chronic inflammation, and fibrous tissue proliferation, leading to arterial wall thickening and lumen narrowing. As the primary cause of coronary heart disease and acute coronary syndrome, CAD significantly impacts global health. Recent genetic studies have demonstrated CAD's polygenic and multifactorial nature, providing molecular insights for early diagnosis and risk assessment. This review analyzes recent advances in CAD-related genetic markers and evaluates their diagnostic potential, focusing on their applications in diagnosis and risk stratification within precision medicine.

Methods: We conducted a systematic review of CAD genomic studies from PubMed and …

Synesis As A Framework To Enable Safety Interventions In Complex Healthcare Environments, Aarti Bavare, Tiffany Wrenn, Anne Lam, Jamie Cargill, Lauren Salinas, Itode Idowu, Asma Razavi, Venessa Lynn Pinto, Eric Williams

Faculty, Staff and Students Publications

BACKGROUND: Despite wide adoption in the healthcare of safety event report (SER) systems, there is a paucity of unified structures for prompt analysis and action while retaining reporter confidentiality. We used a synesis framework to change siloed reviews of safety reports to a comprehensive appraisal of quality, safety, productivity and reliability to facilitate interventions.

METHODS: After a needs assessment survey, we launched serial plan-do-study-act cycles to (1) enhance teams' ability to access SERs, (2) facilitate regular multidisciplinary review of SERs to identify actionable opportunities, (3) allocate action priority using failure mode and effects analysis, and (4) launch actions and summarise …