Critical Care Commons^™

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 …

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 …

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 …

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, …

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 …

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 …

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 …

Long-Term Anti-Sars-Cov-2 Antibody Trajectories After Neutralizing Monoclonal Antibody Treatment, Elizabeth S Munroe, Greg A Grandits, Robert C Hyzy, Hallie C Prescott, Thomas W Barrett, Robin L Dewar, Nicole Engen, Anna L Goodman, Timothy J Hatlen, Helene Highbarger, Thomas L Holland, Gareth Hughes, Tomas O Jensen, Muhammad A Khan, Ioannis Kalomenidis, Nayon Kang, Sylvain Laverdure, Prasad Manian, Vidya Menon, Ravi Patel, Srikanth Ramachandruni, Tauseef Rehman, Kathryn Shaw-Saliba, Birgit Thorup Røge, David M Vock, Amy C Weintrob, Barnaby E Young, Anne P Frosch, Strive Network And Therapeutics For Inpatients With Covid-19 (Tico) Study Groups

Faculty, Staff and Students Publications

Background: Neutralizing monoclonal antibodies (nMAbs) have been used to treat COVID-19 and are increasingly being used to treat other infections. However, there is concern that by neutralizing the SARS-CoV-2 virus, nMAbs may decrease the availability of antigens to the immune system, potentially impairing the endogenous polyclonal immune response and decreasing long-term immune protection.

Methods: We compared 28 and 90-day anti-SARS-CoV-2 spike protein neutralization activity and anti-SARS-CoV-2 nucleocapsid response for patients hospitalized with COVID-19 infection randomized to receive nMAbs or placebo in the large platform ACTIV-3/TICO trials. We pooled results from four trials of anti-spike nMAbs. For most tested agents, measurements …

B-Cell Immune Repertoire Sequencing In Tobacco Cigarette Smoking, Vaping, And Chronic Obstructive Pulmonary Disease In The Copdgene Cohort, Matthew Moll, Zhonghui Xu, Adel Boueiz, Min Hyung Ryu, Edwin K Silverman, Michael H Cho, Craig P Hersh, Maor Sauler, Francesca Polverino, Gregory L Kinney, Jeffrey L Curtis, Laura E Crotty-Alexander, Christopher Vollmers, Peter J Castaldi

Faculty, Staff and Students Publications

Rationale: Cigarette smoking (CS) impairs B-cell function and antibody production, increasing infection risk. The impact of e-cigarette use ('vaping') and combined CS and vaping ('dual-use') on B-cell activity is unclear.

Objective: To examine B-cell receptor sequencing (BCR-seq) profiles associated with CS, vaping, and dual-use.

Methods: BCR-seq was performed on blood RNA samples from 234 participants in the COPDGene study. We assessed multivariable associations of B-cell function measures (immunoglobulin heavy chain (IGH) subclass expression and usage, class-switching, V allele usage, and clonal expansion) with CS, vaping, and dual-use. We adjusted for multiple comparisons using the Benjamini-Hochberg method, identifying significant associations at …

Mice With Lymphatic Dysfunction Develop Pathogenic Lung Tertiary Lymphoid Organs That Model An Autoimmune Emphysema Phenotype Of Copd, Barbara Summers, Kihwan Kim, Anjali Trivedi, Tyler M Lu, Sean Houghton, Jade Palmer-Johnson, Joselyn Rojas-Quintero, Juan Cala-Garcia, Tania Pannellini, Francesca Polverino, Raphaël Lis, Hasina Outtz Reed

Faculty, Staff and Students Publications

We have previously shown that mice with a loss of C-type lectin-like type II (CLEC2), which have lymphatic dysfunction due to the role of CLEC2 in platelets for maintaining separation between the venous and lymphatic system, develop lung tertiary lymphoid organ (TLO) formation and lung injury that resembles an emphysema phenotype of chronic obstructive pulmonary disease (COPD). We now sought to investigate whether and how TLOs in these mice may play a pathogenic role in lung injury that is relevant to human disease. We found that inhibiting TLO formation using an anti-CD20 antibody in CLEC2-deficient mice partially blocked the development …

Lung Tissue Multilayer Network Analysis Uncovers The Molecular Heterogeneity Of Chronic Obstructive Pulmonary Disease, Nuria Olvera, Jon Sánchez-Valle, Iker Núñez-Carpintero, Joselyn Rojas-Quintero, Guillaume Noell, Sandra Casas-Recasens, Alen Faiz, Philip Hansbro, Angela Guirao, Rosalba Lepore, Davide Cirillo, Alvar Agustí, Francesca Polverino, Alfonso Valencia, Rosa Faner

Faculty, Staff and Students Publications

Rationale: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition. Objectives: We hypothesized that the unbiased integration of different COPD lung omics using a novel multilayer approach might unravel mechanisms associated with clinical characteristics.

Methods: We profiled mRNA, microRNA and methylome in lung tissue samples from 135 former smokers with COPD. For each omic (layer), we built a patient network on the basis of molecular similarity. The three networks were used to build a multilayer network, and optimization of multiplex modularity was used to identify patient communities across the three distinct layers. Uncovered communities were related to clinical features.

Measurements …

Transcutaneous Electrical Nerve Stimulation For Fibromyalgia-Like Syndrome In Patients With Long-Covid: A Pilot Randomized Clinical Trial, Alejandro Zulbaran-Rojas, Rasha O Bara, Myeounggon Lee, Miguel Bargas-Ochoa, Tina Phan, Manuel Pacheco, Areli Flores Camargo, Syed Murtaza Kazmi, Mohammad Dehghan Rouzi, Dipaben Modi, Fidaa Shaib, Bijan Najafi

Faculty, Staff and Students Publications

This study investigated the effect of Transcutaneous Electrical Nerve Stimulation (TENS) for fibromyalgia-like symptoms including chronic widespread musculoskeletal pain, fatigue, and/or gait impairment in twenty-five individuals with long-COVID. Participants were randomized to a high dose (intervention group, IG) or low dose (placebo group, PG) TENS device. Both groups received daily 3-5 h of TENS therapy for 4-weeks. The Brief Pain Inventory assessed functional interference from pain (BPI-I), and pain severity (BPI-S). The global fatigue index (GFI) assessed functional interference from fatigue. Wearable technology measured gait parameters during three 30-feet consecutive walking tasks. At 4-weeks, the IG exhibited a greater decrease …

Effectiveness Of Original Monovalent And Bivalent Covid-19 Vaccines Against Covid-19-Associated Hospitalization And Severe In-Hospital Outcomes Among Adults In The United States, September 2022-August 2023, Jennifer Decuir, Diya Surie, Yuwei Zhu, Adam S Lauring, Manjusha Gaglani, Tresa Mcneal, Shekhar Ghamande, Ithan D Peltan, Samuel M Brown, Adit A Ginde, Aimee Steinwand, Nicholas M Mohr, Kevin W Gibbs, David N Hager, Harith Ali, Anne Frosch, Michelle N Gong, Amira Mohamed, Nicholas J Johnson, Vasisht Srinivasan, Jay S Steingrub, Akram Khan, Laurence W Busse, Abhijit Duggal, Jennifer G Wilson, Nida Qadir, Steven Y Chang, Christopher Mallow, Jennie H Kwon, Matthew C Exline, Nathan I Shapiro, Cristie Columbus, Ivana A Vaughn, Mayur Ramesh, Basmah Safdar, Jarrod M Mosier, Jonathan D Casey, H Keipp Talbot, Todd W Rice, Natasha Halasa, James D Chappell, Carlos G Grijalva, Adrienne Baughman, Kelsey N Womack, Jillian P Rhoads, Sydney A Swan, Cassandra Johnson, Nathaniel Lewis, Sascha Ellington, Fatimah S Dawood, Meredith Mcmorrow, Wesley H Self, Investigating Respiratory Viruses In The Acutely Ill (Ivy) Network

Faculty, Staff and Students Publications

BACKGROUND: Assessments of COVID-19 vaccine effectiveness are needed to monitor the protection provided by updated vaccines against severe COVID-19. We evaluated the effectiveness of original monovalent and bivalent (ancestral strain and Omicron BA.4/5) COVID-19 vaccination against COVID-19-associated hospitalization and severe in-hospital outcomes.

METHODS: During September 8, 2022 to August 31, 2023, adults aged ≥ 18 years hospitalized with COVID-19-like illness were enrolled at 26 hospitals in 20 US states. Using a test-negative case-control design, we estimated vaccine effectiveness (VE) with multivariable logistic regression adjusted for age, sex, race/ethnicity, admission date, and geographic region.

RESULTS: Among 7028 patients, 2924 (41.6%) were …

Gender And Sexuality Awareness In Medical Education And Practice: Mixed Methods Study, Rola Khamisy-Farah, Eden Biras, Rabie Shehadeh, Ruba Tuma, Hisham Atwan, Anna Siri, Manlio Converti, Francesco Chirico, Łukasz Szarpak, Carlo Biz, Raymond Farah, Nicola Bragazzi

Faculty, Staff and Students Publications

BACKGROUND: The integration of gender and sexuality awareness in health care is increasingly recognized as vital for patient outcomes. Despite this, there is a notable lack of comprehensive data on the current state of physicians' training and perceptions in these areas, leading to a gap in targeted educational interventions and optimal health care delivery.

OBJECTIVE: The study's aim was to explore the experiences and perceptions of attending and resident physicians regarding the inclusion of gender and sexuality content in medical school curricula and professional practice in Israel.

METHODS: This cross-sectional survey targeted a diverse group of physicians across various specializations …

Continuous Kidney Replacement Therapy And Survival In Children And Young Adults: Findings From The Multinational We-Rock Collaborative, Michelle C Starr, Katja M Gist, Huaiyu Zang, Nicholas J Ollberding, Shanthi Balani, Andrea Cappoli, Eileen Ciccia, Catherine Joseph, Aadil Kakajiwala, Aaron Kessel, Melissa Muff-Luett, María J Santiago Lozano, Matthew Pinto, Stephanie Reynaud, Sonia Solomon, Cara Slagle, Rachana Srivastava, Weiwen V Shih, Tennille Webb, Shina Menon

Faculty, Staff and Students Publications

RATIONALE & OBJECTIVE: There are limited studies describing the epidemiology and outcomes in children and young adults receiving continuous kidney replacement therapy (CKRT). We aimed to describe associations between patient characteristics, CKRT prescription, and survival.

STUDY DESIGN: Retrospective multicenter cohort study.

SETTING & PARTICIPANTS: 980 patients aged from birth to 25 years who received CKRT between 2015 and 2021 at 1 of 32 centers in 7 countries participating in WE-ROCK (Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Diseases).

EXPOSURE: CKRT for acute kidney injury or volume overload.

OUTCOMES: Death before intensive care unit (ICU) discharge.

ANALYTICAL APPROACH: Descriptive …

Evaluation Of Vancomycin Dose Needed To Achieve 24-Hour Area Under The Concentration-Time Curve To Minimum Inhibitory Concentration Ratio Greater Than Or Equal To 400 Using Pharmacometric Approaches In Pediatric Intensive Care Patients, Dawoon Jung, Omayma A Kishk, Adnan T Bhutta, Ginny E Cummings, Hana M El Sahly, Manpreet K Virk, Brady S Moffett, Jennifer L Morris Daniel, Amy Watanabe, Nicholas Fishbane, Karen L Kotloff, Kenan Gu, Varduhi Ghazaryan, Jogarao V S Gobburu, Ayse Akcan-Arikan, James D Campbell

Faculty, Staff and Students Publications

OBJECTIVES: To investigate which independent factor(s) have an impact on the pharmacokinetics of vancomycin in critically ill children, develop an equation to predict the 24-hour area under the concentration-time curve from a trough concentration, and evaluate dosing regimens likely to achieve a 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC24/MIC) greater than or equal to 400.

DESIGN: Prospective population pharmacokinetic study of vancomycin.

SETTING: Critically ill patients in quaternary care PICUs.

PATIENTS: Children 90 days old or older to younger than 18 years who received IV vancomycin treatment, irrespective of the indication for use, in the …

The Association Between Vaso/Pressin And Adverse Kidney Outcomes In Children And Young Adults Requiring Vasopressors On Continuous Renal Replacement Therapy, Denise C Hasson, Katja M Gist, Jangdong Seo, Erin K Stenson, Aaron Kessel, Taiki Haga, Sara Lafever, Maria Jose Santiago, Matthew Barhight, David Selewski, Zaccaria Ricci, Nicholas J Ollberding, Natalja L Stanski, The Worldwide Exploration Of Renal Replacement Outcomes Collaborative In Kidney Disease (We-Rock) Collaborative

Faculty, Staff and Students Publications

OBJECTIVES: Continuous renal replacement therapy (CRRT) and shock are both associated with high morbidity and mortality in the ICU. Adult data suggest renoprotective effects of vasopressin vs. catecholamines (norepinephrine and epinephrine). We aimed to determine whether vasopressin use during CRRT was associated with improved kidney outcomes in children and young adults.

DESIGN: Secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), a multicenter, retrospective cohort study.

SETTING: Neonatal, cardiac, PICUs at 34 centers internationally from January 1, 2015, to December 31, 2021.

PATIENTS/SUBJECTS: Patients younger than 25 years receiving CRRT for acute kidney injury and/or …

The Discover In-Hospital Cardiac Arrest (Discover Ihca) Study: An Investigation Of Hospital Practices After In-Hospital Cardiac Arrest, Luke Andrea, Nathaniel S Herman, Jacob Vine, Katherine M Berg, Saiara Choudhury, Mariana Vaena, Jordan E Nogle, Saleem M Halablab, Aarthi Kaviyarasu, Jonathan Elmer, Gabriel Wardi, Alex K Pearce, Conor Crowley, Micah T Long, J Taylor Herbert, Kipp Shipley, Brittany D Bissell Turpin, Michael J Lanspa, Adam Green, Shekhar A Ghamande, Akram Khan, Siddharth Dugar, Aaron M Joffe, Michael Baram, Cooper March, Nicholas J Johnson, Alexander Reyes, Krassimir Denchev, Michael Loewe, Ari Moskowitz

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

IMPORTANCE: In-hospital cardiac arrest (IHCA) is a significant public health burden. Rates of return of spontaneous circulation (ROSC) have been improving, but the best way to care for patients after the initial resuscitation remains poorly understood, and improvements in survival to discharge are stagnant. Existing North American cardiac arrest databases lack comprehensive data on the post-resuscitation period, and we do not know current post-IHCA practice patterns. To address this gap, we developed the Discover In-Hospital Cardiac Arrest (Discover IHCA) study, which will thoroughly evaluate current post-IHCA care practices across a diverse cohort.

OBJECTIVES: Our study collects granular data on post-IHCA …

Overcoming Egfr-Tki Resistance By Targeting The Tumor Microenvironment, Jinsong Zhang, Natalie Vokes, Man Li, Jiachen Xu, Hua Bai, Jie Wang, Zhijie Wang, Jianjun Zhang

Faculty, Staff and Student Publications

Targeted therapy has ushered in a new era of precision medicine for non-small cell lung cancer (NSCLC). Currently, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) stand as the recommended first-line therapy for advanced NSCLC harboring sensitive EGFR mutations. Nevertheless, most patients inevitably confront the challenge of drug resistance. This phenomenon arises not solely from intrinsic alterations within cancer cells but also from the intricate dynamics of the tumor microenvironment and the complex interactions that occur between cancer cells and their immediate surroundings. This review consolidates the current knowledge regarding EGFR-TKI resistance mechanisms, with a specific emphasis on unraveling the …

Deployment-Related Cigarette Smoking Behaviors And Pulmonary Function Among Us Veterans, Jennifer R Maccarone, Olivia R Sterns, 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, Michael Jerrett, Ware G Kuschner, Octavian C Ioachimescu, Philippe R Montgrain, Susan P Proctor, Carrie A Redlich, Christine H Wendt, Paul D Blanc, Eric Garshick, Emily S Wan

Faculty, Staff and Students Publications

Introduction: The effects of smoking on lung function among post-9/11 Veterans deployed to environments with high levels of ambient particulate matter are incompletely understood.

Materials and methods: We analyzed interim data (04/2018-03/2020) from the Veterans Affairs (VA) Cooperative Studies Program #595, "Service and Health Among Deployed Veterans". Veterans with ≥1 land-based deployments enrolled at 1 of 6 regional Veterans Affairs sites completed questionnaires and spirometry. Multivariable linear regression models assessed associations between cigarette smoking (cumulative, deployment-related and non-deployment-related) with pulmonary function.

Results: Among 1,836 participants (mean age 40.7 ± 9.6, 88.6% male), 44.8% (n = 822) were ever-smokers (mean age …

Vitamin D And Metabolic Bone Disease In Prolonged Continuous Kidney Replacement Therapy: A Prospective Observational Study, Peace Dorothy Imani, Molly Vega, Naile Tufan Pekkucuksen, Poyyapakkam Srivaths, Ayse Akcan Arikan

Faculty, Staff and Students Publications

BACKGROUND: Complications of prolonged continuous kidney replacement therapy (CKRT) have not been well described. Our objective was to describe mineral metabolism and bone findings in children who required prolonged CKRT.

METHODS: In this single center prospective observational study, we enrolled 37 patients who required CKRT for ≥ 28 days with regional citrate anticoagulation. Exposure was duration on CKRT and outcomes were 25-hydroxy vitamin D and osteopenia and/or fractures.

RESULTS: The prevalence of vitamin D deficiency and insufficiency was 17.2% and 69.0%, respectively. 29.7% of patients had radiographic findings of osteopenia and/or fractures. There was no association between vitamin D deficiency …

Pre-Existing Immunocompromising Conditions And Outcomes Of Acute Covid-19 Patients Admitted For Pediatric Intensive Care, Courtney M Rowan, Brenna Labere, Cameron C Young, Laura D Zambrano, Margaret M Newhams, Suden Kucukak, Elizabeth R Mcnamara, Elizabeth H Mack, Julie C Fitzgerald, Katherine Irby, Aline B Maddux, Jennifer E Schuster, Michele Kong, Heda Dapul, Stephanie P Schwartz, Melania M Bembea, Laura L Loftis, Amanda R Kolmar, Christopher J Babbitt, Ryan A Nofziger, Mark W Hall, Shira J Gertz, Natalie Z Cvijanovich, Matt S Zinter, Natasha B Halasa, Tamara T Bradford, Gwenn E Mclaughlin, Aalok R Singh, Charlotte V Hobbs, Kari Wellnitz, Mary A Staat, Bria M Coates, Hillary R Crandall, Mia Maamari, Kevin M Havlin, Adam J Schwarz, Christopher L Carroll, Emily R Levy, Kristin L Moffitt, Angela P Campbell, Adrienne G Randolph, Janet Chou

Faculty, Staff and Students Publications

BACKGROUND: We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care.

METHODS: Fifty-five hospitals in 30 US states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients(PICU) or high-acuity unit for acute COVID-19 were included.

RESULTS: Of 1274 patients, 105 (8.2%) had an ICC, including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid-organ transplantation, 16 (15.2%) solid tumors, and 13 (12.4%) autoimmune disorders. Patients with ICCs were …