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Objectives: To explore the breadth of social, demographic, and economic (SDE) factors reported in critical illness survivorship research, with a focus on how they impact survivorship outcomes., Data Sources: We obtained articles from Medline, Embase, PsycInfo, and CINAHL, as well as reference list reviews of included articles and relevant reviews captured by searches., Study Selection: SDE factors were defined as any nonmedical factor that can influence outcomes. We included primary studies published in English that explored SDE factors as an independent variable or as an outcome in post-ICU survivorship of adults. Two authors independently assessed each study for inclusion in duplicate, and conflicts were resolved by consensus. Our searches returned 7151 records, of which 83 were included for data extraction and final review., Data Extraction: We used a standardized data collection form to extract data, focusing on the characteristics of each study (i.e., year and country of publication), SDE factors explored, how the factors were measured, the impacts of SDE factors on post-ICU survivorship outcomes, and the impacts of ICU admission on SDE outcomes., Data Synthesis: We summarized the relationships between SDE factors and ICU survivorship in table format and performed a narrative synthesis. We identified 16 unique SDE factors explored in the current literature. We found that generally, higher education, income, and socioeconomic status were associated with better outcomes post-ICU; while non-White race, public insurance status, and social vulnerability were associated with poorer outcomes., Conclusions: Various SDE factors have been explored in the critical illness survivorship literature and many are associated with post-ICU outcomes with varying effect sizes. There remains a gap in understanding longitudinal outcomes, mechanisms of how SDE factors interact with outcomes, and of the complexity and interconnectedness of these factors, all of which will be instrumental in guiding interventions to improve post-ICU survivorship., Competing Interests: Dr. Howard holds a Scholar Award from Michael Smith Health Research British Columbia. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2025 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: Most Canadians receive their care in community hospitals, yet most clinical research is conducted in academic hospitals. This study aims to compare patients with community acquired pneumonia (CAP) treated in academic and community hospitals with respect to their demographics, clinical characteristics, treatments and outcomes., Methods: This nested observational cohort substudy of the Community Acquired Pneumonia: Toward InnoVAtive Treatment (CAPTIVATE) trial included 1,329 hospitalized adults with CAP recruited between March 1st, 2018 and September 31st, 2023 from 15 Canadian hospitals. Unadjusted and adjusted analyses for age, sex and co-morbidities using logistic, Cox and censored quantile regressions were conducted., Results: Patients in community hospitals were older (mean [SD] 75.0 [15.7] years vs. 68.3 [16.2] years; p < 0.001), were more likely to be female (49.7% vs. 41.0%, p = 0.002), and had more comorbidities (75.9% vs. 64.8%, p < 0.001). More patients in community hospitals received corticosteroids (49.2% vs. 37.4%, p < 0.001). Community hospital patients had a higher likelihood of developing acute respiratory distress syndrome (OR 3.13, 95% CI: 1.87, 5.24, p = < 0.001), and acute cardiac injury (OR 2.53, 95% CI: 1.33, 4.83, p = 0.005). In unadjusted and adjusted analyses, 28-day mortality difference did not meet statistical significance (OR 1.43, 95% CI: 0.98, 20.7, p = 0.062 and OR 1.23, 95% CI: 0.81, 1.87, p = 0.332, respective)., Conclusion: Patients with CAP in Canadian community and academic hospitals differed with respect to their age, clinical characteristics, treatments and outcomes, emphasizing the importance of including more community hospitals in clinical research studies to ensure the generalizability of results., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval was received from the University of British Columbia Providence Health Care Research Ethics Board (REB Number: H20-00600) and by each of the participating sites. Consent for publication: Not applicable. Competing interests: Support for CAPTIVATE was obtained from grants to J.A.R. from the Canadian Institutes of Health Research (grant number: 439993) and St. Paul’s Hospital Foundation. J.B. is a recipient of a Providence Health Care Research Scholarship. K.W. is supported by Canadian Institutes of Health Research (CIHR) Foundation Grant (FDN 154311). A.F.T. is the chairholder of the Canada Research Chair in Critical care neurology and trauma. D.C.V. is supported by the Fonds de recherche du Québec – Santé (FRQS) clinician-scientist Senior scholar award. D.C.V. has received funding support from the Jeffrey Modell Foundation, FRQS, and Canadian Institutes of Health Research. D.C.V. has served on advisory boards for: Astra Zeneca; CSL Behring; Novartis Canada; Moderna; Takeda. D.C.V. has received speaker honoraria from: CSL Behring; Merck Canada. DCV has a patent application pending (Electronic Filing System ID: 40101099) unrelated to this work. M.C. reports grants from the Canadian Institutes of Health Research during the conduct of the study and is supported by the Fonds de Recherche du Québec – Santé. M.C. reports personal fees from GEn1E Lifesciences and from nomic bio as a member of the scientific advisory board, as well as honoraria from AstraZeneca, Takeda, Merck, and Pfizer. M.C. reports research support from Cidara therapeutics, from Scynexis, Inc., and from Amplyx Pharmaceutics during the conduct of the study but outside the submitted work. M.C. is the co-founder of Kanvas Biosciences, Inc. and owns equity in the company. M.C. has pending patents, including: i) Methods for detecting tissue damage, graft versus host disease, and infections using cell-free DNA profiling, ii) Methods for assessing the severity and progression of SARS-CoV-2 infections using cell-free DNA pending., (© 2024. The Author(s).)

Objectives: There are health disparities and inequities in the outcomes of critical illness survivors related to the influence of social determinants of health on recovery. The purpose of this study was to describe the relationship between critical illness recovery and the intermediary social determinants of health in the Canadian context. Because Canadian healthcare is provided within a universal publicly funded system, this analysis sheds light on the role of social determinants of health in the context of universal health services and a relatively robust social safety net., Design: In this qualitative interpretive description study, data from semi-structured interviews with intensive care unit survivors, family caregivers and healthcare providers were analysed using thematic and constant comparative methods., Setting: Western Canadian Hospital serving a population of 900 000 people., Participants: The 74 study participants included 30 patients (mean age 58 years, 18 men and 12 women) and 25 family caregivers (mean age 55 years, 8 men and 17 women), representing 37 cases, as well as 19 healthcare providers., Results: Challenges with employment and finances, home set-up, transportation, food and nutrition, medications and social support complicated and hindered critical illness recovery. Critical illness sequelae also altered these social determinants of health, suggesting a reciprocal relationship. Furthermore, individuals experiencing socioeconomic disadvantage before critical illness described being at a greater disadvantage following their critical illness, which interfered with their recovery and suggests an accumulation of risk for some., Conclusions: Our findings underscore the significant influence of social determinants of health on critical illness recovery, highlighting the importance of creating and evaluating comprehensive approaches to health and well-being that address health inequities., Competing Interests: Competing interests: RCA has received honoraria from Edwards Lifesciences and HLS Therapeutics. RCA is on the Advisory Board for Renibus Therapeutics. All honoraria and board membership are for work unrelated to this manuscript. SC has received honoraria from Baxter Healthcare for work unrelated to this manuscript. No other authors have any potential competing interests to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Acute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair., Objective: To map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis., Methods: We analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC-MS/MS and DI-MS/MS analytical platforms., Results: Distinct metabolic phenotypes were detected between different infectious causes of ARDS. There were metabolomics differences between ARDSs associated with COVID-19 and H1N1, which include metabolic pathways involving taurine and hypotaurine, pyruvate, TCA cycle metabolites, lysine, and glycerophospholipids. ARDSs associated with bacterial pneumonia and COVID-19 differed in the metabolism of D-glutamine and D-glutamate, arginine, proline, histidine, and pyruvate. The metabolic profile of COVID-19 ARDS (C19/A) patients admitted to the ICU differed from COVID-19 pneumonia (C19/P) patients who were not admitted to the ICU in metabolisms of phenylalanine, tryptophan, lysine, and tyrosine. Metabolomics analysis revealed significant differences between C19/A, H1N1/A, and PNA/A vs ICU-ventilated controls, reflecting potentially different disease mechanisms., Conclusion: Different metabolic phenotypes characterize ARDS associated with different viral and bacterial infections., (© 2024. The Author(s).)

Introduction: The thrombo-inflammatory response and outcomes of community-acquired pneumonia (CAP) due to various organisms (non-COVID-19 CAP) versus CAP due to a single virus, SARS-CoV-2 (i.e., COVID-19) may differ., Methods: Adults hospitalized with non-COVID-19 CAP (December 1, 2021-June 15, 2023) or COVID-19 (March 2, 2020-June 15, 2023) in Canada. We compared non-COVID-19 CAP and COVID-19 baseline, thrombo-inflammatory response, and mortality. We measured plasma cytokine and coagulation factor levels in a sample of patients, did hierarchical clustering, and compared cytokine and coagulation factor levels., Results: In 2,485 patients (non-COVID-19 CAP, n = 719; COVID-19 patients, n = 2,157), non-COVID-19 CAP patients had significantly lower 28-day mortality (CAP vs. COVID-19 waves 1 and 2; 10% vs. 18% and 16%, respectively), intensive care unit admission (CAP vs. all waves; 15% vs. 39%, 37%, 33%, and 24%, respectively), invasive ventilation (CAP vs. waves 1, 2, and 3 patients; 11% vs. 25%, 20%, and 16%), vasopressor use (CAP 12% vs. 23%, 21%, and 18%), and renal replacement therapy use (CAP 3% vs. Omicron 7%). Complexity of hierarchical clustering aligned directly with mortality: COVID-19 wave 1 and 2 patients had six clusters at admission and higher mortality than non-COVID-19 CAP and Omicron that had three clusters at admission. Pooling all COVID-19 waves increased complexity with seven clusters on admission., Conclusion: Complex thrombo-inflammatory responses aligned with mortality of CAP. At a fundamental level, the human thrombo-inflammatory response to a brand new virus was "confused" whereas humans had eons of time to develop a more concise efficient thrombo-inflammatory host response to CAP., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Omicron is the current predominant variant of concern of SARS-CoV-2. We hypothesized that vaccination alters outcomes of patients hospitalized with COVID-19 during the Omicron wave and that these patients have different characteristics and outcomes than in previous waves., Methods: This is a substudy of the Host Response Mediators in Coronavirus (COVID-19) Infection (ARBs CORONA I) trial, which included adults admitted to hospital with acute COVID-19 up to July 2022 from 9 hospitals in British Columbia, Ontario and Quebec. We excluded emergency department visits without hospital admission, readmissions and admissions for another reason. Using adjusted regression analysis, we compared mortality and organ dysfunction between vaccinated (≥ 2 doses) and unvaccinated patients during the Omicron wave, as well as between all patients in the Omicron and first 3 waves of the COVID-19 pandemic., Results: During the Omicron wave, 28-day mortality was significantly lower in vaccinated ( n = 19/237) than unvaccinated hospitalized patients ( n = 12/127) (adjusted odds ratio [OR] 0.36, 95% confidence interval [CI] 0.15-0.89); vaccinated patients had lower risk of admission to the intensive care unit, invasive ventilation and acute respiratory distress syndrome and shorter hospital length of stay. Patients hospitalized during the Omicron wave had more comorbidities than in previous waves, and lower 28-day mortality than in waves 1 and 2 (adjusted OR 0.38, 95% CI 0.24-0.59; and 0.42, 95% CI 0.26-0.65) but not wave 3 (adjusted OR 0.81, 95% CI 0.43-1.51) and had less organ dysfunction than in the first 2 waves., Interpretation: Patients who were at least double vaccinated had lower mortality than unvaccinated patients hospitalized during the Omicron wave. Patients hospitalized during the Omicron wave had more chronic disease and lower mortality than in the first 2 waves, but not wave 3. Changes in vaccination, treatments and predominant SARS-CoV-2 variant may have decreased mortality in patients hospitalized during the Omicron wave., Competing Interests: Competing interests: Keith Walley reports receiving a Canadian Institutes of Health Research (CIHR) Foundation grant, paid to the University of British Columbia. Dr. Walley has also participated on data safety monitoring boards (unpaid) for Northern Therapeutics and the Cellular Immuno-Therapy for COVID-19 Acute Respiratory Distress Syndrome (CIRCA-19) trial. Allison McGeer reports receiving grants from Sanofi, Merck and Pfizer (paid to institution), as well as payment or honoraria from AstraZeneca, Merck, Biogen and Moderna. Dr. McGeer has also received travel support from Moderna and has participated on a data safety monitoring or advisory board for Pfizer, GlaxoSmithKline, Moderna, Medicago, Janssen, AstraZeneca, Novavax and Sanofi., (© 2023 CMA Impact Inc. or its licensors.)

Competing Interests: Dr. Howard holds a Michael Smith Health Research British Columbia Scholar Award. The remaining authors have disclosed that they do not have any potential conflicts of interest

Background: There have been multiple waves in the COVID-19 pandemic in many countries. We sought to compare mortality and respiratory, cardiovascular and renal dysfunction between waves in 3 Canadian provinces., Methods: We conducted a substudy of the ARBs CORONA I study, a multicentre Canadian pragmatic observational cohort study that examined the association of pre-existing use of angiotensin receptor blockers with outcomes in adults admitted to hospital with acute COVID-19 up to April 2021 from 9 community and teaching hospitals in 3 Canadian provinces (British Columbia, Ontario and Quebec). We excluded emergency department admissions without hospital admission, readmissions and admissions for another reason. We used logistic and 0-1-inflated β regression models to compare 28-day and in-hospital mortality, and the use of invasive mechanical ventilation, vasopressors and renal replacement therapy (RRT) between the first 3 waves of the COVID-19 pandemic in these provinces., Results: A total of 520, 572 and 245 patients in waves 1, 2 and 3, respectively, were included. Patients in wave 3 were on average younger and had fewer comorbidities than those in waves 1 and 2. The unadjusted 28-day mortality rate was significantly lower in wave 3 (7.8%) than in wave 1 (18.3%) (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.24-0.78) and wave 2 (16.3%) (OR 0.46, 95% CI 0.27-0.79). After adjustment for differences in baseline characteristics, the difference in 28-day mortality remained significant (adjusted OR wave 3 v. wave 1: 0.46, 95% CI 0.26-0.81; wave 3 v. wave 2: 0.52, 95% CI 0.29-0.91). In-hospital mortality findings were similar. Use of invasive mechanical ventilation or vasopressors was less common in waves 2 and 3 than in wave 1, and use of RRT was less common in wave 3 than in wave 1., Interpretation: Severity of illness decreased (lower mortality and less use of organ support) across waves among patients admitted to hospital with acute COVID-19, possibly owing to changes in patient demographic characteristics and management, such as increased use of dexamethasone. Continued application of proven therapies may further improve outcomes., Study Registration: ClinicalTrials.gov, no. NCT04510623., Competing Interests: Competing interests: James Russell reports an investigator-initiated grant from Grifols that was provided to and administered by the University of British Columbia (UBC). He reports patents owned by UBC that are related to the use of PCSK9 inhibitor(s) in sepsis and the use of vasopressin in septic shock, and a patent owned by Ferring Pharmaceuticals for use of selepressin in septic shock. He is an inventor on these patents. He was a founder, director and shareholder in Cyon Therapeutics and is a shareholder in Molecular You. He reports consulting fees from SIB Therapeutics (developing a sepsis drug) and Ferring Pharmaceuticals (manufactures vasopressin and developing selepressin). He is no longer actively consulting for any industry. He was a nonfunded science advisor and member of the Government of Canada COVID-19 Therapeutics Task Force (June 2020–December 2021) and a nonfunded member of the data and safety monitoring board of a trial of plasma in COVID-19 (PassITON) (2020–2021) sponsored by the National Institutes of Health. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Individuals with chronic critical illness experience multiple complex physiological disturbances including ongoing respiratory failure, requiring prolonged mechanical ventilation, and thus communication impairments. In conducting a qualitative interpretive description study, we sought to ensure that individuals with chronic critical illness themselves were included as participants. Our commitment to recruiting these individuals to the study and ensuring their data meaningfully informed the analysis and findings required us to reconsider and challenge some of the traditional notions of high-quality qualitative research and develop appropriate practical strategies. These strategies included: (1) centering participant abilities and preferences, (2) adopting a flexible approach to conducting interviews, (3) engaging in a therapeutic relationship, and (4) valuing "thin" data. In this article, we extend existing literature describing the complexities of conducting research with individuals with communication impairments and strategies to consider in the hopes of informing future research with other populations historically excluded from study participation., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Competing Interests: Intérêts concurrents: Aucun intérêt concurrent déclaré

Design: This is a retrospective case series describing the feasibility and tolerability of postextubation prone positioning (PEPP) and its impact on physiologic parameters in a tertiary intensive care unit during the COVID-19 pandemic. Setting and Patients . This study was conducted on patients with COVID-19 respiratory failure hospitalized in a tertiary Intensive Care Unit at Surrey Memorial Hospital during the COVID-19 pandemic. Measurements and Results . We did not find prior reports of PEPP following prolonged intubation in the literature. Four patients underwent a total of 13 PEPP sessions following liberation from prolonged mechanical ventilation. Each patient underwent a median of 3 prone sessions (IQR: 2, 4.25) lasting a median of 1.5 hours (IQR: 1.2, 2.1). PEPP sessions were associated with a reduction in median oxygen requirements, patient respiratory rate, and reintubation rate. The sessions were well tolerated by patients, nursing, and the allied health team., Conclusions: The novel practice of PEPP after liberation from prolonged mechanical ventilation in patients with COVID-19 respiratory failure is feasible and well tolerated, and may be associated with favourable clinical outcomes including improvement in oxygenation and respiratory rate and a low rate of reintubation. Larger prospective studies of PEPP are warranted., Competing Interests: The authors do not have conflicts of interest to disclose., (Copyright © 2020 Andrei Karpov et al.)

Competing Interests: Intérêts concurrents: Aucun déclaré.

Background: Pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with high intensive care unit (ICU) mortality. We aimed to describe the clinical characteristics and outcomes of critically ill patients with coronavirus disease 2019 (COVID-19) in a Canadian setting., Methods: We conducted a retrospective case series of critically ill patients with laboratory-confirmed SARS-CoV-2 infection consecutively admitted to 1 of 6 ICUs in Metro Vancouver, British Columbia, Canada, between Feb. 21 and Apr. 14, 2020. Demographic, management and outcome data were collected by review of patient charts and electronic medical records., Results: Between Feb. 21 and Apr. 14, 2020, 117 patients were admitted to the ICU with a confirmed diagnosis of COVID-19. The median age was 69 (interquartile range [IQR] 60-75) years, and 38 (32.5%) were female. At least 1 comorbidity was present in 86 (73.5%) patients. Invasive mechanical ventilation was required in 74 (63.2%) patients. The duration of mechanical ventilation was 13.5 (IQR 8-22) days overall and 11 (IQR 6-16) days for patients successfully discharged from the ICU. Tocilizumab was administered to 4 patients and hydroxychloroquine to 1 patient. As of May 5, 2020, a total of 18 (15.4%) patients had died, 12 (10.3%) remained in the ICU, 16 (13.7%) were discharged from the ICU but remained in hospital, and 71 (60.7%) were discharged home., Interpretation: In our setting, mortality in critically ill patients with COVID-19 admitted to the ICU was lower than in previously published studies. These data suggest that the prognosis associated with critical illness due to COVID-19 may not be as poor as previously reported., Competing Interests: Competing interests: None declared., (© 2020 Joule Inc. or its licensors.)

Competing Interests: Competing interests: None declared.

Background: While 80% of critically ill patients treated in an intensive care unit (ICU) will survive, survivors often suffer a constellation of new or worsening physical, cognitive, and psychiatric complications, termed post-intensive care syndrome. Emerging evidence paints a challenging picture of complex, long-term complications that are often untreated and culminate in substantial dependence on acute care services. Clinicians and decision-makers in the Fraser Health Authority of British Columbia are working to develop evidence-based community healthcare solutions that will be successful in the context of existing healthcare services. The objective of the proposed review is to provide the theoretical scaffolding to transform the care of survivors of critical illness by a synthesis of relevant clinical and healthcare service programs., Methods: Realist review will be used to develop and refine a theoretical understanding of why, how, for whom, and in what circumstances post-ICU program impact ICU survivors' outcomes. This review will follow the recommended five steps of realist review which include (1) clarifying the scope of the review and articulating a preliminary program theory, (2) searching for evidence, (3) appraising primary studies and extracting data, (4) synthesizing evidence and sharing conclusions, and (5) disseminating and implementing recommendations., Discussion: This realist review will provide a program theory, encompassing the contexts, mechanisms, and outcomes, to explain how clinical and health service interventions to improve ICU survivor outcomes operate in different contexts for different survivors, and with what effect. This review will be an evidentiary pillar for health service development and implementation by our knowledge user team members as well as advance scholarly knowledge relevant nationally and internationally., Systematic Review Registration: PROSPERO CRD42018087795.

Introduction: Cardiomyocytes exposed to inflammatory processes express intracellular adhesion molecule-1 (ICAM-1). We investigated whether fibrinogen and fibrinogen degradation products, including D-dimer, could alter cardiomyocyte contractile function through interaction with ICAM-1 found on inflamed cardiomyocytes., Methods: In vivo, rats were injected with endotoxin to model systemic inflammation, whereas isolated rat cardiomyocytes were treated with tumor necrosis factor-alpha to model the inflammatory environment seen following exposure to bacterial products such as lipopolysaccharide., Results: In vivo, endotoxin administration profoundly decreased cardiac contractile function associated with a large increase in intracardiac ICAM-1 and perivascular fibrinogen. Confocal microscopy with double-staining of isolated rat cardiomyocytes demonstrated colocalization of ICAM-1 and fibrinogen. This interaction was disrupted through pre-treatment of the cells with an ICAM-1-blocking antibody. Functionally, isolated rat cardiomyocyte preparations exhibited decreased fractional shortening when incubated with fibrinogen, and through the use of synthetic peptides, we determined that residues 117-133 of the fibrinogen gamma chain are responsible for this interaction with ICAM-1. Despite having crosslinked gamma chains, D-dimer retained the ability to decrease cardiomyocyte contractility., Conclusion: Site 117-133 of the fibrinogen gamma chain is able to depress cardiomyocyte contractility through binding ICAM-1.

Adenovirus (Ad) vectors can produce inflammatory responses at high doses. Intravenous administration of an Ad vector expressing green fluorescent protein (AdGFP) to naive mice induced a biphasic pattern of liver cytokine/chemokine gene expression over 7 days. Tumor necrosis factor alpha (TNF-alpha), macrophage inflammatory protein 2 (MIP-2), and interferon gamma-inducible protein 10 (IP-10) genes were upregulated, with two distinct peaks of mRNA expression occurring at 6 hr and 5 days. The administration of transcription-defective AdGFP particles induced the early but not the late peak of chemokine/cytokine gene expression, confirming that Ad vector-induced inflammation is capsid dependent in the early phase and transcription dependent in the late phase. To determine the role of adenoviral capsid motifs in the early phase, capsid-modified Ad vectors were employed. The intravenous administration of the RGD-deleted Ad vector AdL.PB*, the fiber mutant AdL.F*, or the double mutant AdL.F*PB* induced similar levels of cytokine/chemokine expression compared with the wild-type vector AdLuc. Kupffer cell blockade significantly reduced liver TNF-alpha, MIP-2, and IP-10 gene expression and liver inflammation after the administration of AdL.PB* or AdL.F*PB*. Fluorescence microscopy of AdLuc- and AdL.PB*-transduced liver at 1 hr revealed localization of Ad vectors to liver sinusoids in Kupffer cell-depleted mice. AdL.PB* induced less E-selectin and VCAM-1 gene expression in liver, confirming reduced endothelial activation in mice receiving RGD-deleted Ad vectors. In vitro studies of endothelial cells demonstrated reduced transduction and endothelial activation by AdL.PB* compared with AdLuc. These results demonstrate that adenovirus capsid RGD motifs are required for efficient transduction and endothelial cell activation. Altering vector tropism represents a feasible strategy to modulate the innate response to Ad vectors in nontargeted tissues.