SeptiCyte RAPID is a transcriptional host response assay that discriminates between sepsis and non-infectious systemic inflammation (SIRS) with a one-hour turnaround time. The overall performance of this test in a cohort of 419 patients has recently been described [Balk et al., J Clin Med 2024, 13, 1194].
View Article and Find Full Text PDFUnlabelled: We sought to identify the primary causes of death of adult patients admitted to the medical ICU with symptomatic COVID-19 who ultimately suffered in-hospital mortality over the span of three major waves of COVID-19: Wild-type, alpha/epsilon, and delta.
Design: Retrospective single-center cohort study from March 2020 to December 2021.
Setting: One medical ICU in a 600-bed Tertiary Care Hospital in Los Angeles, CA.
Objectives: The COVID-19 pandemic threatened standard hospital operations. We sought to understand how this stress was perceived and manifested within individual hospitals and in relation to local viral activity.
Design: Prospective weekly hospital stress survey, November 2020-June 2022.
Unlabelled: Vascular dysfunction and capillary leak are common in critically ill COVID-19 patients, but identification of endothelial pathways involved in COVID-19 pathogenesis has been limited. Angiopoietin-like 4 (ANGPTL4) is a protein secreted in response to hypoxic and nutrient-poor conditions that has a variety of biological effects including vascular injury and capillary leak.
Objectives: To assess the role of ANGPTL4 in COVID-19-related outcomes.
Objectives: Few surveys have focused on physician moral distress, burnout, and professional fulfilment. We assessed physician wellness and coping during the COVID-19 pandemic.
Design: Cross-sectional survey using four validated instruments.
Unlabelled: Respiratory virus infections cause significant morbidity and mortality ranging from mild uncomplicated acute respiratory illness to severe complications, such as acute respiratory distress syndrome, multiple organ failure, and death during epidemics and pandemics. We present a protocol to systematically study patients with severe acute respiratory infection (SARI), including severe acute respiratory syndrome coronavirus 2, due to respiratory viral pathogens to evaluate the natural history, prognostic biomarkers, and characteristics, including hospital stress, associated with clinical outcomes and severity.
Design: Prospective cohort study.
Background: Although specific interventions previously demonstrated benefit in patients with ARDS, use of these interventions is inconsistent, and patient mortality remains high. The impact of variability in center management practices on ARDS mortality rates remains unknown.
Research Question: What is the impact of treatment variability on mortality in patients with moderate to severe ARDS in the United States?
Study Design And Methods: We conducted a multicenter, observational cohort study of mechanically ventilated adults with ARDS and Pao to Fio ratio of ≤ 150 with positive end-expiratory pressure of ≥ 5 cm HO, who were admitted to 29 US centers between October 1, 2016, and April 30, 2017.
Importance: For critically ill patients with advanced medical illnesses and poor prognoses, overuse of invasive intensive care unit (ICU) treatments may prolong suffering without benefit.
Objective: To examine whether use of time-limited trials (TLTs) as the default care-planning approach for critically ill patients with advanced medical illnesses was associated with decreased duration and intensity of nonbeneficial ICU care.
Design, Setting, And Participants: This prospective quality improvement study was conducted from June 1, 2017, to December 31, 2019, at the medical ICUs of 3 academic public hospitals in California.
Background: Invasive intensive care unit (ICU) treatments for patients with advanced medical illnesses and poor prognoses may prolong suffering with minimal benefit. Unfortunately, the quality of care planning and communication between clinicians and critically ill patients and their families in these situations are highly variable, frequently leading to overutilization of invasive ICU treatments. Time-limited trials (TLTs) are agreements between the clinicians and the patients and decision makers to use certain medical therapies over defined periods of time and to evaluate whether patients improve or worsen according to predetermined clinical parameters.
View Article and Find Full Text PDFRationale: We propose renin angiotensin system (RAS) peptides are critical in wound reparative processes such as in acute respiratory distress syndrome (ARDS). Their role in predicting clinical outcomes in ARDS has been unexplored; thus, we used a targeted metabolomics approach to investigate them as potential predictors of outcomes.
Methods: Thirty-nine ARDS patients were enrolled within 24 hours of ARDS diagnosis.
Background: Studies exploring the effect of body mass index (BMI) on outcomes in the intensive care unit (ICU) have yielded mixed results, with few studies assessing patients at the extremes of obesity. We sought to understand the clinical characteristics and outcomes of patients with super obesity (BMI > 50 kg/m) as compared to morbid obesity (BMI > 40 kg/m) and obesity (BMI > 30 kg/m).
Methods: A retrospective review of patients admitted to the Los Angeles County + University of Southern California medical intensive care unit (MICU) service between 2008 and 2013 was performed.
Claudins, the integral tight junction (TJ) proteins that regulate paracellular permeability and cell polarity, are frequently dysregulated in cancer; however, their role in neoplastic progression is unclear. Here, we demonstrated that knockout of Cldn18, a claudin family member highly expressed in lung alveolar epithelium, leads to lung enlargement, parenchymal expansion, increased abundance and proliferation of known distal lung progenitors, the alveolar epithelial type II (AT2) cells, activation of Yes-associated protein (YAP), increased organ size, and tumorigenesis in mice. Inhibition of YAP decreased proliferation and colony-forming efficiency (CFE) of Cldn18-/- AT2 cells and prevented increased lung size, while CLDN18 overexpression decreased YAP nuclear localization, cell proliferation, CFE, and YAP transcriptional activity.
View Article and Find Full Text PDFAm J Physiol Lung Cell Mol Physiol
January 2017
Previous studies have demonstrated resistance to naphthalene-induced injury in proximal airways of mice with lung epithelial-specific deletion of the tumor-suppressor gene Pten, attributed to increased proliferation of airway progenitors. We tested effects of Pten loss following bleomycin injury, a model typically used to study distal lung epithelial injury, in conditional Pten knockout mice. Pten-deficient airway epithelium exhibited marked hyperplasia, particularly in small bronchioles and at bronchoalveolar duct junctions, with reduced E-cadherin and β-catenin expression between cells toward the luminal aspect of the hyperplastic epithelium.
View Article and Find Full Text PDFAm J Respir Cell Mol Biol
September 2016
Active ion transport by basolateral Na-K-ATPase (Na pump) creates an Na(+) gradient that drives fluid absorption across lung alveolar epithelium. The α1 and β1 subunits are the most highly expressed Na pump subunits in alveolar epithelial cells (AEC). The specific contribution of the β1 subunit and the relative contributions of alveolar epithelial type II (AT2) versus type I (AT1) cells to alveolar fluid clearance (AFC) were investigated using two cell type-specific mouse knockout lines in which the β1 subunit was knocked out in either AT1 cells or both AT1 and AT2 cells.
View Article and Find Full Text PDFAm J Physiol Lung Cell Mol Physiol
January 2016
Distal lung epithelium is maintained by proliferation of alveolar type II (AT2) cells and, for some daughter AT2 cells, transdifferentiation into alveolar type I (AT1) cells. We investigated if subpopulations of alveolar epithelial cells (AEC) exist that represent various stages in transdifferentiation from AT2 to AT1 cell phenotypes in normal adult lung and if they can be identified using combinations of cell-specific markers. Immunofluorescence microscopy showed that, in distal rat and mouse lungs, ∼ 20-30% of NKX2.
View Article and Find Full Text PDFObjective: Clinical protocols may decrease unnecessary variation in care and improve compliance with desirable therapies. We evaluated whether highly protocolized ICUs have superior patient outcomes compared with less highly protocolized ICUs.
Design: Observational study in which participating ICUs completed a general assessment and enrolled new patients 1 day each week.
Am J Respir Cell Mol Biol
August 2014
Claudin proteins are major constituents of epithelial and endothelial tight junctions (TJs) that regulate paracellular permeability to ions and solutes. Claudin 18, a member of the large claudin family, is highly expressed in lung alveolar epithelium. To elucidate the role of claudin 18 in alveolar epithelial barrier function, we generated claudin 18 knockout (C18 KO) mice.
View Article and Find Full Text PDFInteractions between transforming growth factor-β (TGF-β) and Wnt are crucial to many biological processes, although specific targets, rationale for divergent outcomes (differentiation versus block of epithelial proliferation versus epithelial-mesenchymal transition (EMT)) and precise mechanisms in many cases remain unknown. We investigated β-catenin-dependent and transforming growth factor-β1 (TGF-β1) interactions in pulmonary alveolar epithelial cells (AEC) in the context of EMT and pulmonary fibrosis. We previously demonstrated that ICG-001, a small molecule specific inhibitor of the β-catenin/CBP (but not β-catenin/p300) interaction, ameliorates and reverses pulmonary fibrosis and inhibits TGF-β1-mediated α-smooth muscle actin (α-SMA) and collagen induction in AEC.
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