American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Jul 2019
Understanding Heterogeneity in Biological Phenotypes of ARDS by Leukocyte Expression Profiles.
Rationale: Two biologic phenotypes of acute respiratory distress syndrome (ARDS) have been identified based on plasma protein markers in four previous studies. Objectives: To determine if blood leukocyte gene expression is different between the "reactive" and "uninflamed" phenotype. Methods: This is a new study adding blood leukocyte transcriptomics and bioinformatics analysis to an existing patient cohort of ARDS in patients with sepsis admitted to two ICUs during a 1.5-year period. ⋯ The uninflamed phenotype was characterized by upregulation of mitogen-activated protein kinase pathways. Conclusions: A third of genes are differentially expressed between biologic phenotypes of ARDS supporting the observation that the subgroups of ARDS are incomparable in terms of pathophysiology. These data provide additional support for biologic heterogeneity in patients with ARDS and suggests that a personalized approach to intervention focusing on oxidative phosphorylation is pivotal in this condition.
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Am. J. Respir. Crit. Care Med. · Jul 2019
Critical Care Management of Chimeric Antigen Receptor-T Cells-Related Toxicity: Be Aware and Prepared.
CAR (chimeric antigen receptor) T cells (CARTs) are genetically engineered T cells that express CARs, with impressive clinical activity in relapsed and refractory hematologic malignancies, primarily acute lymphoblastic leukemia and diffuse large B-cell lymphoma. The most frequent life-threatening adverse events after CART infusion are cytokine release syndrome and CAR-related encephalopathy syndrome, which can occur within hours or days after administration. ⋯ As new treatment indications and CART constructs enter the clinic, the number of patients requiring ICU admission will rapidly increase, with profound consequences for the use of ICU resources, training requirements, clinical expertise, multidisciplinary collaboration, and hospital organization. Research is also needed to validate at large scale biomarkers that allow doctors to risk-stratify patients for both their risk to develop severe toxicity and their likelihood to respond to therapy.
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Am. J. Respir. Crit. Care Med. · Jul 2019
Alveolar Macrophage Apoptosis-Associated Bacterial Killing Helps Prevent Murine Pneumonia.
Rationale: Antimicrobial resistance challenges therapy of pneumonia. Enhancing macrophage microbicidal responses would combat this problem but is limited by our understanding of how alveolar macrophages (AMs) kill bacteria. Objectives: To define the role and mechanism of AM apoptosis-associated bacterial killing in the lung. ⋯ Apoptosis-associated killing was not activated during Staphylococcus aureus lung infection. Conclusions: Mcl-1 upregulation prevents macrophage apoptosis-associated killing and establishes that apoptosis-associated killing is required to allow AMs to clear ingested bacteria. Engagement of macrophage apoptosis should be investigated as a novel, host-based antimicrobial strategy.