Defining the host dependencies and the transcriptional landscape of RSV infection.

Respiratory syncytial virus (RSV) is a globally prevalent pathogen, causes severe disease in older adults, and is the leading cause of bronchiolitis and pneumonia in the United States for children during their first year of life. Despite its prevalence worldwide, RSV-specific treatments remain unavailable for most infected patients. Here, we leveraged a combination of genome-wide CRISPR knockout screening and single-cell RNA sequencing to improve our understanding of the host determinants of RSV infection and the host response in both infected cells and uninfected bystanders.

Integrating pulmonary and systemic transcriptomes to characterize lung injury after pediatric hematopoietic stem cell transplant.

Hematopoietic stem cell transplantation (HCT) is a potentially life-saving therapy but can lead to lung injury due to chemoradiation toxicity, infection, and immune dysregulation. We previously showed that bronchoalveolar lavage (BAL) transcriptomes representing pulmonary inflammation and cellular injury can phenotype post-HCT lung injury and predict mortality. To test whether peripheral blood might be a suitable surrogate for BAL, we compared 210 paired BAL and blood transcriptomes obtained from 166 pediatric HCT patients at 27 hospitals.

Biologic Mechanisms Underlying the Heterogeneous Response to Tight Glycemic Control among Differentially Inflamed Patients in the HALF-PINT Trial.

Tight glycemic control (TGC) with insulin has not consistently shown benefit in critically ill patients. We previously reported that the subset of children with a hyperinflammatory subphenotype benefited from TGC in the HALF-PINT (Heart and Lung Failure - Pediatric Insulin Titration) study of hyperglycemic children with heart and lung failure and the IIT-SBPP (Intensive Insulin Treatment - Severely Burned Pediatric Patients) study in severely burned pediatric patients. However, whether this effect was mediated through a reduction in inflammation or some other biologic process is not fully understood.

Plasma Soluble Intercellular Adhesion Molecule-1 Has a Central Role in Biomarker Network Analysis and Is Associated With Poor Outcomes in Two Distinct Pediatric Cohorts of Acute Respiratory Distress Syndrome and Acute Respiratory Failure.

Objectives: Intercellular adhesion molecule-1 (ICAM-1) is a glycoprotein expressed on immune, endothelial, and epithelial cells. In the setting of inflammation, it becomes upregulated and spliced into a soluble form (soluble ICAM-1 [sICAM-1]). This study examined the association of sICAM-1 with clinical outcomes in two large pediatric cohorts with acute respiratory distress syndrome (ARDS) and acute respiratory failure (ARF) and examined the relationships between sICAM-1 and other protein biomarkers utilizing network analysis to contextualize its role in ARDS pathophysiology.

Integrating Pulmonary and Systemic Transcriptomic Profiles to Characterize Lung Injury after Pediatric Hematopoietic Stem Cell Transplant.

Hematopoietic stem cell transplantation (HCT) is potentially curative for numerous malignant and non-malignant diseases but can lead to lung injury due to chemoradiation toxicity, infection, and immune dysregulation. Bronchoalveolar lavage (BAL) is the most commonly used procedure for diagnostic sampling of the lung but is invasive, cannot be performed in medically fragile patients, and is challenging to perform serially. We previously showed that BAL transcriptomes representing pulmonary inflammation and cellular injury can phenotype post-HCT lung injury and predict mortality outcomes.

Defining the host dependencies and the transcriptional landscape of RSV infection and bystander activation.

Respiratory syncytial virus (RSV) is a globally prevalent pathogen, causes severe disease in older adults, and is the leading cause of bronchiolitis and pneumonia in the United States for children during their first year of life [1]. Despite its prevalence worldwide, RSV-specific treatments remain unavailable for most infected patients. Here, we leveraged a combination of genome-wide CRISPR knockout screening and single-cell RNA sequencing to improve our understanding of the host determinants of RSV infection and the host response in both infected cells, and uninfected bystanders.

Multidisciplinary approach to treating complex immune dysregulation disorders: an adaptive model for institutional implementation.

Patients with immune dysregulation may present with varying combinations of autoimmunity, autoinflammation, immunodeficiency, atopy, lymphoproliferation, and/or malignancy, often with multisystem involvement. Recognizing specific patterns of immune dysregulation, coordinating and interpreting complex diagnostic testing, and choosing initial (often empiric) treatment can be challenging. Centers are increasingly assembling multidisciplinary teams (MDTs) to standardize evaluation and optimize treatment of patients with complex immune dysregulation (immune dysregulation MDTs [immMDTs]).

Assessing Clinical Improvement of Infants Hospitalized for Respiratory Syncytial Virus-Related Critical Illness.

Background: Pediatric respiratory syncytial virus (RSV)-related acute lower respiratory tract infection (LRTI) commonly requires hospitalization. The Clinical Progression Scale Pediatrics (CPS-Ped) measures level of respiratory support and degree of hypoxia across a range of disease severity, but it has not been applied in infants hospitalized with severe RSV-LRTI.

Methods: We analyzed data from a prospective surveillance registry of infants hospitalized for RSV-related complications across 39 U.

Pediatric Hematology and Oncology Patients on Extracorporeal Membrane Oxygenation: Outcomes in a Multicenter, Retrospective Cohort, 2009-2021.

Objective: To describe characteristics associated with survival for pediatric patients with an oncologic diagnosis or hematopoietic cell transplant (HCT) supported with extracorporeal membrane oxygenation (ECMO).

Design: Multicenter, retrospective study.

Setting: Sixteen PICUs in the United States and Israel.

Pathobiological signatures of dysbiotic lung injury in pediatric patients undergoing stem cell transplantation.

Hematopoietic cell transplantation (HCT) uses cytotoxic chemotherapy and/or radiation followed by intravenous infusion of stem cells to cure malignancies, bone marrow failure and inborn errors of immunity, hemoglobin and metabolism. Lung injury is a known complication of the process, due in part to disruption in the pulmonary microenvironment by insults such as infection, alloreactive inflammation and cellular toxicity. How microorganisms, immunity and the respiratory epithelium interact to contribute to lung injury is uncertain, limiting the development of prevention and treatment strategies.

Durability of Original Monovalent mRNA Vaccine Effectiveness Against COVID-19 Omicron-Associated Hospitalization in Children and Adolescents - United States, 2021-2023.

Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S.

Healthcare Burden and Resource Utilization After Pediatric Acute Respiratory Distress Syndrome: A Secondary Analysis of the Collaborative Pediatric Critical Care Research Network Acute Respiratory Distress Syndrome Study.

Objectives: To describe family healthcare burden and health resource utilization in pediatric survivors of acute respiratory distress syndrome (ARDS) at 3 and 9 months.

Design: Secondary analysis of a prospective multisite cohort study.

Setting: Eight academic PICUs in the United States (2019-2020).

Whole blood transcriptomics identifies subclasses of pediatric septic shock.

Background: Sepsis is a highly heterogeneous syndrome, which has hindered the development of effective therapies. This has prompted investigators to develop a precision medicine approach aimed at identifying biologically homogenous subgroups of patients with septic shock and critical illnesses. Transcriptomic analysis can identify subclasses derived from differences in underlying pathophysiological processes that may provide the basis for new targeted therapies.

Risk factors for health impairments in children after hospitalization for acute COVID-19 or MIS-C.

Objective: To identify risk factors for persistent impairments after pediatric hospitalization for acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome in children (MIS-C) during the SARS-CoV-2 pandemic.

Methods: Across 25 U.S.

Whole Blood Transcriptomics Identifies Subclasses of Pediatric Septic Shock.

Background: Sepsis is a highly heterogeneous syndrome, that has hindered the development of effective therapies. This has prompted investigators to develop a precision medicine approach aimed at identifying biologically homogenous subgroups of patients with septic shock and critical illnesses. Transcriptomic analysis can identify subclasses derived from differences in underlying pathophysiological processes that may provide the basis for new targeted therapies.

Infants Admitted to US Intensive Care Units for RSV Infection During the 2022 Seasonal Peak.

Importance: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide.

Objective: To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission.

Design, Setting, And Participants: This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states.