Immunoregulatory Macrophages Modify Local Pulmonary Immunity and Ameliorate Hypoxic Pulmonary Hypertension.

Background: Macrophages play a significant role in the onset and progression of vascular disease in pulmonary hypertension, and cell-based immunotherapies aimed at treating vascular remodeling are lacking. We aimed to evaluate the effect of pulmonary administration of macrophages modified to have an anti-inflammatory/proresolving phenotype in attenuating early pulmonary inflammation and progression of experimentally induced pulmonary hypertension.

Methods: Mouse bone marrow-derived macrophages were polarized in vitro to a regulatory (M2) phenotype.

Child Opportunity Index and Pediatric Extracorporeal Membrane Oxygenation Outcomes; the Role of Diagnostic Category.

Objectives: To study the impact of social determinants of health (SDoH) on pediatric extracorporeal membrane oxygenation (ECMO) outcomes.

Design, Setting, And Patients: Retrospective study of children (< 18 yr) supported on ECMO (October 1, 2015 to March 1, 2021) using Pediatric Health Information System (44 U.S.

Immunoregulatory macrophages modify local pulmonary immunity and ameliorate hypoxic-pulmonary hypertension.

Rationale: Macrophages play a central role in the onset and progression of vascular disease in pulmonary hypertension (PH) and cell-based immunotherapies aimed at treating vascular remodeling are lacking.

Objective: To evaluate the effect of pulmonary administration of macrophages modified to have an anti-inflammatory/pro-resolving phenotype in attenuating early pulmonary inflammation and progression of experimentally induced PH.

Methods: Mouse bone marrow derived macrophages (BMDMs) were polarized to a regulatory (M2 ) phenotype.

Long-Term Functional Outcomes at 1-Year After Hospital Discharge in Critically Ill Neonates With Congenital Diaphragmatic Hernia.

Objectives: Congenital diaphragmatic hernia (CDH) is a birth defect associated with long-term morbidity. Our objective was to examine longitudinal change in Functional Status Scale (FSS) after hospital discharge in CDH survivors.

Design: Single-center retrospective cohort study.

Inadequate Oxygen Delivery Dose and Major Adverse Events in Critically Ill Children With Sepsis.

Background: The inadequate oxygen delivery (IDo2) index is used to estimate the probability that a patient is experiencing inadequate systemic delivery of oxygen. Its utility in the care of critically ill children with sepsis is unknown.

Objective: To evaluate the relationship between IDo2 dose and major adverse events, illness severity metrics, and outcomes among critically ill children with sepsis.

Supraventricular Tachycardia in Infants With Congenital Diaphragmatic Hernia: Prevalence, Associations, and Outcomes.

Objectives: To characterize the prevalence, associations, management, and outcomes of supraventricular tachycardia (SVT) in neonates with congenital diaphragmatic hernia (CDH).

Design: Retrospective chart and cardiology code review within a cohort of patients with CDH was used to define a subpopulation with atrial arrhythmia. SVT mechanisms were confirmed by electrocardiogram analysis.

Clinical Characteristics and Outcomes of Children with Acute Catastrophic Brain Injury: A 13-Year Retrospective Cohort Study.

Background: The purpose of this study was to describe and analyze clinical characteristics and outcomes in children with acute catastrophic brain injury (CBI).

Methods: This was a single-center, 13-year (2008-2020) retrospective cohort study of children in the pediatric and cardiac intensive care units with CBI, defined as (1) acute neurologic injury based on clinical and/or imaging findings, (2) the need for life-sustaining intensive care unit therapies, and (3) death or survival with a Glasgow Coma Scale score < 13 at discharge. Patients were excluded if they were discharged directly to home < 14 days from admission or had a chronic neurologic condition with a baseline Glasgow Coma Scale score < 13.

A Novel Protective Role for Matrix Metalloproteinase-8 in the Pulmonary Vasculature.

Mechanical signaling through cell-matrix interactions plays a major role in progressive vascular remodeling in pulmonary arterial hypertension (PAH). MMP-8 (matrix metalloproteinase-8) is an interstitial collagenase involved in regulating inflammation and fibrosis of the lung and systemic vasculature, but its role in PAH pathogenesis remains unexplored. To evaluate MMP-8 as a modulator of pathogenic mechanical signaling in PAH.

Acetazolamide Improves Right Ventricular Function and Metabolic Gene Dysregulation in Experimental Pulmonary Arterial Hypertension.

Right ventricular (RV) performance is a key determinant of mortality in pulmonary arterial hypertension (PAH). RV failure is characterized by metabolic dysregulation with unbalanced anaerobic glycolysis, oxidative phosphorylation, and fatty acid oxidation (FAO). We previously found that acetazolamide (ACTZ) treatment modulates the pulmonary inflammatory response and ameliorates experimental PAH.

Coagulations Studies Do Not Correlate With Each Other or With Hematologic Complications During Pediatric Extracorporeal Membrane Oxygenation.

Objectives: Anticoagulation plays a key role in the management of children supported with extracorporeal membrane oxygenation. However, the ideal strategy for monitoring anticoagulation remains unclear. Our objective was to evaluate the utility of laboratory measures of anticoagulation in pediatric extracorporeal membrane oxygenation.

Immune dysregulation and multisystem inflammatory syndrome in children (MIS-C) in individuals with haploinsufficiency of SOCS1.

Background: We studied 2 unrelated patients with immune thrombocytopenia and autoimmune hemolytic anemia in the setting of acute infections. One patient developed multisystem inflammatory syndrome in children in the setting of a severe acute respiratory syndrome coronavirus 2 infection.

Objectives: We sought to identify the mechanisms underlying the development of infection-driven autoimmune cytopenias.

Echocardiographic markers of pulmonary hemodynamics and right ventricular hypertrophy in rat models of pulmonary hypertension.

Echocardiography is the gold standard non-invasive technique to diagnose pulmonary hypertension. It is also an important modality used to monitor disease progression and response to treatment in patients with pulmonary hypertension. Surprisingly, only few studies have been conducted to validate and standardize echocardiographic parameters in experimental animal models of pulmonary hypertension.

Heme oxygenase-1 dampens the macrophage sterile inflammasome response and regulates its components in the hypoxic lung.

Exposure to hypoxia causes an inflammatory reaction in the mouse lung, and this response can be modulated by overexpressing the hypoxia-inducible stress-response enzyme, heme oxygenase-1 (HO-1). We hypothesized that the inflammasome activity may be a central pathway by which HO-1 controls pulmonary inflammation following alveolar hypoxia. Therefore, we investigated whether HO-1 controls inflammasome activation by altering its expression in macrophages primed with classic NOD-like receptor containing a pyrin domain 3 (NLRP3) inducers, and in murine lungs lacking HO-1 and exposed to acute hypoxia.

Mortality and Factors Associated With Hemorrhage During Pediatric Extracorporeal Membrane Oxygenation.

Objectives: To quantify and identify factors associated with bleeding events during pediatric extracorporeal membrane oxygenation.

Design: Retrospective cohort study with primary outcome of bleeding days on extracorporeal membrane oxygenation.

Setting: Single tertiary care children's hospital.

Mesenchymal Stromal Cell Exosomes Ameliorate Experimental Bronchopulmonary Dysplasia and Restore Lung Function through Macrophage Immunomodulation.

Rationale: Mesenchymal stem/stromal cell (MSC) therapies have shown promise in preclinical models of pathologies relevant to newborn medicine, such as bronchopulmonary dysplasia (BPD). We have reported that the therapeutic capacity of MSCs is comprised in their secretome, and demonstrated that the therapeutic vectors are exosomes produced by MSCs (MSC-exos).

Objectives: To assess efficacy of MSC-exo treatment in a preclinical model of BPD and to investigate mechanisms underlying MSC-exo therapeutic action.

Distal vessel stiffening is an early and pivotal mechanobiological regulator of vascular remodeling and pulmonary hypertension.

Pulmonary arterial (PA) stiffness is associated with increased mortality in patients with pulmonary hypertension (PH); however, the role of PA stiffening in the pathogenesis of PH remains elusive. Here, we show that distal vascular matrix stiffening is an early mechanobiological regulator of experimental PH. We identify cyclooxygenase-2 (COX-2) suppression and corresponding reduction in prostaglandin production as pivotal regulators of stiffness-dependent vascular cell activation.

The Sugen 5416/hypoxia mouse model of pulmonary hypertension revisited: long-term follow-up.

The combination of a vascular endothelial growth factor receptor antagonist, Sugen 5416 (SU5416), and chronic hypoxia is known to cause pronounced pulmonary hypertension (PH) with angioobliterative lesions in rats and leads to exaggerated PH in mice as well. We sought to determine whether weekly SU5416 injections during 3 weeks of hypoxia leads to long-term development of angioobliterative lesions and sustained or progressive PH in mice. Male C57BL/6J mice were injected with SU5416 (SuHx) or vehicle (VehHx) weekly during 3 weeks of exposure to 10% oxygen.

Continuous infusion, general anesthesia and other intensive care treatment for uncontrolled status epilepticus.

Purpose Of Review: To discuss the use of continuous infusions, general anesthesia, hypothermia, and ketogenic diet as treatment for uncontrolled status epilepticus in pediatric patients.

Recent Findings: Recent studies demonstrate that clinical practitioners have a hierarchy in approach in controlling refractory status epilepticus (RSE) and super-refractory status epilepticus in children. In the acute setting of RSE, midazolam achieves clinical seizure control at a mean of 41 min after starting an infusion.

Mechanical ventilation guided by electrical impedance tomography in experimental acute lung injury.

Objective: To utilize real-time electrical impedance tomography to guide lung protective ventilation in an animal model of acute respiratory distress syndrome.

Design: Prospective animal study.

Setting: Animal research center.