Extubation Failure in the PICU: A Virtual Pediatric Systems Database Study, 2017-2021.

Objectives: Extubation failure (EF) in PICU patients is reintubation within 48, 72, or 96 hours of planned extubation (EF48, EF72, and EF96, respectively). Standardized sedation protocols, extubation readiness testing, and noninvasive respiratory support are used to improve efficient liberation from mechanical ventilation (MV). We therefore aimed to review EF rates, time to failure, and the use of noninvasive respiratory support after extubation, 2017-2021.

Patient Characteristics and Outcomes Associated with Sentinel Protection Device Use in Patients with Aortic Valve Disease Undergoing TAVR in a "Real-World" Setting.

Background: Transcatheter aortic valve replacement (TAVR) has become the dominant treatment for aortic valve disease. While TAVR safety has improved over time, concern remains over the occurrence of cerebrovascular accidents (CVA) secondary to device placement, which is associated with increased morbidity and mortality. The Sentinel Cerebral Protection System (CPS) was developed to reduce the risk of embolic strokes associated with debris produced during TAVR.

Dapagliflozin reduces systemic inflammation in patients with type 2 diabetes without known heart failure.

Objective: Sodium glucose cotransporter 2 (SGLT2) inhibitors significantly improve cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that dapagliflozin improves cardiac outcomes via beneficial effects on systemic and cardiac inflammation and cardiac fibrosis.

Research And Design Methods: This randomized placebo-controlled clinical trial enrolled 62 adult patients (mean age 62, 17% female) with type 2 diabetes (T2D) without known heart failure.

Dapagliflozin Reduces Systemic Inflammation in Patients with Type 2 Diabetes Without Known Heart Failure.

Objective: Sodium glucose cotransporter 2 (SGLT2) inhibitors significantly improve cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that dapagliflozin improves cardiac outcomes via beneficial effects on systemic and cardiac inflammation and cardiac fibrosis.

Research And Design Methods: This randomized placebo-controlled clinical trial enrolled 62 adult patients (mean age 62, 17% female) with type 2 diabetes (T2D) without known heart failure.

Transcatheter Aortic Valve Replacement and Impact of Subclinical Leaflet Thrombosis in Low-Risk Patients: LRT Trial 4-Year Outcomes.

Background: The LRT trial (Low-Risk Transcatheter Aortic Valve Replacement [TAVR]) demonstrated the safety and feasibility of TAVR in low-risk patients, with excellent 1- and 2-year outcomes. The objective of the current study is to provide the overall clinical outcomes and the impact of 30-day hypoattenuated leaflet thickening (HALT) on structural valve deterioration at 4 years.

Methods: The prospective, multicenter LRT trial was the first Food and Drug Administration-approved investigational device exemption study to evaluate feasibility and safety of TAVR in low-risk patients with symptomatic severe tricuspid aortic stenosis.

Coronary endothelial dysfunction: from pathogenesis to clinical implications.

Endothelial dysfunction (ED) has a substantial role in the pathogenesis of atherosclerosis and other vascular diseases. Multiple risk factors, including smoking, hyperlipiadaemia and diabetes, can have associated ED, which is correlated with cardiac events. Measurement of coronary artery endothelial function requires the use of invasive techniques to assess both epicardial coronary artery and microvascular beds.

Factors Associated with Early Withdrawal of Life-Sustaining Treatments After Out-of-Hospital Cardiac Arrest: A Subanalysis of a Randomized Trial of Prehospital Therapeutic Hypothermia.

Background: The objective of this study is to describe incidence and factors associated with early withdrawal of life-sustaining therapies based on presumed poor neurologic prognosis (WLST-N) and practices around multimodal prognostication after out-of-hospital cardiac arrest (OHCA).

Methods: We performed a subanalysis of a randomized controlled trial assessing prehospital therapeutic hypothermia in adult patients admitted to nine hospitals in King County with nontraumatic OHCA between 2007 and 2012. Patients who underwent tracheal intubation and were unconscious following return of spontaneous circulation were included.

Experience Using Ustekinumab in Pediatric Patients With Medically Refractory Crohn Disease.

Introduction: Ustekinumab (UST), a human monoclonal antibody against interleukin-12 and 23, is approved to treat adult patients with psoriasis or Crohn disease (CD). Outcomes data for off-label use in pediatric patients with CD are limited.

Aim: We conducted a retrospective cohort study to analyze the long-term efficacy of UST, including dose adjustments, in the treatment of pediatric patients with medically refractory CD.

Risk Factors for Perioperative Morbidity in Adults Undergoing Cardiac Surgery at Children's Hospitals.

Background: Increasing numbers of adults with congenital heart disease (ACHD) undergo cardiac surgical procedures in children's hospitals, yet surgical outcomes data are limited. We sought to better understand the impact of preoperative risk factors on postoperative complications and cardiac intensive care unit (CICU) length of stay (LOS).

Methods: Surgical CICU admissions for patients aged 18 years and older in the Pediatric Cardiac Critical Care Consortium registry from August 2014 to January 2019 in 34 hospitals were included.

Loss of Transforming Growth Factor Beta Signaling in Aortic Smooth Muscle Cells Causes Endothelial Dysfunction and Aortic Hypercontractility.

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Effect of Out-of-Hospital Sodium Nitrite on Survival to Hospital Admission After Cardiac Arrest: A Randomized Clinical Trial.

Importance: Therapeutic delivery of sodium nitrite during resuscitation improved survival in animal models of cardiac arrest, but efficacy has not been evaluated in clinical trials in humans.

Objective: To determine whether parenteral administration of sodium nitrite given by paramedics during resuscitation for out-of-hospital cardiac arrest improved survival to hospital admission.

Design, Setting, And Participants: Double-blind, placebo-controlled, phase 2 randomized clinical trial including 1502 adults in King County, Washington, with out-of-hospital cardiac arrest from ventricular fibrillation or nonventricular fibrillation.

Adipocyte-Derived Versican and Macrophage-Derived Biglycan Control Adipose Tissue Inflammation in Obesity.

Obesity is characterized by adipose tissue inflammation. Because proteoglycans regulate inflammation, here we investigate their role in adipose tissue inflammation in obesity. We find that adipose tissue versican and biglycan increase in obesity.

Non-catalytic ubiquitin binding by A20 prevents psoriatic arthritis-like disease and inflammation.

A20 is an anti-inflammatory protein that is strongly linked to human disease. Here, we find that mice expressing three distinct targeted mutations of A20's zinc finger 7 (ZF7) ubiquitin-binding motif uniformly developed digit arthritis with features common to psoriatic arthritis, while mice expressing point mutations in A20's OTU or ZF4 motifs did not exhibit this phenotype. Arthritis in A20 mice required T cells and MyD88, was exquisitely sensitive to tumor necrosis factor and interleukin-17A, and persisted in germ-free conditions.

Nitrite elicits divergent NO-dependent signaling that associates with outcome in out of hospital cardiac arrest.

Brain and heart injury cause most out-of-hospital cardiac arrest deaths but limited pharmacotherapy exists to protect these tissues. Nitrite is a nitric oxide precursor that is protective in pre-clinical models of ischemic injury and safe in Phase I testing. Protection may occur by cGMP generation via the sGC pathway or through S-nitrosothiol and nitrated conjugated linoleic acid (NO-CLA) formation.

Hematopoietic Cell-Expressed Endothelial Nitric Oxide Protects the Liver From Insulin Resistance.

Objective: Mice genetically deficient in endothelial nitric oxide synthase (Nos3) have fasting hyperinsulinemia and hepatic insulin resistance, indicating the importance of Nos3 (nitric oxide synthase) in maintaining metabolic homeostasis. Although the current paradigm holds that these metabolic effects are derived specifically from the expression of Nos3 in the endothelium, it has been established that bone marrow-derived cells also express Nos3. The aim of this study was to investigate whether bone marrow-derived cell Nos3 is important in maintaining metabolic homeostasis.

Nitrite pharmacokinetics, safety and efficacy after experimental ventricular fibrillation cardiac arrest.

Introduction: Besides therapeutic hypothermia or targeted temperature management no novel therapies have been developed to improve outcomes of patients after cardiac arrest (CA). Recent studies suggest that nitrite reduces neurological damage after asphyxial CA. Nitrite is also implicated as a new mediator of remote post conditioning produced by tourniquet inflation-deflation, which is under active investigation in CA.

The role of vasodilator-stimulated phosphoprotein (VASP) in the control of hepatic gluconeogenic gene expression.

During periods in which glucose absorption from the gastrointestinal (GI) tract is insufficient to meet body requirements, hepatic gluconeogenesis plays a key role to maintain normal blood glucose levels. The current studies investigated the role in this process played by vasodilatory-associated phosphoprotein (VASP), a protein that is phosphorylated in hepatocytes by cAMP/protein kinase A (PKA), a key mediator of the action of glucagon. We report that following stimulation of hepatocytes with 8Br-cAMP, phosphorylation of VASP preceded induction of genes encoding key gluconeogenic enzymes, glucose-6-phosphatase (G6p) and phosphoenolpyruvate carboxykinase (Pck1), and that VASP overexpression enhanced this gene induction.

Does the Infant-Driven Feeding Method Positively Impact Preterm Infant Feeding Outcomes?

Background: Achievement of independent oral feeding is a major determinant of discharge and contributes to long lengths of stay. Accumulating evidence suggests that there is great variation between and within newborn intensive care units in the initiation and advancement of oral feeding. The Infant-Driven Feeding (IDF) method is composed of 3 behavioral assessments including feeding readiness, quality of feeding, and caregiver support.

Usefulness of Intravenous Sodium Nitrite During Resuscitation for the Treatment of Out-of-Hospital Cardiac Arrest.

It is hypothesized that intravenous (IV) sodium nitrite given during resuscitation of out-of-hospital cardiac arrest (OHCA) will improve survival. We performed a phase 1 open-label study of IV sodium nitrite given during resuscitation of 120 patents with OHCA from ventricular fibrillation or nonventricular fibrillation initial rhythms by Seattle Fire Department paramedics. A total of 59 patients received 25 mg (low) and 61 patients received 60 mg (high) of sodium nitrite during resuscitation from OHCA.

ABCA1 Overexpression in Endothelial Cells In Vitro Enhances ApoAI-Mediated Cholesterol Efflux and Decreases Inflammation.

Atherosclerosis, a disease of blood vessels, is driven by cholesterol accumulation and inflammation. Gene therapy that removes cholesterol from blood vessels and decreases inflammation is a promising approach for prevention and treatment of atherosclerosis. In previous work, we reported that helper-dependent adenoviral (HDAd) overexpression of apolipoprotein A-I (apoAI) in endothelial cells (ECs) increases cholesterol efflux in vitro and reduces atherosclerosis in vivo.

Pulmonary artery smooth muscle cell HIF-1α regulates endothelin expression via microRNA-543.

Pulmonary artery smooth muscle cells (PASMCs) express endothelin (ET-1), which modulates the pulmonary vascular response to hypoxia. Although cross-talk between hypoxia-inducible factor-1α (HIF-1α), an O-sensitive transcription factor, and ET-1 is established, the cell-specific relationship between HIF-1α and ET-1 expression remains incompletely understood. We tested the hypotheses that in PASMCs 1) HIF-1α expression constrains ET-1 expression, and 2) a specific microRNA (miRNA) links HIF-1α and ET-1 expression.

Type 2 diabetes is associated with loss of HDL endothelium protective functions.

Aims/hypothesis: One of the hallmarks of diabetes is impaired endothelial function. Previous studies showed that HDL can exert protective effects on endothelium stimulating NO production and protecting from inflammation and suggested that HDL in obese people with diabetes and dyslipidemia may have lower endothelial protective function. We aimed to investigate whether type 2 diabetes impairs HDL endothelium protective functions in people with otherwise normal lipid profile.

Care Through the Newborn's Eyes.

Separation of mothers and infants after birth is standard practice for many hospitals, yet not evidence-based. Nonseparation clearly has numerous benefits. However, newborns lack a voice to make choices to direct their course of care.

Hemodynamic effects of IV sodium nitrite in hospitalized comatose survivors of out of hospital cardiac arrest.

Background: Patients resuscitated from cardiac arrest have brain and cardiac injury. Recent animal studies suggest that the administration of sodium nitrite after resuscitation from 12min of asystole limits acute cardiac dysfunction and improves survival and neurologic outcomes. It has been hypothesized that low doses of IV sodium nitrite given during resuscitation of out of hospital cardiac arrest (OHCA) will improve survival.