Reduced basal macrovascular and microvascular cerebral blood flow in young adults with metabolic syndrome: potential mechanisms.

Ninety-million Americans suffer metabolic syndrome (MetSyn), increasing the risk of diabetes and poor brain outcomes, including neuropathology linked to lower cerebral blood flow (CBF), predominantly in anterior regions. We tested the hypothesis that total and regional CBF is lower in MetSyn more so in the anterior brain and explored three potential mechanisms. Thirty-four controls (25 ± 5 yr) and 19 MetSyn (30 ± 9 yr), with no history of cardiovascular disease/medications, underwent four-dimensional flow magnetic resonance imaging (MRI) to quantify macrovascular CBF, whereas arterial spin labeling quantified brain perfusion in a subset (n = 38/53). Contributions of cyclooxygenase (COX; n = 14), nitric oxide synthase (NOS, n = 17), or endothelin receptor A signaling (n = 13) were tested with indomethacin, NG-monomethyl-L-arginine (L-NMMA), and Ambrisentan, respectively. Total CBF was 20 ± 16% lower in MetSyn (725 ± 116 vs. 582 ± 119 mL/min, P < 0.001). Anterior and posterior brain regions were 17 ± 18% and 30 ± 24% lower in MetSyn; reductions were not different between regions (P = 0.112). Global perfusion was 16 ± 14% lower in MetSyn (44 ± 7 vs. 36 ± 5 mL/100 g/min, P = 0.002) and regionally in frontal, occipital, parietal, and temporal lobes (range 15-22%). The decrease in CBF with L-NMMA (P = 0.004) was not different between groups (P = 0.244, n = 14, 3), and Ambrisentan had no effect on either group (P = 0.165, n = 9, 4). Interestingly, indomethacin reduced CBF more in Controls in the anterior brain (P = 0.041), but CBF decrease in posterior was not different between groups (P = 0.151, n = 8, 6). These data indicate that adults with MetSyn exhibit substantially reduced brain perfusion without regional differences. Moreover, this reduction is not due to loss of NOS or gain of ET-1 signaling but rather a loss of COX vasodilation.NEW & NOTEWORTHY We tested the impact of insulin resistance (IR) on resting cerebral blood flow (CBF) in adults with metabolic syndrome (MetSyn). Using MRI and research pharmaceuticals to study the role of NOS, ET-1, or COX signaling, we found that adults with MetSyn exhibit substantially lower CBF that is not explained by changes in NOS or ET-1 signaling. Interestingly, adults with MetSyn show a loss of COX-mediated vasodilation in the anterior but not posterior circulation.

Feasibility of Aerosol Bronchodilators Delivery Through High-Flow Nasal Cannula in Pediatric Subjects With Respiratory Distress.

BACKGROUND: High-flow nasal cannula (HFNC) is commonly used to provide respiratory support to pediatric patients with respiratory failure. Although the use of bronchodilators via HFNC has been described, the feasibility and safety of aerosolized bronchodilator delivery via HFNC are controversial. In this study, we sought to evaluate whether the HFNC system can be used to deliver nebulized bronchodilators at lower gas flow of 2-4 L/min, increase patient comfort, and minimize respiratory therapist (RT) bedside time when compared to traditional interfaces. METHODS: A retrospective chart review of all pediatric subjects who were admitted to the pediatric ICU in a tertiary care children's hospital and required nebulized bronchodilators between December 2017 and June 2018. RESULTS: A total of 205 nebulizations were administered to 28 children; 31% of nebulized bronchodilators were given using a nebulization system integrated into the HFNC. Nebulized treatments resulted in an average increase in heart rate of 9.98 (95% CI 3.72-16.2) beats/min when HFNC was used and 0.64 (95% CI -1.65 to 2.93) beats/min when traditional interfaces were used, a difference of 9.34 (95% CI 2.30-16.4) beats/min (P < .001). RT bedside time was significantly longer for HFNC nebulized treatments (P = .031). Subjective level of comfort was not statically different when nebulized bronchodilators were delivered via HFNC or via traditional interfaces. Length of pediatric ICU stay was not statistically different between subjects who received some aerosol nebulized bronchodilators via HFNC versus those who received all bronchodilators through traditional interfaces (P = .11). CONCLUSIONS: Aerosol bronchodilator delivery using HFNC is feasible at low gas flow (ie, 2-4 L/min). However, the use of HFNC did not improve subjects' comfort, and it increased RT bedside time. Further prospective randomized studies are needed to determine the efficacy and efficiency of aerosol therapy delivered through HFNC and potential patient-oriented outcomes.

Pediatric Critical Care in Resource-Limited Settings-Overview and Lessons Learned.

Pediatric critical care is an important component of reducing morbidity and mortality globally. Currently, pediatric critical care in low middle-income countries (LMICs) remains in its infancy in most hospitals. The majority of hospitals lack designated intensive care units, healthcare staff trained to care for critically ill children, adequate numbers of staff, and rapid access to necessary medications, supplies and equipment. In addition, most LMICs lack pediatric critical care training programs for healthcare providers or certification procedures to accredit healthcare providers working in their pediatric intensive care units (PICU) and high dependency areas. PICU can improve the quality of pediatric care in general and, if properly organized, can effectively treat the severe complications of high burden diseases, such as diarrhea, severe malaria, and respiratory distress using low-cost interventions. Setting up a PICU in a LMIC setting requires planning, specific resources, and most importantly investment in the nursing and permanent medical staff. A thoughtful approach to developing pediatric critical care services in LMICs starts with fundamental building blocks: training healthcare professionals in skills and knowledge, selecting resource appropriate effective equipment, and having supportive leadership to provide an enabling environment for appropriate care. If these fundamentals can be built on in a sustainable manner, an appropriate critical care service will be established with the potential to significantly decrease pediatric morbidity and mortality in the context of public health goals as we reach toward the sustainable development goals.

Symptomatic Presentation of an Anamalous Left Coronary Artery from the Pulmonary Artery in an 8-Day-Old.

An 8-day-old presented in extremis and was subsequently diagnosed with an anomalous left coronary artery from the pulmonary artery. Symptomatic presentation at her young age and atypical echocardiogram findings make this case unique and suggest that demonstration of retrograde coronary flow is unnecessary in symptomatic presentation.

Neonatal Repair in a Patient With Heterotaxy, Truncus Arteriosus, Pulmonary Artery Sling, and Tracheal Stenosis.

We present a newborn with heterotaxy features, multiple congenital anomalies, truncus arteriosus with long segment tracheal stenosis, and a left pulmonary artery sling. The patient had complete neonatal repair with slide tracheoplasty and repair of the left pulmonary artery sling with anterior translocation of the pulmonary artery. The truncus was repaired with a transventricular ventricular septal defect closure with a patch and right ventricle to pulmonary artery conduit. Complete repair of complex cardiac neonatal lesions with critical tracheal stenosis is feasible and should be the strategy of choice in these complex patients.

Simulation Use for Global Away Rotations (SUGAR): preparing residents for emotional challenges abroad--a multicenter study.

BACKGROUND: Preparation for residents participating in global health (GH) experiences is critical. Active preparatory curricula allowing residents to experience and debrief emotional challenges they may encounter abroad are generally lacking. We sought to evaluate a novel simulation curriculum designed to prepare residents for emotions they may experience in response to challenges abroad. METHODS: Pediatric GH educators from 7 institutions developed case vignettes incorporating common challenges residents experience abroad. Residents participating in a GH training track or planning to participate in a GH rotation from the 7 institutions were eligible to participate in the simulation curriculum. Participants and trained facilitators completed postsimulation evaluations that were analyzed using descriptive statistics and thematic analysis of written comments to assess the utility of the curriculum, emotions evoked, and changes residents anticipated making to their GH rotation preparation. RESULTS: Fifty-one residents and 16 facilitators completed 160 and 52 evaluations, respectively. Overall, respondents found the simulations useful (mean [SD] resident score 4.49 [0.82] and facilitator score 4.85 [0.36] on a 5-point scale [1 = completely useless, 5 = very useful]). Residents reported strong emotions in 153 (98%) of 156 comments. After the sessions, 131 (96%) of 137 comments reflected anticipated changes to GH rotation preparation plans. CONCLUSIONS: Active preparation for GH rotations using simulated cases appears to be a useful tool that can be implemented across a variety of sites with minimal facilitator training or simulation experience. The curriculum successfully elicited powerful emotions in residents and provided an opportunity to debrief these experiences before encountering them abroad.

Development, implementation, and initial participant feedback of a pediatric sedation provider course.

BACKGROUND: No standardized educational curriculum exists for pediatric sedation practitioners. We sought to describe the curriculum and implementation of a pediatric sedation provider course and assess learner satisfaction with the course curriculum. DESCRIPTION: The course content was determined by formulating a needs assessment using published sedation guidelines, reports of sedation related adverse events, and a survey of sedation practitioners. Students provided feedback regarding satisfaction with the course immediately following the course and 6 months later. EVALUATION: The course consisted of 5 didactic lectures, 1 small-group session, 6 simulation scenarios, a course syllabus, and a written examination. The course was conducted over 1 day at 3 different locations. Sixty-nine students completed the course and were uniformly satisfied with the course curriculum. CONCLUSIONS: A standardized pediatric sedation provider course was developed for sedation practitioners and consisted of a series of lectures and simulation scenarios. Overall satisfaction with the course was positive.

Mechanically ventilated pediatric stem cell transplant recipients: effect of cord blood transplant and organ dysfunction on outcome.

OBJECTIVES: To compare survival of pediatric umbilical cord blood and bone marrow transplant recipients requiring admission to a pediatric intensive care unit for mechanical ventilation and to determine the effect of organ dysfunction on outcome. DESIGN: Retrospective chart review. SETTING: Tertiary care referral center for pediatric stem cell transplants. PATIENTS: All children 0-18 yrs old admitted to the pediatric intensive care unit for mechanical ventilation after receiving a stem cell transplant. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were collected from medical records of 86 patients who received a stem cell transplant and were subsequently admitted to the pediatric intensive care unit for mechanical ventilation. Demographic data were collected at the time of intubation, and physiologic data were collected at 6 hrs and 96 hrs after intubation. The pediatric intensive care unit, hospital, and 2-yr survival rates for umbilical cord blood transplant recipients were 37%, 25%, and 19%, respectively. The survival rates for bone marrow transplant recipients were 47%, 32%, and 21% for the same time periods. Umbilical cord blood and bone marrow transplant recipients with hepatic dysfunction had a significantly worse outcome, as did patients admitted for respiratory failure or sepsis. CONCLUSIONS: Pediatric recipients of an umbilical cord blood transplant who subsequently required mechanical ventilation had lower pediatric intensive care unit and hospital survival rates compared with patients receiving bone marrow transplantation. Survival at 2 yrs for umbilical cord blood transplant and bone marrow transplant patients was similar. Predictors of outcome for all stem cell transplant recipients requiring mechanical ventilation included pediatric intensive care unit diagnosis requiring intubation and hepatic function. Predictors of outcome can be identified shortly after intubation in pediatric stem cell transplant recipients and may aid in therapeutic decision making and family counseling.

Cardiopulmonary bypass decreases G protein-coupled receptor kinase activity and expression in human peripheral blood mononuclear cells.

BACKGROUND: Cardiopulmonary bypass (CPB) has been implicated in the development of organ injury associated with cardiac surgery. At the molecular level, CPB is accompanied by a pronounced proinflammatory response including an increase in plasma interleukin (IL)-6. The IL-6 has been shown to be increased in rheumatoid arthritis, a chronic inflammatory disease, where it has been implicated in decreasing G protein-coupled receptor kinases (GRKs) in peripheral blood mononuclear cells. Since IL-6 is substantially increased after CPB, the study tested whether the increase of IL-6 during CPB leads to a decrease of GRKs in mononuclear cells. This is important because GRKs regulate the function of G protein-coupled receptors involved in inflammation. METHODS: Fifteen patients had blood withdrawn before CPB, 2 h after CPB, and on postoperative day one (POD1). Plasma IL-6 concentrations were determined by enzyme-linked immunosorbent assay. The GRK protein expression and activity were determined by Western blot and phosphorylation of rhodopsin using [gamma-(32)P] adenosine triphosphate, respectively. RESULTS: Plasma IL-6 increased over 20-fold after CPB and remained increased on POD1. Cytosolic GRK activity in mononuclear cells decreased by 39 +/- 29%; cytosolic GRK2 and membrane-bound GRK6 decreased by 90 +/- 15 and 65 +/- 43%, respectively. The GRK activity and expression of GRK2/GRK6 on POD1 returned to basal levels in many but not all patients. CONCLUSIONS: The CPB causes a profound decrease in mononuclear cell GRKs, and the recovery of these kinases on POD1 is quite variable. The significance of the variable recovery of GRKs after CPB and their potential role as a marker of clinical outcome deserves further investigation.