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Objectives: Hospitalized children with underlying heart disease are at high risk for cardiac arrest, particularly when they undergo invasive catheterization procedures for diagnostic and therapeutic interventions. Outcomes for children experiencing cardiac arrest in the cardiac catheterization laboratory remain under-reported with few studies reporting survival beyond the catheterization laboratory. We aim to describe survival outcomes after cardiac arrest in the cardiac catheterization laboratory while identifying risk factors associated with hospital mortality after these events., Design: Retrospective observational study of data from a multicenter cardiac arrest registry from November 2005 to November 2016. Cardiac arrest in the cardiac catheterization laboratory was defined as the need for chest compressions greater than or equal to 1 minute in the cardiac catheterization laboratory. Primary outcome was survival to discharge. Variables analyzed using generalized estimating equations for association with survival included age, illness category (surgical cardiac, medical cardiac), preexisting conditions, pharmacologic interventions, and event duration., Setting: American Heart Association's Get With the Guidelines-Resuscitation registry of in-hospital cardiac arrest., Patients: Consecutive patients less than 18 years old experiencing an index (i.e., first) cardiac arrest event reported to the Get With the Guidelines-Resuscitation., Interventions: None., Measurements and Main Results: A total of 203 patients met definition of index cardiac arrest in the cardiac catheterization laboratory composed primarily of surgical and medical cardiac patients (54% and 41%, respectively). Children less than 1 year old comprised the majority of patients, 58% (117/203). Overall survival to hospital discharge was 69% (141/203). No differences in survival were observed between surgical and medical cardiac patients (p = 0.15). The majority of deaths (69%, 43/62) occurred in patients less than 1 year old. Bradycardia (with pulse) followed by pulseless electrical activity/asystole were the most common first documented rhythms observed (50% and 27%, respectively). Preexisting metabolic/electrolyte abnormalities (p = 0.02), need for vasoactive infusions (p = 0.03) prior to arrest, and use of calcium products (p = 0.005) were found to be significantly associated with lower rates of survival to discharge on multivariable regression., Conclusions: The majority of children experiencing cardiac arrest in the cardiac catheterization laboratory in this large multicenter registry analysis survived to hospital discharge, with no observable difference in outcomes between surgical and medical cardiac patients. Future investigations that focus on stratifying medical complexity in addition to procedural characteristics at the time of catheterization are needed to better identify risks for mortality after cardiac arrest in the cardiac catheterization laboratory.

Only a few studies provided data on the clinical history of sepsis within internal Medicine units. The aim of the study was to assess the short-term mortality and to evaluate the prognostic risk factors in a large cohort of septic patients treated in internal medicine units. Thirty-one internal medicine units participated to the study. Within each participating unit, all admitted patients were screened for the presence of sepsis. A total of 533 patients were included; 78 patients (14.6%, 95%CI 11.9, 18.0%) died during hospitalization; mortality rate was 5.5% (95% CI 3.1, 9.6%) in patients with nonsevere sepsis and 20.1% (95%CI 16.2, 28.8%) in patients with severe sepsis or septic shock. Severe sepsis or septic shock (OR 4.41, 95%CI 1.93, 10.05), immune system weakening (OR 2.10, 95%CI 1.12, 3.94), active solid cancer (OR 2.14, 95% CI 1.16, 3.94), and age (OR 1.03 per year, 95% CI 1.01, 1.06) were significantly associated with an increased mortality risk, whereas blood culture positive for Escherichia coli was significantly associated with a reduced mortality risk (OR 0.46, 95%CI 0.24, 0.88). In-hospital mortality of septic patients treated in internal medicine units appeared similar to the mortality rate obtained in recent studies conducted in the ICU setting., Competing Interests: The authors have no conflicts of interest to disclose.

Objective: Endothelial sphingosine-1-phosphate (S1P) receptor-1 (S1P(1)) affects different vascular functions, including blood vessel maturation and permeability. Here, we characterized the role of the zS1P(1) ortholog in vascular development in zebrafish., Methods and Results: zS1P(1) is expressed in dorsal aorta and posterior cardinal vein of zebrafish embryos at 24 to 30 hours postfertilization. zS1P(1) downregulation by antisense morpholino oligonucleotide injection causes early pericardial edema, lack of blood circulation, alterations of posterior cardinal vein structure, and late generalized edema. Also, zS1P(1) morphants are characterized by downregulation of vascular endothelial cadherin (VE-cadherin) and Eph receptor EphB4a expression and by disorganization of zonula occludens 1 junctions in posterior cardinal vein endothelium, with no alterations of dorsal aorta endothelium. VE-cadherin knockdown results in similar vascular alterations, whereas VE-cadherin overexpression is sufficient to rescue venous vascular integrity defects and EphB4a downregulation in zS1P(1) morphants. Finally, S1P(1) small interfering RNA transfection and the S1P(1) antagonist (R)-3-amino-(3-hexylphenylamino)-4-oxobutylphosphonic acid (W146) cause EPHB4 receptor down-modulation in human umbilical vein endothelial cells and the assembly of zonula occludens 1 intercellular contacts is prevented by the EPHB4 antagonist TNYL-RAW peptide in these cells., Conclusions: The data demonstrate a nonredundant role of zS1P(1) in the regulation of venous endothelial barrier in zebrafish and identify a S1P(1)/VE-cadherin/EphB4a genetic pathway that controls venous vascular integrity.

Objective: The goal of this study was to determine the in vivo functions of the synaptic proteins neurexins and neuroligins in embryonic vascular system development using zebrafish as animal model., Methods and Results: In the present study, we show that the knockdown of the α-form of neurexin 1a induces balance defects and reduced locomotory activity, whereas β-neurexin 1a and neuroligin 1 morphants present defects in sprouting angiogenesis and vascular remodeling, in particular in the caudal plexus and subintestinal vessels. Coinjection of low doses of morpholinos for β-neurexin 1a and neuroligin 1 together or in combination with morpholinos targeting the -heparin--binding isoforms of vascular endothelial growth factor A (encoded by the VEGFAb gene) recapitulates the observed abnormalities, suggesting synergistic activity of these molecules. Similar coinjection experiments with morpholinos, targeting the enzyme heparan sulfate 6-O-sulfotransferase 2, confirm the presence of a functional correlation between extracellular matrix maturation and β-neurexin 1a or neuroligin 1., Conclusions: Our data represent the first in vivo evidence of the role of neurexin and neuroligin in embryonic blood vessel formation and provide insights into their mechanism of action.