Mortality among infants with evolving bronchopulmonary dysplasia increases with major surgery and with pulmonary hypertension.

OBJECTIVE: To assess whether mortality in patients with evolving bronchopulmonary dysplasia (BPD, defined as ⩾28 days of oxygen exposure with lung disease) is independently associated with pulmonary arterial hypertension (PAH) and surgery. STUDY DESIGN: Single institution retrospective birth cohort of preterm infants with gestational age (GA) 230/7 to 366/7 weeks, and evolving BPD delivered between 2001 and 2014. Surgery was classified as minor or major using published criteria. Mortality was analyzed by stepwise logistic regression analysis. RESULTS: Among 577 patients with evolving BPD, 33 (6%) died prior to discharge. Mortality decreased with GA (adjusted odds ratio (aOR): 0.69; 95% confidence interval (CI): 0.55, 0.87), birth weight Z-score (aOR: 0.69, 95% CI: 0.47, 0.996) and increased with PAH (aOR: 30, 95% CI: 2.1, 415), major surgery (aOR; 2.8, 95% CI: 1.3, 6.3), and PAH and surgery (aOR: 10.3, 95% CI: 2.5, 42.1). CONCLUSION: Among preterm patients with evolving BPD, PAH and surgery are independently associated with mortality.

Impact of hypothermia on predictors of poor outcome: how do we decide to redirect care?

Therapeutic hypothermia is now considered the standard of care for neonates with neonatal encephalopathy due to perinatal asphyxia. Outcomes following hypothermia treatment are favorable, as demonstrated in recent meta-analyses, but 45-50% of these neonates still suffer major disability or die due to global multi-organ injury or after redirection of care from life support due to severe brain injury. The ability to determine which patients are at highest risk of severe neurologic impairment and death and those in whom redirection of care should be considered is limited. This is especially true in the first few days after birth and in situations where the brain might be more significantly affected than other organ systems, making it difficult to discuss redirection of care. Clinical history, neurologic examination, serum biomarkers, neurophysiology [amplitude-integrated electroencephalography (aEEG) or EEG], near-infrared spectroscopy, and magnetic resonance imaging have all been studied as predictors of severe neurologic injury and poor outcome, although none is 100% predictive. Serial evaluation over time seems to be an important element to facilitate discussion regarding anticipated poor prognosis and decision-making for transition to comfort care. Thus far, brain monitoring in the form of aEEG and conventional EEG seem to be the best objective tools to identify the highest-risk patients. A delay or lack of recovery of the aEEG background during hypothermia treatment is an established important predictor of poor outcome (death or disability). This paper highlights the prognostic indicators that have been considered and focuses on aEEG as an important predictor of death or severe disability, which may facilitate conversations regarding redirection of care.

Clathrin-coated vesicles bearing GAIP possess GTPase-activating protein activity in vitro.

Galpha-interacting protein (GAIP) is a member of the RGS (regulators of G protein signaling) family, which serve as GAPs (GTPase-activating proteins) for Galpha subunits. Previously, we demonstrated that GAIP is localized on clathrin-coated vesicles (CCVs). Here, we tested whether GAIP-enriched vesicles could accelerate the GTPase activity of Galphai proteins. A rat liver fraction containing vesicular carriers (CV2) was enriched (4.5x) for GAIP by quantitative immunoblotting, and GAIP was detected on some of the vesicles in the CV2 fraction by immunoelectron microscopy. When liver fractions were added to recombinant Galphai3 and tested for GAP activity, only the CV2 fraction contained GAP activity. Increasing amounts of CV2 increased the activity, whereas immunodepletion of the CV2 fraction with an antibody against the C terminus of GAIP decreased GAP activity. CCV fractions were prepared from rat liver by using a protocol that maintains the clathrin coats. GAIP was enriched in these fractions and was detected on CCVs by immunogold labeling. Addition of increasing amounts of CCV to recombinant Galphai3 protein increased the GTPase activity. We conclude that CCVs possess GAP activity for Galphai3 and that membrane-associated GAIP is capable of interacting with Galphai3. The reconstitution of the interaction between a heterotrimeric G protein and GAIP on CCVs provides biochemical evidence for a model whereby the G protein and its GAP are compartmentalized on different membranes and come into contact at the time of vesicle fusion. Alternatively, they may be located on the same membrane and segregate at the time of vesicle budding.

Aortic regurgitation. Detection of left ventricular dysfunction by exercise echocardiography.

Left ventricular performance was assessed in 20 symptom free patients and 10 with symptoms, all with isolated aortic regurgitation, by measuring the echocardiographic peak velocity of circumferential fibre shortening (echo peak Vcf) at rest and during graded bicycle ergometer exercise in the supine position. The normal left ventricular response during such exercise was first determined in 20 healthy controls. On the basis of their resting and exercise echo peak Vcf, the 30 patients with aortic regurgitation could be separated into three groups: Group 1 comprised 11 symptom free patients with a normal resting echo peak Vcf which increased normally with exercise; group 2 comprised nine symptom free patients with a normal resting echo peak Vcf but with a subnormal response to exercise; group 3 consisted of 10 patients with symptoms with a depressed resting echo peak Vcf which remained subnormal with exercise. Subsequent cardiac catheterisation disclosed normal ejection fractions in patients in group 1, borderline ejection fractions in those in group 2, and reduced ejection fractions in those in group 3. Echocardiographic assessment of left ventricular performance during supine isotonic exercise may provide a simple noninvasive method for the early detection of left ventricular dysfunction in symptom free patients with aortic regurgitation.