Red blood cell volume, but not platelet or plasma volume is associated with mortality in neonatal ECMO.

BACKGROUND: Blood product transfusions are necessary for critically ill neonates on extracorporeal membrane oxygenation (ECMO). Transfusions are administered in response to unstudied arbitrary thresholds and may be associated with adverse outcomes. The objective of this study was to identify relationships between blood product components and mortality in neonates receiving ECMO support for respiratory indications. STUDY DESIGN AND METHODS: A retrospective review of neonates receiving ECMO for respiratory indications from 2002 to 2019 from a single quaternary-referral neonatal intensive care unit (NICU). Demographic and outcome data and transfusion volume (ml/kg/day) were harvested from the medical record, and baseline mortality risk was assessed using NEO-RESCUERS scores. The association between volume of red blood cells (RBC), platelet, plasma transfusion rates (ml/kg/day), and mortality on ECMO were assessed after adjustment for NEO-RESCUERS score. Cox proportional hazards (CPH) competing risk model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for each variable and mortality outcome. MEASUREMENTS AND MAIN RESULTS: Among 248 neonates undergoing ECMO for respiratory failure, overall survival was 93%. RBC, platelet, and plasma volume were highly associated with mortality during ECMO in an unadjusted model. After adjusting for NEO-RESCUERS score, RBC volume was associated with increased mortality risk (HR 1.013, 95% CI 1.004-1.022, p = .0043), but platelet and plasma volume were not associated with mortality. CONCLUSIONS: RBC, but not platelet or plasma volume, is associated with mortality in neonates on ECMO. Our findings refute previous studies demonstrating an association between platelet volume and mortality for neonates on ECMO.

PKC signaling contributes to chromatin decondensation and is required for competence to respond to IL-2 during T cell activation.

The clonal proliferation of antigen-specific T cells during an immune response critically depends on the differential response to growth factors, such as IL-2. While activated T cells proliferate robustly in response to IL-2 stimulation, naïve (quiescent) T cells are able to ignore the potent effects of growth factors because they possess chromatin that is tightly condensed such that transcription factors, such as STAT5, cannot access DNA. Activation via the T cell receptor (TCR) induces a rapid decondensation of chromatin, permitting STAT5-DNA engagement and ultimately promoting proliferation of only antigen-specific T cells. Previous work demonstrated that the mobilization of intracellular calcium following TCR stimulation is a key event in the decondensation of chromatin. Here we examine PKC-dependent signaling mechanisms to determine their role in activation-induced chromatin decondensation and the subsequent acquisition of competence to respond to IL-2 stimulation. We found that a calcium-dependent PKC contributes to activation-induced chromatin decondensation and that the p38 MAPK and NFκB pathways downstream of PKC each contribute to regulating the proper decondensation of chromatin. Importantly, we found that p44/42 MAPK activity is required for peripheral T cells to gain competence to properly respond to IL-2 stimulation. Our findings shed light on the mechanisms that control the clonal proliferation of antigen-specific peripheral T cells during an immune response.

Cannulation approach and mortality in neonatal ECMO.

OBJECTIVE: Identify associations between cannulation approach and mortality in neonates who received ECMO support for respiratory failure. STUDY DESIGN: A retrospective analysis of neonates receiving ECMO for respiratory indications at a single quaternary-referral NICU. Associations between cannulation approach and mortality were assessed after adjustment for Neo-RESCUERS score. Cox Proportional Hazards (CPH) model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for each variable and outcome. RESULTS: Among 244 neonates, overall survival was 88%, with 71% undergoing VV cannulation. After adjusting for Neo-RESCUERS score, VA cannulation was associated with higher mortality during ECMO when compared with VV cannulation (HR 4.189, 95% CI 1.480-11.851, P = 0.0069). Disease-specific comparisons revealed no statistical difference in Neo-RESCUERS score between VA and VV cohorts; however, VA cannulation was associated with higher ECMO mortality for neonates with congenital diaphragmatic hernia (50% vs. 5.5%, Χ2 = 8.5965, P = 0.0034) and PPHN (20% vs. 1.8%, Χ2 = 9.1047, P = 0.0025) when compared with VV cannulation. CONCLUSION: VA cannulation was associated with increased mortality in neonates while on ECMO for respiratory failure, which was independent of illness severity.