The detection of microorganisms and danger signals by pattern recognition receptors on dendritic cells (DCs) and the consequent formation of inflammasomes are pivotal for initiating protective immune responses. Although the activation of inflammasomes leading to secretion of the cytokine IL-1β is typically accompanied by pyroptosis (an inflammatory form of lytic programmed cell death), some cells can survive and exist in a state of hyperactivation. Here, we found that the conventional type 2 DC (cDC2) subset is the major human DC subset that is transcriptionally and functionally poised for inflammasome formation and response without pyroptosis. When cDC2 were stimulated with ligands that relatively weakly activated the inflammasome, the cells did not enter pyroptosis but instead secreted IL-12 family cytokines and IL-1β. These cytokines induced prominent T helper type 1 (T_H1) and T_H17 responses that were superior to those seen in response to Toll-like receptor (TLR) stimulation alone or to stronger, classical inflammasome ligands. These findings not only define the human cDC2 subpopulation as a prime target for the treatment of inflammasome-dependent inflammatory diseases but may also inform new approaches for adjuvant and vaccine development.

Dendritic cells (DCs) are major regulators of innate and adaptive immune responses. DCs can be classified into plasmacytoid DCs and conventional DCs (cDCs) type 1 and 2. Murine and human cDC1 share the mRNA expression of XCR1. Murine studies indicated a specific role of the XCR1–XCL1 axis in the induction of immune responses. Here, we describe that human cDC1 can be distinguished into XCR1 ⁻ and XCR1 ⁺ cDC1 in lymphoid as well as nonlymphoid tissues. Steady-state XCR1 ⁺ cDC1 display a preactivated phenotype compared to XCR1 ⁻ cDC1. Upon stimulation, XCR1 ⁺ cDC1, but not XCR1 ⁻ cDC1, secreted high levels of inflammatory cytokines as well as chemokines. This was associated with enhanced activation of NK cells mediated by XCR1 ⁺ cDC1. Moreover, XCR1 ⁺ cDC1 excelled in inhibiting replication of Influenza A virus. Further, under DC differentiation conditions, XCR1 ⁻ cDC1 developed into XCR1 ⁺ cDC1. After acquisition of XCR1 expression, XCR1 ⁻ cDC1 secreted comparable level of inflammatory cytokines. Thus, XCR1 is a marker of terminally differentiated cDC1 that licenses the antiviral effector functions of human cDC1, while XCR1 ⁻ cDC1 seem to represent a late immediate precursor of cDC1.

Fontan patients with protein‐losing enteropathy (PLE) represent poor candidates for cardiac transplantation due to end‐organ injury and severely impaired clinical condition. Ventricular assist device (VAD) therapy has evolved as a promising bridge to transplant strategy improving quality of life and survival on the waiting list. However, VAD therapy for the Fontan circulation remains challenging. For Fontan patients with preserved ventricular function implantation of a right ventricular assist device (RVAD) has been described by Prêtre et al as bridge to transplant. We present the second case of RVAD support in a Fontan patient with PLE.

This study reports a single-centre experience of the Medos Deltastream diagonal-pump (DP3) for extracorporeal cardiac, pulmonary, or combined support in a single-center pediatric cohort. Twenty-seven consecutive patients with 28 runs of the DP3 between January 2013 and June 2014 were included for analysis. Median patient age, weight, and duration of support were 278 days (range: 0 days–14.2 years), 7.2 kg (range: 2.5–39 kg), and 8 days (range: 2–69 days). Midline sternotomy (n = 20, 71.4%) or cervical approaches (n = 8, 28.6%) were used for cannulation. The DP3 was employed for either veno-arterial extracorporeal life support (ECLS, n = 16), veno-venous extracorporeal membrane oxygenation (ECMO, n = 5), or ventricular assist devices (right ventricular assist device [RVAD], n = 1; left ventricular assist device [LVAD], n = 1; and univentricular assist device [UNIVAD], n = 5). Three patients initially supported with ECLS were switched to UNIVAD and one patient with UNIVAD was changed to ECLS. Required flow for neonates (n = 8) ranged between 0.2 and 0.75 L/min. Irreversible pump damage occurred in one patient during deairing after air block. Successful weaning, 30 day and hospital survival were 89.3% (n = 25), 85.7% (n = 24), and 71.4% (n = 20). All patients on UNIVAD, who did not require further extracorporeal respiratory assist, survived. In conclusion, the DP3 can be used for individual patient demands and adapted to their most suitable method of support. Meticulous flow adjustments render this pump highly effective for extracorporeal support particularly in pediatric patients.

Aortic coarctation with distal aortic arch hypoplasia can be effectively addressed by coarctation resection with extended end-to-end-anastomosis (REEEA). Particularly, when unilateral cerebral perfusion (UCP) is established by clamping of left-sided supra-aortic vessels, the extent of cerebral blood flow distribution during repair remains undetermined, so far. Transfontanellar contrast-enhanced ultrasound (T-CEUS) can be utilized for real-time visualization and quantitative evaluation of cerebral blood flow. This study quantitatively evaluates cerebral perfusion during REEEA by using intraoperative T-CEUS. In a prospective study, 9 infants with open fontanelle undergoing REEEA [median age: 13 days (range 1–34) and median weight 3.1 kg (range 2.2–4.4)] were intraoperatively examined with T-CEUS at 3 consecutive time-points: before skin incision, during UCP and after skin suture. A software-based analysis of 11 parameters was used for data evaluation. Absolute and relative blood flow in contralateral hemispheres was measured in side-by-side comparison, and referenced to baseline measurements. No side-depend absolute or relative cerebral perfusion differences were found during REEEA, except for an increased relative ‘wash-out-rate’ (P = 0.0013) in favour of the right hemisphere after surgery. Compared to ipsilateral baseline levels, ‘rise time’ was transiently increased in right (P = 0.0277) and ‘time-to-peak’ in both hemispheres (right: P = 0.0403 and left: P = 0.0286), all during UCP. The use of T-CEUS provided evidence for homogenous distribution of contrast agent in both hemispheres during UCP. T-CEUS can be utilized for the postprocedural evaluation of cerebral perfusion during congenital cardiac surgery. URL: http://www.clinicaltrials.gov Unique, Identifier: NCT03215628.