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.

Reduction of mortality and morbidity in congenital cardiac surgery has always been and remains a major target for the complete team involved. As operative techniques are more and more standardized and refined, surgical risk and associated complication rates have constantly been reduced to an acceptable level but are both still present. Aortic arch surgery in neonates seems to be of particular interest, because perfusion techniques differ widely among institutions and an ideal form of a so called “total body perfusion (TBP)” is somewhat difficult to achieve. Thus concepts of deep hypothermic circulatory arrest (DHCA), regional cerebral perfusion (RCP/with cardioplegic cardiac arrest or on the perfused beating heart) and TBP exist in parallel and all carry an individual risk for organ damage related to perfusion management, chosen core temperature and time on bypass. Patient safety relies more and more on adequate end organ perfusion on cardiopulmonary bypass, especially sensitive organs like the brain, heart, kidney, liver and the gut, whereby on adequate tissue protection, temperature management and oxygen delivery should be visualized and monitored.

Background: Stage I palliation of hypoplastic left heart syndrome (HLHS) and its variants is usually performed by a Norwood operation. The management of pulmonary blood flow during this procedure remains controversial. The RV‐to-PA conduit (RVPAC) has been proposed as the better alternative compared to a systemic-to-pulmonary shunt (SPS). Methods: A retrospective single center chart review of consecutive patients who underwent a Norwood I procedure between 01/1997 and 09/2006 was performed. All patients were operated in deep hypothermia, with or without circulatory arrest, using different shunt modifications according to surgeon's preference. Patients were divided into two groups depending on surgical management for pulmonary blood flow (modified BT shunt [BT] and non-valved RVPAC [Sano]). Results: Fifty-four patients were included in the study (BT: 31 patients vs. Sano: 23 patients). Diastolic blood pressure during the first 24 hours postoperatively was significantly lower in the BT group (BT: 38.6 ± 6.9 mmHg vs. Sano: 42.4 ± 7.2 mmHg; p < 0.01) with a trend towards a higher systolic blood pressure (BT: 74.1 ± 13.5 mmHg vs. Sano: 69.8 ± 12.1 mmHg; p = 0.08). Mean circulatory arrest time in the BT group was significantly longer compared to the Sano patients (BT: 41 ± 21 min vs. Sano: 25 ± 23 min; p < 0.01). The mean hospital stay was 18.5 days for BT patients and 20 days for Sano patients (p = 0.45). Early mortality for the total cohort was 14.8 % (n = 8) (BT 19.4 % [n = 6] vs. Sano 8.7 % [n = 2]; p = 0.12). There was no significant difference in inter-stage mortality between the two groups (BT: 18.2 % vs. Sano: 21.1 %; p = 0.47). Conclusion: The results for both established surgical methods (BT and Sano) for the palliation of HLHS and its variants have improved over time and are reaching acceptable early mortality rates. There was a trend towards a favorable early outcome for Sano patients, which did not reach statistical significance in this study due to the low patient numbers.