Branch-first Continuous Perfusion Aortic Arch Replacement: Midterm Results.

BACKGROUND: Aortic arch surgery necessitates interruption of perfusion, thus conferring higher morbidity and mortality compared with other aortic surgery. This report describes a branch-first continuous perfusion aortic arch replacement (BF-CPAR) technique that overcomes these shortcomings and describes midterm results with this technique. METHODS: This report represents the corresponding author's 15-year experience with BF-CPAR, which involves preliminary mobilization and branch reconstruction before circulatory arrest by using a modified trifurcation graft. Demographic, procedural, and outcome (mortality, reintervention, morbidity, and stroke) were analyzed with Kaplan-Meier and Cox regression. RESULTS: Over 15 years (July 2005-February 2021), 155 patients underwent BF-CPAR, at a median age of 66.8 years, 106 (68.3%) on an elective basis and 49 (31.6%) on an emergency basis. There were no aortic deaths after the first postoperative year, thereby resulting in a 1- and 10-year freedom from aortic death constant at 95.6% in patients undergoing elective BF-CPAR and 93.3% in patients undergoing emergency BF-CPAR patients, respectively. Freedom from reintervention on the operated segment at 5 and 9 years was 93.2% and 93.2% in patients undergoing elective cases and 97.1% and 91.4% in emergency cases, respectively. The 10-year freedom from any aortic reintervention was 72.8% in elective patients and 29.2% in emergency patients; there were 38 reinterventions, 76.3% (n = 29/38) done for progression of aneurysmal or dissection disease, of which 79.3% (n = 23/29) were completed endovascularly. Freedom from cerebrovascular-related events at 5 and 10 years was 90.3% and 82.6% in patients undergoing elective BF-CPAR and 75.4% for both time points in patients undergoing emergency BF-CPAR, respectively. CONCLUSIONS: BF-CPAR has excellent 10-year results for elective and emergency cases of arch replacement.

Natural killer cell receptors regulate responses of HLA-E-restricted T cells.

Human cytomegalovirus (CMV) infection can stimulate robust human leukocyte antigen (HLA)-E-restricted CD8+ T cell responses. These T cells recognize a peptide from UL40, which differs by as little as a single methyl group from self-peptides that also bind HLA-E, challenging their capacity to avoid self-reactivity. Unexpectedly, we showed that the UL40/HLA-E T cell receptor (TCR) repertoire included TCRs that had high affinities for HLA-E/self-peptide. However, paradoxically, lower cytokine responses were observed from UL40/HLA-E T cells bearing TCRs with high affinity for HLA-E. RNA sequencing and flow cytometric analysis revealed that these T cells were marked by the expression of inhibitory natural killer cell receptors (NKRs) KIR2DL1 and KIR2DL2/L3. On the other hand, UL40/HLA-E T cells bearing lower-affinity TCRs expressed the activating receptor NKG2C. Activation of T cells bearing higher-affinity TCRs was regulated by the interaction between KIR2D receptors and HLA-C. These findings identify a role for NKR signaling in regulating self/non-self discrimination by HLA-E-restricted T cells, allowing for antiviral responses while avoiding contemporaneous self-reactivity.