Midterm outcomes of emergency surgery for acute type A aortic dissection in octogenarians.

OBJECTIVE: The incidence of elderly patients with acute type A aortic dissection is increasing. A recent analysis of the International Registry of Acute Aortic Dissection failed to show a mortality benefit with surgery compared with medical management in octogenarians. Therefore, we compared our institutional outcomes of emergency surgery for acute type A aortic dissection in octogenarians versus septuagenarians to understand the outcomes of surgical intervention in elderly patients. METHODS: From 2002 to 2017, 70 octogenarians (aged ≥80 years) and 165 septuagenarians (70-79 years) underwent surgery for acute type A aortic dissection (N = 235, total). Quality of life was assessed by the RAND Short Form-36 quality of life survey. Midterm clinical and functional data were obtained retrospectively. RESULTS: At baseline, septuagenarians had a higher prevalence of diabetes (20.6% vs 5.7%, P = .01). The prevalence of cardiopulmonary resuscitation was 4.8% versus 10.0% (P = .24) in septuagenarians and octogenarians. The prevalence of cardiogenic shock was 18.2% versus 27.1% (P = .17). Thirty-day/in-hospital mortality was 21.2% versus 28.6% (P = .29). Multivariable logistic regression identified cardiogenic shock as an independent risk factor for in-hospital mortality (odds ratio, 10.07; 95% confidence interval, 2.30-44.03) in octogenarians. Survival at 5 years was 49.7% (42.1%-58.6%) versus 34.2% (23.9%-48.8%) in septuagenarians and octogenarians, respectively. Responses to the quality of life survey were no different between septuagenarians and octogenarians across all 8 quality of life categories. CONCLUSIONS: Clinical outcomes after surgery for acute type A aortic dissection are similar in octogenarians and septuagenarians. For discharged survivors, quality of life remains favorable and does not differ between the 2 groups.

Immune suppressive landscape in the human esophageal squamous cell carcinoma microenvironment.

Cancer immunotherapy has revolutionized cancer treatment, and it relies heavily on the comprehensive understanding of the immune landscape of the tumor microenvironment (TME). Here, we obtain a detailed immune cell atlas of esophageal squamous cell carcinoma (ESCC) at single-cell resolution. Exhausted T and NK cells, regulatory T cells (Tregs), alternatively activated macrophages and tolerogenic dendritic cells are dominant in the TME. Transcriptional profiling coupled with T cell receptor (TCR) sequencing reveal lineage connections in T cell populations. CD8 T cells show continuous progression from pre-exhausted to exhausted T cells. While exhausted CD4, CD8 T and NK cells are major proliferative cell components in the TME, the crosstalk between macrophages and Tregs contributes to potential immunosuppression in the TME. Our results indicate several immunosuppressive mechanisms that may be simultaneously responsible for the failure of immuno-surveillance. Specific targeting of these immunosuppressive pathways may reactivate anti-tumor immune responses in ESCC.

Circulating Donor Heart Exosome Profiling Enables Noninvasive Detection of Antibody-mediated Rejection.

BACKGROUND: Endomyocardial biopsy remains the gold standard for distinguishing types of immunologic injury-acute versus antibody-mediated rejection (AMR). Exosomes are tissue-specific extracellular microvesicles released by many cell types, including transplanted heart. Circulating transplant heart exosomes express donor-specific human leukocyte antigen (HLA) I molecules. As AMR is mediated by antibodies to donor HLAs, we proposed that complement deposition that occurs with AMR at tissue level would also occur on circulating donor heart exosomes. METHODS: Plasma exosomes in 4 patients were isolated by column chromatography and ultracentrifugation. Donor heart exosomes were purified using anti-donor HLA I antibody beads and complement C4d protein expression was assessed in this subset as marker for AMR. RESULTS: Three patients had no rejection episodes. Circulating donor heart exosomes showed troponin protein and mRNA expression at all follow-up time points. One patient developed AMR on day 14 endomyocardial biopsy that was treated with rituximab, IVIG/plasmapheresis. Time-specific detection of C4d protein was seen in donor heart exosome subset in this patient, which resolved with treatment. C4d was not seen in other 3 patients' donor exosomes. CONCLUSIONS: Anti-donor HLA I specificity enables characterization of circulating donor heart exosomes in the clinical setting. Further characterization may open the window to noninvasively diagnose rejection type, such as AMR.