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Kawasaki disease (KD) is an acute vasculitis that mostly affects children and is characterized by inflammation of medium-sized arteries, particularly the coronary arteries. The absent in melanoma 2 (AIM2) inflammasome senses cytosolic dsDNA and regulates IL-1β-driven inflammation. We investigated the role of AIM2 in Candida albicans water-soluble fraction (CAWS)-induced vasculitis in a murine model mimicking KD. Aim2 -/- mice exhibited reduced vasculitis, inflammatory cell infiltration, and vascular fibrosis in the aorta and coronary arteries. In addition, dsDNA damage was detected in Dectin-2 + cells infiltrating vasculitis areas. In vitro experiments showed that CAWS induced dsDNA damage in Dectin-2 + bone marrow-derived dendritic cells (BMDC) isolated from wild-type (WT) and Aim2 -/- mice. Furthermore, CAWS induces nuclear membrane deformation and DNA leakage into the cytosol, leading to AIM2 inflammasome activation and subsequent IL-1β production in WT BMDC. These findings suggest that AIM2 inflammasome activation in dendritic cells, triggered by dsDNA damage and leakage, contributes to the development of CAWS-induced vasculitis, and provides important insights into the inflammatory mechanisms underlying KD.

Caspase-11 is an inflammatory caspase that triggers an inflammatory response by regulating non-canonical NLRP3 inflammasome activation. Although the deficiency of both caspase-11 and caspase-1, another inflammatory caspase that functions as an executor of the inflammasome, prevents the development of atherosclerosis, the effect of caspase-11 deficiency alone on the development of atherosclerosis has not been fully evaluated. In the present study, we found that caspase-11 deficiency prevented the formation of the necrotic core, whereas it did not affect the development of atherosclerosis in Apoe-deficient mice. Notably, the infiltration of neutrophils into atherosclerotic lesions was attenuated by caspase-11 deficiency. RNA-seq analysis of stage-dependent expression of atherosclerotic lesions revealed that both upregulations of caspase-11 and neutrophil migration are common features of advanced atherosclerotic lesions. Furthermore, similar expression profiles were observed in unstable human plaque. These data suggest that caspase-11 regulates neutrophil recruitment and plaque destabilization in advanced atherosclerotic lesions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A 72-year-old man was diagnosed with posterior ventricular septal rupture after acute myocardial infarction with dissection in the posterior wall of the ventricular septum. On admission, cardiogenic shock was identified, and an Impella CP was inserted to improve his hemodynamics. Extended sandwich patch repair through the right ventricle with a Dacron patch was successfully performed, achieving an excellent postoperative course with stable hemodynamics. Preoperative Impella introduction may be a useful strategy for ventricular septal rupture repair in the acute phase., (© 2023 The Authors.)

Objectives: The aim of this study is to evaluate our surgical strategy for acute aortic dissection Stanford A and determine whether it is safe regardless of the experience of the primary surgeon., Methods: Between April 2015 and September 2020, a total of 160 patients who underwent open surgery for type A aortic dissection at Shonan Kamakura General Hospital were reviewed. Data were collected from reviews of computerized medical records. From this study cohort, we retrospectively reviewed the cases of trainee (group T) and experienced primary surgeons (group E). We evaluated rates of 30 day and in-hospital mortality, stroke, aortic reintervention, and mid-term survival for both groups., Results: The rates of 30 day and in-hospital mortalities in group T were 5.1 and 7.7%, respectively, whereas those in group E were 4.7 and 4.7%, respectively. One and 3 year survival rates in group T were 88.4 and 87.1% and in group E were 95.3 and 95.3%, respectively (log-rank test, p = 0.11). The 1 year and 3 year rates of freedom from reintervention were 90.9 and 72.8% in group T and 96.8 and 92.7% in group E, respectively (log-rank test, p = 0.29). The permanent neurological dysfunction rate was 8.1% overall, 8.5% in group T, and 7.0% in group E, with no significant difference., Conclusions: Our surgical strategy for acute type A aortic dissection is safe and appropriate regardless of the experience of the primary surgeon., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

The transcription factor MYB is a crucial regulator of hematopoietic stem and progenitor cells. However, the nature of lineage-specific enhancer usage of the Myb gene is largely unknown. We identify the Myb -68 enhancer, a regulatory element which marks basophils and mast cells. Using the Myb -68 enhancer activity, we show a population of granulocyte-macrophage progenitors with higher potential to differentiate into basophils and mast cells. Single cell RNA-seq demonstrates the differentiation trajectory is continuous from progenitors to mature basophils in vivo, characterizes bone marrow cells with a gene signature of mast cells, and identifies LILRB4 as a surface marker of basophil maturation. Together, our study leads to a better understanding of how MYB expression is regulated in a lineage-associated manner, and also shows how a combination of lineage-related reporter mice and single-cell transcriptomics can overcome the rarity of target cells and enhance our understanding of gene expression programs that control cell differentiation in vivo., (© 2022. The Author(s).)