Association between left atrial appendage fibrosis and thrombus formation: A histological approach.

INTRODUCTION: Although recent echocardiographic studies have suggested that left atrial appendage (LAA) remodeling contributes to the development of LAA thrombus (LAAT), histological evidence is absent. The objective of this study was to examine clinical parameters and histological findings to clarify the factors involved in LAAT formation. METHODS: A total of 64 patients (no atrial fibrillation [AF], N = 22; paroxysmal AF, N = 16; nonparoxysmal AF, N = 26) who underwent LAA excision during surgery were enrolled. Transthoracic and transesophageal echocardiography were performed before surgery. We evaluated the fibrosis burden (%) in the excised LAA sections with Azan-Mallory staining in patients with a LAAT compared with those without. RESULTS: Patients with paroxysmal and non-paroxysmal AF had a higher LAA fibrosis burden than those without AF (p = .005 and p < .0001, respectively). Among the patients enrolled, 16 had a LAAT and 15 of them had nonparoxysmal AF. Among the nonparoxysmal AF patients, those with a LAAT had significantly higher LAA fibrosis burden than those without (23.8% [14.8%-40.3%] vs. 12.8% [7.4%-18.2%], p = .004) and echocardiographic parameters of the left atrial volume index (R = 0.543, p = .01), LAA depth (R = 0.452, p = .02), and LAA flow velocity (R = - 0.487, p = .01) were correlated with the LAA fibrosis burden. CONCLUSION: This study provided histological evidence that LAA fibrosis is related to LAAT formation. Echocardiographic parameters of LAA remodeling and function were correlated with the LAA fibrosis burden.

Long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s.

Breastfeeding influences the immune system development in infants and may even affect various immunological responses later in life. Breast milk provides a rich source of early nutrition for infant growth and development. However, the presence of certain compounds in breast milk, related to an unhealthy lifestyle or the diet of lactating mothers, may negatively impact infants. Based on a cohort study of atopic dermatitis (AD), we find the presence of damage-associated molecular patterns (DAMPs) activity in the mother's milk. By non-targeted metabolomic analysis, we identify the long-chain saturated fatty acids (LCSFA) as a biomarker DAMPs (+) breast milk samples. Similarly, a mouse model in which breastfed offspring are fed milk high in LCSFA show AD onset later in life. We prove that LCSFA are a type of damage-associated molecular patterns, which initiate a series of inflammatory events in the gut involving type 3 innate lymphoid cells (ILC3s). A remarkable increase in inflammatory ILC3s is observed in the gut, and the migration of these ILC3s to the skin may be potential triggers of AD. Gene expression analysis of ILC3s isolated from the gut reveal upregulation of genes that increase ILC3s and chemokines/chemokine receptors, which may play a role in ILC migration to the skin. Even in the absence of adaptive immunity, Rag1 knockout mice fed a high-LCSFA milk diet develop eczema, accompanied by increased gut ILC3s. We also present that gut microbiota of AD-prone PA milk-fed mice is different from non-AD OA/ND milk-fed mice. Here, we propose that early exposure to LCSFAs in infants may affect the balance of intestinal innate immunity, inducing a highly inflammatory environment with the proliferation of ILC3s and production of interleukin-17 and interleukin-22, these factors may be potential triggers or worsening factors of AD.