In native tissues, microscale variations in the extracellular matrix (ECM) structure can drive different cellular behaviors. Although control over ECM structure could prove useful in tissue engineering and in studies of cellular behavior, isotropic 3D matrices poorly replicate variations in local microenvironments. In this paper, we demonstrate a method to engineer local variations in the density and size of collagen fibers throughout 3D tissues. The results showed that, in engineered multiphase tissues, the structures of collagen fibers in both the bulk ECM phases (as measured by mesh size and width of fibers) as well as at tissue interfaces (as measured by density of fibers and thickness of tissue interfaces) could be modulated by varying the collagen concentrations and gelling temperatures. As the method makes use of a previously published technique for tissue bonding, we also confirmed that significant adhesion strength at tissue interfaces was achieved under all conditions tested. Hence, this study demonstrates how collagen fiber structures can be engineered within all regions of a tightly integrated multiphase tissue scaffold by exploiting knowledge of collagen assembly.
Multisystem inflammatory syndrome in children (MIS-C) after COVID-19 is commonly associated with cardiac involvement. Studies found myocardial dysfunction, as measured by decreased ejection fraction and abnormal strain, to be common early in illness. However, there is limited data on longitudinal cardiac outcomes. We aim to describe the evolution of cardiac findings in pediatric MIS-C from acute illness through at least 2-month follow-up. A retrospective single-center review of 36 patients admitted with MIS-C from April 2020 through September 2021 was performed. Echocardiographic data including cardiac function and global longitudinal strain (GLS) were analyzed at initial presentation, discharge, 2-4-week follow-up, and at least 2-month follow-up. Patients with mild and severe disease, normal and abnormal left ventricular ejection fraction (LVEF), and normal and abnormal GLS at presentation were compared. On presentation, 42% of patients with MIS-C had decreased LVEF < 55%. In patients in whom GLS was obtained (N = 18), 44% were abnormal (GLS < |− 18|%). Of patients with normal LVEF, 22% had abnormal GLS. There were no significant differences in troponin or brain natriuretic peptide between those with normal and abnormal LVEF. In most MIS-C patients with initial LVEF < 55% (90%), LVEF normalized upon discharge. At 2-month follow-up, all patients had normal LVEF with 21% having persistently abnormal GLS. Myocardial systolic dysfunction and abnormal deformation were common findings in MIS-C at presentation. While EF often normalized by 2 months, persistently abnormal GLS was more common, suggesting ongoing subclinical dysfunction. Our study offers an optimistic outlook for recovery in patients with MIS-C and carditis, however ongoing investigation for longitudinal effects is warranted.
Atrial size and function have been recognized as markers of diastolic function, and diastolic dysfunction has been identified as a predictor of adverse outcomes in repaired tetralogy of Fallot (rTOF). This was a retrospective single-center study with the objective of investigating the use of atrial measurements obtained via CMR for predicting outcomes in rTOF patients. Automated contours of the left and right atria (LA and RA) were performed. A novel parameter, termed the Right Atrioventricular Coupling Index (RACI), was defined as the ratio of RA end-diastolic volume to right ventricle (RV) end-diastolic volume. Patients were risk-stratified using a previously validated Importance Factor Score for the prediction of life-threatening arrhythmias in rTOF. Patients with a high-risk Importance Factor Score (>2) had a significantly larger minimum RA volume (p = 0.04) and RACI (p = 0.03) compared to those with scores ≤2. ROC analysis demonstrated RACI to be the best overall predictor of a high-risk Importance Factor Score (AUC 0.73, p = 0.03). Older age at the time of repair and a diagnosis of pulmonary atresia were associated with a larger RACI. Automated atrial CMR measurements are easily obtained from standard CMRs and have the potential to serve as noninvasive predictors of adverse outcomes in rTOF.
Mitral regurgitation in the neonatal period is relatively rare. It can be secondary to a congenital malformation of the valve apparatus or mitral valve dysfunction and deformation secondary to myocardial dysfunction or volume load of the left ventricle. Less commonly, it can be due to coronary artery abnormalities leading to mitral valve papillary muscle ischaemia and subsequent dysfunction. Such coronary artery abnormalities include anomalous left coronary artery from pulmonary artery, left main coronary artery atresia, or a thromboembolic phenomenon. In this study, we describe a newborn with a dysplastic aortic valve causing obstruction of the os of the left coronary artery leading to progressive mitral insufficiency.
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