Evolution and Current Results of a Unified Strategy for Sinus Venosus Surgery.

BACKGROUND: Given recent reports of percutaneous closure of sinus venosus atrial septal defects, we reviewed our experience with surgical repair. Owing to the high incidence of arrhythmias with the two-patch technique, since 2001 we have used either one-patch repairs or the Warden procedure. METHODS: A retrospective review was performed of pediatric patients undergoing sinus venosus atrial septal defect repair at our institution from January 1, 1990, to July 1, 2018. Standard demographic data such as echocardiographic and cross-sectional imaging along with operative details and clinical echocardiographic outcomes were collected. RESULTS: The cohort included 144 patients with a median age of 4.3 years (interquartile range, 8.5). Inferior SVASD was present in 24 patients (17%). A single autologous untreated pericardial patch was used for 114 patients (79%), a two-patch technique for 20 patients (14%, last performed in 2000), and a Warden procedure in 10 patients (7%). Median length of stay was 4 days (interquartile range, 2). On echocardiogram follow-up, no patient had pulmonary vein stenosis. One patient who had the Warden procedure required a balloon dilation of the superior caval vein 2 years postoperatively and a stent 3 years later. Two-patch patients were substantially less likely to be in normal sinus rhythm (41%) on postoperative electrocardiograms compared with the other two techniques (81% one-patch and 89% Warden, P = .02). CONCLUSIONS: The great majority of patients with sinus venosus atrial septal defects can be successfully repaired with a single patch of autologous pericardium. We transitioned to using either a single pericardial patch or the Warden procedure, resulting in a higher frequency of normal sinus rhythm on postoperative electrocardiograms.

Diagnostic performance of cardiovascular magnetic resonance native T1 and T2 mapping in pediatric patients with acute myocarditis.

BACKGROUND: Multiple studies in adult patients suggest that tissue mapping performed by cardiovascular magnetic resonance (CMR) has excellent diagnostic accuracy in acute myocarditis, however, these techniques have not been studied in depth in children. METHODS: CMR data on 23 consecutive pediatric patients from 2014 to 2017 with a clinical diagnosis of acute myocarditis were retrospectively analyzed and compared to 39 healthy controls. The CMR protocol included native T1, T2, and extracellular volume fraction (ECV) in addition to standard Lake Louise Criteria (LLC) parameters on a 1.5 T scanner. RESULTS: Mean global values for novel mapping parameters were significantly elevated in patients with clinically suspected acute myocarditis compared to controls, with native T1 1098 ± 77 vs 990 ± 34 ms, T2 52.8 ± 4.6 ms vs 46.7 ± 2.6 ms, and ECV 29.8 ± 5.1% vs 23.3 ± 2.6% (all p-values < 0.001). Ideal cutoff values were generated using corresponding ROC curves and were for global T1 1015 ms (AUC 0.936, sensitivity 91%, specificity 86%), for global T2 48.5 ms (AUC 0.908, sensitivity 91%, specificity 74%); and for ECV 25.9% (AUC 0.918, sensitivity 86%, specificity 89%). While the diagnostic yield of the LLC was 57% (13/23) in our patient cohort, 70% (7/10) of patients missed by the LLC demonstrated abnormalities across all three global mapping parameters (native T1, T2, and ECV) and another 20% (2/10) of patients demonstrated at least one abnormal mapping value. CONCLUSIONS: Similar to findings in adults, pediatric patients with acute myocarditis demonstrate abnormal CMR tissue mapping values compared to controls. Furthermore, we found CMR parametric mapping techniques measurably increased CMR diagnostic yield when compared with conventional LLC alone, providing additional sensitivity and specificity compared to historical references. Routine integration of these techniques into imaging protocols may aid diagnosis in children.

Flagellin stimulates protective lung mucosal immunity: role of cathelicidin-related antimicrobial peptide.

TLRs are required for generation of protective lung mucosal immune responses against microbial pathogens. In this study, we evaluated the effect of the TLR5 ligand flagellin on stimulation of antibacterial mucosal immunity in a lethal murine Pseudomonas aeruginosa pneumonia model. The intranasal pretreatment of mice with purified P. aeruginosa flagellin induced strong protection against intratracheal P. aeruginosa-induced lethality, which was attributable to markedly improved bacterial clearance, reduced dissemination, and decreased alveolar permeability. The protective effects of flagellin on survival required TLR5 and were observed even in the absence of neutrophils. Flagellin induced strong induction of innate genes, most notably the antimicrobial peptide cathelicidin-related antimicrobial peptide. Finally, flagellin-induced protection was partially abrogated in cathelicidin-related antimicrobial peptide-deficient mice. Our findings illustrate the profound stimulatory effect of flagellin on lung mucosal innate immunity, a response that might be exploited therapeutically to prevent the development of gram-negative bacterial infection of the respiratory tract.

Cooperative interactions between TLR4 and TLR9 regulate interleukin 23 and 17 production in a murine model of gram negative bacterial pneumonia.

Toll like receptors play an important role in lung host defense against bacterial pathogens. In this study, we investigated independent and cooperative functions of TLR4 and TLR9 in microbial clearance and systemic dissemination during Gram-negative bacterial pneumonia. To access these responses, wildtype Balb/c mice, mice with defective TLR4 signaling (TLR4(lps-d)), mice deficient in TLR9 (TLR9(-/-)) and TLR4/9 double mutant mice (TLR4(lps-d)/TLR9(-/-)) were challenged with K. pneumoniae, then time-dependent lung bacterial clearance and systemic dissemination determined. We found impaired lung bacterial clearance in TLR4 and TLR9 single mutant mice, whereas the greatest impairment in clearance was observed in TLR4(lps-d)/TLR9(-/-) double mutant mice. Early lung expression of TNF-alpha, IL-12, and chemokines was TLR4 dependent, while IFN-gamma production and the later expression of TNF-alpha and IL-12 was dependent on TLR9. Classical activation of lung macrophages and maximal induction of IL-23 and IL-17 required both TLR4 and TLR9. Finally, the i.t. instillation of IL-17 partially restored anti-bacterial immunity in TLR4(lps-d)/TLR9(-/-) double mutant mice. In conclusion, our studies indicate that TLR4 and TLR9 have both non-redundant and cooperative roles in lung innate responses during Gram-negative bacterial pneumonia and are both critical for IL-17 driven antibacterial host response.

Cytokine networks in the infected lung.

The generation of an innate immune response is essential for rapid clearance of microbes from the respiratory tract, whereas acquired immunity is required for the generation of cellular immunity necessary for the killing of certain intracellular pathogens and the development of immunological memory. Cytokines play an integral role in host defense by serving as leukocyte chemoattractants, leukocyte-activating factors or afferent signals in the induction or regulation of other effector molecules. This review assesses the contribution of cytokine networks to the generation of antimicrobial host defenses in the lung, with an emphasis on cytokines/cytokine networks that are instrumental in innate antibacterial responses, including mucosal immunity, and also introduces networks that instruct the development of adaptive immunity.