Lymphatic malformation treatment improvements have been made through radiographic characterization and staging of lymphatic malformations. Direct malformation involvement of the upper aerodigestive tract can cause significant functional compromise that is difficult to treat.

The etiology and pathogenesis of head and neck lymphatic malformations are poorly understood, but understanding is improving through ongoing investigation. Reduction of lymphatic malformation size is generally possible, but further work is necessary to optimize methods for measuring therapeutic outcomes in problematic areas.

Inflammation stimulates new lymphatic vessel growth (inflammatory lymphangiogenesis). One key question is how recurrent inflammation, a common clinical condition, regulates lymphatic vessel remodeling. We show here that recurrent inflammation accelerated the development a functional lymphatic vessel network. This observation suggests a novel program of lymphangiogenesis and identifies a property of lymphatic vessel memory in response to recurrent inflammation. A brief episode of initial inflammation regressed lymphatic vessels, and a significant increase in CD11b(+) macrophages were associated with the development of lymphatic vessel memory. These vessels had major differences in the structure and the spatial distribution of specialized lymphatic vessel features. Surprisingly, we found that the lymphatic vessel memory response did not depend on the vascular endothelial growth factor C or A pathway, indicating that different molecular pathways regulate inflammatory lymphangiogenesis and lymphatic vessel memory. These findings uncover a priming mechanism to facilitate a rapid lymphatic vessel memory response: a potential important component of peripheral host defense.

Objectives: The objective of this work is to determine whether there is a systematic effect of middle ear effusion volume on wideband acoustic immittance in children with surgically confirmed otitis media with effusion. Design: Wideband acoustic immittance was measured in 49 ears from children (9 months to 11 years) who had a diagnosis of otitis media with effusion and compared to 14 ears from children (10 months to 10 years) without a recent history of otitis media. For children with otitis media with effusion, wideband acoustic immittance testing took place in the child’s preoperative waiting room before surgical placement of tympanostomy tubes. Testing was completed in a pressurized condition (wideband tympanometry) for all ears as well as in an ambient condition in a subset of ears. Intraoperative findings regarding effusion volume were reported by the surgeons immediately before tube placement and confirmed following myringotomy. This classified the volume of effusion as compared to middle ear volume categorically as either full, partial, or clear of effusion. The type of wideband acoustic immittance explored in this work was absorbance. Absorbance responses were grouped based on effusion volume into one of four groups: full effusions, partial effusions, ears clear of effusion at the time of surgery, and normal control ears. Standard tympanometry was also completed on all ears. Results: Absorbance is systematically reduced as the volume of the middle ear effusion increases. This reduction is present at most frequencies but is greatest in the frequency range from 1 to 5 kHz. A multivariate logistic regression approach was utilized to classify ears based on effusion volume. The regression approach classified ears as effusion present (full and partial ears) or absent (clear ears and normal control ears) with 100% accuracy, ears with effusion present as either partial or full with 100% accuracy, and ears without effusion as either normal control ears or ears clear of effusion with 75% accuracy. Regression performance was also explored when the dataset was split into a training set (70% of the data) and a validation test set (30% of the data) to simulate how this approach would perform on unseen data in a clinical setting. Accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve are reported. Overall, this approach demonstrates high sensitivity and specificity for classifying ears as effusion being present or absent and as present effusions being full or partial with areas under the curve ranging from 1 to 0.944. Despite the lack of effusion present in both clear ears and normal control ears, this approach was able to distinguish between these ears, but with a more moderate sensitivity and specificity. No systematic effect of effusion volume was found on standard tympanometry. Conclusions: Wideband acoustic immittance, and more specifically, absorbance, is a strong and sensitive indicator of the volume of a middle ear effusion in children with otitis media with effusion.

Previous work has shown that integrin alpha1-null Alport mice exhibit attenuated glomerular disease with decreased matrix accumulation and live much longer than strain-matched Alport mice. However, the mechanism underlying this observation is unknown. Here we show that glomerular gelatinase expression, specifically matrix metalloproteinase-2 (MMP-2), MMP-9, and MMP-14, was significantly elevated in both integrin alpha1-null mice and integrin alpha1-null Alport mice relative to wild-type mice; however, only MMP-9 was elevated in glomeruli of Alport mice that express integrin alpha1. Similarly, cultured mesangial cells from alpha1-null mice showed elevated expression levels of all three MMPs, whereas mesangial cells from Alport mice show elevated expression levels of only MMP-9. In both glomeruli and cultured mesangial cells isolated from integrin alpha1-null mice, activation of the p38 and ERK branches of the mitogen-activated protein kinase pathway was also observed. The use of small molecule inhibitors demonstrated that the activation of the p38, but not ERK, pathway was linked to elevated MMP-2, -9, and -14 expression levels in mesangial cells from integrin alpha1-null mice. In contrast, elevated MMP-9 levels in mesangial cells from Alport mice were linked to ERK pathway activation. Blockade of gelatinase activity using a small molecule inhibitor (BAY-12-9566) ameliorated progression of proteinuria and restored the architecture of the glomerular basement membrane in alpha1 integrin-null Alport mice, suggesting that elevated gelatinase activity exacerbates glomerular disease progression in these mice.