Reconstruction of Nasal Defects With Dermal Skin Substitutes-A Retrospective Study of 36 Defects.

OBJECTIVES: It is uncertain whether dermal regeneration templates (DRTs) are helpful to reconstruct nasal defects. The aim of this study was to assess whether the aesthetic subunits determine the outcome. METHODS: In this unicentric, retrospective study, the surgical procedures and outcomes of patients who received DRTs to reconstruct nasal defects were assessed and compared with the involved aesthetic subunits. RESULTS: DRTs were used for reconstruction of 36 nasal defects in 35 patients with involvement of 76 aesthetic subunits: nasal sidewall (n = 21), nasal ala (n = 13), nasal tip/columella (n = 12, n = 1, respectively), nasal dorsum (n = 12), and extranasal aesthetic areas (n = 17). Fifty-eight nasal and 8 extranasal aesthetic subunits were reconstructed with DRTs, 10 subunits with a flap. Twenty-nine of 36 defects healed without any complications (80.5%). All reconstructed nasal tips/columella and the nasal dorsa healed without any complications. Region-specific complications were retraction of the ala rim (4/12; 33.3% of the patients with involvement of the nasal ala) and the formation of a fistula in the nasal sidewall (1/21; 4.8%). Region-specific complications of extranasal subunits were the development of an ectropium (2/3; 66.7% of the patients with involvement of the lower lid). CONCLUSIONS: DRTs can be helpful to reconstruct nasal defects. However, if the defect involves the aesthetic subunits nasal ala or the infraorbital region, different techniques should be preferred.

T-lymphocyte profiles differ between keratoacanthomas and invasive squamous cell carcinomas of the human skin.

BACKGROUND: T-lymphocytes are involved in tumor progression and regression. Actinic keratoses (AK) are atypical proliferations of keratinocytes of the skin. Some AK progress into invasive cutaneous squamous cell carcinomas (cSCC). Keratoacanthomas (KA) are either classified as a cSCC subtype or a benign tumor with histologic resemblance to well-differentiated cSCC as it is supposed to regress spontaneously. In contrast, cSCC represent malignant tumors that may metastasize. OBJECTIVES: To compare the T-lymphocyte profiles of AK, KA and cSCC in relation to PD-L1 expression. METHODS: Tissue micro-arrays of 103 cases of AK, 43 cases of KA and 106 cases of cSCC were stained by immunohistochemistry for E-cadherin, CD3, CD4, CD8, FOXp3, and the receptor-ligand pair PD-1/PD-L1. Immunohistological scores were computationally determined to assess PD-L1 expression as well as the expression profiles of T-lymphocytes. RESULTS: AK had lower numbers of CD3+ and PD-1+ cells compared to KA and lower numbers of CD3+, CD8+ and PD-1+ cells in comparison with cSCC. KA showed significantly higher numbers of CD4+ and FOXp3+ cells as well as lower numbers of CD8+ cells in comparison with invasive cSCC. cSCC expressed significantly more PD-L1 in comparison with AK and KA. Among cSCC PD-L1 expression was higher in moderately and poorly-differentiated cSCC than in well-differentiated cSCC. Increased PD-L1 expression also correlated with increased numbers of CD4+, CD8+ and FOXp3+ cells in cSCC. CONCLUSIONS: Tumor-associated T-lymphocyte infiltrates showed significant differences between AK, KA and invasive cSCC. PD-L1 expression correlated with invasion of T-cell infiltrates in invasive cSCC.

Ultralarge von Willebrand factor fibers mediate luminal Staphylococcus aureus adhesion to an intact endothelial cell layer under shear stress.

BACKGROUND: During pathogenesis of infective endocarditis, Staphylococcus aureus adherence often occurs without identifiable preexisting heart disease. However, molecular mechanisms mediating initial bacterial adhesion to morphologically intact endocardium are largely unknown. METHODS AND RESULTS: Perfusion of activated human endothelial cells with fluorescent bacteria under high-shear-rate conditions revealed 95% attachment of the S aureus by ultralarge von Willebrand factor (ULVWF). Flow experiments with VWF deletion mutants and heparin indicate a contribution of the A-type domains of VWF to bacterial binding. In this context, analyses of different bacterial deletion mutants suggest the involvement of wall teichoic acid but not of staphylococcal protein A. The presence of inactivated platelets and serum increased significantly ULVWF-mediated bacterial adherence. ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13) caused a dose-dependent reduction of bacterial binding and a reduced length of ULVWF, but single cocci were still tethered by ULVWF at physiological levels of ADAMTS13. To further prove the role of VWF in vivo, we compared wild-type mice with VWF knockout mice. Binding of fluorescent bacteria was followed in tumor necrosis factor-α-stimulated tissue by intravital microscopy applying the dorsal skinfold chamber model. Compared with wild-type mice (n=6), we found less bacteria in postcapillary (60±6 versus 32±5 bacteria) and collecting venules (48±5 versus 18±4 bacteria; P<0.05) of VWF knockout mice (n=5). CONCLUSIONS: Our data provide the first evidence that ULVWF contributes to the initial pathogenic step of S aureus-induced endocarditis in patients with an apparently intact endothelium. An intervention reducing the ULVWF formation with heparin or ADAMTS13 suggests novel therapeutic options to prevent infective endocarditis.