Therapeutic, III.

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Therapeutic, IV.

Infantile hemangiomas (IHs) are the most common vascular tumor and arise from a hemangioma stem cell (HemSC). Propranolol has proved efficacious against IHs. A selective β2-adrenergic receptor (AR) antagonist mirrored propranolol’s effects on HemSCs. These results show that propranolol acts on HemSCs in IH to suppress proliferation and promote apoptosis in a dose-dependent fashion via β2AR perturbation.

Background: Capsular contracture following breast augmentation is prone to recurrence with conventional surgical therapy. Adding acellular dermal matrix improves results but significantly increases operating time and cost. This study tested a new treatment algorithm that uses acellular dermal matrix selectively to optimize success rates while minimizing its drawbacks. Methods: All patients surgically treated by the authors for Baker grade III/IV capsular contracture between 2007 and 2018 were included in this retrospective cohort study. Data were collected on patient, breast augmentation, capsular contracture, and surgical treatment characteristics, in addition to follow-up findings. Treatment success was defined as Baker grade II or better. Results: One hundred eighty patients underwent 217 surgical treatments for capsular contracture. Conventional treatment was used in 185 cases and acellular dermal matrix in 32. Twenty-six patients were treated for a second occurrence and four were treated for a third. The average follow-up was 2.4 years. Conventional treatment was successful in 72.5 percent of first occurrences, 62.5 percent of second occurrences, and 50.0 percent of third occurrences. Acellular dermal matrix was successful in 96.9 percent of cases. The odds of failure were increased by bilateral capsular contracture (3.9 times) and previous treatment failure (3.5 times). When acellular dermal matrix was used selectively for bilateral capsular contracture or in unilateral cases with a previous treatment failure, the overall treatment success rate improved to 85.6 percent compared with 64.2 percent when this algorithm was not followed (p < 0.001). Conclusion: This study demonstrates that selective acellular dermal matrix use can increase success rate to over 85 percent in the overall treatment of capsular contracture, and to nearly 100 percent in individual cases.

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Background Prolyl hydroxylase domain 2 (PHD2) has been implicated in several pathways of cell signaling, most notably in its regulation of hypoxia inducible factor (HIF)-1α stability. In normoxia, PHD2 hydroxylates proline residues on HIF-1α, rendering it inactive. However in hypoxia, PHD2 is inactive, HIF-1α is stabilized and downstream effectors such as VEGF and FGF-2 are produced to promote angiogenesis. In the present study we utilize RNAi to PHD2 to promote therapeutic angiogenesis in a diabetic wound model, presumably by the stabilization of HIF-1α. Methods Stented wounds were created on the dorsum of diabetic Lpr db/db mice. Mice were treated with PHD2 siRNA or nonsense siRNA. Wounds were measured photometrically on days 0–28. Wounds were harvested for histology, protein, and RNA analysis. Results Diabetic wounds treated with siRNA closed within 21 +/−1.2 days; sham treated closed in 28 +/−1.5 days. By day 7, Western blot revealed near complete suppression of PHD protein and corresponding increased HIF-1α. Angiogenic mediators VEGF and FGF-2 were elevated, corresponding to increased CD31 staining in the treated groups. Conclusions siRNA-mediated silencing of PHD2 increases HIF-1α and several mediators of angiogenesis. This corresponded to improved time to closure in diabetic wounds compared to sham treated wounds. These findings suggest that impaired wound healing in diabetes can be ameliorated with therapeutic angiogenesis.

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