Matrix remodeling is crucial for neovascularization, however its utilization to control this process in synthetic biomaterials has been limited. Here, we utilized hyaluronic acid (HA) hydrogels to spatially control cellular remodeling during vascular network formation. Specifically, we exploited a secondary radical polymerization to alter the ability of cells to degrade the hydrogel and utilized it to create spatial patterning using light initiation. We first demonstrated the ability of the hydrogel to either support or inhibit in vitro vasculogenesis of endothelial colony-forming cells (ECFCs) or angiogenesis from ex ovo chorioallantoic membranes. We showed that vascular tube branching and sprouting, which required matrix metalloproteinases (MMPs)-dependent remodeling, could be achieved in hydrogels formed by primary addition-crosslinking only. Although ECFCs expressed higher levels of MMPs in the hydrogels with the secondary radical-crosslinking, the generated kinetic chains disabled cell-mediated remodeling and therefore vascular formation was arrested at the vacuole and lumen stage. We then patterned hydrogels to have regions that either permitted or inhibited cell-mediated degradation during in vitro vasculogenesis or angiogenesis. Our ability to control degradation cues that regulate vascular tube formation is important for the study of vascular biology and the application of synthetic biomaterials in tissue regeneration.

Rash is one of the most common adverse events observed with mogamulizumab, an anti-C-C chemokine receptor 4 monoclonal antibody approved for previously treated mycosis fungoides (MF) and Sezary syndrome (SS). Given the nonspecific clinical presentations of this rash, histopathologic distinction from MF/SS is critical for informing clinical management. We performed a comprehensive characterization of the histopathologic findings in mogamulizumab-associated rash (MAR) with the integration of high-throughput sequencing of T-cell receptor (TCR) genes. Fifty-two biopsy specimens from 19 patients were evaluated retrospectively. Three major histologic reaction patterns were identified: spongiotic/psoriasiform dermatitis (33/52), interface dermatitis (11/52), and granulomatous dermatitis (8/52). Almost half of the specimens (21/52) showed at least 2 of these reaction patterns concurrently. Dermal eosinophils were not a consistent feature, being present in only half (27/52) of specimens and prominent in only 3. Features mimicking MF/SS, including lymphocyte exocytosis, lamellar fibroplasia, and adnexal involvement, were commonly seen but tended to be focal and mild. In 38/43 specimens with available immunohistochemistry, intraepidermal lymphocytes demonstrated a CD4:CD8 ratio ≤1 : 1. Low background levels of the patient’s previously identified MF/SS-associated TCR sequence(s) were demonstrated in 20/46 specimens analyzed by high-throughput sequencing of TCR. We conclude that MAR may demonstrate diverse histologic features. Findings that may distinguish MAR from MF/SS include the inverted or normalized CD4:CD8 ratio within intraepidermal lymphocytes and demonstration of absent or nondominant levels of disease-associated TCR sequences. Correlation with the clinical findings and immunohistochemical and molecular characterization of the patient’s MF/SS before mogamulizumab, when possible, may facilitate recognition of MAR.

IMPORTANCEMogamulizumab is a monoclonal antibody against CCR4 approved for treatment for mycosis fungoides (MF) and Sézary syndrome (SS). Mogamulizumabassociated rash (MAR) is difficult to differentiate from cutaneous MF or SS, which can lead to unnecessary discontinuation of drug use because of concern for severe drug reaction or incorrect presumption of disease relapse or progression in the skin.OBJECTIVE To examine the most common clinical presentations of MAR in patients with MF or SS and the diagnostic and management challenges.DESIGN, SETTING, AND PARTICIPANTS This retrospective case series assessed patients from a multidisciplinary cutaneous lymphoma clinic and supportive oncodermatology clinic at a major academic referral center who had a diagnosis of MF or SS and received mogamulizumab from January 1, 2013, to January 1, 2020. Treatment was followed by new or worsening rash with skin biopsy results compatible with drug eruption determined by clinicopathologic correlation and molecular testing to exclude active malignant disease.EXPOSURES At least 1 dose of mogamulizumab.MAIN OUTCOMES AND MEASURES Mogamulizumab-associated rash was characterized by clinical features, including time to onset, clinical presentation, histopathologic features, and management approach. RESULTSThe study included 19 patients with MF or SS who developed MAR (median age, 65 years; age range, 38-82 years; 10 [52.6%] male). Median time to MAR onset was 119 days (range, 56 days to 3.8 years). Patients with MAR exhibited 4 predominant clinical presentations: (1) folliculotropic MF-like scalp plaques with alopecia, (2) papules and/or plaques, (3) photoaccentuated dermatitis, and (4) morbilliform or erythrodermic dermatitis. The most common anatomical region involved was the head and neck, including the scalp. Histopathologic findings were variable and did not correspond to primary clinical morphologic findings. Immunohistochemistry and T-cell clonality ancillary testing were helpful to distinguish MAR from disease. Most patients with MAR (14 of 19) discontinued mogamulizumab treatment; however, no life-threatening severe cutaneous adverse drug reactions occurred, and the decision for drug therapy cessation was usually multifactorial. Four patients were treated again with mogamulizumab with no life-threatening drug-related events. Approaches to management of MAR include topical corticosteroids, systemic corticosteroids, and/or methotrexate.CONCLUSIONS AND RELEVANCE This case series found that mogamulizumab-associated rash had a heterogeneous clinical presentation with variable and delayed onset in patients with MF or SS. Mogamulizumab-associated rash exhibited a predilection for the head and neck and was difficult to clinically distinguish from relapse or progression of disease. Recognition of the most common clinical presentations can help prevent unnecessary discontinuation of mogamulizumab treatment. The presence of MAR does not necessitate permanent discontinuation of or avoidance of retreatment with mogamulizumab.

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BACKGROUND Hypertrophic granulation tissue (HGT) is an uncommon but a frustrating complication of wound healing. Given its low prevalence and often refractory nature, many treatment options have been explored. OBJECTIVE No comprehensive review exists on HGT management in dermatology literature; thus, the authors hope to compile a review of available treatments. MATERIALS AND METHODS An exhaustive key word search of 3 databases was performed for treatment of HGT. Results from these reports were summarized in this review. RESULTS Methods of treatment included silver nitrate, topical steroids (n = 11), intralesional steroids (n = 55), steroid tape (n = 25), surgical removal, polyurethane foam dressing (n = 32), and pulsed-dye laser (n = 13). CONCLUSION With all treatment methods, the cases and studies reported varying degrees of successful treatment with HGT reduction. Given the lack of published literature, it remains unknown whether the initial injury preceding HGT formation determines treatment modality success. For HGT refractory to silver nitrate, choice of treatment depends on accessibility, ease of use, cost, and location of the wound. Intralesional and topical steroids should both be considered. Polyurethane foam can be considered an adjunct treatment. If resources allow, laser treatment should also be considered.

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Thoracic endovascular aortic repair results in relative straightening of the stented aortic region and also accentuates the native curvature of the ascending aorta when the endograft has a more proximal landing zone. Supra-aortic branch vessel angulation remains relatively static when proximal landing zones are distal to the left common carotid artery.