Surgical Management of Lower Extremity Pyoderma Gangrenosum With Viable Cryopreserved Umbilical Tissue: A Case Series.

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare skin disease that often presents as a uniquely painful and necrotic ulceration of the lower extremity. Pyoderma gangrenosum is often misdiagnosed and can have deleterious consequences to the patient, as there is no gold standard treatment and it can be difficult to manage. Surgery for these wounds is controversial, as pathergy can develop, worsening the ulceration. Advanced wound care products such as cellular- and/or tissue-based products (CTPs) are effective in helping stagnant chronic wounds reach full closure. Amnion/chorion-based skin substitutes that have been cryopreserved and contain viable cells have been shown to promote more cell recruitment and reduce inflammation. OBJECTIVE: This case series presents evidence of using a cryopreserved umbilical cord tissue with living cells in adjunctive treatment of wounds associated with PG. MATERIALS AND METHODS: This report presents 3 different clinical scenarios of lower extremity PG treated surgically with viable cryopreserved umbilical tissue (vCUT). RESULTS: All 3 patients were successfully treated with vCUT and resulted in complete healing. CONCLUSIONS: To the best of the authors' knowledge, this is the first case series demonstrating the ability of vCUT to heal these difficult-to-treat ulcers. In addition, it may be an effective modality to adjunctive management of PG.

Huntingtons Disease Mice Infected with Toxoplasma gondii Demonstrate Early Kynurenine Pathway Activation, Altered CD8+ T-Cell Responses, and Premature Mortality.

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a polyglutamine-repeat expansion in the huntingtin protein. Activation of the kynurenine pathway of tryptophan degradation is implicated in the pathogenesis of HD. Indoleamine-2,3-dioxygenase (IDO) catalyzes the oxidation of tryptophan to kynurenine, the first step in this pathway. The prevalent, neuroinvasive protozoal pathogen Toxoplasma gondii (T. gondii) results in clinically silent life-long infection in immune-competent individuals. T. gondii infection results in activation of IDO which provides some protection against the parasite by depleting tryptophan which the parasite cannot synthesize. The kynurenine pathway may therefore represent a point of synergism between HD and T. gondii infection. We show here that IDO activity is elevated at least four-fold in frontal cortex and striata of non-infected N171-82Q HD mice at 14-weeks corresponding to early-advanced HD. T. gondii infection at 5 weeks resulted in elevation of cortical IDO activity in HD mice. HD-infected mice died significantly earlier than wild-type infected and HD control mice. Prior to death, infected HD mice demonstrated decreased CD8+ T-lymphocyte proliferation in brain and spleen compared to wild-type infected mice. We demonstrate for the first time that HD mice have an altered response to an infectious agent that is characterized by premature mortality, altered immune responses and early activation of IDO. Findings are relevant to understanding how T. gondii infection may interact with pathways mediating neurodegeneration in HD.