Limb salvage can be achieved in most patients with arterial insufficiency and uncomplicated chronic nonhealing limb ulcers using a program of wound management without revascularization. Healing proceeds slowly, however, requiring more than a year in many cases. Patients with an ABI <0.5 are more likely to require amputation. Interventions designed to improve outcomes in critical limb ischemia should stratify outcomes based on hemodynamic data and should include a comparative control group given the natural history of ischemic ulcers treated in a dedicated wound program.

Objective Elevated inflammatory cytokine levels have been implicated in the pathogenesis of non3 healing chronic venous insufficiency (CVI) ulcers. The goal of this study was to determine the protein levels of a wide range of inflammatory cytokines in untreated CVI ulcer tissue before and after 4 weeks of high strength compression therapy. These levels were compared to cytokines present in healthy tissue. Methods Thirty limbs with untreated CVI and leg ulceration received therapy for 4 weeks with sustained high compression bandaging at an ambulatory wound center. Biopsies were obtained from healthy and ulcerated tissue before and after therapy. A multiplexed protein assay was used to measure multiple cytokines in a single sample. Patients were designated as rapid or delayed healers based on ulcer surface area change. Results The majority of pro-inflammatory cytokine protein levels were elevated in ulcer tissue compared to healthy tissue, and compression therapy significantly reduced these cytokines. TGF-β1 was up-regulated in ulcer tissue following compression therapy. Rapid healing ulcers had significantly higher levels of IL-1α, IL-1β, IFN-γ, IL-12p40 and GM-CSF before compression therapy, and IL-1 Ra after therapy. IFN-γ levels significantly decreased following therapy in the rapidly healing patients. Conclusion CVI ulcer healing is associated with a pro-inflammatory environment prior to treatment that reflects metabolically active peri-wound tissue that has the potential to heal. Treatment with compression therapy results in healing that is coupled with reduced pro-inflammatory cytokine levels and higher levels of the anti-inflammatory cytokine IL-1 Ra. Clinical Relevance This data suggests that cytokines may provide targets in which topical therapeutic inhibition or promotion at appropriate time points in the healing process may provide novel therapeutic approaches to the healing of CVI ulcers.

These results provide the first evidence that FAK is overexpressed in VSMCs involved in IH and suggest that FAK upregulation may be part of a mechanism for migration and proliferation of VSMCs during this process. Furthermore, the dramatic upregulation of FAK in IH and the relative lack of expression in healthy vessels suggest that FAK may be a rational target for controlling IH.

In patients with a minimal cephalic vein size of 2.0 mm or less, a procedure other than wrist fistula should be considered for optimization of dialysis access.

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The treatment of venous stasis ulcers with compression techniques results in reliable, cost-effective healing in most patients. Current adjuvant techniques may prove to be useful but are likely to be cost effective only in a minority of cases, particularly in patients with large initial ulcer size or arterial insufficiency.

Elevated matrix metalloproteinases (MMP) levels have been implicated in the pathogenesis of chronic venous insufficiency ulcers. Quantitative measurements of a broad range of MMP proteins in human tissue treated with compression bandaging have not been reported. The goal of this study was to determine the expression of a wide range of proteases in untreated venous leg ulcer tissue and the changes in these levels after 4 weeks of high-strength compression therapy. Twenty-nine limbs with new or untreated chronic venous insufficiency and leg ulceration received therapy for 4 weeks with sustained high compression bandaging. Biopsies were obtained from healthy tissue and from ulcerated tissue before and after therapy. A novel multiplexed protein assay was used to measure multiple MMPs in a single sample. MMP protein activity, TIMP protein levels, and gene expression levels were also addressed. MMP1, 2, 3, 8, 9, 12, and 13 protein levels were elevated in ulcer tissue compared with healthy tissue. MMP8 and 9 were highly expressed in ulcer tissue. MMP3, 8, and 9 significantly decreased following treatment. Reduction in the levels of MMP1, 2, and 3 was associated with significantly higher rates of ulcer healing at 4 weeks. We conclude that compression therapy results in a reduction of the pro-inflammatory environment characterizing chronic venous ulcers, and ulcer healing is associated with resolution of specific elevated levels of protease expression.

Intentional coverage of the origin of the left subclavian artery to obtain an adequate proximal landing zone during endovascular repair of thoracic aortic lesions is well tolerated and may be managed expectantly, with some exceptions.