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In the last years, DFD showed an evolution of its characteristics with an increase of the ischaemic\/neuro-ischaemic foot in comparison to the pure neuropathic foot. Simultaneously, there was and increased incidence of concomitant cardiovascular co-morbidities, which influences the higher fragility of patients with DFS. Peripheral arterial disease (PAD) in subjects with diabetic foot seems to show a more aggressive pattern, being more distal and difficult to treat. Untreatable PAD remains the unmet need for clinicians and the main risk factor of major amputation in patients with diabetic foot ulcers. 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