It is important to emphasise the need to transfer ischaemic patients to a specialised, JAK inhibitor multidisciplinary centre as soon as possible [49]. Published data show that ischaemic lesions are less likely to heal, and that the onset of infection can transform an originally mild lesion into gangrene. This risk increases with the duration of the lesion and the continuation of ineffective treatment without appropriate revascularisation. PAD should be sought in all diabetic subjects with foot ulcers. The evaluation begins with a search for arterial pulses (femoral, popliteal, posterior tibial and dorsalis pedis) but, despite this being essential in the case of epidemiological investigations,

it has some limitations when it comes to verifying the presence of an ischaemic component in patients affected by ongoing ulcers. In particular, the dorsalis pedis pulse may be absent in up to 30% of patients free of vascular disease, is poorly reproducible and may sometimes be detected even in the presence of ischaemia. The posterior tibial pulse seems to be more reliable and provides more certain information concerning the presence or absence of ischaemic condition. It needs to be underlined that the obstruction of one tibial artery (or only the plantar arch in diabetics)

can lead to an ischaemic ulcer, and so the presence of a single well-palpated tibial pulse does not exclude it. However, the greatest limitation of Entinostat using pulses to evaluate ischaemia is the fact that an absent pulse does not provide any information concerning perfusion deficit and therefore the healing potential of the lesion itself [50]. In a large-scale survey of diabetics with an ulcer and peripheral ischaemia, Apelqvist found that >50% of the patients would not have been classified as ischaemic if they had not undergone an instrumental evaluation [51]. Furthermore, the semiotic methods that are widely used when Adenylyl cyclase diagnosing non-diabetics, such as the search for femoral pulse or position-related changes in foot colour, can be influenced by many confounding factors

and so using them alone to diagnose PAD in diabetic subjects is considered not sufficient [52]. It is clear that the presence of an ulcer requires a more objective evaluation, not least because this can guide therapeutic decision-making, particularly the need for revascularisation. Diabetic patients with limb ischaemia can be non-invasively evaluated in different ways but, as each of them has different advantages, disadvantages and limitations, it is often necessary to integrate them. The ankle/brachial pressure index (ABI) is the ratio of the systolic pressure in the ankle to that in the arm and is considered a reference test insofar as it is reproducible, sensitive and specific in detecting PAD.