Carmelo Pintaudi

Peripheral artery disease (PAD) is an atherosclerotic condition commonly complicating type 2 diabetes (T2D), leading to poor quality of life and increased risk of major adverse lower-limb (MALE) and cardiovascular (CV) events (MACE). Therapeutic management of PAD in T2D patients is much more arduous, often due to bilateral, multi-vessel, and distal vascular involvement, in addition to increased systemic polyvascular atherosclerotic burden. On the other hand, the pathophysiological link between PAD and T2D is very complex, involving mechanisms such as endothelial dysfunction and increased subclinical inflammation in addition to chronic hyperglycemia. Therefore, the clinical approach should not ignore vascular protection with the aim of reducing limb and overall CV events besides a mere glucose-lowering effect. However, the choice of the best medications in this setting is challenging due to low-grade evidence or lacking targeted studies in PAD patients. The present review highlighted the strong relationship between T2D and PAD, focusing on the best treatment strategy to reduce CV risk and prevent PAD occurrence and worsening in patients with T2D. The Medline databases were searched for studies including T2D and PAD up to June 2024 and reporting the CV effectiveness and safety of the most used glucose-lowering agents, with no restriction on PAD definition, study design, or country. The main outcomes considered were MACE—including nonfatal acute myocardial infarction, nonfatal stroke, and CV death—and MALE—defined as lower-limb complications, amputations, or need for revascularization. To the best of our current knowledge, GLP-1 receptor agonists and SGLT2 inhibitors represent the best choice to reduce CV risk in T2D and PAD settings, but a personalized approach should be considered. GLP-1 receptor agonists should be preferred in subjects with prevalent atherosclerotic burden and a history of previous MALE, while SGLT2 inhibitors should be used in those with heart failure if overall CV benefits outweigh the risk of lower-limb complications.

Long COVID is a complex condition affecting quality of life, with limited therapeutic options. We investigated the occurrence of long COVID in subjects receiving early therapy with monoclonal antibodies (mAbs) or antivirals to reduce the risk of COVID-19 progression. In this retrospective study we enrolled 737 adult patients (aged 65.16 ± 13.46; 361F), who experienced COVID-19 between January 2021 and March 2022. Antiviral or mAbs were administered to symptomatic patients who did not require oxygen therapy or hospital admission for SARS-CoV-2 infection, and who were at high risk of progression to severe disease, as identified by age > 65 years or the presence of comorbidities. Long COVID, defined as newly or persistent long-term symptoms 4 weeks after the onset of the acute illness, was reported in 204 cases (28%). Age (OR 1.03; p < 0.001), gender (OR 1.88; p < 0.001) and at least three comorbidities (OR 3.49; p = 0.049) were directly associated with long COVID; conversely, vaccination (OR 0.59; p = 0.005) and mAbs/antivirals (OR 0.44; p = 0.002) were independently associated with a reduced risk of long COVID. At a propensity-score-matched analysis, the mAbs/antivirals group had a significantly lower occurrence of long COVID in comparison with untreated controls (11% vs. 34%; p = 0.001). In conclusion, mAbs and antivirals administered against the progression of COVID-19 were associated with a reduced risk of long COVID.