Circulating Biomarkers of Endothelial Dysfunction and Inflammation in Predicting Clinical Outcomes in Diabetic Patients with Critical Limb Ischemia.

Critical limb ischemia (CLI) is a severe manifestation of peripheral artery disease characterized by ischemic pain, which is frequently associated with diabetes and non-healing lesions to inferior limbs. The clinical management of diabetic patients with CLI typically includes percutaneous transluminal angioplasty (PTA) to restore limb circulation and surgical treatment of diabetic foot ulcers (DFU). However, even after successful treatment, CLI patients are prone to post-procedure complications, which may lead to unplanned revascularization or foot surgery. Unfortunately, the factors predicting adverse events in treated CLI patients are only partially known. This study aimed to identify potential biomarkers that predict the disease course in diabetic patients with CLI. For this purpose, we measured the circulating levels of a panel of 23 molecules related to inflammation, endothelial dysfunction, platelet activation, and thrombophilia in 92 patients with CLI and DFU requiring PTA and foot surgery. We investigated whether these putative biomarkers were associated with the following clinical endpoints: (1) healing of the treated DFUs; (2) need for new revascularization of the limb; (3) appearance of new lesions or relapses after successful healing. We found that sICAM-1 and endothelin-1 are inversely associated with DFU healing and that PAI-1 and endothelin-1 are associated with the need for new revascularization. Moreover, we found that the levels of thrombomodulin and sCD40L are associated with new lesions or recurrence, and we show that the levels of these biomarkers could be used in a decision tree to assign patients to clusters with different risks of developing new lesions or recurrences.

Cardiac conduction disorders in young adults: Clinical characteristics and genetic background of an underestimated population.

BACKGROUND: Cardiac conduction disorder (CCD) in patients <50 years old is a rare and mostly unknown condition. OBJECTIVE: We aimed to assess clinical characteristics and genetic background of patients <50 years old with CCD of unknown origin. METHODS: We retrospectively reviewed a consecutive series of patients with a diagnosis of CCD before the age of 50 years referred to our center between January 2019 and December 2021. Patients underwent complete clinical examination and genetic evaluation. RESULTS: We enrolled 39 patients with a median age of 40 years (28-47 years) at the onset of symptoms. A cardiac implantable electronic device was implanted in 69% of the patients. In 15 of 39 CCD index patients (38%), we found a total of 13 different gene variations (3 pathogenic, 6 likely pathogenic, and 4 variants of uncertain significance), mostly in 3 genes (SCN5A, TRPM4, and LMNA). In our cohort, genetic testing led to the decision to implant an implantable cardioverter-defibrillator in 2 patients for the increased risk of sudden cardiac death. CONCLUSION: Patients with the occurrence of CCD before the age of 50 years present with a high rate of pathologic gene variations, mostly in 3 genes (SCN5A, TRPM4, and LMNA). The presence of pathogenic variations may add information about the prognosis and lead to an individualized therapeutic approach.