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Purpose: Although some studies have suggested an association between cardiovascular disease and restless legs syndrome (RLS), the mechanisms underlying this relationship remain unclear. The intima-media thickness (IMT) and vasomotor reactivity are two simple, non-invasive tools to investigate preclinical atherosclerosis and microangiopathy, respectively. The aims of this study were to evaluate carotid IMT and to explore vasomotor reactivity in idiopathic RLS (iRLS) patients., Patients and Methods: We enrolled 44 iRLS after exclusion of patients with secondary causes of RLS, history of vascular events, known uncontrolled vascular risk factors and other neurological disorders. Forty-four age and sex matched controls were therefore recruited. No significant differences in demographic data and vascular risk factors were found between the two groups. Carotid IMT was measured with a high-resolution B-mode ultrasound on the far-wall of common carotid artery, 10 mm and 30 mm to the carotid bulb. Vasomotor reactivity to hypo- and hypercapnia was assessed, by right middle cerebral artery transcranial Doppler, accordingly to the changes in peak systolic velocity, peak diastolic velocity and mean blood flow velocity., Results: Mean IMT was significantly increased in patients with iRLS when measured immediately proximally to carotid bifurcation (0.73; sd=0.17), versus controls (0.65; sd=0.13); p=0.035. Patients showed higher cerebrovascular flow velocities (CBFVs) compared to controls. After multivariate analysis, age, hypertension and iRLS proved to be independent IMT predictors., Conclusion: Increased IMT and higher CBFVs in iRLS support the association of iRLS with vascular damage, possibly through enhanced atherogenesis and sympathetic hyperactivity. However, to clarify a causal relationship, further longitudinal assessment of these parameters is needed, trying to control all their physiological modifying factors., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Janes et al.)

Objectives: The effectiveness of evaluation of the severity of epidermal growth-factor receptor inhibitor (EGFRI)-associated dermatological toxicities remains a topic of debate. This study was designed to assess the correlation between quality of life (QoL) and severity of dermatological toxicity, evaluated using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) and our novel scale, the Eruption Scoring System (ESS), in metastatic colorectal cancer (CRC) patients treated with first-line chemotherapy combined with cetuximab., Methods: Cutaneous toxicity was evaluated, by oncologists and dermatologists, in patients (n=30) with histologically confirmed metastatic CRC who were scheduled to begin first-line chemotherapy combined with the EGFRI, cetuximab, using the NCI-CTCAE and ESS tools. Health-related QoL (HRQoL) was evaluated using the Skindex-29 and Skindex-17 dermatology-specific instruments. Correlations between QoL and skin toxicity severity were assessed using Spearman's rank tests. Interclass correlation coefficients were used to assess interoperator agreement for ESS and NCI-CTCAE v4.0 scoring., Results: A positive correlation was identified between dermatology HRQoL and the severity of dermatological toxicities assessed using the NCI-CTCAE v4.0 scale for cutaneous papulopustular acneiform rash; however, a stronger correlation was observed between HRQoL and toxicities evaluated using the ESS tool. Both NCI-CTCAE v4.0 and ESS tools demonstrated good interobserver agreement for grading of skin toxicity., Conclusion: There is a strong correlation between the scores generated by the ESS and NCI-CTCAE tools to grade cutaneous toxicity related to treatment with the anti-EGFR monoclonal antibody, cetuximab. ESS can be considered a valid instrument for identification and grading of the severity of skin toxicity induced by cetuximab, with some advantages over the standard NCI-CTCAE scoring system., Competing Interests: Disclosure The authors report no conflicts of interest in this work.