Andreina Carbone

Clinically equivocal melanocytic skin lesions with features of regression: a dermoscopic-pathological study.

Background  Benign melanocytic skin lesions may be difficult to differentiate from melanoma both clinically and dermoscopically. One of the most confounding dermoscopic features, commonly seen in melanoma but in our experience also in melanocytic naevi, is represented by the so‐called blue–white structures (BWS).

Functional analyses and molecular modeling of two c-Kit mutations responsible for imatinib secondary resistance in GIST patients

Imatinib-acquired resistance related to the presence of secondary point mutations has become a frequent event in gastrointestinal stromal tumors. Here, transient transfection experiments with plasmids carrying two different KIT-acquired point mutations were performed along with immunoprecipitation of total protein extracts, derived from imatinib-treated and untreated cells. The molecular mechanics/Poisson Boltzmann surface area computational techniques were applied to study the interactions of the wild-type and mutated receptors with imatinib at the molecular level. Biochemical analyses showed KIT phosphorylation in cells transfected with vectors carrying the specific mutant genes. Imatinib treatment demonstrated that T670I was insensitive to the drug at all the applied concentrations, whereas V654A was inhibited by 6 μM of imatinib. The modeling of the mutated receptors revealed that both substitutions affect imatinib-binding site, but to a different extent: T670I substantially modifies the binding pocket, whereas V654A induces only relatively confined structural changes. We demonstrated that T670I and V654A cause indeed imatinib-acquired resistance and that the former is more resistant to imatinib than the latter. The application of molecular simulations allowed us to quantify the interactions between the mutated receptors and imatinib, and to propose a molecular rationale for this type of drug resistance.

Abdominal aortic aneurysm in patients affected by intermittent claudication: prevalence and clinical predictors

BackgroundAbdominal aortic aneurysm (AAA) is a frequent cause of death among elderly. Patients affected by lower extremity peripheral arterial disease (LE-PAD) seem to be particularly at high risk for AAA. We aimed this study at assessing the prevalence and the clinical predictors of the presence of AAA in a homogeneous cohort of LE-PAD patients affected by intermittent claudication.MethodsWe performed an abdominal ultrasound in 213 consecutive patients with documented LE-PAD (ankle/brachial index ≤0.90) attending our outpatient clinic for intermittent claudication. For each patient we registered cardiovascular risk factors and comorbidities, and measured neutrophil count.ResultsThe ultrasound was inconclusive in 3 patients (1.4%), thus 210 patients (169 males, 41 females, mean age 65.9 ± 9.8 yr) entered the study. Overall, AAA was present in 19 patients (9.0%), with a not significant higher prevalence in men than in women (10.1% vs 4.9%, p = 0.300). Patients with AAA were older (71.2 ± 7.0 vs 65.4 ± 9.9 years, p = 0.015), were more likely to have hypertension (94.7% vs 71.2%, p = 0.027), and greater neutrophil count (5.5 [4.5 – 6.2] vs 4.1 [3.2 – 5.5] x103/μL, p = 0.010). Importantly, the c-statistic for neutrophil count (0.73, 95% CI 0.60 – 0.86, p =0.010) was higher than that for age (0.67, CI 0.56–0.78, p = 0.017). The prevalence of AAA in claudicant patients with a neutrophil count ≥ 5.1 x103/μL (cut-off identified at ROC analysis) was as high as 29.0%.ConclusionsPrevalence of AAA in claudicant patients is much higher than that reported in the general population. Ultrasound screening should be considered in these patients, especially in those with an elevated neutrophil count.

Use of statins in lower extremity artery disease: a review

BackgroundLower extremity artery disease (LE-PAD) is one of the most common manifestations of atherosclerosis, particularly in elderly patients, and it is related to a high cardiovascular risk.DescriptionIt is well established that statin therapy is characterized by crucial benefits on cardiovascular system by limiting atherosclerotic progression and reducing cardiovascular events and mortality. A growing body of evidence support efficacy of statins in LE-PAD due to the ability of both reducing cardiovascular risk and improving walking distance and, hence, quality of life. Consequently, statin therapy should be considered in all LE-PAD patients and new LDL-cholesterol targets should be reached.ConclusionsOur opinion is that statin therapy remains still underutilized or with inadequate dosage, so therapy of LE-PAD patients should be improved to obtain all the demonstrated benefits of statins.

The role of atherectomy in the treatment of lower extremity peripheral artery disease

BackgroundThe incidence of lower extremity peripheral artery disease (LE-PAD) continues to increase and associated morbidity remains high. Despite the significant development of percutaneous revascularization strategies, over the past decade, LE-PAD still represents a unique challenge for interventional cardiologists and vascular surgeons.MethodTypical features of atherosclerosis that affects peripheral vascular bed (diffuse nature, poor distal runoff, critical limb ischemia, chronic total occlusion) contribute to the disappointing results of traditional percutaneous transluminal angioplasty (PTA). New technologies have been developed in attempt to improve the safety and effectiveness of percutaneous revascularization. Among these, atherectomy, debulking and removing atherosclerotic plaque, offers the potential advantage of eliminating stretch on arterial walls and reducing rates of restenosis.ConclusionsThis review summarizes the features and the current applications of new debulking devices.

Cardiac Side Effects of Chemotherapy: State of Art and Strategies for a Correct Management

In recent years, the development of more effective drugs has provided a better prognosis and an increase in life expectancy for patients at all-stages of cancer. On the other hand, the price for the improving effectiveness of therapies against malignant tumors is the development of severe and potentially life-threatening drug reactions. Among these, cardiac toxic effects have recently gained particular attention. The term cardiotoxicity includes many possible pathological manifestations, but the most frequent is the reduction in cardiac function, potentially leading to heart failure and death. Importantly, the development of cardiac dysfunction may occur immediately after drug administration, or after years. The purpose of this review is to discuss the clinical features of cardiotoxicity, its molecular basis and novel possible strategies to reduce the likelihood of serious cardiac complications.

Physical activity in the prevention of peripheral artery disease in the elderly

Aging is a well-known cardiovascular risk factor and cardiovascular diseases (CVD) are estimated to be the most common cause of death in the elderly. Peripheral arterial disease (PAD) represents an important clinical manifestation of CVD leading to increase morbidity and mortality, especially in elderly population. The correct management of PAD population includes the prevention of cardiovascular events and relief of symptoms, most commonly intermittent claudication. Progressive physical activity is an effective treatment to improve walking distance and to reduce mortality and cardiovascular events in patients with PAD, however the ability to effectively engage in physical activity often declines with increasing age. The maintenance and increase of reserve functional capacity are important concepts in the elderly population. Ultimately, the goal in participation of physical activity in the healthy elderly population is maintenance and development of physical functional reserve capacity. Therefore, for individuals suffering of PAD, appropriate physical activity in the form of supervised exercise may serve as a primary therapy. Although there are few direct comparisons of therapeutic exercise programs vs. pharmacological or surgical interventions, these increases in walking distance are greater than those reported for the most widely used agents for claudication, pentoxyphylline, and cilostazol. Despite a reduction in mortality and improvement of quality of life caused by physical activity in the PAD population, the molecular, cellular, and functional changes that occur during physical activity are not completely understood. Therefore, this review article aims at presenting an overview of recent established clinical and molecular findings addressing the role of physical activity on PAD in the older population.

A 9‐month, randomized, assessor‐blinded, parallel‐group study to evaluate clinical effects of film‐forming medical devices containing photolyase and sun filters in the treatment of field cancerization compared with sunscreen in patients after successful photodynamic therapy for actinic keratosis

DEAR EDITOR, Actinic keratosis (AK) is a precancerous lesion caused by chronic exposure to sunlight. Photodynamic therapy (PDT) is a well-established therapeutic approach for the treatment of AK. PDT is effective in clearance of AK lesions and improving field cancerization. However, > 20% of patients need a second procedure in the following months after the first treatment. After PDT, sun protection strategies are important in order to reduce the risk of new lesions or the need for another session of PDT. A film-forming medical class II device containing photolyase, a DNA-repairing enzyme with a broad photoprotection action (Eryfotona AK-NMSC Fluid; Isdin, Barcelona, Spain), has been shown, in open clinical studies, to induce both subclinical and clinical improvements in patients with AK. This product seems to be more effective than sunscreen products in improving clinical outcomes (clearance of AK lesions) and field cancerization. So far, there are no published controlled data regarding the use of Eryfotona vs. sunscreen in patients with AK after successful PDT treatment. We assessed the efficacy of Eryfotona vs. sunscreen in the development of new AKs in patients with AK after successful PDT. In a prospective, two-arm, parallel-group, 9-month, assessor-blinded, comparative trial, immunocompetent patients between the age of 40 and 85 years with multiple AKs of the face and/or scalp suitable for PDT treatment, were enrolled. This study (clinical trial number: ISRCTN12347628) was conducted between January 2014 and June 2015. After obtaining institutional review board approval and written informed consent from the participants, 30 patients (22 men; mean age 69 years) with a total of 225 AK lesions (7 5 lesions per patient) were included. Exclusion criteria were age < 18 or > 75 years, presence of skin tumours, xeroderma pigmentosum and a history of skin conditions other than AK which might interfere with the study evaluations. Patients were randomized 1 : 1 to Eryfotona (n = 15) or to sunscreen (n = 15) Sunscrean SPF 50+ (Fotoprotector, ISDIN, Barcelona, Spain). The primary outcome of the study was the evolution of new AK lesions in the previous PDT-treated area or in another area. The secondary outcome of the study was the need to perform new PDT or other lesion-targeted or field-cancerization targeted therapies. Eryfotona or sunscreen were applied in the treatment evaluation area (scalp and face) for nine consecutive months, in the morning and 4–6 h later. For each application, patients were instructed to apply a total of 2 5 fingertip units for both products. All patients completed the trial. Table 1 summarizes the patient demographics and AK characteristics at baseline. At baseline, the mean SD number of AK lesions was 6 6 2 8 in the Eryfotona group and 8 4 3 0 in the sunscreen group. All patients underwent one standardized session of methylaminolaevulinate PDT using a 630-nm light-emitting diode lamp at 37 J cm . Immediately after PDT (evaluation performed 2 weeks after the procedure) mean SD residual lesions were 2 0 2 0 in the Eryfotona group and 0 6 0 5 in the sunscreen group (nonsignificant). A progressive increase of AK lesions was observed in the sunscreen group, with a mean SD number of lesions of 3 6 3 8 at the end of study period (month 9). In contrast, a significant reduction of AK lesions was observed at month 9 in patients in the Eryfotona group, with a mean SD number of lesions of 1 0 1 1 in comparison with baseline and with the comparator group (P < 0 01). Evolution of new AK lesions after PDT is shown in Figure 1. In the sunscreen group, 13 of 15 patients (87%) presented new AK lesions during the study: in 10 patients new lesions appeared in the area previously treated

Ankle/brachial index to everyone

BackgroundIn the last years significant attention has been paid in identifying markers of subclinical atherosclerosis or of increased cardiovascular risk.MethodAn abnormal ankle/brachial index (ABI) identifies patients affected by lower extremity peripheral arterial disease, and even more important, represents a powerful predictor of the development of future ischemic cardiovascular events.ConclusionsIn our opinion, ABI is a cardiovascular risk prediction tool with very desirable properties that might become a routine measurement in clinical practice.

Endovascular treatment of lower extremity arteries is associated with an improved outcome in diabetic patients affected by intermittent claudication

BackgroundLower extremity peripheral arterial disease (LE-PAD) is a highly prevalent condition among diabetic patients, associated with reduced walking capacity and a high incidence of cardiovascular events. Endovascular revascularization of lower extremities arteries improves walking performance and quality of life of diabetic patients affected by intermittent claudication, but few studies evaluated the impact of revascularization on cardiovascular outcome in this high-risk population. Accordingly, in the present study we evaluated if leg-ischemia resolution by effective lower limbs percutaneous revascularization can also impact cardiovascular outcome in a homogeneous group of diabetic patients affected by intermittent claudication.Methods236 diabetic patients affected by LE-PAD at stage II of Fontaine’s classification, with ankle/brachial index ≤0.90 and one or more hemodynamically significant stenosis in at least one artery of the ileo-femoro-popliteal axis were enrolled in the study. According to the Trans-Atlantic Inter Society Consensus II recommendations, 123 (52.1%) underwent percutaneous transluminal angioplasty (PTA group), while 113 (47.9%) underwent conservative medical therapy only (MT group). The incidence of major cardiovascular events (cardiovascular death, myocardial infarction, ischemic stroke, coronary or carotid revascularization) was prospectively analyzed with Kaplan-Meier curves and the risk of developing a cardiovascular event calculated by Cox analyses.ResultsNo baseline difference in cardiovascular risk factors were observed between the PTA and MT groups, except for a lower prevalence of males in PTA group (74.8% vs. 85.8%, p=0.034). Furthermore, patients in the PTA group showed a worse walking capacity as expressed by maximum walking distance (108.7 ± 300.9 vs 378.4 ± 552.3 meters, p<0.001). During a median follow-up of 20 months (12.0-29.0), the incidence of cardiovascular events was markedly lower in patients in the PTA group with respect to patients in the MT group (7.3% vs. 22.1%, p=0.001), and patients of the MT group had at Cox analysis a 3.9 increased risk with respect to PTA group, after adjustment for potential confounding factors (95% CI 1.1-15.3, p=0.049).ConclusionsThe present study shows that lower limbs revascularization of diabetic patients affected by intermittent claudication, in addition to improve walking performance, is associated with a reduction in the incidence of future major cardiovascular events.