The emerging therapeutic landscape of alk inhibitors in non-small cell lung cancer

The treatment of metastatic non-small cell lung cancer (NSCLC) has undergone a paradigm shift over the last decade. Better molecular characterization of the disease has led to the rapid improvement of personalized medicine and the prompt delivery of targeted therapies to patients with NSCLC. The discovery of the EML4-ALK fusion gene in a limited subset of patients affected by NSCLC and the subsequent clinical development of crizotinib in 2011 has been an impressive milestone in lung cancer research. Unfortunately, acquired resistances regularly develop, hence disease progression occurs. Afterward, modern tyrosine kinase inhibitors (TKIs), such as ceritinib, alectinib, brigatinib, and lorlatinib, have been approved by the Food and Drug Administration (FDA) for the management of anaplastic lymphoma kinase (ALK)-positive NSCLCs. Several compounds are currently under investigation to achieve the optimal strategy of therapy. Additionally, the results of ongoing clinical trials with novel-generation TKI will provide more evidence on the best sequence in the treatment of ALK-positive NSCLC patients. In this review, we provide a comprehensive overview of the state-of-the-art targeted therapy options in ALK-positive NSCLCs. Resistance, potential therapeutic strategies to overcome drug resistance, and future perspectives for this subset of patients are critically analyzed and summarized

Environmental Impact of Dietary Choices: Role of the Mediterranean and Other Dietary Patterns in an Italian Cohort

Background: Current scientific literature suggests healthy dietary patterns may have less environmental impact than current consumption patterns, but most of the studies rely on theoretical modeling. The aim of this study was to assess the impact on resources (land, water, and energy) use and greenhouse gas (GHG) emissions of healthy dietary patterns in a sample of Italian adults. Methods: Participants (n = 1806) were recruited through random sampling in the city of Catania, southern Italy. Dietary consumption was assessed through a validated food frequency questionnaire (FFQ); dietary patterns were calculated through dietary scores. The specific environmental footprints of food item production/processing were obtained from various available life-cycle assessments; a sustainability score was created based on the impact of the four environmental components calculated. Results: The contribution of major food groups to the environmental footprint showed that animal products (dairy, egg, meat, and fish) represented more than half of the impact on GHG emissions and energy requirements; meat products were the stronger contributors to GHG emissions and water use, while dairy products to energy use, and cereals to land use. All patterns investigated, with the exception of the Dietary Approach to Stop Hypertension (DASH), were linearly associated with the sustainability score. Among the components, higher adherence to the Mediterranean diet and Alternate Diet Quality Index (AHEI) was associated with lower GHG emissions, dietary quality index-international (DQI-I) with land use, while Nordic diet with land and water use. Conclusions: In conclusion, the adoption of healthy dietary patterns involves less use of natural resources and GHG emissions, representing eco-friendlier options in Italian adults

Total nut, tree nut, and peanut consumption and metabolic status in southern Italian adults

Background: Nut consumption has been associated with cardio-metabolic health benefits. However, studies conducted in the Southern Italian population, where adherence to the Mediterranean diet has been reported being relatively high, are rather scarce. The aim of this study was to test the association between consumption of total and specific types of nuts and metabolic status among adults living in Sicily, Southern Italy. Methods: Demographic and dietary characteristics of 2044 adults living in Southern Italy were analyzed. Multivariate logistic regression analyses were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of the association between nut consumption and metabolic status adjusting for potential confounding factors. Results: The energy-adjusted model revealed that higher nut intake was inversely associated with occurrence of hypertension, type-2 diabetes, and dyslipidemia. However, the association did not remain significant for the latter after adjusting for the main background characteristics, while an inverse association was stably confirmed for hypertension (OR = 0.61, 95% CI: 0.46–0.80 and OR = 0.44, 95% CI: 0.26–0.74, respectively) even after adjusting for adherence to the Mediterranean diet. Among individual nut types, most of the associations were null except for higher almond intake, which was inversely associated with occurrence of hypertension (OR = 0.70, 95% CI: 0.49–0.99). Conclusions: Higher nut consumption is associated with overall better metabolic status in individuals living in the Mediterranean area

Pre-pectoral Breast Reconstruction: Surgical and Patient-Reported Outcomes of Two-Stages vs Single-Stage Implant-Based Breast Reconstruction

Background: Two-stages pre-pectoral breast reconstruction may confer advantages over direct to implant (DTI) and subpectoral reconstruction in selected patients who have no indication for autologous reconstruction. The primary endpoint of the study was to evaluate and compare the incidence of capsular contracture in the pre-pectoral two-stages technique versus the direct to implant technique. Complications related to the two surgical techniques and patient satisfaction were also evaluated. Methods: A retrospective review of 45 two stages and 45 Direct-to-implant, DTI patients was completed. Acellular dermal matrix was used in all patients. An evaluation of anthropometric and clinical parameters, surgical procedures and complications was conducted. Minimum follow-up was 12 months after placement of the definitive implant. Results: There was no statistically significant difference in the rate of capsular contracture in the two groups. Rippling occurred more in DTI reconstruction. In the two-stages reconstruction, lipofilling was applied more often and there was a higher incidence of seroma. Patient satisfaction extrapolated from the Breast Q questionnaire was better for patients submitted to two-stage implant-based breast reconstruction. Conclusion: Dual-stage pre-pectoral reconstruction with acellular dermal matrix appears to be a good reconstructive solution in patients with relative contraindications for one-stage heterologous reconstruction with definitive prosthesis and no desire for autologous reconstruction

Dietary Fats and Cardio-Metabolic Outcomes in a Cohort of Italian Adults

Background: Dietary fats, and especially saturated fatty acid (SFA), have been blamed for being the culprit in the dramatic increase in obesity and its associated diseases. However multiple systematic reviews and recent meta-analyses do not support the association between SFA and cardiovascular diseases. Thus, the objective of this study was to test whether specific types and subtypes of dietary fats are associated with metabolic outcomes in a cohort of Italian adults. Methods: Nutritional and demographic data of 1936 adults living in the south of Italy were examined. Food frequency questionnaires (FFQs) were administered to assess the intake of total dietary fat and each specific class of dietary fat, such as SFA, monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA). The intake of fatty acids was also examined according to the carbon-chain length of each individual class. Cases of hypertension, type-2 diabetes and dyslipidemias were collected from previous doctor-confirmed diagnosis records (or direct measurement of blood pressure). Results: After adjustment for potential confounding factors, individuals reporting higher intakes of total and saturated fats were associated with lower likelihood of having hypertension (odds ratio (OR) = 0.57, 95% CI: 0.35, 0.91 and OR = 0.55, 95% CI: 0.34, 0.89, respectively). Moreover, higher intake of short-chain saturated fatty acids (SCSFAs) and medium-chain saturated fatty acids (MCSFAs) was inversely associated with dyslipidemia and diabetes (OR = 0.43, 95% CI: 0.23, 0.82 and OR = 0.25, 95% CI: 0.09, 0.72, respectively). Among MUFAs, C18:1 was inversely associated with hypertension and diabetes (OR = 0.52, 95% CI: 0.30, 0.92 and OR = 0.21, 95% CI: 0.07, 0.67, respectively), while C14:1 intake was inversely associated only with hypertension (OR = 0.57, 95% CI: 0.37, 0.88). In contrast, C20:1 intake was associated with dyslipidemia (OR = 3.35, 95% CI: 1.33, 8.42). Regarding PUFA, C18:2 and 20:5 were inversely associated with hypertension (OR = 0.33, 95% CI: 0.18, 0.60 and OR = 0.30, 95% CI: 0.10, 0.89, respectively). Conclusions: The consumption of SFA does not seem to be harmful to cardio-metabolic health and, on the contrary, SCSFA may exert beneficial effects. Further studies are needed to clearly validate the results of the present study

Potential therapeutic effects of natural heme oxygenase-1 inducers in cardiovascular diseases.

Significance: Many physiological effects of natural antioxidants, their extracts or their major active components, have been reported in recent decades. Most of these compounds are characterized by a phenolic structure, similar to that of α-tocopherol, and present antioxidant properties that have been demonstrated both in vitro and in vivo. Polyphenols may increase the capacity of endogenous antioxidant defenses and modulate the cellular redox state. Such effects may have wide-ranging consequences for cellular growth and differentiation. Critical Issues: The majority of in vitro and in vivo studies conducted so far have attributed the protective effect of bioactive polyphenols to their chemical reactivity toward free radicals and their capacity to prevent the oxidation of important intracellular components. One possible protective molecular mechanism of polyphenols is nuclear factor erythroid 2-related factor (Nrf2) activation, which in turn regulates a number of detoxification enzymes. Recent Advances: Among the latter, the heme oxygenase-1 (HO-1) pathway is likely to contribute to the established and powerful antioxidant/anti-inflammatory properties of polyphenols. In this context, it is interesting to note that induction of HO-1 expression by means of natural compounds contributes to prevention of cardiovascular diseases in various experimental models. Future Directions: The focus of this review is on the role of natural HO-1 inducers as a potential therapeutic strategy to protect the cardiovascular system against various stressors in several pathological conditions

Factors Associated with Adherence to the Mediterranean Diet among Adolescents Living in Sicily, Southern Italy

The present study aimed to examine the factors associated with increased Mediterranean diet (MD) adherence among a sample of Italian adolescents. A cross-sectional survey was conducted on 1135 students (13–16 years) attending 13 secondary schools of Sicily, southern Italy. Validated instruments were used for dietary assessment and the KIDMED score to assess adolescents’ adherence to the MD. A higher adherence to the MD was associated with high socioeconomic status (Odds Ratio [OR] 1.53, 95% Confidence Interval [CI]: 1.03–2.26) and high physical activity (OR 1.19, 95% CI: 1.02–1.70), whereas lower adherence was associated with living in an urban environment (OR 0.65, 95% CI: 0.44–0.97) and being obese (OR 0.59, 95% CI: 0.37–0.94). The adolescents’ KIDMED scores were inversely associated with adolescents’ intake of sweets, fast foods, fried foods, and sugary drinks, and directly with fruit, vegetables, pasta, fish, and cheese intakes. Urban-living adolescents were less likely to eat fruit and more prone to consume meat, sugary drinks, and fast food than rural-living adolescents. The latter were more likely to eat sweets and snacks. A general poor quality of food consumption in Italian adolescents away from the MD was reported, especially among those living in urban areas

Nintedanib in NSCLC: Evidence to date and place in therapy

The treatment of advanced non-small cell lung cancer (NSCLC) is currently driven by the detection of targetable oncogenic drivers, i.e. epidermal growth factor receptor, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase, etc. Those patients who are wildtype for known and valuable oncogenes can receive standard chemotherapy as first-line treatment, with the possibility of adding bevacizumab. With regard to second-line treatment, nintedanib can improve the efficacy of docetaxel. Nintedanib is a tyrosine kinase inhibitor targeting three angiogenesis-related transmembrane receptors. The usefulness of nintedanib as an anticancer agent for NSCLC has been proved by both preclinical and clinical phase I and II trials; however, its approval for the use in clinical practice has been possible because of the positive results of the LUME-Lung 1 trial (nintedanib + docetaxel versus docetaxel alone) in terms of progression-free survival and overall survival, and a manageable tolerability profile. Therefore, the good results seen in the clinical trials with nintedanib in the second-line setting for NSCLC patients with adenocarcinoma subtype are encouraging enough to recommend it in clinical practice