Lipid-lowering therapy in high cardiovascular risk patients during COVID-19 pandemic: keep focused on the target

To the Editor COVID-19 (COrona VIrus Disease) patients with cardiovascular (CV) disease, multiple CV risk factors or comorbidities (i.e., arterial hypertension and diabetes) were shown to be more prone to a worse prognosis. SARS-CoV-2 is a still unknown enemy and the role of concomitant cardiovascular therapies has been controversial in the early stages, particularly with regard to Angiotensin-Converting Enzyme inhibitors..

Wastewater Management in Citrus Processing Industries: An Overview of Advantages and Limits

Citrus-processing industries produce large volumes of wastewater (CPWW). The large variability of these volumes coupled to physicochemical characteristics of CPWW determine severe constraints for their disposal due to both economic and environmental factors. To minimize the management costs and prevent the negative ecological impacts of CPWW, several systems have been proposed and adopted. However, all these treatment/valorization routes have many issues that are not yet thoroughly known by the scientific community and stakeholders of the citrus-processing chain. This paper reports an overview of the possible treatment/valorization opportunities for CPWW: intensive biological treatment, lagooning, direct land application, energy conversion, and biorefinery uses for the extraction of added-value compounds. Advantages and constraints are presented and discussed, and the following conclusions are achieved: (i) there is not a unique solution for CPWW treatment, since the best management system of CPWW must be chosen case by case, taking into account the quality/quantity of the effluent and the location of the transformation industry; (ii) the adoption of a biorefinery approach can increase the competitiveness and the further development of the whole citrus sector, but the cost of novel technologies (some of which have not been tested at real scale) still limits their development

Upregulation of TH/IL-17 Pathway-Related Genes in Human Coronary Endothelial Cells Stimulated with Serum of Patients with Acute Coronary Syndromes

Inflammation plays an essential role in the development and complications of atherosclerosis plaques, including acute coronary syndromes (ACS). Indeed, previous reports have shown that within the coronary circulation of ACS patients, several soluble mediators are released. Moreover, it has been demonstrated that endothelial dysfunction might play an important role in atherosclerosis as well as ACS pathophysiology. However, the mechanisms by which these soluble mediators might affect endothelial functions are still largely unknown. We have evaluated whether soluble mediators contained in serum from coronary circulation of ACS patients might promote changes of gene profile in human coronary endothelial cells (HCAECs)

Oral Antiplatelet Therapy for Secondary Prevention of Non-Cardioembolic Ischemic Cerebrovascular Events

Stroke is the leading cause of disability and mortality worldwide. After an acute cerebrovascular ischemia, recurrent vascular events, including recurrent stroke or transient ischemic accidents (TIA), occur in around 20% of cases within the first 3 months. In order to minimize this percentage, antiplatelet therapy may play a key role in the management of non-cardioembolic cerebrovascular events. This review will focus on the current evidence of antiplatelet therapies most commonly discussed in practice guidelines and used in clinical practice for the treatment of stroke/TIA complications. The antiplatelet therapies most commonly used and discussed are as follows: aspirin, clopidogrel, and ticagrelor

Use of benzylglycinamide by a HIV-seropositive polysubstance user: : the changing pattern of novel psychoactive substance use among youths

This document is the Accepted Manuscript of the following article: Matteo Caloro, et al, ‘Use of benzylglycinamide by a HIV-seropositive polysubstance user: The changing pattern of novel psychoactive substance use among youths’, Addictive Behaviors, Vol. 60, pp. 53-57, September 2016. The Version of Record is available online at doi: https://doi.org/10.1016/j.addbeh.2016.03.032. © 2016 Elsevier Ltd. All rights reserved.A 24-year old woman with multisubstance use since the age of 13, including opioids and cocaine, and long-standing HIV/HCV seropositivity status, presented with psychosis, agitation, and insomnia at the emergency department of a university hospital. She had been abusive and physically aggressive frequently without specific reasons and was involved in criminal legal cases. She was hospitalized twice. During her first hospital stay she experienced a brief episode of detachment from her environment, similar to episodes reportedly suffered at home. Psychosis had developed following heavy polysubstance abuse. Her mother provided sachets containing benzylglycinamide, a substance with no known psychotropic effects, which were also present in the patient's urine. She was occasionally positive for cannabinoids. She used to buy various novel psychoactive substances (NPSs) from the internet and used experimentally various substances freely made available to her by drug suppliers/dealers. She was unable to explain clearly why she was taking any of the identified NPS. She stated she was taking benzylglycinamide to calm her when smoking synthetic cannabinoids. While it appears that benzylglycinamide is not likely to constitute a novel drug of abuse, her polysubstance use exemplifies trends in NPS use patterns among the youths in the Western world and should alert mental health workers as to the possible dangers of such behavior and its reflection on social behavior and psychopathology.Peer reviewedFinal Accepted Versio

The Biological Role of Vitamins in Athletes’ Muscle, Heart and Microbiota

Physical activity, combined with adequate nutrition, is considered a protective factor against cardiovascular disease, musculoskeletal disorders, and intestinal dysbiosis. Achieving optimal performance requires a significantly high energy expenditure, which must be correctly supplied to avoid the occurrence of diseases such as muscle injuries, oxidative stress, and heart pathologies, and a decrease in physical performance during competition. Moreover, in sports activities, the replenishment of water, vitamins, and minerals consumed during training is essential for safeguarding athletes’ health. In this scenario, vitamins play a pivotal role in numerous metabolic reactions and some muscle biochemical adaptation processes induced by sports activity. Vitamins are introduced to the diet because the human body is unable to produce these micronutrients. The aim of this review is to highlight the fundamental role of vitamin supplementation in physical activity. Above all, we focus on the roles of vitamins A, B6, D, E, and K in the prevention and treatment of cardiovascular disorders, muscle injuries, and regulation of the microbiome

Primary Analysis and 4-Year Follow-Up of the Phase III NIBIT-M2 Trial in Melanoma Patients With Brain Metastases

Purpose: Phase II trials have shown encouraging activity with ipilimumab plus fotemustine and ipilimumab plus nivolumab in melanoma brain metastases. We report the primary analysis and 4-year follow-up of the NIBIT-M2 study, the first phase III trial comparing these regimens with fotemustine in patients with melanoma with brain metastases. Patients and methods: This phase III study recruited patients 18 years of age and older with BRAF wild-type or mutant melanoma, and active, untreated, asymptomatic brain metastases from nine centers, randomized (1:1:1) to fotemustine, ipilimumab plus fotemustine, or ipilimumab plus nivolumab. The primary endpoint was overall survival (OS). Results: From January, 2013 to September, 2018, 27, 26, and 27 patients received fotemustine, ipilimumab plus fotemustine, and ipilimumab plus nivolumab. Median OS was 8.5 months [95% confidence interval (CI), 4.8-12.2] in the fotemustine arm, 8.2 months (95% CI, 2.2-14.3) in the ipilimumab plus fotemustine arm (HR vs. fotemustine, 1.09; 95% CI, 0.59-1.99; P = 0.78), and 29.2 months (95% CI, 0-65.1) in the ipilimumab plus nivolumab arm (HR vs. fotemustine, 0.44; 95% CI, 0.22-0.87; P = 0.017). Four-year survival rate was significantly higher for ipilimumab plus nivolumab than fotemustine [(41.0%; 95% CI, 20.6-61.4) vs. 10.9% (95% CI, 0-24.4; P = 0.015)], and was 10.3% (95% CI, 0-22.6) for ipilimumab plus fotemustine. In the fotemustine, ipilimumab plus fotemustine, and ipilimumab plus nivolumab arms, respectively, 11 (48%), 18 (69%), and eight (30%) patients had treatment-related grade 3 or 4 adverse events, without treatment-related deaths. Conclusions: Compared with fotemustine, ipilimumab plus nivolumab significantly improved overall and long-term survival of patients with melanoma with asymptomatic brain metastases

Bone metastases and immunotherapy in patients with advanced non-small-cell lung cancer

Background Bone metastases (BoM) are a negative prognostic factor in non-small-cell lung cancer (NSCLC). Beyond its supportive role, bone is a hematopoietic organ actively regulating immune system. We hypothesized that BoM may influence sensitivity to immunotherapy. Methods Pretreated non-squamous (cohort A) and squamous (cohort B) NSCLCs included in the Italian Expanded Access Program were evaluated for nivolumab efficacy according to BoM. Results Cohort A accounted for 1588 patients with non-squamous NSCLC, including 626 (39%) with (BoM+) and 962 (61%) without BoM (BoM-). Cohort B accounted for 371 patients with squamous histology including 120 BoM+ (32%) and 251 (68%) BoM- cases. BoM+ had lower overall response rate (ORR; Cohort A: 12% versus 23%, p < 0.0001; Cohort B: 13% versus 22%, p = 0.04), shorter progression free survival (PFS; Cohort A: 3.0 versus 4.0 months, p < 0.0001; Cohort B: 2.7 versus 5.2 months, p < 0.0001) and overall survival (OS; Cohort A: 7.4 versus 15.3 months, p < 0.0001; Cohort B: 5.0 versus 10.9 months, p < 0.0001). Moreover, BoM negatively affected outcome irrespective of performance status (PS; OS in both cohorts: p < 0.0001) and liver metastases (OS cohort A: p < 0.0001; OS Cohort B: p = 0.48). At multivariate analysis, BoM independently associated with higher risk of death (cohort A: HR 1.50; cohort B: HR 1.78). Conclusions BoM impairs immunotherapy efficacy. Accurate bone staging should be included in clinical trials with immunotherapy

Design of Approaches for Dependability and Initial Prototypes

The aim of CONNECT is to achieve universal interoperability between heterogeneous Networked Systems. For this, the non-functional properties required at each side of the connection going to be established must be fulfilled. By the one inclusive term "CONNECTability" we comprehend properties belonging to all four non-functional concerns of interest for CONNECT, namely dependability, performance, security and trust. We model such properties in conformance with a meta-model which establishes the relevant concepts and their relations. Then, building on the conceptual models proposed in the first year in Deliverable D5.1, in this document we present the approaches developed for assuring CONNECTability both at synthesis time and at runtime. The contributions include: the Dependability&Performance analysis Enabler, for which we release a modular architecture supporting stochastic verification and state-based analysis; incremental verification and event-based monitoring for runtime analysis; a model-based approach to interoperable trust management; the Security-by-Contract-with-Trust framework, which guarantees and enforces the expected trust levels and security policies