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The Mediterranean diet (MD) is a combination of foods mainly rich in antioxidants and anti-inflammatory nutrients that have been shown to have many health-enhancing effects. Extra-virgin olive oil (EVOO) is an important component of the MD. The importance of EVOO can be attributed to phenolic compounds, represented by phenolic alcohols, hydroxytyrosol, and tyrosol, and to secoiridoids, which include oleocanthal, oleacein, oleuropein, and ligstroside (along with the aglycone and glycosidic derivatives of the latter two). Each secoiridoid has been studied and characterized, and their effects on human health have been documented by several studies. Secoiridoids have antioxidant, anti-inflammatory, and anti-proliferative properties and, therefore, exhibit anti-cancer activity. This review summarizes the most recent findings regarding the pharmacological properties, molecular targets, and action mechanisms of secoiridoids, focusing attention on their preventive and anti-cancer activities. It provides a critical analysis of preclinical, in vitro and in vivo, studies of these natural bioactive compounds used as agents against various human cancers. The prospects for their possible use in human cancer prevention and treatment is also discussed.

Non-alcoholic fatty liver disease (NAFLD), the most frequent liver disease in the Western world, is a common hepatic manifestation of metabolic syndrome (MetS). A specific cure has not yet been identified, and its treatment is currently based on risk factor therapy. Given that the initial accumulation of triglycerides in the liver parenchyma, in the presence of inflammatory processes, mitochondrial dysfunction, lipotoxicity, glucotoxicity, and oxidative stress, can evolve into non-alcoholic steatohepatitis (NASH). The main goal is to identify the factors contributing to this evolution because, once established, untreated NASH can progress through fibrosis to cirrhosis and, ultimately, be complicated by hepatocellular carcinoma (HCC). Several drugs have been tested in clinical trials for use as specific therapy for NAFLD; most of them are molecules used to cure type 2 diabetes mellitus (T2DM), which is one of the main risk factors for NAFLD. Among the most studied is pioglitazone, either alone or in combination with vitamin E, glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors. Actually, the most promising category seems to be sodium-glucose cotransporter (SGLT2) inhibitors. Their action is carried out by inhibiting glucose reabsorption in the proximal renal tubule, leading to its increased excretion in urine and decreased levels in plasma. Experimental studies in animal models have suggested that SGLT2 inhibitors may have beneficial modulatory effects on NAFLD/NASH, and several trials in patients have proven their beneficial effects on liver enzymes, BMI, blood lipids, blood glucose, and insulin resistance in NAFLD patients, thus creating strong expectations for their possible use in preventing the evolution of liver damage in these patients. We will review the main pathogenetic mechanisms, diagnostic modalities, and recent therapies of NAFLD, with particular attention to the use of SGLT2 inhibitors.

In respiratory infections, anemia is both a consequence of acute inflammation and a predictor of poor clinical outcomes. There are few studies investigating the role of anemia in COVID-19, suggesting a potential role in predicting disease severity. In this study, we aimed to assess the association between the presence of anemia at admission and incidence of severe disease and death in patients hospitalized for COVID-19. Data from all adult patients admitted for COVID-19 in University Hospital “P. Giaccone” Palermo, and University Hospital of Bari, Italy, were retrospectively collected from 1st of September 2020 to 31 August 2022. The association between anemia (defined as Hb < 13 g/dl and < 12 g/dl in males and females, respectively), in-hospital mortality and severe COVID-19 was tested using a Cox’s regression analysis. Severe COVID-19 forms were defined as admission to intensive or sub-intensive care unit or a qSOFAscore ≥ 2 or CURB65scores ≥ 3. p values were calculated using the Student’s t test for continuous variables and the Mantel–Haenszel Chi-square test for categorical ones. The association between anemia and the mortality was made using a Cox’s regression analysis, adjusted, in two models, for the potential confounders and using a propensity score. Among the 1562 patients included in the analysis, prevalence of anemia was 45.1% (95% CI 43–48%). Patients with anemia were significantly older ( p  < 0.0001), reported more co-morbidities, and presented higher baseline levels of procalcitonin, CRP, ferritin and IL-6. Overall, the crude incidence of mortality was about four times higher in patients with anemia compared to those without. After adjusting for 17 potential confounders, the presence of anemia significantly increased the risk of death (HR = 2.68; 95% CI: 1.59–4.52) and of risk of severe COVID-19 (OR = 2.31; 95% CI: 1.65–3.24). The propensity score analysis substantially confirmed these analyses. Our study provides evidence that, in patients hospitalized for COVID-19, anemia is both associated with a more pronounced baseline pro-inflammatory profile and higher incidence of in-hospital mortality and severe disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), is becoming the most common liver disease, affecting between 30 and 40% of the global population. MASLD is a multifaceted disease spectrum that is closely associated with obesity, insulin resistance, type 2 diabetes mellitus and, more broadly, metabolic syndrome. All these conditions increase the risk of liver-related mortality, which explains the intense research efforts in recent years to better elucidate its pathogenesis. The crucial impact of environmental pollutants on the development of MASLD is now well recognized. Polychlorinated biphenyls (PCBs) are environmental contaminants that act as endocrine disruptors. Recently, they have been associated with the development of diabetes, obesity, MASLD, and cancer. The association between liver diseases, namely toxicant-associated steatotic liver disease and steatohepatitis (TASLD and TASH, respectively), and occupational exposure to PCBs and other industrial chemicals has been documented by several lines of evidence, whereas the potential role of low-level environmental pollution in liver disease and in MASLD remains incompletely understood. Previous studies on animal models have shown that PCB exposure is associated with steatosis/steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma (HCC), altered liver enzymes, and mortality in exposed populations. This review investigates the mechanisms underlying hepatic steatogenesis in preclinical and animal models and analyzes the existing literature on the possible role of PCBs, together with the other conventional risk factors, in the development of MASLD in humans.

Oxidative stress plays a central role in most chronic liver diseases and, in particular, in metabolic dysfunction-associated fatty liver disease (MAFLD), the new definition of an old condition known as non-alcoholic fatty liver disease (NAFLD). The mechanisms leading to hepatocellular fat accumulation in genetically predisposed individuals who adopt a sedentary lifestyle and consume an obesogenic diet progress through mitochondrial and endoplasmic reticulum dysfunction, which amplifies reactive oxygen species (ROS) production, lipid peroxidation, malondialdehyde (MDA) formation, and influence the release of chronic inflammation and liver damage biomarkers, such as pro-inflammatory cytokines. This close pathogenetic link has been a key stimulus in the search for therapeutic approaches targeting oxidative stress to treat steatosis, and a number of clinical trials have been conducted to date on subjects with NAFLD using drugs as well as supplements or nutraceutical products. Vitamin E, Vitamin D, and Silybin are the most studied substances, but several non-pharmacological approaches have also been explored, especially lifestyle and diet modifications. Among the dietary approaches, the Mediterranean Diet (MD) seems to be the most reliable for affecting liver steatosis, probably with the added value of the presence of extra virgin olive oil (EVOO), a healthy food with a high content of monounsaturated fatty acids, especially oleic acid, and variable concentrations of phenols (oleocanthal) and phenolic alcohols, such as hydroxytyrosol (HT) and tyrosol (Tyr). In this review, we focus on non-pharmacological interventions in MAFLD treatment that target oxidative stress and, in particular, on the role of EVOO as one of the main antioxidant components of the MD.

Background: A hypersensitivity reaction has been hypothesized as one of the possible pathophysiological mechanisms involved in non-celiac wheat sensitivity (NCWS). Some studies have reported a high frequency of atopic diseases in NCWS patients. Objectives: This study aimed (A) to define the presence and features of atopic diseases and other hypersensitivities in NCWS patients and (B) to search for possible allergic features which could address a NCWS diagnosis. Methods: Clinical, laboratory and histological data from NCWS patients before the start of a wheat-free diet were retrospectively analyzed and compared to control subjects with celiac disease (CeD) or irritable bowel syndrome/functional dyspepsia (IBS/FD). Results: Atopic disease prevalence was higher in the NCWS patients (32.8%) than in those with CeD (19.3%) and IBS/FD (21.5%) (p = 0.001 for both). Similarly, NCWS subjects reported a higher frequency of multiple food sensitivities (MFSs) (39.8%) and self-reported milk intolerance (SRMI) (65.9%) compared to the control groups (p < 0.001 for both). On multiple logistic regression analysis, a coexistent atopic disease (OR 1.481), MFS (OR 3.882) and SRMI (OR 2.259) proved to be variables associated with the NCWS diagnosis. Conclusions: NCWS subjects have a higher frequency of atopic disease, MFS and SRMI when compared to both CeD and IBS/FD patients. All these conditions could be considered as an expression of an underlying hypersensitivity milieu characterizing NCWS and might be of support in the differential diagnosis between NCWS and functional gastrointestinal disorders, if inserted into a broader diagnostic panel.

Remdesivir (RDV) was the first Food and Drug Administration (FDA)-approved medication for COVID-19, with discordant data on efficacy in reducing mortality risk and disease progression. In the context of a dynamic and rapidly changing pandemic landscape, the utilization of real-world evidence is of utmost importance. The objective of this study is to evaluate the impact of RDV on patients who have been admitted to two university referral hospitals in Italy due to COVID-19. All patients older than 18 years and hospitalized at two different universities (Bari and Palermo) were enrolled in this study. To minimize the effect of potential confounders, we used propensity score matching with one case (Remdesivir) and one control that never experienced this kind of intervention during hospitalization. Mortality was the primary outcome of our investigation, and it was recorded using death certificates and/or medical records. Severe COVID-19 was defined as admission to the intensive care unit or a qSOFAscore ≥ 2 or CURB65scores ≥ 3. After using propensity score matching, 365 patients taking Remdesivir and 365 controls were included. No significant differences emerged between the two groups in terms of mean age and percentage of females, while patients taking Remdesivir were less frequently active smokers (p < 0.0001). Moreover, the patients taking Remdesivir were less frequently vaccinated against COVID-19. All the other clinical, radiological, and pharmacological parameters were balanced between the two groups. The use of Remdesivir in our cohort was associated with a significantly lower risk of mortality during the follow-up period (HR 0.56; 95% CI 0.37–0.86; p = 0.007). Moreover, RDV was associated with a significantly lower incidence of non-invasive ventilation (OR 0.27; 95% CI 0.20–0.36). Furthermore, in the 365 patients taking Remdesivir, we observed two cases of mild renal failure requiring a reduction in the dosage of Remdesivir and two cases in which the physicians decided to interrupt Remdesivir for bradycardia and for QT elongation. Our study suggests that the use of Remdesivir in hospitalized COVID-19 patients is a safe therapy associated with improved clinical outcomes, including halving of mortality and with a reduction of around 75% of the risk of invasive ventilation. In a constantly changing COVID-19 scenario, ongoing research is necessary to tailor treatment decisions based on the latest scientific evidence and optimize patient outcomes.

Extra virgin olive oil (EVOO) intake is associated with reduced cardiovascular risk, and its phenolic compound oleocanthal (OC) has anti-oxidant and anti-inflammatory properties. The cardiometabolic effects of EVOO with a high OC concentration have not been fully elucidated. We administered EVOO with a high OC concentration daily to 23 subjects with the metabolic syndrome (MetS) and hepatic steatosis (15 men and 8 women, age: 60 ± 11 years) for 2 months. Anthropometric data, metabolic parameters, hepatic steatosis (by fatty liver index, FLI), abdominal fat distribution (by ultrasound), and pro- and anti-inflammatory cytokines were assessed before and after the intervention. EVOO supplementation was associated with a reduction in body weight, waist circumference, body mass index (BMI), alanine transaminase and FLI, as well as interleukin (IL)-6, IL-17A, tumor necrosis factor-α and IL-1B, while IL-10 increased. Maximum subcutaneous fat thickness (SFT max) also increased, with a concomitant decrease in the ratio of visceral fat layer thickness/SFT max. Correlation analysis revealed positive associations between changes in body weight and BMI and those in SFT max, along with an inverse association between changes in IL-6 and those in SFT max. In conclusion, ingestion of EVOO with a high OC concentration had beneficial effects on metabolic parameters, inflammatory cytokines and abdominal fat distribution in MetS subjects with hepatic steatosis, a category of patients at high cardiometabolic risk.

Management for HCV has undergone a notable change using direct-acting antiviral drugs (DAAs), which are safe and effective even in elderly. Here, we define impact of comorbidities, concomitant medication and drug–drug interactions in elder patients with HCV related disease before starting DAAs regimen. We analyzed data of 814 patients prospectively enrolled at our Unit within the web based model HCV Sicily Network. Out of 814, 590 were treated with DAAs and 414 of them were older than 65 years. We divided those 414 in two groups, one including 215 patients, aged between 65 and 74 years, and another with 199 patients, aged of 75 years and over. Charlson Comorbidity Index (CCI) was assessed for each patient; drug–drug interactions (DDI) and de-prescribing process were carried out appropriately. Within 414 patients included, percentage rates of women treated was higher than males, BMI was lower and cirrhosis was frequently reported in patients older than 75 years. Hypertension, diabetes mellitus, dyslipidemia (p < 0.0001), prostatic pathologies, kidney disease, gastrointestinal disease (p < 0.0001), osteoporosis (p < 0.01) and depression were most common co-morbidities. CCI showed lower scores in the first group as compared with the second one (p < 0.0001). Among drugs, statins were frequently suspended and anti-hypertensive often replaced. DAAs are useful and effective regardless of disease severity, comorbidities, medications and age. De-prescribing allows a stable reduction of number of medications taken with real improvement of quality of life.

The aim of this brief report is to evaluate sodium-glucose cotransporter 2 inhibitors (SGLT2-I) effects on patients with both refractory ascites and type 2 diabetes mellitus (T2D). We consecutively recruited all the diabetic patients with refractory ascites due to decompensated liver cirrhosis admitted between February and May 2023 at the Internal Medicine Unit of the University Hospital of Palermo. Clinical and laboratory data were collected after starting SGLT2-I therapy. SGLT2-I use was associated with a reduction/resolution of ascites and with an improvement in serum albumin and sodium levels and estimated glomerular filtration rate. SGLT2-I might represent a valid therapeutic option in the treatment of patients with refractory ascites and T2D, as already hypothesized by other research groups.