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Background and objectives: ischemic stroke (IS) is among the most frequent causes of death worldwide, thus, it is of paramount relevance to know predisposing factors that may help to identify and treat the high-risk subjects. Materials and Methods:we tested nine variants in genes involved in thrombotic pathway in 282 patients that experienced IS and 87 that had transient ischemic attacks (TIA) in comparison to 430 subjects from the general population (GP) of the same geographic area (southern Italy). We included cases of young and child IS to evaluate the eventual differences in the role of the analyzed variants. Results: we did not observe significant differences between TIA and the GP for any of the variants, while the allele frequencies of methylene-tetrahydrofolate reductase (MTHFR) C677T, beta-fibrinogen -455G&gt, A and factor (FXIII) V34L were significantly higher in patients with IS than in the subjects from the GP. No significant interaction was observed with sex. Conclusions: the present data argue that some gene variants have a role in IS and this appears to be an interesting possibility to be pursued in large population studies to help design specific strategies for IS prevention.

Increased concentrations of B-type natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin I (HsTnI) in COVID-19 patients have already been reported. The aim of this study is to evaluate which of these common markers of cardiac disease is the most useful predictor of fatal outcome in COVID-19 patients. One hundred and seventy-four patients affected with COVID-19 were recruited, and markers of cardiac disease and the clinical history of the patients were collected at admission in the infectious disease unit or intensive care unit. NT-proBNP, BNP and HsTnI values were higher in in-hospital non-surviving patients. Receiver operating characteristic (ROC) curve analysis of NT-proBNP, BNP and HsTnI was performed, with NT-proBNP (AUC = 0.951) and HsTnI (AUC = 0.947) being better performers (p = 0.01) than BNP (AUC = 0.777). Logistic regression was performed assessing the relation of HsTnI and NT-proBNP to fatal outcome adjusting for age and gender, with only NT-proBNP being significant. The population was then divided into two groups, one with higher NT-proBNP values at admission than the cut-off resulted from the ROC curve (511 ng/L) and a second one with lower values. The Kaplan–Meier analysis showed an absence of fatal outcome in the group of patients with NT-proBNP values lower than the cut-off (p &lt, 0.001). NT-proBNP proved to be the best prognostic tool for fatal outcome among markers of cardiac disease in COVID-19 patients.

Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it remains still orphan of an adequate therapeutic strategy. Herein we focus on the interplay between oxidative stress (OS) and the other causal pathogenetic factors. Different reactive oxygen species (ROS) generators contribute to NAFLD inflammatory and fibrotic progression, which is quite strictly linked to the lipotoxic liver injury from fatty acids and/or a wide variety of their biologically active metabolites in the context of either a two-hit or a (more recent) multiple parallel hits theory. An antioxidant defense system is usually able to protect hepatic cells from damaging effects caused by ROS, including those produced into the gastrointestinal tract, i.e., by-products generated by usual cellular metabolic processes, normal or dysbiotic microbiota, and/or diet through an enhanced gut–liver axis. Oxidative stress originating from the imbalance between ROS generation and antioxidant defenses is under the influence of individual genetic and epigenetic factors as well. Healthy diet and physical activity have been shown to be effective on NAFLD also with antioxidant mechanisms, but compliance to these lifestyles is very low. Among several considered antioxidants, vitamin E has been particularly studied; however, data are still contradictory. Some studies with natural polyphenols proposed for NAFLD prevention and treatment are encouraging. Probiotics, prebiotics, diet, or fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. In the near future, precision medicine taking into consideration genetic or environmental epigenetic risk factors will likely assist in further selecting the treatment that could work best for a specific patient.

Background: Morbidity and mortality of primary and secondary antibody deficiencies (AD) are frequently associated with diagnostic delays. These could be avoided by a combination of factors including a widespread and effective development in screening tests. Methods: Calculated globulin (CG), derived from the difference between serum total protein and albumin levels, reflects immunoglobulin serum levels and has shown to have a predictive value in the early diagnosis of antibody deficiencies. This study investigated the possibility to use low levels of CG to detect antibody deficiency in an Italian University Hospital. Results: First, we conducted an analysis of anonymized adult samples collected at our biochemistry laboratory with a range of calculated globulin levels from 15 to 22 g/l. A CG cut-off of 19 g/l detected subjects with IgG lower than 600 mg/dl with a sensitivity of 70% and a specificity of 75%. To further verify the clinical usefulness of CG, we retrospectively evaluated the relationship between CG values and serum IgG levels in 38 patients diagnosed with CVID at our Institution. Using a CG cut-off of 19 g/l, we detected antibody deficiency in 97.3% (37/38) of the subjects present in our cohort. Conclusion: Finally, we chose a CG value of 19 g/l as the cut-off for a prospective AD screening program. The results of this study show that a screening CG test can be used as a tool to reduce diagnostic delays, improve long-term prognosis and reduce the healthcare costs of antibody deficiency.

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Coffee consumption is inversely associated with the risk of non-alcoholic fatty liver disease (NAFLD). A gap in the literature still exists concerning the intestinal mechanisms that are involved in the protective effect of coffee consumption towards NAFLD. In this study, twenty-four C57BL/6J mice were divided into three groups each receiving a standard diet, a high-fat diet (HFD) or an HFD plus decaffeinated coffee (HFD+COFFEE) for 12 weeks. Coffee supplementation reduced HFD-induced liver macrovesicular steatosis (P P P PPAR- α(P P ABCA1) and subfamily G1 (ABCG1) (P P P P Alcaligenaceaein the faeces (P

Aim: Atherosclerosis is one of the leading causes of death and morbidity worldwide. Plaque instability is the most relevant predisposing factor for acute events. We aim to better understand the role of Galectin-3 (Gal-3) and Lipoprotein(a) (Lp(a)) in atherosclerotic process and to define their potential role as peripheral marker of plaque instability. Methods: Advanced human carotid plaques from 99 patients undergoing carotid endarterectomy were classified histologically according to American Heart Association (AHA) guidelines. Plaque complication (type VI) is defined by the presence of hemorrhage, ulceration or hematoma. Gal-3 and Lp(a) was measured in serum samples from patients and 17 healthy controls by immunometric assays. The quantification of Gal-3 in plaque was performed by immunohistochemistry. Results: Gal-3 and Lp(a)/LDL serum levels showed increased levels in patients compared with the control group (p¼0.0001 and p¼0.001 respectively). No correlations have been observed between Gal-3 serum levels and Gal-3 levels in atherosclerotic plaques. No differences were found between Gal-3 serum levels among the different plaques types, nor between complicated and uncomplicated plaques. At multivariate logistic regression the presence of complicated lesion or patient symptoms (surrogate marker of plaque instability) are not related to both Gal-3 or Lp(a)/LDL. Conclusions: Our data showed that Gal-3 and Lp(a) are good markers of advanced atherosclerotic plaque. The absence of differences among the different lesion types suggest that the increase of Gal-3 and Lp(a) is independent by the specific plaque features. Both Gal-3 and Lp(a)/LDL levels cannot be considered markers of plaque instability.

Background Celiac disease (CD) is the most common autoimmune enteropathy. Clinical manifestations may range from a typical malabsorption syndrome to several apparently unrelated extra-intestinal symptoms. Aim Here we specifically focus on the spectrum of CD-related liver disorders and the underlying pathomechanisms. Methods A computer-based search up to August 2015 was completed using appropriate keywords. References from selected papers were also reviewed and used if relevant. Results An unexplained hypertransaminasemia with nonspecific histologic hepatic changes is the most common hepatic presentation. CD however can coexist with a number of liver disorders such as Autoimmune Hepatitis, Autoimmune Cholangitis, Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis requiring a specific treatment in addition to gluten-free diet. CD has also been associated with Viral Hepatitis, Fatty Liver, Non-Alcoholic Steatohepatitis and some severe cryptogenic hepatopaties in the liver transplantation list. Pathomechanisms underlying hepatic injury in CD are multiple, appear still not completely defined and may probably co-occur. Conclusions An ever-increasing number of CD-related liver injuries exist, probably representing a continuum of a same disorder where genetic predisposition, timing, and duration of previous gluten exposure might influence the reversibility of liver damage. Evidences, although not conclusive, support therefore testing for CD also in cryptogenic hepatobiliary conditions where the relationship with CD has not yet been fully investigated.

Background Calcium (Ca2+) and vitamin D (VitD) play an important role in child health. We evaluated the daily intake of Ca2+ and VitD in healthy children. Moreover, we demonstrate the efficacy of Ca2+ and VitD supplementation. Methods Daily Ca2 + and VitD intake was evaluated in consecutive healthy children through a validated questionnaire. Subjects with 2+ and VitD were invited to participate in a prospective randomized trial with 2 groups of nutritional intervention: Group 1, dietary counseling aiming to optimize daily Ca2+ and VitD intake plus administration of a commercially available Ca2 + and VitD supplementation product; Group 2, dietary counseling alone. At the enrollment (T0) and after 4 months (T1) serum 25(OH) Vitamin D levels were assessed. Results We evaluated 150 healthy children (male 50%, mean age 10 years); at baseline a low VitD intake was observed in all subjects (median 0.79 μg/die, IQR 1.78; range 0.01-5.02); this condition was associated with Ca2+ intake Conclusions Adequate Ca2+ and VitD intakes are difficult to obtain through dietary counseling alone in pediatric subjects. Oral supplementation with of Ca2+ and VitD is a reliable strategy to prevent this condition. Trial registration The study was registered in Clinical Trials Protocol Registration System (ID number: NCT01638494).

OBJECTIVE: A beneficial role of antioxidants in hepatopathic obese individuals has hitherto been inferred only from uncontrolled pilot studies. The authors compared the effect of vitamin E and weight loss on transaminase values and on ultrasonographic bright liver in a controlled group of children with obesity-related liver dysfunction. METHODS: Twenty-eight children with obesity-related hypertransaminasemia and bright liver were randomly allocated to two single-blind groups: group 1 (n = 14) treated with a low-calorie diet associated with oral placebo for 5 months, and group 2 (n = 14) treated with a low-calorie diet associated with oral vitamin E (400 mg/d x 2 months, 100 mg/d x 3 months). Transaminase values and ultrasonographic liver brightness along with weight loss and vitamin E levels were monitored. RESULTS: Variations in transaminase levels and percentage of patients with normalized transaminase values were comparable in the two groups. The disappearance of bright liver was observed only in patients who lost weight and was twice as common in patients from group 1. Two subgroups of patients with complete normalization of transaminase values emerged as a consequence of controlled adherence to diet alone (n = 6; significant decrease of percent overweight: P = 0.0019 ) and to vitamin E alone (n = 7; unmodified percent overweight and significant increase of vitamin E/cholesterol ratio: P < 0.0001). Changes in treatment-induced alanine aminotransferase levels in these two subgroups were comparable at month 2, whereas values at month 5 were significantly lower in the subgroup adherent to diet alone (P = 0.04). In the subgroup adherent to vitamin E alone, after 2 months washout, transaminase remained stable in 5 patients and increased in 2; bright liver persisted in all. CONCLUSIONS: Oral vitamin E warrants consideration in obesity-related liver dysfunction for children unable to adhere to low-calorie diets.