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Nowadays harmful alcohol consumption represents one of the most important risk factors for the development of several type of chronic and acute diseases in the western countries, contributing to a great number of deaths. Focusing the attention on cancer development and progression, the scientific community has a large consensus in declaring the existence of a harmful association between alcohol consumption and liver, breast, upper aerodigestive tract (mouth, oropharynx, hypopharynx, and esophagus), pancreas and colon cancer appearance. However the precise biological links by which the alcohol could be responsible for cancer initiation and progression are not fully understood yet, even if the International Agency for Research on Cancer (IARC) indicated both ethanol and acetaldehyde as carcinogen for humans. The possible explanation of the effect exerted by ethanol and acetaldehyde could be related to direct genotoxicity, hormonal disturbance, triggering of oxidative stress and inflammation. In this review, we examine the relationship between alcohol dosage and associated diseases, with focus on alcohol-related cancers. Furthermore, to understand the potential molecular mechanisms of these diseases, the results of in vivo experiments on animal models were discussed.

Nowadays, the nonalcoholic fatty liver disease represents the main chronic liver disease in the Western countries, and the correct medical therapy remains a big question for the scientific community. The aim of our study was to evaluate the effect derived from the administration for six months of silybin with vitamin D and vitamin E (RealSIL 100D®) on metabolic markers, oxidative stress, endothelial dysfunction, and worsening of disease markers in nonalcoholic fatty liver disease patients. We enrolled 90 consecutive patients with histological diagnosis of nonalcoholic fatty liver disease and 60 patients with diagnosis of reflux disease (not in therapy) as healthy controls. The nonalcoholic fatty liver disease patients were randomized into two groups: treated (60 patients) and not treated (30 patients). We performed a nutritional assessment and evaluated clinical parameters, routine home tests, the homeostatic model assessment of insulin resistance, NAFLD fibrosis score and fibrosis-4, transient elastography and controlled attenuation parameter, thiobarbituric acid reactive substances, tumor necrosis factor α , transforming growth factor β , interleukin-18 and interleukin-22, matrix metalloproteinase 2, epidermal growth factor receptor, insulin growth factor-II, cluster of differentiation-44, high mobility group box-1, and Endocan. Compared to the healthy controls, the nonalcoholic fatty liver disease patients had statistically significant differences for almost all parameters evaluated at baseline ( p < 0.05). Six months after the baseline, the proportion of nonalcoholic fatty liver disease patients treated that underwent a statistically significant improvement in metabolic markers, oxidative stress, endothelial dysfunction, and worsening of disease was greater than not treated nonalcoholic fatty liver disease patients ( p < 0.05). Even more relevant results were obtained for the same parameters by analyzing patients with a concomitant diagnosis of metabolic syndrome ( p < 0.001). The benefit that derives from the use of RealSIL 100D could derive from the action on more systems able to advance the pathology above all in that subset of patients suffering from concomitant metabolic syndrome., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 Alessandro Federico et al.)

Non-alcoholic fatty liver disease (NAFLD) is considered a predominant chronic liver disease worldwide and a component of metabolic syndrome. Due to its relationship with multiple organs, it is extremely complex to precisely define its pathogenesis as well as to set appropriate therapeutic and preventive strategies. Endocrine disruptors (EDCs) in general, and bisphenol A (BPA) in particular, are a heterogeneous group of substances, largely distributed in daily use items, able to interfere with the normal signaling of several hormones that seem to be related to type 2 diabetes mellitus (T2DM), obesity, and other metabolic disorders. It is reasonable to hypothesize a BPA involvement in the pathogenesis and evolution of NAFLD. However, its mechanisms of action as well as its burden in the vicious circle that connects obesity, T2DM, metabolic syndrome, and NAFLD still remain to be completely defined. In this review we analyzed the scientific evidence on this promising research area, in order to provide an overview of the harmful effects linked to the exposure to EDCs as well as to frame the role that BPA would have in all phases of NAFLD evolution.

Different strategies have been adopted for prevention of spontaneous preterm birth, including use of progestogens. So far, five randomized trials have been published evaluating the efficacy of progestogens in women with PPROM, including a total of 425 participants. All the five trials enrolled pregnant women with singleton pregnancies randomized between 20 and 34 weeks of gestation. In four trials women were randomized to either weekly intramuscular 250 mg 17α-hydroxyprogesterone-caproate or placebo, while Mirzaei et al. was a three arms trials in which women received weekly intramuscular 250 mg 17α-hydroxyprogesterone-caproate, or rectal progesterone 400 mg daily, or no treatment. In all the trials, latency antibiotics were used, and tocolysis was used permitted for first 48 hours at discretion of attending physician. Recently a meta-analysis including the five trials has been published. They found that when compared to placebo weekly intramuscular 250 mg 17α-hydroxyprogesterone-caproate did not alter the latency period to delivery in singleton gestations with PPROM. Additionally, there was no difference in gestational age at delivery between groups or in mode of delivery. No significant differences were reported in maternal or neonatal outcomes, with latency not significantly altered in sensitivity analyses. So far, no trials have been published evaluating natural vaginal progesterone in women with PPROM.

Pertussis is quite frequent and severe among infants; therefore, rapid diagnosis and timely targeted therapy are essential. Although a molecular test for etiological diagnosis is now available, it may not be available everywhere, and therefore adjunctive diagnostic tests are still useful for presumptive diagnosis. We describe the use of procalcitonin (PCT) and lymphocyte count to discriminate among pertussis, bacterial and viral infections. Fourteen infants per group were studied. The decision tree, built considering all available variables, showed a major role of PCT in predicting the different groups. A PCT value equal to or greater than 0.75 ng/ml selected for bacterial infections. A PCT value lower than 0.75 ng/ml and a lymphocyte count equal to or greater than 10,400/mm3 selected the subjects with pertussis, while a lymphocyte count lower than 10,400/mm3 selected for viral etiology. PCT should be used in the diagnosis of infants suspected of having pertussis.

Objective Data: Preterm prelabor rupture of membranes occurs in 3% of all pregnancies. Neonatal benefit is seen in uninfected women who do not deliver immediately after preterm prelabor rupture of membranes. The purpose of this study was to evaluate whether the administration of progestogens in singleton pregnancies prolongs pregnancy after preterm prelabor rupture of membranes., Study: Searches were performed in MEDLINE, OVID, Scopus, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials with the use of a combination of keywords and text words related to "progesterone," "progestogen," "prematurity," and "preterm premature rupture of membranes" from the inception of the databases until January 2018. We included all randomized controlled trials of singleton gestations after preterm prelabor rupture of membranes that were randomized to either progestogens or control (either placebo or no treatment). Exclusion criteria were trials that included women who had contraindications to expectant management after preterm prelabor rupture of membranes (ie, chorioamnionitis, severe preeclampsia, and nonreassuring fetal status) and trials on multiple gestations. We planned to include all progestogens, including but not limited to 17-α hydroxyprogesterone caproate, and natural progesterone., Study Appraisal and Synthesis Methods: The primary outcome was latency from randomization to delivery. Metaanalysis was performed with the use of the random effects model of DerSimonian and Laird to produce relative risk with 95% confidence interval. Analysis was performed for each mode of progestogen administration separately., Results: Six randomized controlled trials (n=545 participants) were included. Four of the included trials assessed the efficacy of 17-α hydroxyprogesterone caproate; 1 trial assessed rectal progestogen, and 1 trial had 3 arms that compared 17-α hydroxyprogesterone caproate, rectal progestogen, and placebo. The mean gestational age at time randomization was 26.9 weeks in the 17-α hydroxyprogesterone caproate group and 27.3 weeks in the control group. 17-α Hydroxyprogesterone caproate administration was not found to prolong the latency period between randomization and delivery (mean difference, 0.11 days; 95% confidence interval, -3.30 to 3.53). There were no differences in mean gestational age at delivery, mode of delivery, or maternal or neonatal outcomes between the 2 groups. Similarly, there was no difference in latency for those women who received rectal progesterone (mean difference, 4.00 days; 95% confidence interval, -0.72 to 8.72)., Conclusion: Progestogen administration does not prolong pregnancy in singleton gestations with preterm prelabor rupture of membranes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Obesity, diabetes and metabolic disorders represent hugely significant problems concerning the health in Western countries and the study of gut microbiota in metabolic pathologies is part of this framework. Diet effects on intestinal microbial composition and its role in pathogenetic mechanisms responsible for both obesity and systemic, hepatic and adipose tissue inflammation, represent at the moment one of this mostpromising topic in gastroenterology research. Gut health safety is essential, but it needs to be further explored in order to understand and interrupt the pathogenetic mechanisms, which support a large number of diseases. The aim of this review is to describe what are the modifications of gut microbial composition that occur in metabolic disorders and the role of gut microbiota in the pathogenesis of several diseases such as obesity, metabolic syndrome and type II diabetes mellitus, showing how gut microbiota and adipose tissue, liver and brain, together with intestinal permeability increase, carry out an interconnection systemthat plays a pivotal role in the field.

Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is emerging as an independent cardiovascular risk factor. Recently, Endocan has been studied as an early marker of endothelial dysfunction. Our aim was to evaluate Endocan serum levels in patients with NAFLD with or without type 2 diabetes mellitus., Method: We enrolled 56 patients: 19 with NAFLD and 37 with type 2 diabetes mellitus with or without NAFLD, and compared them to 25 healthy controls. Endocan serum level was measured by using the ELISA EndoMark assay., Results: Endocan level was significantly higher in NAFLD subjects, compared to controls (1.23+/-1.51 vs 0.68+/-0.4 ng/mL; p=0.016). It was higher in patients with non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH) (1.12+/-1.11, 1.49+/-2.16 and 0.68+/-0.4 ng/ml vs controls, respectively), independently from presence of type 2 diabetes mellitus. The increase was more marked in patients with NASH and in those with NAFL versus controls (p=0.001 and p=0.004, respectively), but not statistically different between the two groups (p=0.448). Finally, we found a statistically relevant increase of this marker in diabetic NAFLD patients compared to those non diabetic (1.56+/-0.81 vs 0.72+/-0.58 ng/ml; p=0.01)., Conclusion: We demonstrated an increased Endocan serum level in NAFLD patients, higher in those with type 2 diabetes mellitus and/or NASH because of an endothelial dysfunction in these pathologies.

Aim: To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus (HCV) genotype 1 in the real-world settings., Methods: This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-TaqMan2.0 (Roche, LLQ 25 IU/mL)., Results: All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57 (range 18-78), of whom 18.3% were over 65; mean body mass index 25.6 (range 16-39); genotype 1b (79.4%); diagnosis of cirrhosis (38.2%); and fibrosis F3/4 (71.2%). The following drugs were used: Telaprevir (66.2%) and PEG-IFN-alpha2a (67.6%). Patients were naïve (24.4%), relapsers (30.5%), partial responders (14.8%) and null responders (30.3%). Overall, adverse events (AEs) occurred in 617 patients (73.9%) during the treatment. Anemia was the most frequent AE (52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure (15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age., Conclusion: In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, non-responders to peginterferon + ribavirin.