Early improvement of glycaemic control after virus clearance in patients with chronic hepatitis C and severe liver fibrosis: a cohort study

HCV has been recognized as the cause of chronic hepatitis C (CHC) since 1990. CHC is associated with progressive liver damage and extrahepatic conditions. Direct antiviral agents (DAAs), approved in 2014, have shown effectiveness in eradicating HCV in most patients. However, little is known about the effect of viral eradication on hepatic and extra-hepatic damage. We performed a historical cohort study of patients with HCV-related liver diseases who achieved SVR from March 2015 to October 2016 at INMI Lazzaro Spallanzani liver Unit in Rome (Italy). Repeated measures of glycaemia were analysed through a multilevel analysis framework to assess short time kinetics of blood glucose level at different times after therapy and for different levels of HCV viremia. The analysis included 205 patients. A model assessing temporal kinetics and variation of glycaemia according to HCV viremia provided evidence that blood glucose levels significantly dropped in patients with diabetes achieving SVR. Most of the variations occurred at 3-5 weeks of therapy (-17.96 mg/dL; p<0.001) and in coincidence with HCV clearance (-13.92 mg/dL; p<0.001). A weak, non-statistically significant reduction was observed in normoglycemic patients. Our study provides evidence that DAAs therapy may significantly improve glycaemic control in patients with CHC achieving SVR even when liver diseases are already established

Value of a Multidisciplinary Approach in Sinonasal Inverted Papilloma with Extensive Ossification

Objective: Background: Casa Report: Conclusions: Rare disease Inverted papilloma is a benign epithelial lesion of the nasal cavities. Although commonly encountered in clinical practice, it rarely presents with extensive ossification and few cases have been described in the literature. Herein, we describe the case of a 51-year-old man who presented to clinical attention for persistent right nasal obstruction. Magnetic resonance imaging (MRI) and computed tomography (CT) scans of the facial bones showed a lobated lesion with ossification occupying most of the right nasal cavity. The lesion was removed by endoscopic sinus surgery, leaving the surrounding bone structures intact. On pathological examination, mature bone tissue was found within an inverted papilloma. The pathologist contacted the surgeon, who confirmed that no healthy bone tissue was removed during the procedure. Therefore, a diagnosis of inverted papilloma with ossification could be made without the use of ancillary techniques. Inverted papilloma with ossification is a common lesion with a rare feature. Our report investigates the diagnostic difficulties of a paradigmatic case, highlighting the importance of multidisciplinary teamwork in reach-ing the final diagnosis

po 320 gene panel mutation screening for a better molecular stratification of colorectal cancer patients

Introduction Colorectal carcinoma (CRC) is one of the most commonly diagnosed cancers worldwide. The metastatic disease contributes to the high mortality rate reported for such tumours. Significant benefit on overall survival was brought about the introduction of monoclonal antibodies anti-EGFR and anti-VEGF used in combination with chemotherapy in metastatic CRC (mCRC). While anti-VEGF treatment does not require biomarker-based selection criteria, the potential efficacy of anti-EGFR antibodies is neglected to patients with activating mutations in KRAS and NRAS (RAS) genes, whose molecular analysis became a clinical routine. The advent of Next Generation Sequencing (NGS) instruments, able to reach quick testing of multiple clinically-relevant hotspots, yet maintaining precision and low costs, allows the simultaneous determination of the mutation status of an expanding number of genes. Despite only few of these molecular biomarkers have gained clinical utility in the routine oncological practice, the acquisition of more complex cancer mutational patterns may provide more efficient tumour characterisation for prognostic and predictive purposes and highlight actionable targets. Material and methods We sequenced 639 mCRC samples by IT-PGM platform using a panel of hotspots and targeted regions of 22 genes (including RAS) commonly involved in CRCs. MSI analyses on 89 patients have been performed with a single fluorescent system comprising BAT25 and BAT26 mononucleotide repeats. Results and discussions We identified recurrent mutations (≥1%) in 12/22 genes, being KRAS, TP53 and PIK3CA the most frequently mutated ones. Statistical analysis, indicated that the mutation associations follow a non-random distribution. Categorization of the cases on the base of KRAS and p53 mutation status led us the definition of 8 Mutation Association Patterns (MAPs) characterised by specific mutation associations. Analysis of the clinicopathological data available for 89 out of 639 cases indicates interesting trends for the associations of MAPs with specific parameters, some of which reached statistical significance. Conclusion Application of NGS gene panel as a routine for the characterisation of RAS/BRAF status required for predictive purposes in CRC patients, may provide additional prognostic/predictive information, with no significant extra-costs

Maitotoxin-4, a Novel MTX Analog Produced by Gambierdiscus excentricus

Maitotoxins (MTXs) are among the most potent toxins known. These toxins are produced by epi-benthic dinoflagellates of the genera Gambierdiscus and Fukuyoa and may play a role in causing the symptoms associated with Ciguatera Fish Poisoning. A recent survey revealed that, of the species tested, the newly described species from the Canary Islands, G. excentricus, is one of the most maitotoxic. The goal of the present study was to characterize MTX-related compounds produced by this species. Initially, lysates of cells from two Canary Island G. excentricus strains VGO791 and VGO792 were partially purified by (i) liquid-liquid partitioning between dichloromethane and aqueous methanol followed by (ii) size-exclusion chromatography. Fractions from chromatographic separation were screened for MTX toxicity using both the neuroblastoma neuro-2a (N2a) cytotoxicity and Ca2+ flux functional assays. Fractions containing MTX activity were analyzed using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to pinpoint potential MTX analogs. Subsequent non-targeted HRMS analysis permitted the identification of a novel MTX analog, maitotoxin-4 (MTX4, accurate mono-isotopic mass of 3292.4860 Da, as free acid form) in the most toxic fractions. HRMS/MS spectra of MTX4 as well as of MTX are presented. In addition, crude methanolic extracts of five other strains of G. excentricus and 37 other strains representing one Fukuyoa species and ten species, one ribotype and one undetermined strain/species of Gambierdiscus were screened for the presence of MTXs using low resolution tandem mass spectrometry (LRMS/MS). This targeted analysis indicated the original maitotoxin (MTX) was only present in one strain (G. australes S080911_1). Putative maitotoxin-2 (p-MTX2) and maitotoxin-3 (p-MTX3) were identified in several other species, but confirmation was not possible because of the lack of reference material. Maitotoxin-4 was detected in all seven strains of G. excentricus examined, independently of their origin (Brazil, Canary Islands and Caribbean), and not detected in any other species. MTX4 may therefore serve as a biomarker for the highly toxic G. excentricus in the Atlantic area

A large ongoing outbreak of hepatitis A predominantly affecting young males in Lazio, Italy; August 2016 - March 2017

The hepatitis A virus (HAV) is mainly transmitted through the faecal-oral route. In industrialized countries HAV infection generally occurs as either sporadic cases in travelers from endemic areas, local outbreak within closed/semi-closed population and as foodborne community outbreak. Recently, an increasing number of HAV infection clusters have been reported among young men-who-have-sex-with-men (MSM). The Lazio Regional Service for the epidemiology and control for infectious diseases (SeRESMI) has noticed an increase of acute hepatitis A (AHA) since September 2016. Temporal analysis carried out with a discrete Poisson model using surveillance data between January 2016 and March 2017 evidenced an ongoing outbreak of AHA that started at the end of August. Molecular investigation carried out on 130 out of 513 cases AHA reported until March 2017 suggests that this outbreak is mainly supported by an HAV variant which is currently spreading within MSM communities across Europe (VRD_521_2016). The report confirms that AHA is an emerging issue among MSM. In addition through the integration of standard (case based) surveillance with molecular investigation we could discriminate, temporally concomitant but epidemiologically unrelated, clusters due to different HAV variants. As suggested by the WHO, in countries with low HAV circulation, vaccination programmes should be tailored on the local epidemiological patterns to prevent outbreaks among high risk groups and eventual spillover of the infection in the general population

A large ongoing outbreak of hepatitis A predominantly affecting young males in Lazio, Italy; August 2016 - March 2017

The hepatitis A virus (HAV) is mainly transmitted through the faecal-oral route. In industrialized countries HAV infection generally occurs as either sporadic cases in travelers from endemic areas, local outbreak within closed/semi-closed population and as foodborne community outbreak. Recently, an increasing number of HAV infection clusters have been reported among young men-who-have-sex-with-men (MSM). The Lazio Regional Service for the epidemiology and control for infectious diseases (SeRESMI) has noticed an increase of acute hepatitis A (AHA) since September 2016. Temporal analysis carried out with a discrete Poisson model using surveillance data between January 2016 and March 2017 evidenced an ongoing outbreak of AHA that started at the end of August. Molecular investigation carried out on 130 out of 513 cases AHA reported until March 2017 suggests that this outbreak is mainly supported by an HAV variant which is currently spreading within MSM communities across Europe (VRD_521_2016). The report confirms that AHA is an emerging issue among MSM. In addition through the integration of standard (case based) surveillance with molecular investigation we could discriminate, temporally concomitant but epidemiologically unrelated, clusters due to different HAV variants. As suggested by the WHO, in countries with low HAV circulation, vaccination programmes should be tailored on the local epidemiological patterns to prevent outbreaks among high risk groups and eventual spillover of the infection in the general population