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| 1 | A randomized trial of iron depletion in patients with nonalcoholic fatty liver disease and hyperferritinemia显示文摘AIM:To compare iron depletion to lifestyle changes alone in patients with severe nonalcoholic fatty liver disease(NAFLD)and hyperferritinemia,a frequent feature associated with more severe liver damage,despite at least 6 mo of lifestyle changes.METHODS:Eligible subjects had to be 18-75 years old who underwent liver biopsy for ultrasonographically detected liver steatosis and hyperferritinemia,ferritin levels≥250 ng/mL,and NAFLD activity score>1.Iron depletion had to be achieved by removing 350 cc of blood every 10-15 d according to baseline hemoglobin values and venesection tolerance,until ferritin<30 ng/mL and/or transferrin saturation(TS)<25%.Thirty-eight patients were randomized 1:1 to phlebotomy(n=21)or lifestyle changes alone(n=17).The main outcome of the study was improvement in liver damage according to the NAFLD activity score at 2 years,secondary outcomes were improvements in liver enzymes[alanine aminotransferases(ALT),aspartate aminotransferase(AST),and gamma-glutamyl-transferases(GGT)].RESULTS:Phlebotomy was associated with normalization of iron parameters without adverse events.In the21 patients compliant to the study protocol,the rate of histological improvement was higher in iron depleted vs control subjects(8/12,67%vs 2/9,22%,P=0.039).There was a better improvement in steatosis grade in iron depleted vs control patients(P=0.02).In patients followed-up at two years(n=35),ALT,AST,and GGT levels were lower in iron-depleted than in control patients(P<0.05).The prevalence of subjects with improvement in histological damage or,in the absence of liver biopsy,ALT decrease≥20%(associated with histological improvement in biopsied patients)was higher in the phlebotomy than in the control arm(P=0.022).The effect of iron depletion on liver damage improvement as assessed by histology or ALT decrease≥20%was independent of baseline AST/ALT ratio and insulin resistance(P=0.0001).CONCLUSION:Iron depletion by phlebotomy is likely associated with a higher rate of improvement of histological liver damage than lifestyle changes alone in patients with NAFLD and hyperferritinemia,and with amelioration of liver enzymes. | Luca Valenti Anna Ludovica Fracanzani Paola Dongiovanni Serena Rovida Raffaela Rametta Erika Fatta Edoardo Alessandro Pulixi Marco Maggioni Silvia Fargion | 2014 | World Journal of Gastroenterology2014，20，11： | 8 |
| 2 | Patatin-like phospholipase domain containing-3 gene I148M polymorphism, steatosis, and liver damage in hereditary hemochromatosis显示文摘AIM: To investigate whether the patatin-like phospholipase domain containing-3 gene (PNPLA3 ) I148M polymorphism is associated with steatosis, fibrosis stage, and cirrhosis in hereditary hemochromatosis (HH). METHODS: We studied 174 consecutive unrelated homozygous for the C282Y HFE mutation of HH (C282Y+/+ HH) patients from Northern Italy, for whom the presence of cirrhosis could be determined based on histological or clinical criteria, without excessive alcohol intake (< 30/20 g/d in males or females) or hepatitis B virus and hepatitis C virus viral hepatitis. Steatosis was evaluated in 123 patients by histology (n = 100) or ultrasound (n = 23). The PNPLA3 rs738409 single nucleotide polymorphism, encoding for the p.148M protein variant, was genotyped by a Taqman assay (assay on demand, Applied Biosystems). The association of the PNPLA3 I148M protein variant (p.I148M) with steatosis, fibrosis stage, and cirrhosis was evaluated by logistic regression analysis. RESULTS: PNPLA3 genotype was not associated with metabolic parameters, including body mass index (BMI), the presence of diabetes, and lipid levels, but the presence of the p.148M variant at risk was independently associated with steatosis [odds ratio (OR) 1.84 per p.148M allele, 95% confidence interval (CI): 1.05-3.31; P = 0.037], independently of BMI and alanine amino-transaminase (ALT) levels. The p.148M variant was also associated with higher aspartate aminotransferase (P = 0.0014) and ALT levels (P = 0.017) at diagnosis, independently of BMI and the severity of iron overload. In patients with liver biopsy, the 148M variant was independently associated with the severity (stage) of fibrosis (estimated coefficient 0.56 ± 0.27, P = 0.041). In the overall series of patients, the p.148M variant was associated with cirrhosis in lean (P = 0.049), but not in overweight patients (P = not significant). At logistic regression analysis, cirrhosis was associated with BMI ≥ 25 (OR 1.82, 95% CI: 1.02-3.55), ferritin > 1000 ng/mL at diagnosis (OR 19.3, 95% CI: 5.3-125), and with the G allele in patients with BMI < 25 (OR 3.26, 95% CI: 1.3-10.3). CONCLUSION: The PNPLA3 I148M polymorphism may represent a permissive factor for fibrosis progression in patients with C282Y+/+ HH. | Luca Valenti Paolo Maggioni Alberto Piperno Raffaela Rametta Sara Pelucchi Raffaella Mariani Paola Dongiovanni Anna Ludovica Fracanzani Silvia Fargion | 2012 | World Journal of Gastroenterology2012，18，22： | 4 |
| 3 | Contrast-enhanced sonography versus biopsy for the differential diagnosis of thrombosis in hepatocellular carcinoma patients显示文摘AIM:To clarify which method has accuracy:2nd gen-eration contrast-enhanced ultrasound or biopsy of portal vein thrombus in the differential diagnosis of portal vein thrombosis.METHODS:One hundred and eighty-six patients with hepatocellular carcinoma and portal vein thrombosis underwent in blinded fashion a 2nd generation contrast-enhanced ultrasound and biopsy of portal vein thrombus;both results were examined on the basis of the follow-up of patients compared to reference-standard.RESULTS:One hundred and eight patients completed the study.Benign thrombosis on 2nd generation contrast-enhanced ultrasound was characterised by progressive hypoenhancing of the thrombus;in malignant portal vein thrombosis there was a precocious homo-geneous enhancement of the thrombus.On follow-up there were 50 of 108 patients with benign thrombosis:all were correctly diagnosed by both methods.There were 58 of 108 patients with malignant thrombosis:amongst these,52 were correctly diagnosed by both methods,the remainder did not present malignant cells on portal vein thrombus biopsy and showed on 2nd generation contrast-enhanced ultrasound an inho-mogeneous enhancement pattern.A new biopsy during the follow-up,guided to the area of thrombus that showed up on 2nd generation contrast-enhanced ultra-sound,demonstrated an enhancing pattern indicating malignant cells.CONCLUSION:In patients with hepatocellular carcinoma complicated by portal vein thrombosis,2nd generation contrast-enhanced ultrasound of portal vein thrombus is very useful in assessing the benign or malignant nature of the thrombus.Puncture biopsy of thrombus is usually accurate but presents some sampling errors,so,when pathological results are required,2nd generation contrast-enhanced ultrasound could guide the sampling needle to the correct area of the thrombus. | Paolo Sorrentino Salvatore D'Angelo Luciano Tarantino Umberto Ferbo Alessandra Bracigliano Raffaela Vecchione | 2009 | World Journal of Gastroenterology2009，15，18： | 4 |
| 4 | Dietary Iron Overload Induces Visceral Adipose Tissue Insulin Resistance显示文摘 | Paola Dongiovanni Massimiliano Ruscica Raffaela Rametta Stefania Recalcati Liliana Steffani Stefano Gatti Domenico Girelli Gaetano Cairo Paolo Magni Silvia Fargion Luca Valenti | 2013 | The American Journal of Pathology2013，，6： | 3 |
| 5 | Failure of interferon-γ pre-treated mesenchymal stem cell treatment in a patient with crohn's disease显示文摘Mesenchymal stem cells(MSC) are cells of stromal origin which exhibit unlimited self-renewal capacity and pluripotency in vitro.It has recently been observed that MSC may also exert a profound immunosuppressive and anti-inflammatory effect both in vitro and in vivo with consequent potential use in autoimmune disorders.We present the case of a patient suffering from childhood-onset, multidrug resistant and steroiddependent Crohn's disease who underwent systemic infusions of MSC, which led to a temporary reduction in CCR4, CCR7 and CXCR4 expression by T-cells, and a temporary decrease in switched memory B-cells, In addition, following MSC infusion, lower doses of steroids were needed to inhibit proliferation of the patient's peripheral blood mononuclear cells.Despite these changes, no significant clinical benefit was observed, and the patient required rescue therapy with infliximab and subsequent autologous hematopoietic stem cell transplantation.The results of biological and in vitro observations after MSC use and the clinical effects of infusion are discussed, and a brief description is provided of previous data on MSC-based therapy in autoimmune disorders. | Andrea Taddio Alberto Tommasini Erica Valencic Ettore Biagi Giuliana Decorti Sara De Iudicibus Eva Cuzzoni Giuseppe Gaipa Raffaela Badolato Alberto Prandini Andrea Biondi Alessandro Ventura | 2015 | World Journal of Gastroenterology2015，21，14： | 2 |
| 6 | Current controversies and future perspectives on treatment of intensive care unit delirium in adults显示文摘Delirium is the most frequent manifestation of acute brain dysfunction in intensive care unit(ICU).Although antipsychotics are widely used to treat this serious complication,recent evidence has emphasized that these agents did not reduce ICU delirium(ICU-D)prevalence and did not improve survival,length of ICU or hospital stay after its occurrence.Of note,no pharmacological strategy to prevent or treat delirium has been identified,so far.In this scenario,new scientific evidences are urgently needed.Investigations on specific ICU-D subgroups,or focused on different clinical settings,and studies on medications other than antipsychotics,such as dexmedetomidine or melatonin,may represent interesting fields of research.In the meantime,because there is some evidence that ICU-D can be effectively prevented,the literature suggests strengthening all the strategies aimed at prevention through no-pharmacological approaches mostly focused on the correction of risk factors.The more appropriate strategy useful to treat established delirium remains the use of antipsychotics managed by choosing the right doses after a careful case-by-case analysis.While the evidence regarding the use of dexmedetomidine is still conflicting and sparse,this drug offers interesting perspectives for both ICU-D prevention and treatment.This paper aims to provide an overview of current pharmacological approaches of evidence-based medicine practice.The state of the art of the on-going clinical research on the topic and perspectives for future research are also addressed. | Marco Cascella Marco Fiore Sebastiano Leone Domenico Carbone Raffaela Di Napoli | 2019 | World Journal of Critical Care Medicine2019，8，3： | 2 |
| 7 | Statin use and non-alcoholic steatohepatitis in at risk individuals显示文摘 | Paola Dongiovanni Salvatore Petta Ville Mannisto Rosellina Margherita Mancina Rosaria Pipitone Vesa Karja Marco Maggioni Pirjo Kakela Olov Wiklund Enrico Mozzi Stefania Grimaudo Dorota Kaminska Raffaela Rametta Antonio Craxi Silvia Fargion Valerio Nobili | 2015 | Journal of Hepatology2015，，3： | 2 |
| 8 | HLA class II favors clearance of HCV infection and progression of the chronic liver damage显示文摘 | Alessandra Mangia Raffaela Gentile Isabella Cascavilla Maurizio Margaglione Maria Rosaria Villani Francesco Stella Giovanni Modola Valeria Agostiano Carlo Gaudiano Angelo Andriulli | 1999 | Journal of Hepatology1999，，6： | 1 |
| 9 | Metabolic engineering of carotenoid biosynthesis in plants显示文摘 | Giovanni Giuliano Raffaela Tavazza Gianfranco Diretto Peter Beyer Mark A. Taylor | 2008 | Trends in Biotechnology2008，，3： | 1 |
| 10 | Helicobacter pylori regulates iNOS promoter by histone modifications in human gastric epithelial cells显示文摘 | Tiziana Angrisano Francesca Lembo Silvia Peluso Simona Keller Lorenzo Chiariotti Raffaela Pero | 2012 | Medical Microbiology and Immunology2012，，： | 1 |
| 11 | Liver iron excess in patients with hepatocellular carcinoma developed on non-alcoholic steato-hepatitis显示文摘 | Paolo Sorrentino Salvatore D’Angelo Umberto Ferbo Pietro Micheli Alessandra Bracigliano Raffaela Vecchione | 2008 | Journal of Hepatology2008，，2： | 1 |
| 12 | The APOC3 T-455C and C-482T promoter region polymorphisms are not associated with the severity of liver damage independently of PNPLA3 I148M genotype in patients with nonalcoholic fatty liver显示文摘 | Luca Valenti Valerio Nobili Ahmad Al-Serri Raffaela Rametta Julian B.S. Leathart Marco A. Zappa Paola Dongiovanni Anna L. Fracanzani Arianna Alterio Giancarlo Roviaro Ann K. Daly Silvia Fargion Christopher P. Day | 2011 | Journal of Hepatology2011，，6： | 1 |
| 13 | Liver transplantation for hepatocellular carcinoma in a patient with a novel telomerase mutation and steatosis显示文摘 | Luca Valenti Paola Dongiovanni Marco Maggioni Benedetta Maria Motta Raffaela Rametta Marta Milano Silvia Fargion Paolo Reggiani Anna Ludovica Fracanzani | 2012 | Journal of Hepatology2012，，： | 1 |
| 14 | miR‐10b*, a master inhibitor of the cell cycle, is down‐regulated in human breast tumours显示文摘 | Francesca Biagioni Noa Bossel Ben‐Moshe Giulia Fontemaggi Valeria Canu Federica Mori Barbara Antoniani Anna Di Benedetto Raffaela Santoro Sabrina Germoni Fernanda De Angelis Anna Cambria Roi Avraham Giuseppe Grasso Sabrina Strano Paola Muti Marcella Motto | 2012 | EMBO Mol Med2012，，11： | 1 |
| 15 | A case study on the use of the 'added portions exposure techinque APET' to estimate total dierary exposure to flavor substances 显示文摘 | Raffaela P Lorenza M Antonio R | 2013 | Trends Food Sci Techn2013，32，1： | 1 |
| 16 | Mutated Desmoglein‐2 Proteins are Incorporated into Desmosomes and Exhibit Dominant‐Negative Effects in Arrhythmogenic Right Ventricular Cardiomyopathy显示文摘 | Torsten B. Rasmussen Johan Palmfeldt Peter H. Nissen Raffaela Magnoni S?ren Dalager Uffe B. Jensen Won Y. Kim Lene Heickendorff Henning M?lgaard Henrik K. Jensen Ulrik T. Baandrup Peter Bross Jens Mogensen | 2013 | Human Mutation2013，，5： | 1 |
| 17 | DNA methylation state of the galectin?3 gene represents a potentialnew marker of thyroid malignancy显示文摘 | Simona Keller Tiziana Angrisano Ermanno Florio Raffaela Pero Miriam Decaussin?Petrucci Giancarlo Troncone Mario Capasso Francesca Lembo Alfredo Fusco Lorenzo Chiariotti | 2013 | Oncology Letters2013，，1： | 1 |
| 18 | Diagnosis of chronic liver disease: reproducibility and validation of liver biopsy显示文摘 | Marcello Persico Bruno Palmentieri Raffaela Vecchione Roberto Torella Ilario de Sio | 2002 | The American Journal of Gastroenterology2002，，2： | 1 |
| 19 | Impact of HBV, HCV and GBV-C/HGV on hepatocellular carcinomas in Europe: results of a European concerted action显示文摘 | Christian Bréchot Franck Jaffredo David Lagorce Guido Gerken Karl Meyer zum Büschenfelde Anastasia Papakonstontinou Stephanos Hadziyannis Raffaela Romeo Massimo Colombo Joan Rodes Jordi Bruix Roger Williams Nikolai Naoumov | 1998 | Journal of Hepatology1998，，2： | 1 |
| 20 | Tumors of the lateral ventricles显示文摘 | Roberto Delfini Michele Acqui Piero Andrea Oppido Raffaela Capone Antonio Santoro Luigi Ferrante | 1991 | Neurosurgical Review1991，，2： | 1 |
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