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The aim of this study is to provide updates on the characteristics of chronic HBsAg carriers in Italy before the advent of new drugs eliminating or functionally inactivating the genome HBV reservoirs. HBV endemicity has greatly decreased in Italy over the past decades. A not negligible number of chronic HBsAg carriers are still alive in the country. Chronic HBsAg carriers consecutively referring to 9units in Italy were prospectively enrolled for a 6-month period in 2019. Multiple logistic regression analysis was performed to identify independent predictors of treatment. A total of 894 cases was recruited (sex ratio 1.6; mean age 53.7 ± 13.5years). The proportion of subjects born abroad was 19.0%; only 1% of cases reported current heavy alcohol intake (> 4 units/day). Chronic HBV infection, chronic HBV hepatitis, and subjects with liver cirrhosis and/or HCC represented 24.8%, 55%, and 19.3% of cases, respectively. After exclusion of the 222 subjects with chronic HBV infection, the proportion of subjects under therapy was as high as 89.3%. A more severe liver disease (OR 2.52; 95% CI = 1.25–5.14) resulted an independent predictor of the likelihood of treatment; male sex was marginally associated (OR 1.67; 95% CI = 1.02–2.76) to the chance of treatment. People born abroad had same chance than Italians native to be treated (OR 2.12; 95% CI = 0.9–4.97). The high proportion of subjects under treatment and the absence of gender and ethnic barrier against treatment sound good news. These updated figures may represent reference data for evaluating the potential impact of forthcoming new therapy against HBV-related disease.

Sodium phosphate enemas and laxatives are widely used for the treatment of constipation, even if a number of cases of significant toxicity due to alterations of the fluid and electrolyte equilibria (hypernatremia, hyperphosphatemia, and hypocalcemia) have been reported. We present the case of an 83-year-old man who died of fecal and chemical peritonitis secondary to an iatrogenic colon perforation (produced performing a Fleet enema through the patient's iliac colostomy) with peritoneal absorption of sodium phosphate. Environmental scanning electron microscopy coupled with an X-ray fluorescence energy dispersive spectrometry discovered multiple bright crystals formed of calcium, phosphorus, and oxygen in the brain, heart, lung, and kidney sections of the victim. The absence of these kinds of precipitates in two control samples chronically treated with Fleet enemas led us to assume that the deceased had adsorbed a great quantity of phosphorus ions from the peritoneal cavity with subsequent systemic dissemination and precipitation of calcium phosphate bindings.

Background. Bone diseases such as osteoporosis lead to changes in the trabecular bone mass and architecture. Improved methods for the quantitative assessment of trabecular bone are needed to better understand the role of trabecular architecture in bone strength. MR microscopy (MRM),'with its ability to achieve resolutions below 50 micromol has proved to be particularlyuseful for the ex vivo evaluation of the complex archi- tecture oftrabecular bone. In this study, we describe the use of projection reconstruction (PR) with MRM for the quantitative evaluation of the three-dimensional structure of trabecular bone explants and for the predictionof their biomechanical properties. Material and methods. High-resolution 3D PR and trabecular bone explants were analysed to determine standard morphologic parameters such as trabecular bone volume fraction (BV/TVor Vv), trabecular thick- ness (Tb.Th) and trabecular separation (Tb.Sp). Segmentation of the high-resolution images into bone and bone marrow was obtained by using a Bayesian approach. The derived parameters were finallyincluded in non-linear mathematical models for the prediction of Young's modulus (YM). Results. The parameters derived from the PR spin-echo were found to be stronger predictor of YM (RZ = 0.86) than those derived from the conventional spinecho images (R2 = 0.75) used for comparison. Conclusions.This ex vivo approach should be readily adaptable to the studies in human subjects. Izhodišča. Kostne bolezni, kot je osteoporoza, vodijo v spremembe trabekularnemase in arhitekture kosti, Za boljše razumevanje trabekularne strukture in kostne moči potrebujemo izboljšane kvantitativne metode. MR mikroskopija (MRM) se je s svojo zmožnostjo doseči resolucijo pod 50 microm izkazala za zelo uporabno pri ex vivo oceni kompleksne arhitekture trabekularnih kosti. V pričujoči študiji opisujemo uporabo projekcijske rekonstrukcije (PR) z MRM pri kvantitativni oceni tridimenzionalne trabekularne strukture kostnih eksplantatov in pri napovedovanju njihovih biomehaničnih značilnosti. Material in metode. Analizirali smo 3D PR visoke ločljivosti in eksplantate trabekularnih kosti, da bi določili standardne morfološke parametre kot so volumska frakcija trabekularne kosti, debelina trabekul in trabekularna separacija. Razločevanje slik visoke ločljivosti na kost in na kostni mozeg smo opravili z uporabo "Bayesianskega" pristopa. Pridobljene parametre smo na koncu vključili v nelinearen matematični model zadoločitev Youngovega modula (YM). Rezultati. Ugotovili smo, da so parametri,ki smo jih dobili pri spinskem odboju PR močnejši napovedovalci Youngovega modula (R2 = 0.86) kot parametri pridobljeni z konvencionalnimi spinskimi odbojnimi slikami (R2= 0.75), ki smo jih uporabljali za primerjavo. Zaključki. Opisani ex vivo pristop bi lahko zlahka prilagodili in vivo študijam.

Health-status of elderly patients with hepatocellular carcinoma (HCC) may limit surgical approach; other options are thus auspicable.The authors reviewed 98 selected patients, aged 65 to 90 years, with 149 HCC treated between 2002 and 2011. According to the extent of malignancy, health status and treatment, patients were divided into 3 groups. Sixty-one, submitted to major and minor curative resections, were in group A and B while group C included 37 patients, unsuitable for high-risk procedures and percutaneous ablation, submitted to intraoperative-radiofrequency ablation (IRFA) alone or combined with minor resections. Assessment of safety and therapeutic efficacy of this managment was evaluated.A postoperative mortality rate of 1,02% and an overall survival rate at 5 years of 62.3% were observed. Indeeed matched post-operative morbidity and mortality rates of A, B, C groups were 45%, 8%, 16.21% (p0.004) and 9 %, 0%, 0% (p= 0.112 ) respectively. 3 years overall-survival was not statistically different (p= 0.585). However 5 years survival rate and disease-free-survival rate were significantly higher in patients of group A and B (p= 0.003; p0.001).Treatment strategies to minimize treatment-related morbidity and mortality have resulted satisfactory for early and late outcomes of an heterogeneous group of elderly patients with HCC.

Pyoderma gangrenosum is a rare neutrophilic dermatosis, often associated with underlying systemic diseases. Treatment usually consists of topics and sometimes systemic immunosuppression. We present the case of a 32-year-old female patient undergoing radiation therapy for extensive recalcitrant pyoderma gangrenosum in which immunosuppressive measures were ineffective to control the disease. Treatment outcome was favourable with only mild side effects in the irradiated areas. Localized radiation therapy hence is a potential effective palliation for refractory cases of pyoderma gangrenosum, or patients unfit to undergo aggressive systemic immunosuppression.

Background The potential link between educational level and chronic liver diseases (CLD) were explored using the mortality records of liver cirrhosis, which lack accuracy and are unable to identify the different etiological factors of liver cirrhosis. Information on the association of low educational level with the severity of CLD is lacking. Aim To evaluate the potential association linking education level to etiology and clinical stage of CLD cases. Methods Consecutive enrolment of 11,107 subjects with CLD aged≥18 years prospectively recruited in two national surveys in 2001 and 2014 at one of the participating Italian liver units throughout the country. Subjects were pooled in two groups: low education level (less than high school) and high education level (completed high school or beyond). The association of demographic, etiological, and clinical stage of subjects with educational level was assessed using logistic regression analysis. In the analysis low educational level was the outcome variable. Results A total of 11,107 subjects born in Italy (mean age 55.5 years, sex ratio 1.5) were evaluated. Multiple logistic regression analysis shows that chronic HCV infection (O.R.1,38:95%,C.I.1.23-1.55), risky alcohol intake (O.R.1.96;95%,C.I.1.73-2.21) and liver cirrhosis (O.R.1.65;95%,C.I.1.46-1.85) all resulted independently associated with less than a completed high school education. HBV infection resulted independently associated with high education level (O.R.0.74;95%,C.I.0.64-0.86), reflecting changes in HBV modes of transmission in recent decades. No association was found with CLD related to non-alcoholic fatty liver disease (O.R.1.03;95%, C.I.0.81-1.30). Conclusions These findings show an independent association linking education level with viruses and alcohol-related CLD. Low educational level is associated with the severity of CLD.

Undifferentiated Nasopharyngeal Carcinoma (UNPC) is associated with Epstein-Barr Virus (EBV) and characterized by an abundant immune infiltrate potentially influencing the prognosis. Thus, we retrospectively assessed the significance of immunosuppression in the UNPC microenvironment as prognostic biomarker of treatment failure in a non-endemic area, and monitored the variation of systemic EBV-specific immunity before and after chemoradiotherapy (CRT). DNA and RNA were extracted from diagnostic biopsies obtained by tumor and adjacent mucosa from 63 consecutive EBV+ UNPC patients who underwent radical CRT. Among these patients 11 relapsed within 2 years. The expression of the EBV-derived UNPC-specific BARF1 gene and several immune-related genes was monitored through quantitative RT-PCR and methylation-specific PCR analyses. Peripheral T cell responses against EBV and BARF1 were measured in 14 patients (7 relapses) through IFN-γ ELISPOT assay. We found significantly higher expression levels of BARF1, CD8, IFN-γ, IDO, PD-L1, and PD-1 in UNPC samples compared to healthy tissues. CD8 expression was significantly reduced in both tumor and healthy tissues in UNPC patients who relapsed within two years. We observed a hypomethylated FOXP3 intron 1 exclusively in relapsed UNPC patients. Finally, we noticed a significant decrease in EBV- and BARF1-specific T-cells after CRT only in relapsing patients. Our data suggest that a high level of immunosuppression (low CD8, hypomethylated FoxP3) in UNPC microenvironment may predict treatment failure and may allow an early identification of patients who could benefit from the addition of immune modulating strategies to improve first line CRT.

In Italy, HDV infection endemicity has greatly decreased overtime. Migratory flow may change this scenario as migrants often come from high HDV endemicity areas. Here, we studied characteristics of HDV infection in Italy, particularly addressed to the birth area of subjects. Chronic HBsAg carriers consecutively referring to 9 units in Italy prospectively enrolled for a six-month period in 2019 were tested for anti-HDV by ELISA. Multiple logistic regression analysis was performed to identify anti-HDV positivity independent predictors. A total of 894 HBsAg-positive subjects were enrolled. Of them, 786 (87.9%) were tested for anti-HDV. Anti-HDV overall prevalence was 9.9% (6.4% in Italian natives and 26.4% in non-natives; P&nbsp

Background and purpose We conducted a prospective phase II multicentric trial to determine if radical radiation therapy to all metastatic sites might improve the progression-free survival (PFS) in oligometastatic breast cancer patients. Secondary endpoints were local control (LC), overall survival (OS) and toxicity. Methods and materials Inclusion criteria were the following: oligometastatic breast cancer with ≤5 metastatic sites, FDG-PET/CT staging, no brain metastases, primary tumor controlled. Radiotherapy could be delivered using stereotactic body radiotherapy (SBRT) technique or fractionated intensity modulated radiotherapy (IMRT). SBRT consisted of 30–45 Gy in 3 fractions, while IMRT was delivered to a total dose of 60 Gy in 25 fractions. We hypothesized that radical radiation therapy could increase the PFS from 30% (according to the published literature) to 50% at two years. Results 54 Patients with 92 metastatic lesions were enrolled. Forty-four were treated with SBRT, and 10 with IMRT. Forty-eight (89%) patients received a form of systemic therapy concomitantly to radiation therapy. Sites of metastatic disease were the following: bones 60 lesions, lymph nodes 23 lesions, lung 4 lesions, liver 5 lesions. After a median follow-up of 30 months (range, 6–55 months), 1- and 2-year PFS was 75% and 53%, respectively. Two-year LC and OS were 97% and 95%, respectively. Radiation therapy was well tolerated, and no Grade ≥3 toxicity was documented. Grade 2 toxicity were pain and fatigue in 2 cases. Conclusions Patients with oligometastatic breast cancer treated with radical radiotherapy to all metastatic sites may achieve long-term progression-free survival, without significant treatment-related toxicity. While waiting for data from randomized trials, the use of radical radiation therapy to all metastatic sites in patients with oligometastatic breast cancer should be considered a valuable option, and its recommendation should be individualized.

Previous cross-sectional studies have shown that hepatitis C virus (HCV) infection had been the main agent associated with liver cirrhosis in Italy. Abstract BACKGROUND: Previous cross-sectional studies have shown that hepatitis C virus (HCV) infection had been the main agent associated with liver cirrhosis in Italy. AIM: To assess epidemiological, laboratory and clinical features of liver cirrhosis in Italy in 2014. PATIENTS: Out of the 2557 consecutive subjects evaluated in 16 hospitals located throughout Italy in 2014, 832 (32.6%) had liver cirrhosis and were enrolled in this study. RESULTS: The mean age of subjects was 60.3years, with a male/female ratio of 1.7; 74.9% of cases had Child A cirrhosis and 17.9% superimposed hepatocellular carcinoma. HCV infection, alone or in combination with other aetiologic agents, was responsible of 58.6% of cases, HBV aetiology accounted for the 17.6% and alcohol abuse for the 16.0%. Compared with virus-related cirrhotic patients, those alcohol-related more frequently showed decompensation (p=0.02). CONCLUSIONS: Compared to previous surveys performed in 1992 and in 2001, we observe a statistically significant (p

The objective of the study was to examine the relationship between HLA genotypes and disease severity as measured by brain MRI quantitative markers of demyelinating and destructive pathology in patients with multiple sclerosis (MS). We studied 100 patients with MS and 122 age, sex-, ethnic- and residence-matched controls. The DNA extraction and the genomic typing (A, B, DRB1 and DQB1 loci) were obtained with sequence-specific oligonucleotide method, using a commercially available reversible line blot assay (INNO-LIPA). All patients underwent a 1.5 tesla MRI examination of the brain. Disease severity was assessed by clinical (Expanded Disability Status Scale (EDSS)) and MRI (T2- and T1-lesion load (LL) and brain parenchymal fraction (BPF)) outcome measures. HLA-DQB1* 02 (OR 19.9, 95% C. I. 16.2-24.3, uncorrected (uncorr)- p

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.

The purpose of this study was to evaluate cortical activation patterns in patients with Parkinson’s disease during a relatively complex motor task. Seven patients (six men and one woman) with lateralised akinetic-rigid Parkinson’s disease underwent functional magnetic resonance imaging (MRI) of the brain with a 1.5-T magnet. Finger tapping was chosen as a motor task. The control group included 11 volunteers (six men and five women) with no neurological disease. Patients showed hyperactivity of the ipsilateral and contralateral motor cortex associated with bilateral over-activation of the parietal cortex during movement of the affected hand. In some cases, there was a lack of activation of the pre-motor and supplementary motor areas whereas, when present, activation in these areas was greater during movement of the healthy hand. Finally, activation of the occipital cortex was found in all patients as a result of their tendency to control movement visually. Results of this study confirm a re-organisation of cortical circuits due to subcortical damage in patient’s with Parkinson’s disease.

The present study was designed to investigate the putative anxiolytic effects of moclobemide (MOC), a reversible inhibitor of type A monoamine oxidase enzyme (RIMA) antidepressant, in an experimental model of anxiety in mice. The test selected was the light/dark aversion test. In the present investigation, an anxiogenic-like behavior was induced by light, alone as the stimulus (standard version of the test) or by pretreatment with a subconvulsant dose of pentylenetetrazole (PTZ) (15 mg/kg IP) 45 min before testing ("enhanced" version of the test). In mice, the effect of repeated administration for 2 weeks of MOC (0.5, 1, and 5 mg/kg IP) was compared with those of selegiline (SEL) (5, 10, and 20 mg/kg IP), an irreversible and selective MAO-B inhibitor. For comparative purpose, the chronic effect of an established reference anxiolytic, such as lorazepam (LOR) (0.025, 0.05, and 0.10 mg/kg IP), was also evaluated. Results demonstrated that PTZ-treated mice showed a decrease in the number of transitions as well as in the time spent in the lit area, when compared with vehicle controls, an effect characteristic of an anxiogenic response. This anxiogenic-like behavior was reduced by chronic administration of LOR as well as MOC, suggesting an anxiolytic-like effect (as shown in the "standard" version of the test). In addition, the increased aversion of mice for the light compartment of the light/dark box was significantly reduced compared to PTZ-treated mice or vehicle controls. SEL failed to significantly alter the anxiogenic-like behavior induced by subconvulsant doses of PTZ. These data provide additional evidence for the anxiolytic-like effects of MOC administered chronically in the mouse.