BOOST: a phase 3 trial of sorafenib vs. best supportive care in first line treatment of hepatocellular carcinoma in patients with deteriorated liver function

Aim: Only patients with good liver function {[Child-Pugh (CP)] A class} were eligible for trials testing sorafenib as first-line treatment of hepatocellular car...     

The modern treatment of early gastric cancer: our experience in an Italian cohort

Background  Endoscopic submucosal dissection (ESD) has been developed as treatment for early gastric cancer (EGC) by Japanese authors. However, there are no reports about its possible implementation in the Western setting. The aim of the present work is to determine the safety and efficacy of the endoscopic treatments for EGC in an Italian cohort. Methods  Forty-five patients for a total of 48 gastric lesions were enrolled in the study. Thirty-six EMR procedures were performed with the strip biopsy technique using a double-channel endoscope. En bloc resection refers to resection in one piece, while piecemeal refers to resections in which the lesion was removed in multiple fragments. A total of 12 ESD were performed and completed with IT knife. We define as curative treatment lateral and vertical margins of the resected specimens free of cancer and repeat endoscopic finding of no recurrent disease. Results  Out of 36 EMR procedures, 10 were piecemeal resections (28%), while 26 were en bloc (72%). ESD led to en bloc resection in 11/12 cases (92%). Histological assessment of curability in the EMR group was achieved in 56% of the cases, and in 92% of the ESD group. Mean follow-up period was 31 months (range: 12–71 months). There was no local recurrence or distant metastasis in the curative group patients. Conclusions  These results seem to confirm the safety and the clinical efficacy of the ESD procedure in the Western world too.     

Systematic review of existing guidelines for NAFLD assessment

Aim: In this systematic review, guidelines on non-alcoholic fatty liver disease (NAFLD) were evaluated, aiming at a guideline synthesis focusing on diagnosis an...     

Epidemiology of hip fractures in northwestern Italy: a multicentric regional study on incidence of hip fractures and their outcome at 3-year follow-up

Piedmont is a region in northwestern Italy counting 4.2 million inhabitants. The purpose of our study was to update data on incidence and outcomes of hip fractures (HF) in our region to present days. The data of all patients affected by HF in 2003 in Piedmont (total: 5,386 patients) were analyzed, determining the incidence of HF, mean age, sex, fracture pattern and treatment adopted. Additionally, 564 patients underwent a questionnaire on comorbidities, complications, functional outcome and survivorship. Overall incidence of HF was 126.13/100,000 inhabitants-year. Mean hospitalization was 13.67 days. Mean time to surgery was 2.67 days. Survivorship was 94% at 3-month, 71.32% at 1-year and 60.21% at 3-year follow-up. These up-to-date data on HF in our region are in accordance with the international literature and could prove useful for Orthopaedic and Trauma surgeons for giving information to patients and their relatives.     

Validity and reliability of the SPORTS score

Purpose  

Successful outcomes for an athlete usually consist of returning to their sport. The Subjective Patient Outcome for Return to Sports (SPORTS) score has been recently proposed as an easy to use score for evaluating an athlete’s ability to return to their sport. The aim of this study was to test the reliability and validity of the SPORTS score in athletes 5–10 years after anterior cruciate ligament reconstruction.     

Absence of Allergic Reactions to Egg White Lysozyme Additive in Grana Padano Cheese

Objective: The negative effects on cheese quality of milk contaminated by spores of Clostridium butyricum and Cl.tyrobutyricum is prevented by the use of egg white lysozyme as additive. Since the presence of lysozyme in cheese could be possibly risky in allergic subjects, we aimed at investigating its absorption as well as serum IgE antibody titers after ingestion of Grana Padano cheese, an Italian DPO, long-ripened hard cheese, in white egg allergic subjects.

Methods: Cheese lysozyme was measured by HPLC. Ten healthy volunteers and 20 patients with hen egg hypersensitivity, RAST positive (binding≥3%) to lysozyme and/or ovomucoid and ovalbumin received 15, 30 and 60 g of cheese at distance of at least 2 weeks each. Serum lysozyme was measured by ELISA and specific IgE binding to lysozyme by the radioallergosorbent test (RAST).

Results: The concentration of lysozyme in cheese was 155 ± 5 mg/kg. The area-under-the-curve of serum lysozyme after 15 g of cheese was 244.5 ± 14.0 in controls and 330.2 ± 9.9 in patients (p < 0.01). Similar results were obtained with 30 and 60 g of cheese. Only 3 patients (15%) showed positive IgE antibody responses to cheese (overall RAST mean 4.45 ± 1.25 % vs. 4.24 ± 1.02 % baseline, p = ns).

Conclusions: The amount of lysozyme absorbed with cheese was globally very low, although it was significantly lower in healthy controls than in allergic patients, where it induced an increase of IgE RAST score in 15% of subjects, without any clinical reaction. Therefore, the use of lysozyme as additive in Grana Padano cheese, does not appear to be harmful in egg allergic subjects.     

Differential effects of glycogen synthase kinase 3 (GSK3) inhibition by lithium or selective inhibitors in the central nervous system

Glycogen synthase kinase (GSK3) is a constitutively active serine-threonine kinase associated to neurological and psychiatric disorders. GSK3 inhibition is considered a mediator of the efficacy of the mood-stabiliser lithium. This study aimed at comparing the central nervous system effect of lithium with the selective GSK3 inhibitors AZ1080 and compound A in biochemical, cellular, and behavioural tests. Collapsin response mediator protein 2 is a neuron-specific GSK3 substrate. Lithium, AZ1080, and compound A inhibited its phosphorylation in rat primary neurons with different pIC₅₀. After systemic treatments with lithium or GSK3 inhibitors to assess specific functional responses, phosphorylation was unchanged in adult rat brain, while it was strongly inhibited by GSK3 inhibitors in pups, differently from lithium. Lithium may exert neurotrophic effect by increasing brain-derived neurotrophic factor (BDNF) levels: in the present experimental conditions, lithium exerted opposite effects on plasma BDNF levels compared to GSK3 inhibitors, suggesting this effect might not be necessarily mediated by GSK3 inhibition alone. While plasma thyroid-stimulating hormone and luteinising hormone were not affected by lithium, they were decreased by selective inhibitors. GH and prolactin displayed similar responses towards reduction. Follicle-stimulating hormone levels were not altered by treatments, whereas melatonin was specifically increased by AZ1080. Lithium impaired mouse spontaneous locomotion and decreased amphetamine-induced hyper-locomotion. AZ1080 had no effects on locomotion, while compound A reduced spontaneous locomotor activity without effects on amphetamine-induced hyper-locomotion. The present results indicate that a broad correlation between the effects of lithium and selective GSK3 inhibitors could not be devised, suggesting alternative mechanisms, whereas overlapping results could be obtained in specific assays.     

The scavenger receptor MARCO mediates cytoskeleton rearrangements in dendritic cells and microglia

Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor expressed in peritoneal macrophages and in a subpopulation of macrophages in the marginal zone of the spleen and in the medullary cord of lymph nodes. By global gene expression analysis, it has been found that the MARCO mRNA was one of the most up-regulated in splenic dendritic cells (DCs) following lipopolysaccharide or bacterial activation and in granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated microglial cells. Here we show that MARCO is expressed on splenic DCs at late time points after activation and that its expression correlates with profound changes in actin cytoskeleton organization in DCs and microglia. During maturation, DCs undergo profound rearrangements of actin cytoskeleton. Immature DCs are adherent with visible actin cables, while fully mature, MARCO-expressing, splenic DCs are nonadherent, round in shape, and have an actin cytoskeleton with a punctate distribution. The simple expression of MARCO was sufficient to induce these cytoskeleton modifications in DCs. MARCO-transfected immature DCs acquired a typical morphology of mature DCs and did not rearrange the actin cytoskeleton following activation. Moreover, DCs in which MARCO was knocked down did not reach the mature phenotype and maintained the typical morphology of transitional DCs. MARCO expression in DCs and microglial cells was also associated with a decrease of antigen internalization capacity. Thus, the MARCO receptor is important for actin cytoskeleton rearrangements and the down-regulation of antigen uptake function during DC and microglial cell maturation.     

A Randomized Comparison of Alternative Techniques to Achieve Coronary Sinus Cannulation During Biventricular Implantation Procedures

INTRODUCTION: Biventricular pacing system implantation is a time-consuming and challenging procedure. A critical step in biventricular pacemaker implantation is coronary sinus (CS) cannulation. CS cannulation can be achieved either using dedicated guiding catheters (guiding catheter alone positioning strategy, GCA) or with the aid of an electrophysiology catheter advanced inside the guiding catheter (electrophysiology catheter aided positioning strategy, EPA). AIM OF THE STUDY: To evaluate whether the EPA technique is useful for reducing CS cannulation time compared to a conventional GCA technique. METHODS: Thirty-four consecutive patients were randomly assigned to the GCA (18 patients) or EPA (16 patients) CS cannulation strategy. RESULTS: Time to successful catheterization of CS was 5.0 +/- 2.4 min in the EPA group versus 10.1 +/- 5.4 min in the GCA group p = 0.004. Fluoroscopy time was 4.6 +/- 2.3 min in the EPA group versus 9.2 +/- 4.9 min in the GCA group p = 0.004. Total contrast dye volume to search and engage the CS ostium was 0.0 ml in the EPA group versus 14.3 +/- 3.4 ml in the GCA group p < 0.001. CONCLUSIONS: Cannulation of CS with the adjunct of an electrophysiology catheter to dedicated delivery systems significantly reduces procedural time, fluoroscopy time and contrast dye volume compared to a conventional strategy.