New specimen of the rare requiem shark Eogaleus bolcensis from the Bolca Lagerst\ue4tte, Italy

A rare carcharhinid specimen (slab and counter-slab, MSNPV 24625-24626) from the world-renowned Eocene Bolca locality was recently rediscovered during a restoration project started in 1989 by the Museo di Storia Naturale di Pavia. The individual, the largest Eogaleus bolcensis known from Bolca, is disarticulated and lies in a massive limestone matrix, suggesting its provenience from the Monte Postale site. While assessing its taxonomic status, multiple morphological affinities and ontogenetic trends within the Bolca Carcharhiniformes assemblage where documented. Eogaleus bolcensis is here distinguished from the school shark Galeorhinus cuvieri exclusively according to dermal denticle morphology, suggesting partial overlap of ecologic and trophic niches between the two species. Further, measurements and meristic counts taken on different traits of E. bolcensis (two individuals) and G. cuvieri (five individuals) specimens show high degree of similarities. The ratios "trunk length/total length"and "sum of vertebral centra (head region)/total length"of four complete individuals of the fossil assemblage were averaged and employed to estimates the total length of MSNPV 24625-24626. Here, the total length of MSNPV 24625-24626 is estimated in about 172.1\ub10.1 cm. The same approach is applied to MCSNV T.311 (E. bolcensis, holotype) and MNHN F.Bol.516 (G. cuvieri, holotype), two partially-preserved fossil individuals from Bolca locality. To support the ontogenetic variability among the Bolca shark assemblage, the age of the fossil individuals was estimated following the Von Bertalanffy Growth Function, using the modern chondrichthyans growth parameters as a reference. Data presented here suggest that all G. cuvieri specimens are juvenile individuals, whereas the E. bolcensis specimens were young-adult

TACE treatment in hepatocellular carcinoma: What should we do now?

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Treatment of hepatocellular carcinoma with immune checkpoint inhibitors and applicability of first-line atezolizumab/bevacizumab in a real-life setting

Immune checkpoint inhibitors (ICIs) are the new frontier for the treatment of advanced hepatocellular carcinoma (HCC). Since the first trial with tremelimumab, a cytotoxic T-lymphocyte-associated protein 4 inhibitor, increasing evidence has confirmed that these drugs can significantly extend the survival of patients with advanced hepatocellular carcinoma (HCC). As a matter of fact, the overall survival and objective response rates reported in patients with advanced HCC treated with ICIs are the highest ever reported in the second-line setting and, most recently, the combination of the anti-programmed death ligand protein-1 atezolizumab with bevacizumab—an anti-vascular endothelial growth factor monoclonal antibody—demonstrated superiority to sorafenib in a Phase III randomized clinical trial. Therefore, this regimen has been approved in several countries as first-line treatment for advanced HCC and is soon expected to be widely used in clinical practice. However, despite the promising results of trials exploring ICIs alone or in combination with other agents, there are still some critical issues to deal with to optimize the prognosis of advanced HCC patients. For instance, the actual proportion of patients who are deemed eligible for ICIs in the real-life ranges from 10% to 20% in the first-line setting, and is even lower in the second-line scenario. Moreover, long-term data regarding the safety of ICIs in the population of patients with cirrhosis and impaired liver function are lacking. Lastly, no biomarkers have been identified to predict response, and thus to help clinicians to individually tailor treatment. This review aimed to summarize the state of the art immunotherapy in HCC and, by analyzing a large, multicenter cohort of Italian patients with HCC, to assess the potential applicability of the combination of atezolizumab/bevacizumab in the real-life setting

Desire thinking as a predictor of drinking status following treatment for alcohol use disorder: A prospective study

© 2019 Elsevier Ltd Research has indicated that craving is one of the strongest predictors of treatment outcome and relapse in Alcohol Use Disorders (AUD) but there is little consensus on the factors that may influence its activation and escalation. Research has also shown that desire thinking is an important cognitive process which may exacerbate craving in problem drinkers. The aim of present study was to explore, for the first time, the role of desire thinking in prospectively predicting relapse, craving and binge drinking in patients receiving treatment for AUD. One hundred and thirty-five patients admitted to two rehabilitation centres and two outpatient services for addiction and mental health problems were administered baseline, treatment completion and three months follow-up measures of anxiety and depression, AUD severity, binge drinking frequency, craving and desire thinking. Results indicated that the verbal perseveration component of desire thinking at treatment completion was the only significant predictor of relapse at follow-up over and above baseline AUD severity and binge drinking frequency. Furthermore, the imaginal prefiguration component of desire thinking and craving levels at treatment completion were found to predict craving levels at follow-up independently of AUD severity and binge drinking frequency at baseline. Finally, both the imaginal prefiguration and verbal perseveration components of desire thinking at treatment completion were found to be the only predictors of binge drinking frequency at follow-up independently of AUD severity and binge drinking frequency at baseline. Treatments for AUD should aim to reduce desire thinking in people to enhance clinical outcomes and reduce relapse risk

Lidocaine for systemic sclerosis: a double-blind randomized clinical trial

Background: Systemic sclerosis (scleroderma; SSc) is an orphan disease with the highest case-specific mortality of any connective-tissue disease. Excessive collagen deposit in affected tissues is a key for the disease's pathogenesis and comprises most of the clinical manifestations. Lidocaine seems to be an alternative treatment for scleroderma considering that: a) the patient's having excessive collagen deposits in tissues affected by scleroderma; b) the patient's demonstrating increased activity of the enzyme prolyl hydroxylase, an essential enzyme for the biosynthesis of collagen; and c) lidocaine's reducing the activity of prolyl hydroxylase. the aim of this study was to evaluate the efficacy and safety of lidocaine in treating scleroderma.Methods: A randomized double-blind clinical trial included 24 patients with scleroderma randomized to receive lidocaine or placebo intravenously in three cycles of ten days each, with a one-month interval between them. Outcomes: cutaneous (modified Rodnan skin score), oesophageal (manometry) and microvascular improvement (nailfold capillaroscopy); improvement in subjective self-assessment and in quality of life (HAQ).Results: There was no statistically significant difference between the groups for any outcome after the treatment and after 6-months follow-up. Improvement in modified Rodnan skin score occurred in 66.7% and 50% of placebo and lidocaine group, respectively (p = 0.408). Both groups showed an improvement in subjective self-assessment, with no difference between them.Conclusions: Despite the findings of a previous cohort study favouring the use of lidocaine, this study demonstrated that lidocaine at this dosage and means of administration showed a lack of efficacy for treating scleroderma despite the absence of significant adverse effects. However, further similar clinical trials are needed to evaluate the efficacy of lidocaine when administered in different dosages and by other means.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Brazilian Cochrane Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Discipline Emergency Med & Evidence Based Med, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Discipline Rheumatol, São Paulo, BrazilUniv Santo Amaro, Discipline Rheumatol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Brazilian Cochrane Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Discipline Emergency Med & Evidence Based Med, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med UNIFESP EPM, Discipline Rheumatol, São Paulo, BrazilFAPESP: 01-13895-9Web of Scienc

Fecal carriage of Escherichia coli O157:H7 and carcass contamination in cattle at slaughter in northern Italy

Feedlot cattle slaughtered at a large abattoir in northern Italy during 2002 were examined for intestinal carriage and carcass contamination with Escherichia coli O157:H7. Carcass samples were taken following the excision method described in the Decision 471/2001/EC, and fecal material was taken from the colon of the calves after evisceration. Bacteria were isolated and identified according to the MFLP-80 and MFLP-90 procedures (Food Directorate’s Health Canada’s). Eighty-eight non-sorbitol-fermenting E. coli O157:H7 isolates were obtained from 12 of the 45 calves examined. In particular, E. coli O157:H7 isolates were found in 11 (24%) fecal and five (11%) carcass samples. PCR analysis showed that all 11 fecal samples and five carcass samples carried eae-γ1-positive E. coli O157:H7 isolates. In addition, genes encoding Shigatoxins were detected in O157:H7 isolates from nine and two of those 11 fecal and five carcasses, respectively. A representative group of 32 E. coli O157:H7 isolates was analyzed by phage typing and DNA macrorestriction fragment analysis (PFGE). Five phage types (PT8, PT32v, PT32, PT54, and PT not typable) and seven (I–VII) distinct restriction patterns of similarity > 85% were detected. Up to three different O157:H7 strains in an individual fecal sample and up to four from the same animal could be isolated. These findings provide evidence of the epidemiological importance of subtyping more than one isolate from the same sample. Phage typing together with PFGE proved to be very useful tools to detect cross-contamination among carcasses and should therefore be included in HACCP programs at abattoirs. The results showed that the same PFGE-phage type E. coli O157:H7 profile was detected in the fecal and carcass samples from an animal, and also in two more carcasses corresponding to two animals slaughtered the same day. [Int Microbiol 2007; 10(2):109-116

Unusual association of NDM-1 with KPC-2 and armA among Brazilian Enterobacteriaceae isolates

We report the microbiological characterization of four New Delhi metallo-beta-lactamase-1 (bla(NDM-1))-producing Enterobacteriaceae isolated in Rio de Janeiro, Brazil. bla(NDM-1) was located on a conjugative plasmid and was associated with Klebsiella pneumoniae carbapenemase-2 (bla(KPC-2)) or aminoglycoside-resistance methylase ( armA), a 16S rRNA methylase not previously reported in Brazil, in two distinct strains of Enterobacter cloacae. Our results suggested that the introduction of bla(NDM-1) in Brazil has been accompanied by rapid spread, since our isolates showed no genetic relationship.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Med, Lab Especial Microbiol Clin, São Paulo, SP, BrazilDASA, Lab Diagnost Amer, São Paulo, SP, BrazilUniversidade Federal de São Paulo, Dept Med, Lab Especial Microbiol Clin, São Paulo, SP, BrazilWeb of Scienc