Antagonistic interactions between gemcitabine and 5-fluorouracil in the human pancreatic carcinoma cell line Capan-2.

Although the recently-developed Gemcitabine (GEM) has renewed interest in clinical research in pancreatic carcinoma, it offers modest improvement of tumor-related symptoms and marginal survival advantage, even when combined with other currently-available chemotherapeutic agents such as 5-Fluorouracil (5-FU). We hypothesized that this disappointing result could be due to an interaction between the two drugs affecting cytotoxic activity. We measured in-vitro growth inhibition, cell cycle distribution, gene and protein expression of apoptosis regulators bcl-2, bcl-x and survivin, NFkappaB and telomerase activities of human pancreatic carcinoma cell line Capan-2 following exposure to GEM and 5-FU singly or combined, by MTT assay and median effect analysis, flow cytometry, real-time RT-PCR, Western blotting, electrophoretic mobility shift assay (EMSA) and telomeric repeat amplification protocol (TRAP) assay, respectively. We found cell growth to be inhibited by both drugs, decreasing the percentage of cells in S and G2/M phases and inducing apoptosis, dependent on the levels of bcl-2, bcl-xL and survivin expression in the case of 5-FU, but not for GEM. Moreover, while telomerase activity was reduced equally by both drugs, 5-FU but not GEM effectively downregulated NFkappaB binding activity. Intriguingly, a substantial antagonistic effect was noticed when GEM was combined with 5-FU in the concentration range tested, with the exception of the TRAP assay. These indications of an antagonistic interaction between GEM and 5-FU in some pancreatic cancer context urge further investigation of both genetic and non-genetic differences to identify the variables most relevant for optimal selection and dosing of treatment for the individual patient

Survey on the Knowledge and the Management of <i>Helicobacter pylori</i> Infection by Italian General Practitioners and Doctors in General Practice Training

The management of gastric Helicobacter pylori (H. pylori) infection represents a significant concern in primary healthcare. This survey evaluates the approaches, attitudes, and knowledge regarding gastric H. pylori infection among Italian general practitioners (GPs) and young doctors undergoing general practice training (ITGPs). The survey enrolled 466 GPs and 70 ITGPs. Among GPs, specialist recommendations and the Maastricht–Florence guidelines were frequently referenced sources, while ITGPs relied more on the Maastricht–Florence guidelines and internet resources. ITGPs demonstrated more proactive approaches than GPs in investigating and treating conditions such as gastric ulcers, atrophic gastritis, and iron-deficiency anemia. However, there was limited attention given to the role of H. pylori treatment in first-degree relatives of gastric cancer patients. The most used diagnostic methods were the urea breath test and fecal test. Triple therapy was the most frequently chosen initial treatment regimen, with quadruple bismuth therapy becoming the primary option after initial treatment failure, followed by quinolone therapy and concomitant therapy. This survey underscores a disparity between real-world practices and the recommendations outlined in current guidelines, indicating a need for improved understanding of H. pylori guidelines among both GPs and ITGPs

Association between coeliac disease and psoriasis: Italian primary care multicentre study

25noBACKGROUND: Studies assessing the association between coeliac disease (CD) and psoriasis show conflicting results. OBJECTIVE: To assess in the primary care setting the prevalence of CD in patients with psoriasis and the response to a gluten-free diet (GFD) in subjects with psoriasis and CD. METHODS: We enrolled 218 patients with psoriasis and 264 controls. Coeliac screening was carried out in all subjects (Eurospital, Trieste, Italy). In subjects with a positive serology, the diagnosis of CD was confirmed histologically. RESULTS: Nine (4.1%) psoriatic patients had positive anti-tissue transglutaminase antibodies compared to only 1 among controls (0.4%, p < 0.05; OR 2.03, 95% CI 1.42-90.11). The diagnosis of CD was confirmed histologically in all 10 subjects. At 6 months GFD was associated with a great improvement of skin lesions in 7 out of 8 patients with psoriasis. CONCLUSION: Our multicentre primary care study showed an high prevalence of CD in psoriasis and an improvement of skin lesions in CD under GFD.nonenoneDe Bastiani, Rudi; Gabrielli, Maurizio; Lora, Liliana; Napoli, Luigi; Tosetti, Cesare; Pirrotta, Enzo; Ubaldi, Enzo; Bertolusso, Luciano; Zamparella, Maria; De Polo, Manuela; Nebiacolombo, Cristina; Bortot, Mario; Mancuso, Maurizio; Bacchin, Paolo; Marsala, Valerio; Pinna, Roberto; Tursi, Antonio; Benedetto, Edoardo; Cuffari, Alfredo; Pati, Antonino; Di Caro, Simona; Perenzin, Gastone; Sala, Raffaella; Calzavara Pinton, P; Gasbarrini, AntonioDe Bastiani, Rudi; Gabrielli, Maurizio; Lora, Liliana; Napoli, Luigi; Tosetti, Cesare; Pirrotta, Enzo; Ubaldi, Enzo; Bertolusso, Luciano; Zamparella, Maria; De Polo, Manuela; Nebiacolombo, Cristina; Bortot, Mario; Mancuso, Maurizio; Bacchin, Paolo; Marsala, Valerio; Pinna, Roberto; Tursi, Antonio; Benedetto, Edoardo; Cuffari, Alfredo; Pati, Antonino; Di Caro, Simona; Perenzin, Gastone; Sala, Raffaella; CALZAVARA PINTON, Piergiacomo; Gasbarrini, Antoni

Virtual histology of cortical thickness and shared neurobiology in 6 psychiatric disorders

Importance Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. Objective To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia. Design, Setting, and Participants Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244. Main Outcomes and Measures Interregional profiles of group difference in cortical thickness between cases and controls. Results A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders. Conclusions and Relevance In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders

Safety and efficacy of COVID-19 vaccines in patients on dialysis: a multicentre cohort study in Italy

Background The aim of this study was to evaluate the efficacy and safety of COVID-19 vaccines in patients undergoing haemodialysis in Italy compared to the general population.Methods In this cohort study, 118 dialysis centres from 18 Italian Regions participated. Individuals older than 16 years on dialysis treatment for at least 3 months, who provided informed consent were included. We collected demographic and clinical information, as well as data on vaccination status, hospitalisations, access to intensive care units and adverse events. We calculated the incidence, hospitalisation, mortality, and fatality rates in the vaccinated dialysis cohort, adjusted for several covariates. The incidence rates of infection in the dialysis cohort and the general population were compared through Standardised Incidence Rate Ratio.Results The study included 6555 patients vaccinated against SARS-CoV-2 infection according to the schedule recommended in Italy. Between March 2021 and May 2022, there were 1096 cases of SARS-CoV-2 infection, with an incidence rate after completion of the three-dose vaccination cycle of 37.7 cases per 100 person-years. Compared to the general population, we observed a 14% reduction in the risk of infection for patients who received three vaccine doses (Standardised Incidence Rate Ratio: 0.86; 95% Confidence Interval: 0.81-0.91), whereas no statistically significant differences were found for COVID-19-related hospitalisations, intensive care unit admissions or death. No safety signals emerged from the reported adverse events.Conclusions The vaccination program against SARS-CoV-2 in the haemodialysis population showed an effectiveness and safety profile comparable to that seen in the general population