Mediterranean diet and nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease, and is characterized by a wide spectrum of fat-liver disorders that can result in severe liver disease and cirrhosis. Inflammation and oxidative stress are the major risk factors involved in the pathogenesis of NAFLD. Currently, there is no consensus concerning the pharmacological treatment of NAFLD. However, lifestyle interventions based on exercise and a balanced diet for quality and quantity, are considered the cornerstone of NAFLD management. Mediterranean diet (MD), rich in polyunsaturated fats, polyphenols, vitamins and carotenoids, with their anti-inflammatory and antioxidant effects, has been suggested to be effective in preventing cardiovascular risk factors. In adults, MD has also been demonstrated to be efficacious in reducing the risk of metabolic syndrome. However, few studies are available on the effects of the MD in both adult and pediatric subjects with NAFLD. Thus, the aims of the present narrative review are to analyze the current clinical evidence on the impact of MD in patients with NAFLD, and to summarize the main mechanisms of action of MD components on this condition

Cardiometabolic risk factors in children with celiac disease on a gluten-free diet

Celiac disease (CD) is an immune-mediated systemic condition evoked by gluten and related prolamines in genetically predisposed subjects. It is characterised by a variable combination of gluten-dependent clinical symptoms, CD-specific antibodies, HLA-DQ2 and HLA-DQ8 haplotypes, and enteropathy. The only therapy of CD consists of a life-long gluten free diet (GFD). Strict GFD adherence results in full clinical, serological and histological remission, avoiding long-term complications in CD patients. However, this diet is not without problems. Gluten free products have high levels of lipids, sugar and salt to improve food palatability and consistency, and subjects with CD show an excessive consumption of hypercaloric and hyperlipidic foods to compensate dietetic restriction. GFD may therefore have a negative impact on cardiometabolic risk factors such as obesity, serum lipid levels, insulin resistance, metabolic syndrome, and atherosclerosis. In adults, some studies have suggested that GFD have a beneficial effect on cardiovascular profile, whereas others have shown an atherogenic effect of GFD. In children, very few studies are available on the issue. Thus, the aim of the present narrative review was to analyze the current clinical evidence on the impact of GFD on cardiometabolic risk factors in children with CD

CONNECTOR, fitting and clustering of longitudinal data to reveal a new risk stratification system

Motivation: The transition from evaluating a single time point to examining the entire dynamic evolution of a system is possible only in the presence of the proper framework. The strong variability of dynamic evolution makes the definition of an explanatory procedure for data fitting and clustering challenging. Results: We developed CONNECTOR, a data-driven framework able to analyze and inspect longitudinal data in a straightforward and revealing way. When used to analyze tumor growth kinetics over time in 1599 patient-derived xenograft growth curves from ovarian and colorectal cancers, CONNECTOR allowed the aggregation of time-series data through an unsupervised approach in informative clusters. We give a new perspective of mechanism interpretation, specifically, we define novel model aggregations and we identify unanticipated molecular associations with response to clinically approved therapies. Availability and implementation: CONNECTOR is freely available under GNU GPL license at https://qbioturin.github.io/connector and https://doi.org/10.17504/protocols.io.8epv56e74g1b/v1

Prognostic Role of Serum Cytokeratin-19 Fragment (CYFRA 21-1) in Patients with Hepatocellular Carcinoma

Keratin 19 (K19) is a cancer stem cell marker expressed by a subpopulation of hepatocellular carcinoma (HCC), associated with tumor aggressiveness. We evaluated the prognostic value of serum K19 fragment (CYFRA 21-1), in comparison or in combination with alpha-fetoprotein (AFP) and protein induced by vitamin-K absence or antagonist-II (PIVKA-II), in patients with HCC. A total of 160 patients (28F/132M; median age 62, range 44-86 years) with a new diagnosis of HCC and available serum samples collected at tumor diagnosis were analyzed retrospectively. Median overall survival (OS) after HCC diagnosis was 35.1, 95% CI 27.1-70.5 months. Multivariate Cox regression analysis showed that CYFRA 21-1 > 2.7 ng/mL (hazard ratio (HR) = 3.39, p 20 ng/mL (HR = 2.27, p = 0.007), and PIVKA-II > 200 mAU/mL (HR = 2.17, p = 0.020) were independent predictors of OS. The combination of biomarkers positivity allowed us to stratify patients with HCC into four risk categories associated with a progressively lower survival probability (log-rank test, p < 0.001). CYFRA 21-1 resulted an independent prognostic factor of patients with HCC and its combination with AFP and PIVKA-II might be useful to tailor personalized treatment strategies

On-Treatment Decrease of Serum Interleukin-6 as a Predictor of Clinical Response to Biologic Therapy in Patients with Inflammatory Bowel Diseases

In patients with inflammatory bowel diseases (IBD) undergoing biologic therapy, biomarkers of treatment response are still scarce. This study aimed to evaluate whether serum zonulin, a biomarker of intestinal permeability; soluble CD163 (sCD163), a macrophage activation marker; and a panel of serum cytokines could predict the response to biologic treatment in patients with IBD. For this purpose, we prospectively enrolled 101 patients with IBD and 19 patients with irritable bowel syndrome (IBS) as a control group; 60 out of 101 patients underwent treatment with biologics. Zonulin, sCD163, and cytokines were measured at the baseline in all patients and after 10 weeks of treatment in the 60 patients who underwent biologic therapy. We observed that zonulin levels were higher in IBD patients with active disease compared to those in remission (p = 0.035), and that sCD163 values were higher in patients with IBD compared to those with IBS (p = 0.042), but no association with therapy response was observed for either biomarker. Conversely, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha showed a significant reduction from baseline to week 10 of treatment, particularly in responder patients. By multivariate logistic regression analysis corrected for disease (Crohn’s disease or ulcerative colitis), type of biologic drug (Infliximab, Adalimumab, Vedolizumab, or Ustekinumab) and disease activity, the reduction in IL-6 values was associated with a clinical response at 12 months of biological therapy (odds ratio (OR) = 4.75, 95% confidence interval (CI) 1.25–18.02, p = 0.022). In conclusion, the measurement of serum IL-6 in biologics-treated IBD patients may allow for the prediction of response to treatment at 12 months of therapy and thus may help with tailoring personalized treatment strategies

Un database europeo INSPIRE-compliant per migliorare la resilienza dei beni culturali

L'insieme di leggi, azioni e organizzazioni per la tutela dei Beni Culturali (Cultural Heritage) nasce nei diversi paesi dell'Unione Europea dalle situazioni culturali locali, dove la capacità di far fronte all'emergenza è sicuramente diversa. Oltre ai danni che possono verificarsi ai beni culturali dopo un disastro, un intervento di emergenza inadeguato può a volte causare ulteriori perdite al CH. L'efficacia della risposta dipende dall'adeguatezza dell’approfondimento in fase di pianificazione. Alcuni paesi hanno progettato piani di emergenza ma i loro database (DB) sono frammentati, incompleti e non standardizzati. È quindi necessario stabilire un DB per l'assistenza di emergenza e mappe di CH a rischio da confrontare con mappe di rischi e rischi naturali, al fine di adottare misure preventive e operative, nonché concordare una terminologia comune e standard internazionali. Il progetto mira a migliorare la capacità della Protezione Civile di prevenire gli impatti dei disastri sul CH implementando una banca dati europea interoperabile (European Interoperable Database, EID) come strumento di supporto alle decisioni per comprendere il rischio di danni ai beni culturali. L'EID, a partire dagli standard internazionali per rappresentare gli oggetti della mappa (CityGML, INSPIRE), la classificazione di CH in Europa (UNESCO), in Italia (MiBACT), in Germania e in Francia e dall'analisi dei rischi e dei disastri, ha progettato, con il suo modello concettuale di dati, un'estensione del modello UML di INSPIRE. Questo DB supporterà anche modelli 3D per aiutare a trovare e riconoscere le opere disperse e facilitare un restauro post-emergenza, preservando così una memoria digitale in caso di distruzione

The Prognostic Role of Baseline Eosinophils in HPV-Related Cancers: a Multi-institutional Analysis of Anal SCC and OPC Patients Treated with Radical CT-RT

Background and Aim Anal squamous cell carcinoma (SCC) and oropharyngeal cancer (OPC) are rare tumors associated with HPV infection. Bioumoral predictors of response to chemoradiation (CT-RT) are lacking in these settings. With the aim to find new biomarkers, we investigated the role of eosinophils in both HPV-positive anal SCC and HPV-related oropharyngeal cancer (OPC). Methods We retrieved clinical and laboratory data of patients with HPV-positive anal SCC treated with CT-RT in 5 institutions, and patients with locally advanced OPC SCC treated with CT-RT in 2 institutions. We examined the association between baseline eosinophil count (the best cutoff has been evaluated by ROC curve analysis: 100 x 109/L) and disease-free survival (DFS). Unadjusted and adjusted hazard ratios by baseline characteristics were calculated using the Cox proportional hazards model. Results Three hundred four patients with HPV-positive anal SCCs and 168 patients with OPCs (122 HPV-positive, 46 HPV-negative diseases) were analyzed. In anal SCC, low eosinophil count (9/L) correlates to a better DFS (HR = 0.59; p = 0.0392); likewise, in HPV-positive OPC, low eosinophil count correlates to a better DFS (HR = 0.50; p = 0.0428). In HPV-negative OPC, low eosinophil count confers worse DFS compared to high eosinophil count (HR = 3.53; p = 0.0098). After adjustment for age and sex, eosinophils were confirmed to be independent prognostic factors for DFS (HR = 4.55; p = 0.0139). Conclusion Eosinophil count could be used as a prognostic factor in anal HPV-positive SCC. The worse prognosis showed in HPV-positive patients with high eosinophil count is likely to derive from an unfavorable interaction between the HPV-induced immunomodulation and eosinophils, which may hamper the curative effect of RT

The impact of upper motor neuron involvement on clinical features, disease progression and prognosis in amyotrophic lateral sclerosis

ObjectivesIn amyotrophic lateral sclerosis (ALS) both upper (UMNs) and lower motor neurons (LMNs) are involved in the process of neurodegeneration, accounting for the great disease heterogeneity. We evaluated the associations of the burden of UMN impairment, assessed through the Penn Upper Motor Neuron Score (PUMNS), with demographic and clinical features of ALS patients to define the independent role of UMN involvement in generating disease heterogeneity, predicting disease progression and prognosis.MethodsWe collected the following clinical parameters on a cohort of 875 ALS patients: age and site of onset, survival, MRC scale, lower motor neuron score (LMNS), PUMNS, ALSFRS-R, change in ALSFRS-R over time (DFS), MITOS and King’s staging systems (KSS). Transcranial magnetic stimulation was performed on a subgroup of patients and central motor conduction time (CMCT) and cortical silent period (CSP) were calculated.ResultsWe observed that patients with an earlier age at onset and bulbar onset had higher PUMNS values. Higher values were also associated to lower ALSFRS-R and to higher DFS scores, as well as to higher MITOS and KSS, indicating that a greater UMN burden correlates with disease severity. Conversely, we did not appreciate any association between UMN involvement and survival or markers of LMN impairment. Moreover, PUMNS values showed a positive association with CMCT and a negative one with CSP values.InterpretationOur results suggest that the burden of UMN pathology, assessed through PUMNS, has an important independent role in defining clinical characteristics, functional disability, disease progression and prognosis in ALS patients. We also support the role of TMS in defining severity of UMN involvement