A Liver Index and its Relationship to Indices of HCC Aggressiveness

A Hepatocellular (HCC) Aggressiveness Index was recently constructed, consisting of the sum of the scores for the 4 clinical parameters of maximum tumor size, multifocality, presence of portal vein thrombus and blood alphafetoprotein levels. It was observed that there was an association with several liver function tests. We have now formed a Liver Index from the 4 liver parameters with the highest hazard ratios with respect to HCC aggressiveness, namely: blood total bilirubin, gamma glutamyl transpeptidase (GGTP), albumin and platelet levels (cirrhosis surrogate). We found that the scores for the Liver Index related significantly to survival, but also to the Aggressiveness Index and to its individual HCC components as well as showing significant trends with the components. These results support the hypothesis that liver function is not only an important prognostic factor in HCC patients, but may also be involved in HCC biology and aggressiveness. Blood albumin, GGTP, albumin and platelet levels were used to create a Liver Index that related significantly to parameters of HCC aggressiveness

Appropriate management of growth hormone deficiency during the age of transition: an Italian Delphi consensus statement

No abstract availabl

Paediatric recurrent pericarditis: Appropriateness of the standard of care and response to IL1-blockade

Objective: To analyse, in a cohort of paediatric patients with recurrent pericarditis (RP) undergoing anti-IL-1 treatment: the agent and dosing used as first line treatment, the long-term efficacy of IL1-blockers, the percentage of patients achieving a drug-free remission, the presence of variables associated with drug-free remission. Study design: Data were collected from patients' charts. Annualized relapse rate (ARR) was used for evaluation of treatment efficacy, bivariate logistic regression analysis for variables associated with drug-free remisison. Results: 58 patients, treated between 2008 and 2018, were included in the study (mean follow-up 2.6 years). 14/56 patients non-responsive to first line drugs were under-dosed. 57 patients were treated with anakinra: the ARR before and during daily treatment was 3.05 and 0.28, respectively (p<0.0001); an increase to 0.83 was observed after the reduction/withdrawal of treatment (p<.0001). The switch from anakinra to canakinumab (5 patients) was associated to an increase of the ARR (0.49 vs 1.46), but without statistical significance (p=0.215). At last follow-up only 9/58 patients had withdrawn all treatments. With the limits of a retrospective study and the heterogeneity between the patients enrolled in the study, a shorter duration of treatment with anakinra was the only variable associated with drug-free remission. Conclusion: This study shows that most of the pediatric patients with RP needing IL-1 blockade received an inadequate treatment with first line agents. The effectiveness of anakinra is supported by this study, but few patients achieved drug free-remission. The different rate of response to anakinra and canakinumab may suggest a possible role of IL1α in the pathogenesis of RP

Lung transplantation from donation after controlled cardiocirculatory death: Systematic review and meta-analysis

Background: The interest in donation after cardiocirculatory death (DCD) donors for lung transplantation (LT) has been recently rekindled due to lung allograft shortage. Clinical outcomes following DCD have proved satisfactory. The aim of this systematic review is to provide a thorough analysis of published experience regarding outcomes of LT after controlled DCD compared with donation after brain death (DBD) donors. Methods: We performed a literature search in Cochrane Database of Systematic Reviews, PubMed and Web of Science using the items "lung transplantation" AND "donation after circulatory death" on November 1, 2018. The full text of relevant articles was evaluated by two authors independently. Quality assessment was performed using the NIH protocol for case-control and case series studies. A pooled Odds ratio (OR) and mean differences with inverse variance weighting using DerSimonian-Laird random effect models were computed to account for between-trial variance (tau 2). Results: Of the 508 articles identified with our search, 9 regarding controlled donation after cardiac death (cDCD) were included in the systematic review, including 2973 patients (403 who received graft from DCD and 2570 who had DBD). Both 1-year survival and 2 and 3-grade primary graft dysfunction (PGD) were balanced between the two cohorts (OR = 1.00 and 1.03 respectively); OR for airway complications was 2.07 against cDCD. We also report an OR = 0.57 for chronic lung allograft dysfunction (CLAD) and an OR = 0.57 for 5-year survival against cDCD. Conclusions: Our meta-analysis shows no significant difference between recipients after cDCD or DBD regarding 1-year survival, PGD and 1-year freedom from CLAD. Airway complications and long-term survival were both related with transplantation after cDCD, but these statistical associations need further research

WHO standards-based tools to measure service providers' and service users' views on the quality of hospital child care: development and validation in Italy

Objectives Evidence showed that, even in high-income countries, children and adolescents may not receive high quality of care (QOC). We describe the development and initial validation, in Italy, of two WHO standards-based questionnaires to conduct an assessment of QOC for children and young adolescents at inpatient level, based on the provider and user perspectives. Design Multiphase, mixed-methods study. Setting, participants and methods The two questionnaires were developed in four phases equally conducted for each tool. Phase 1 which included the prioritisation of the WHO Quality Measures according to predefined criteria and the development of the draft questionnaires. In phase 2 content face validation of the draft questionnaires was assessed among both experts and end-users. In phase 3 the optimised questionnaires were field tested to assess acceptability, perceived utility and comprehensiveness (N=163 end-users). In phase 4 intrarater reliability and internal consistency were evaluated (N=170 and N=301 end-users, respectively). Results The final questionnaires included 150 WHO Quality Measures. Observed face validity was excellent (kappa value of 1). The field test resulted in response rates of 98% and 76% for service users and health providers, respectively. Among respondents, 96.9% service users and 90.4% providers rated the questionnaires as useful, and 86.9% and 93.9%, respectively rated them as comprehensive. Intrarater reliability was good, with Cohen's kappa values exceeding 0.70. Cronbach alpha values ranged from 0.83 to 0.95, indicating excellent internal consistency. Conclusions Study findings suggest these tools developed have good content and face validity, high acceptability and perceived utility, and good intrarater reliability and internal consistency, and therefore could be used in health facilities in Italy and similar contexts. Priority areas for future research include how tools measuring paediatric QOC can be more effectively used to help health professionals provide the best possible care

Oral CorticoSteroid sparing with biologics in severe asthma: A remark of the Severe Asthma Network in Italy (SANI)

According to the data derived from several national and international registries, including SANI (Severe Asthma Network Italy), and considering the strong impact that frequent or regular use of oral corticosteroid has on quality of life (QoL) of severe asthmatics, as well as on the costs for managing corticosteroid-related diseases, oral corticosteroid sparing up to withdrawal should be considered a primary outcome in the management of severe asthma. New biologics have clearly demonstrated that this effect is possible, with concomitant reduction in the rate of exacerbations and in symptom control. Then, there is no reason for using so frequently oral corticosteroid before having explored all alternatives currently available for a large part of severe asthmatics

Automatic speech analysis to early detect functional cognitive decline in elderly population

This study aimed at evaluating whether people with a normal cognitive function can be discriminated from subjects with a mild impairment of cognitive function based on a set of acoustic features derived from spontaneous speech. Voice recordings from 90 Italian subjects (age &gt;65 years; group 1: 47 subjects with MMSE&gt;26; group 2: 43 subjects with 20≤ MMSE ≤26) were collected. Voice samples were processed using a MATLAB-based custom software to derive a broad set of known acoustic features. Linear mixed model analyses were performed to select the features able to significantly distinguish between groups. The selected features (% of unvoiced segments, duration of unvoiced segments, % of voice breaks, speech rate, and duration of syllables), alone or in addition to age and years of education, were used to build a learning-based classifier. The leave-one-out cross validation was used for testing and the classifier accuracy was computed. When the voice features were used alone, an overall classification accuracy of 0.73 was achieved. When age and years of education were additionally used, the overall accuracy increased up to 0.80. These performances were lower than the accuracy of 0.86 found in a recent study. However, in that study the classification was based on several tasks, including more cognitive demanding tasks. Our results are encouraging because acoustic features, derived for the first time only from an ecologic continuous speech task, were able to discriminate people with a normal cognitive function from people with a mild cognitive decline. This study poses the basis for the development of a mobile application performing automatic voice analysis on-the-fly during phone calls, which might potentially support the detection of early signs of functional cognitive decline

Utilization of livers donated after circulatory death for transplantation - An international comparison.

BACKGROUND AND AIM Liver graft utilization rates are a hot topic due to the worldwide organ shortage and an increasing number of transplant candidates on waiting lists. Liver perfusion techniques have been introduced in several countries, and may help to increase the organ supply, as they potentially allow the assessment of livers before use. METHODS Liver offers were counted from donation after circulatory death (DCD) donors (Maastricht-type-III) arising during the past decade in eight countries, including Belgium, France, Italy, the Netherlands, Spain, Switzerland, UK, and US. Initial DCD-type-III liver offers were correlated with accepted, recovered and implanted livers. RESULTS A total number of 34`269 DCD livers were offered, resulting in 9`780 liver transplants (28.5%). The discard rates were highest in UK and US, ranging between 70 and 80%. In contrast, much lower DCD liver discard rates, e.g., between 30-40%, were found in Belgium, France, Italy, Spain and Switzerland. In addition, large differences were recognized in the use of various machine perfusion techniques, and in terms of risk factors in the cohorts of implanted livers. For example, the median donor age and functional donor warm ischemia were highest in Italy, e.g., >40minutes, followed by Switzerland, France, and the Netherlands. Importantly, such varying risk profiles of accepted DCD livers between countries did not translate into large differences in five-year graft survival rates, which ranged between 60-82% in this analysis. CONCLUSIONS We highlight a significant number of discarded and consequently unused DCD liver offers. Countries with more routine use of in- and ex-situ machine perfusion strategies showed better DCD utilization rates without compromised outcome. IMPACT AND IMPLICATIONS A significant number of Maastricht type III DCD livers are discarded across Europe and North America today. The overall utilization rate among eight Western countries is 28.5%, but varies significantly between 18.9% and 74.2%. For example, the median DCD III liver utilization in five countries, e.g., Belgium, France, Italy, Switzerland, and Spain is 65%, in contrast to 24% in the Netherlands, UK and US. Despite this, and despite different rules and strategies for organ acceptance and preservation, the one and five-year graft survival remains currently relatively comparable among all participating countries. Factors which impact on DCD liver acceptance rates include the national pre-selections of donors, before the offer is made, as well as cutoffs for key risk factors, including donor age and donor warm ischemia time. In addition, a highly varying experience with modern machine perfusion technology is noticed. In situ and ex situ liver perfusion concepts, and assessment tools for type III DCD livers before transplantation may be one key part for the observed differences in better DCD III utilization

Effects of anti-IL5 biological treatments on blood IgE levels in severe asthmatic patients: A real-life multicentre study (BIONIGE)

Background: Mepolizumab and benralizumab are clinically effective biological treatments for severe eosinophilic asthmatic patients by hampering eosinophilic inflammation. The effects of these compound on the immunoglobulin (Ig)E T2 component are virtually unknown. Objectives: To evaluate the change in total IgE levels at 4&nbsp;±&nbsp;2&nbsp;months after initiation of the mepolizumab (primary outcome) or benralizumab. When available, the changes of blood inflammatory cell counts, lung function and asthma control test (ACT) were also assessed and correlated with changes in total IgE levels. Methods: Observational, retrospective, multicentre, cohort study. Severe eosinophilic atopic asthmatic patients treated with mepolizumab or benralizumab were included in the analysis. Results: Three-month treatment (on average) with mepolizumab (n&nbsp;=&nbsp;104) or benralizumab (n&nbsp;=&nbsp;82) resulted in significantly higher reduction of blood eosinophil and basophil levels in patients treated with benralizumab compared to mepolizumab. Mepolizumab did not significantly modified the levels of blood total IgE during the study period, whereas benralizumab significantly reduced (−35%, p&nbsp;&lt;&nbsp;0.001) total blood IgE levels. In patients treated with benralizumab the reduction of blood total Ig-E levels correlated with the reduction of blood basophils (but not eosinophils) and weakly with the improvement of asthma control. Conclusion: Benralizumab but not mepolizumab, treatment led to a significant reduction of circulating IgE level. The study provides different and specific mechanisms of action for anti-IL5-pathway treatments

Classification and Statistical Trend Analysis in Detecting Glaucomatous Visual Field Progression

Aim. To evaluate the agreement between different methods in detection of glaucomatous visual field progression using two classification-based methods and four statistical approaches based on trend analysis. Methods. This is a retrospective and longitudinal study. Twenty Caucasian patients (mean age 73.8 \ub1 13.43 years) with open-Angle glaucoma were recruited in the study. Each visual field was assessed by Humphrey Field Analyzer, program SITA standard 30-2 or 24-2 (Carl Zeiss Meditec, Inc., Dublin, CA). Full threshold strategy was also accepted for baseline tests. Progression was analyzed by using Hodapp-Parrish-Anderson classification and the Advanced Glaucoma Intervention Study visual field defect score. For the statistical analysis, linear regression (r2) was calculated for mean deviation (MD), pattern standard deviation (PSD), and visual field index (VFI), and when it was significant, each series of visual field was considered progressive. We also used Progressor to look for a significant progression of each visual field series. The agreement between methods, based on statistical analysis and classification, was evaluated using a weighted kappa statistic. Results. Thirty-eight visual field series were analyzed. The mean follow-up time was 6.2 \ub1 1.53 years (mean \ub1 standard deviation). At baseline, the mean MD was-7.34 \ub1 7.18 dB; at the end of the follow-up, the mean MD was-9.25 \ub1 8.65 dB; this difference was statistically significant (p&lt;0.001). The agreement to detect progression was fair between all methods based on statistical analysis and classification except for PSD r2. A substantial agreement ( = 0.698 \ub1 0.126) was found between MD r2 and VFI r2. With the use of all the statistical analysis, there was a better time-saving. Conclusions. The best agreement to detect progression was found between MD r2 and VFI r2. VFI r2 showed the best agreement with all the other methods. GPA2 can help ophthalmologists to detect glaucoma progression and to help in treatment decisions. PSD r2 was the worse method to detect progression