Buildings Temporary Yet Efficient

With the aim of valorising and spreading the environmental legacy of Expo Milano 2015, the Italian Ministry for the Environment has realised a technical-educational publication in cooperation with Expo 2015 SpA, Politecnico di Milano and IEFE – Università Bocconi. “The EXPO we learned. The legacy of a mega-event in a circular economy perspective” is a well reasoned evaluation about the sustainable achievements obtained thanks to the “best practices” applied during the Event and the “lessons learned”: from the construction of temporary buildings with energy efficiency and materials reusage expedients, and the prescription of green procurement requirements to waste management

The temporary structures for Expo Milan 2015: environmental assessment and solutions for the end of life management

Politecnico di Milano University worked for the Italian Ministry of Environment, land and sea on the sustainability assessment of Expo Milan 2015 self-built temporary pavilions. The work has been focused on the improvement of the buildings environmental performances. Given the buildings short durability in place (Expo lasts for 6 months), the strategies for their end of life are of great importance for the carbon footprint reduction. Starting from the specific work on Expo Milan 2015, the Politecnico di Milano working group proceeded with the methodology research about this issue, applicable also to future events. This paper presents the different relevant aspects of mega events temporary buildings end of life management; dealing with methodological, technical and managerial aspects

Outcomes of Radiofrequency Ablation for Dysplastic Barrett’s Esophagus: A Comprehensive Review

Barrett's esophagus is a condition in which the normal squamous lining of the esophagus has been replaced by columnar epithelium containing intestinal metaplasia induced by recurrent mucosal injury related to gastroesophageal reflux disease. Barrett's esophagus is a premalignant condition that can progress through a dysplasia-carcinoma sequence to esophageal adenocarcinoma. Multiple endoscopic ablative techniques have been developed with the goal of eradicating Barrett's esophagus and preventing neoplastic progression to esophageal adenocarcinoma. For patients with high-grade dysplasia or intramucosal neoplasia, radiofrequency ablation with or without endoscopic resection for visible lesions is currently the most effective and safe treatment available. Recent data demonstrate that, in patients with Barrett's esophagus and low-grade dysplasia confirmed by a second pathologist, ablative therapy results in a statistically significant reduction in progression to high-grade dysplasia and esophageal adenocarcinoma. Treatment of dysplastic Barrett's esophagus with radiofrequency ablation results in complete eradication of both dysplasia and of intestinal metaplasia in a high proportion of patients with a low incidence of adverse events. A high proportion of treated patients maintain the neosquamous epithelium after successful treatment without recurrence of intestinal metaplasia. Following successful endoscopic treatment, endoscopic surveillance should be continued to detect any recurrent intestinal metaplasia and/or dysplasia. This paper reviews all relevant publications on the endoscopic management of Barrett's esophagus using radiofrequency ablation

Evaluation of the prognostic value of liver stiffness in patients with hepatitis C virus treated with triple or dual antiviral therapy: A prospective pilot study

AIM: To evaluate the association between liver stiffness (LS) prior to the initiation of dual/triple therapy and viral response. METHODS: LS was measured in all patients before treatment was administered. The therapeutic approach was based on hepatic, virological, and immunological evaluations and considered the fact that patients with severe fibrosis (F3) or compensated cirrhosis (F4) in Child-Pugh class A are the primary candidates for triple therapy. In total, 65 hepatitis C virus (HCV) patients were treated with Peg-interferon/ribavirin (Peg-IFN/RBV); 24 patients were classified as genotypes 1/4 (36.92%), and 41 patients were classified as genotypes 2/3 (63.08%) (dual therapy). In addition, 20 HCV treatment-experienced genotype 1 patients were treated with PegIFN-RBV and boceprevir (triple therapy). Wilcoxon rank-sum tests were used to compare the groups. RESULTS: LS significantly differed between dual therapy and triple therapy (P = 0.002). The mean LS value before dual therapy treatment was 8.61 ± 5.79 kPa and was significantly different between patients achieving a sustained virologic response (SVR) 24 weeks after therapy and those who did not (7.23 ± 5.18 kPa vs 11.72 ± 5.99 kPa, respectively, P = 0.0003). The relative risk of non-response to therapy was 4.45 (95%CI: 2.32-8.55). The attributable risk of non-response to therapy was 49%. The mean LS value before triple therapy treatment was 13.29 ± 8.57 kPa and was significantly different between patients achieving and not achieving SVR24 (9.41 ± 5.05 vs 19.11 ± 9.74, respectively; P = 0.008). The relative risk of non-response to therapy was 5.57% (95%CI: 1.50-20.65). The attributable risk of non-response to therapy (70%) was increased compared with dual therapy patients. Pre-treatment stiffness > 12 kPa was significantly associated with non-SVR (P < 0.025) in both groups. CONCLUSION: Pre-treatment liver stiffness may be useful for predicting the response to treatment in patients treated with either dual or triple anti-HCV therapy

Long-term effect of HCV eradication in patients with mixed cryoglobulinemia: A prospective, controlled, open-label, cohort study

Limited data are available about the efficacy of antiviral treatment in hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC), especially concerning the long-term effects of HCV eradication. The aim of this study was to evaluate the influence of MC on the virological response and the long-term effects of viral eradication on MC. We prospectively enrolled 424 HCV+ patients belonging to the following groups: MCS-HCV (121 patients with symptomatic MC); MC-HCV (132 patients with asymptomatic MC); HCV group (158 patients without MC). Peg-IFN+RBV treatment was administered according to standard protocols. Post-treatment follow-up ranged from 35 to 124 months (mean: 92.5 months). A significant difference was observed in the rate of sustained virological response (SVR) between HCV and both MC-HCV (p=0.009) and MC-HCV+MCS-HCV (p=0.014) groups. Multivariate logistic regression analysis identified cryoglobulinemia as an independent prognostic factor of non-response. The clinical-immunological response in MCS-HCV correlated with the virological one. All patients with SVR also experienced a sustained clinical response, either complete or partial. In the majority of SVR patients all MCS symptoms persistently disappeared (36 patients, 57%); in only 2 (3%) did definite MCS persist. All virological non-responders were also clinical non-responders, in spite of a transient improvement in some cases. No evolution to lymphoma was observed. For the first time we have evaluated both the effects of IFN-based therapy on HCV patients with or without MC, and with or without symptoms, and the long-term effects of viral eradication on MC. MC was shown to be a negative prognostic factor of virological response. HCV clearance led to persistent resolution or improvement of MC syndrome, strongly suggesting the need for a next generation of highly effective antiviral drugs

P495: UNLOCKING THE POTENTIAL OF SYNTHETIC PATIENTS FOR ACCELERATING CLINICAL TRIALS: RESULTS OF THE FIRST GIMEMA EXPERIENCE

Background: Artificial intelligence is contributing to improve different medicine areas including clinical trial design. One field that holds a great potential is represented by the use of digital data as an alternative to real ones. The generation of a virtual cohort of patients might be advantageous since an artificial group of patients resembles the real dataset in all the key features but it does not include any identifiable real-patient data, tackling - by a privacy standpoint – the “burden” of collecting data subjects’ consent as well as the shortcomings of common anonymization techniques. Aims: To test the feasibility of this approach and evaluate its potential in clinical trial design, we built an in-silico cohort based on the large dataset of patients enrolled in the GIMEMA AML1310 study (Venditti et al. 2019), which entailed a “3 + 7”-like induction and a risk-adapted, MRD-directed post-remission transplant allocation. Methods: To create the synthetic cohort of patients, a machine learning generative model was constructed from the real individual-level data of the AML1310 study, capturing its patterns and statistical properties. AML1310 enrolled 500 patients (median age 49 years old) in 55 GIMEMA Institutions. All patients were NCCN2009 risk classified and analyzed by morphology, cytogenetics, molecular biology and multiparametric flow cytometry. The subset of 445 patients with ELN2017 risk classification available was used. To this purpose, the R package “synthpop” was used considering a parametric method: for binary data the logistic regression, for a factor with &gt; 2 levels the polytomous logistic regression, for an ordered factor with &gt; 2 levels the ordered polytomous logistic regression. For time to event variables the classification and regression trees method was used. Next, we verified the adherence of the virtual cohort to the original one in terms of age, gender, PS, WBC count, FLT3 and NPM1 mutations, risk category, CR achievement, MRD, transplant rate. Virtual and real cohorts were also compared in terms of survival outcomes. Results: By using the real-patient dataset from the AML1310 trial, a virtual cohort of 850 patients, named synthAML1310, was generated. By comparing the two cohorts, we observed that the clinico-biological characteristics and response evaluations (CR and MRD rates) did not differ significantly. Moreover, as depicted in Figure 1, the curves of OS and DFS were superimposable. Indeed, at 2 years, OS was 57% (52.5%-61.9%) in the original and 59.1% (55.9%-62.6%) in the synthAML1310 cohort. DFS was 55.1% (49.8%-60.9%) in the original and 55.1% (51.3%-59.2%) in the synthetic cohort. Summary/Conclusion: These results demonstrate the success of this approach in producing a virtual dataset that perfectly mimics the original and that, from a “privacy by design” perspective, minimizes the risk of re-identification of patients. Mirroring an AML population treated with a conventional chemotherapeutic approach, synthAML1310 is suitable to represent the control group when testing novel innovative treatments, most likely in an in-silico randomized trial, but also in other settings like propensity score matching analyses in observational studies. Shifting to an in-silico trial would overcome the challenges of randomized trials and it would be beneficial also for patients. since, they would receive only the experimental treatment without being exposed to the “less active“ therapy, thus limiting treatment failures and toxicity. Also, enrolment and the attainment of final results would be faster

Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia: Results of the GIMEMA AML1516 Protocol

IDH1/2 mutations are common in acute myeloid leukemia (AML) and represent a therapeutic target. The GIMEMA AML1516 observational protocol was designed to study the prevalence of IDH1/2 mutations and associations with clinico-biological parameters in a cohort of Italian AML patients. We analyzed a cohort of 284 AML consecutive patients at diagnosis, 139 females and 145 males, of a median age of 65 years (range: 19–86). Of these, 38 (14%) harbored IDH1 and 51 (18%) IDH2 mutations. IDH1/2 mutations were significantly associated with WHO PS &gt;2 (p &lt; 0.001) and non-complex karyotype (p = 0.021) when compared to IDH1/2-WT. Furthermore, patients with IDH1 mutations were more frequently NPM1-mutated (p = 0.007) and had a higher platelet count (p = 0.036). At relapse, IDH1/2 mutations were detected in 6 (25%) patients. As per the outcome, 60.5% of IDH1/2-mutated patients achieved complete remission; overall survival and event-free survival at 2 years were 44.5% and 36.1%, respectively: these rates were similar to IDH1/2-WT. In IDH1/2-mutated patients, high WBC proved to be an independent prognostic factor for survival. In conclusion, the GIMEMA AML1516 confirms that IDH1/2 mutations are frequently detected at diagnosis and underlines the importance of recognizing IDH1/2-mutated cases up-front to offer the most appropriate therapeutic strategy, given the availability of IDH1/2 inhibitors

Conversion to secondary progressive multiple sclerosis: patient awareness and needs. results from an online survey in Italy and Germany

Background: Few studies have investigated the experiences of patients around the conversion to secondary progressive multiple sclerosis (SPMS). ManTra is a mixed-method, co-production research project conducted in Italy and Germany to develop an intervention for newly-diagnosed SPMS patients. In previous project actions, we identified the needs and experiences of patients converting to SPMS via literature review and qualitative research which involved key stakeholders.Aims: The online patient survey aimed to assess, on a larger and independent sample of recently-diagnosed SPMS patients: (a) the characteristics associated to patient awareness of SPMS conversion; (b) the experience of conversion; (c) importance and prioritization of the needs previously identified.Methods: Participants were consenting adults with SPMS since &lt;= 5 years. The survey consisted of three sections: on general and clinical characteristics; on experience of SPMS diagnosis disclosure (aware participants only); and on importance and prioritization of 33 pre-specified needs.Results: Of 215 participants, those aware of their SPMS diagnosis were 57% in Italy vs. 77% in Germany (p = 0.004). In both countries, over 80% of aware participants received a SPMS diagnosis from the neurologist; satisfaction with SPMS disclosure was moderate to high. Nevertheless, 28-35% obtained second opinions, and 48-56% reported they did not receive any information on SPMS. Participants actively seeking further information were 63% in Germany vs. 31% in Italy (p &lt; 0.001).Variables independently associated to patient awareness were geographic area (odds ratio, OR 0.32, 95% CI 0.13-0.78 for Central Italy; OR 0.21, 95% CI 0.08-0.58 for Southern Italy [vs. Germany]) and activity limitations (OR 7.80, 95% CI 1.47-41.37 for dependent vs. autonomous patients).All pre-specified needs were scored a lot or extremely important, and two prioritized needs were shared by Italian and German patients: "physiotherapy" and "active patient care involvement." The other two differed across countries: "an individualized health care plan" and "information on social rights and policies" in Italy, and "psychological support" and "cognitive rehabilitation" in Germany.Conclusions: Around 40% of SPMS patients were not aware of their disease form indicating a need to improve patient-physician communication. Physiotherapy and active patient care involvement were prioritized in both countries

Characterization of Carbonic Anhydrase IX Interactome Reveals Proteins Assisting Its Nuclear Localization in Hypoxic Cells

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COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score &gt; 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p &lt; 0.001), RR = 2.19 for ICU admission (p &lt; 0.001), and RR = 2.43 for death (p &lt; 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon