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Lucrezia Ferrario,1 Fabrizio Schettini,1 Angelo Avogaro,2 Chiara Bellia,3 Federico Bertuzzi,4 Graziella Bonetti,5 Antonio Ceriello,6 Marcello Ciaccio,3,7 Massimiliano Corsi Romanelli,8,9 Elena Dozio,9 Luca Falqui,10 Angela Girelli,11 Antonio Nicolucci,12 Gianluca Perseghin,13,14 Mario Plebani,15 Umberto Valentini,11 Martina Zaninotto,15 Silvana Castaldi,9,16 Emanuela Foglia1 1Centre for Health Economics, Social and Health Care Management, Università Carlo Cattaneo - LIUC, Castellanza, Italy; 2Department of Medicine, University-Hospital of Padova, Padova, Italy; 3Section of Clinical Biochemistry and Clinical Molecular Medicine, Department of Biopathology and Medical Biotechnologies, University of Palermo, Palermo, Italy; 4Diabetology Unit, Grande Ospedale Metropolitano Niguarda Hospital, Milan, Italy; 5Department of Medicine Services, Valcamonica Hospital, Esine, Italy; 6Department of Cardiovascular and Metabolic Diseases, Multimedica Research Institute, Milan, Italy; 7Department of Laboratory Medicine, University-Hospital of Palermo, Palermo, Italy; 8Service of Laboratory Medicine 1-Clinical Pathology, Policlinico San Donato, Milan, Italy; 9Department of Biomedical Sciences for Health, Università degli Studi di Milano, Milan, Italy; 10Department of Medicine, Diabetes and Endocrinology, Multimedica Research Institute, Milan, Italy; 11Diabetes Care Unit, Spedali Civili Hospital, Brescia, Italy; 12Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy; 13Department of Medicine and Surgery, Università degli Studi di Milano Bicocca, Milan, Italy; 14Department of Medicine and Rehabilitation, Unit of Metabolic Medicine, Policlinico di Monza, Monza, Italy; 15Department of Laboratory Medicine, University-Hospital of Padova, Padova, Italy; 16Fondazione Ca’ Granda Ospedale Maggiore Policlinico Research Institute of Milano, Milano, ItalyCorrespondence: Lucrezia FerrarioCentre for Health Economics, Social and Health Care Management, Università Carlo Cattaneo – LIUC, Corso Matteotti 22, Castellanza, 21053, VA, ItalyTel +39 033 1572504Fax +39 033 1572513Email lferrario@liuc.itPurpose: To investigate the glycated albumin (GA) introduction implications, as an add-on strategy to traditional glycemic control (Hb1Ac and fasting plasma glucose – FPG) instruments, considering insulin-naïve individuals with type 2 diabetes mellitus (T2DM), treated with oral therapies.Methods: A Health Technology Assessment was conducted in Italy, as a multi-dimensional approach useful to validate any innovative technology. The HTA dimensions, derived from the EUnetHTA Core Model, were deployed by means of literature evidence, health economics tools and qualitative questionnaires, filled-in by 15 professionals.Results: Literature stated that the GA introduction could lead to a higher number of individuals achieving therapeutic success after 3 months of therapy (97.0% vs 71.6% without GA). From an economic point of view, considering a projection of 1,955,447 T2DM insulin-naïve individuals, potentially treated with oral therapy, GA introduction would imply fewer individuals requiring a therapy switch (− 89.44%), with a 1.06% in costs reduction, on annual basis, thus being also the preferable solution from a cost-effectiveness perspective (cost-effectiveness value: 237.74 vs 325.53). According to experts opinions, lower perceptions on GA emerged with regard to equity aspects (0.13 vs 0.72, p-value> 0.05), whereas it would improve both individuals (2.17 vs 1.33, p-value=0.000) and caregivers quality of life (1.50 vs 0.83, p-value=0.000). Even if in the short term, GA required additional investments in training courses (− 0.80 vs 0.10, p-value = 0.036), in the long run, GA could become the preferable technology (0.30 vs 0.01, p-value=0.018) from an organisational perspective.Conclusion: Adding GA to traditional glycaemic control instruments could improve the clinical pathway of individuals with T2DM, leading to economic and organisational advantages for both hospitals and National Healthcare Systems.Keywords: glycated albumin, type 2 diabetes mellitus, T2DM, Health Technology Assessment, economic evaluation, multidimensional approach

Abstract Background The effect of plasma hepcidin concentrations on the long-term risk of developing adverse cardiovascular outcomes in people with type 2 diabetes mellitus (T2DM) is unclear. Methods We followed for a median of 55.6 months 213 outpatients with established T2DM (45.5% women, mean age 69 ± 10 years; BMI 28.7 ± 4.7 kg/m2; median diabetes duration 11 years). Baseline plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively. The primary study outcome was a composite of all-cause mortality or incident nonfatal cardiovascular events (inclusive of myocardial infarction, permanent atrial fibrillation, ischemic stroke, or new hospitalization for heart failure). Results 42 patients developed the primary composite outcome over a median follow-up of 55.6 months. After stratifying patients by baseline hepcidin tertiles [1st tertile: median hepcidin 1.04 (IQR 0.50–1.95) nmol/L, 2nd tertile: 3.81 (IQR 3.01-4-42) nmol/L and 3rd tertile: 7.72 (IQR 6.37–10.4) nmol/L], the risk of developing the primary composite outcome in patients in the 3rd tertile was double that of patients in the 1st and 2nd tertile combined (unadjusted hazard ratio [HR] 2.32, 95%CI 1.27–4.26; p = 0.007). This risk was not attenuated after adjustment for age, sex, adiposity measures, smoking, hypertension, statin use, antiplatelet medication use, plasma hs-C-reactive protein and ferritin concentrations (adjusted HR 2.53, 95%CI 1.27–5.03; p = 0.008). Conclusions In outpatients with T2DM, higher baseline hepcidin concentrations were strongly associated with an increased long-term risk of overall mortality or nonfatal cardiovascular events, even after adjustment for established cardiovascular risk factors, plasma ferritin concentrations, medication use, and other potential confounders.

Abstract Background Advanced Hybrid Closed-Loop system (AHCL) has profoundly changed type 1 diabetes therapy. This study primarily aimed to assess the impact on Glycemia Risk Index (GRI) and other continuous glucose monitoring (CGM) metrics when switching from one of four insulin strategies to AHCL in type 1 adult patients. Methods A single-center, retrospective pre/post observational study; 198 patients (age 44.4 ± 12.7 years, 115 females/83 males, diabetes duration 24.7 ± 11.6 years, HbA1c 7.4 ± 1%), treated with different insulin therapies (MDI, CSII, SAP with PLGS, HCL) were assessed before and after switching to an AHCL (MiniMed 780G, Diabeloop Roche, Tandem Control-IQ) at 1, 3, 6, and 12 months. Mixed-effects multivariable regression models were used to estimate the mean pre/post variations at different time points, adjusted for potential confounders. Results A month after the switch, there was an improvement in CGM metrics and HbA1c for all patients: GRI −10.7, GMI −0.27%, CV −2.1%, TAR>250 −3.7%, TAR180-250 −5.6%, TIR + 9.7%, HbA1c −0.54% (all p 250 at T1 (for all p

Proceedings

O contraturno escolar constitui-se como movimento de Educação Integral, com vistas a potencializar o papel social da escola no desenvolvimento humano. Neste artigo, abordamos o modelo de implementação da Educação Integral na Rede Municipal de Educação do município de Guaporé, Rio Grande do Sul, por meio do contraturno escolar, cujo foco é a integração da robótica educacional, especificamente, o lego robotizado, nas práticas pedagógicas. Analisamos planejamentos didáticos com lego robotizado, tendo como eixo temático a colaboração enquanto pressuposto para a resolução de problemas e desenvolvimento humano integral. Enfatizamos que o lego robotizado é recurso potencializador de práticas colaborativas, as quais são essenciais para a interação em sociedade e atuação cidadã participativa, em movimentos de equidade e justiça social.

Abstract Background The new trend demanding for “natural” agri-food products has encouraged the application of more sustainable and eco-friendly farming methods, which limit or avoid the use of synthetic chemicals. This approach is increasing in viticulture, one of the sectors with the highest commercial value since grapes and derived products are largely consumed foodstuffs, with appreciated nutritional and sensory features. In this work, 1H Nuclear Magnetic Resonance spectroscopy (1H NMR) was applied for the metabolic profiling of cv. Italia table grapes samples, from the same origin area, cultivated with different treatments (biodynamic, organic and integrated) and collected in three subsequent vintages. Multivariate statistical analysis was performed on NMR-data with the aim of comprehensively researching the possible influences on metabolites due to the use of diverse agricultural practices. Results Both inter-annual variability (2020, 2021 and 2022 vintages) and different vineyard treatments (biodynamic, organic and integrated) resulted as significant drivers for samples differentiation in the preliminary unsupervised analysis of the (1H NMR spectra derived) metabolic profile data. Nevertheless, supervised data analyses showed that inter-vineyards variability, due to application of diverse farming methods, had a comparable discriminating effect with respect to harvesting years. Ethanol, sugars (as α-/β-glucose), organic acids (as malate) and amino acids (as arginine, leucine, glutamine) resulted the most viticultural practices-dependent metabolites. Interestingly, results from pairwise comparisons between treatments indicated the biodynamic samples with respect to the organic ones as the best-observed differentiation. This was followed by the biodynamic vs integrated and organic vs integrated samples comparisons, in decreasing discrimination order, as confirmed by the descriptiveness and predictive ability parameters of the corresponding pairwise OPLS-DA models. Conclusions Results highlighted that metabolites’ composition in cv. Italia table grapes juice is significantly affected by the use of different kinds of vineyard managements (biodynamic, organic and integrated, here investigated). Metabolomics study, here employing 1H NMR spectroscopy combined with multivariate statistical analysis, offers powerful tools to elucidate the metabolic differences among classes of samples. Graphical Abstract

Background: Despite the well-known efficacy of anti-COVID-19 vaccines in preventing morbidity and mortality, several vaccinated individuals are diagnosed with SARS-CoV-2 breakthrough infection, which might require hospitalisation. This multicentre, observational, and retrospective study aimed to investigate the clinical characteristics and outcomes of vaccinated vs. non-vaccinated patients, both hospitalised with SARS-CoV-2 infection in 3 major hospitals in Northern Italy. Methods: Data collection was retrospective, and paper and electronic medical records of adult patients with a diagnosed SARS-CoV-2 infection were pseudo-anonymised and analysed. Vaccinated and non-vaccinated individuals were manually paired, using a predetermined matching criterion (similar age, gender, and date of hospitalisation). Demographic, clinical, treatment, and outcome data were compared between groups differing by vaccination status using Pearson’s Chi-square and Mann-Whitney tests. Moreover, multiple logistic regression analyses were performed to assess the impact of vaccination status on ICU admission or intra-hospital mortality. Results: Data from 360 patients were collected. Vaccinated patients presented with a higher prevalence of relevant comorbidities, like kidney replacement therapy or haematological malignancy, despite a milder clinical presentation at the first evaluation. Non-vaccinated patients required intensive care more often than their vaccinated counterparts (8.8% vs. 1.7%, p = 0.002). Contrariwise, no difference in intra-hospital mortality was observed between the two groups (19% vs. 20%, p = 0.853). These results were confirmed by multivariable logistic regressions, which showed that vaccination was significantly associated with decreased risk of ICU admission (aOR=0.172, 95%CI: 0.039–0.542, p = 0.007), but not of intra-hospital mortality (aOR=0.996, 95%CI: 0.582–1.703, p = 0.987). Conclusions: This study provides real-world data on vaccinated patients hospitalised with COVID-19 in Northern Italy. Our results suggest that COVID-19 vaccination has a protective role in individuals with higher risk profiles, especially regarding the need for ICU admission. These findings contribute to our understanding of SARS-CoV-2 infection outcomes among vaccinated individuals and emphasise the importance of vaccination in preventing severe disease, particularly in those countries with lower first-booster uptake rates.

ObjectiveThe present study aims to present a novel cognitive-behavioral intervention protocol focused on treating social isolation through telematic interaction, thus overcoming common barriers characteristic of face-to-face interventions.MethodsWe examined current literature about face-to-face and telematic psychotherapeutic interventions for the treatment of social isolation in early adulthood. Current evidence is mixed, suggesting the need to develop novel interventions focused on patients’ cognitive functioning. Moreover, telematic interventions are promising candidates for overcoming common barriers intrinsic to the condition of social isolation.ResultsThe present 8-session model inspired by cognitive behavioral theoretical models and cognitive interventions currently present in the literature is thought to help socially isolated adult patients reduce clinical symptoms associated with the condition and lead to a reduction in the avoidance of social situations, leading to an improvement of the quality of life.ConclusionWe presented a telematic psychotherapeutic intervention aimed at helping adult patients suffering from social isolation who are unable to seek help from national health systems and face-to-face interventions, thus overcoming barriers intrinsic to social isolation. The present cognitive-behavioral treatment protocol has been developed in the context of a randomized clinical trial ongoing in Italy, aimed at implementing and testing the feasibility and effectiveness of multimodal digital interventions for treating social isolation.

Background: Fabry disease (FD) is a multisystem, monogenic, X-linked storage disorder caused by mutations in the GLA gene, resulting in reduced alfa-galactosidase A enzyme activity. This effect leads to the accumulation of glycosphingolipids, particularly globotriosylceramide, in various tissues, including the heart, kidney, vasculature, smooth muscle and peripheral nervous system. Hemizygous males are usually more severely affected than females, in whom random inactivation of an X-chromosome may lead to variable phenotype. Summary: Among the manifestations of FD, exercise intolerance is commonly diagnosed but often underestimated, even though it significantly limits quality of life, especially in young patients. This review primarily discusses the various pathophysiological mechanisms involved in exercise intolerance in FD patients, such as altered muscle composition, compromised cardiopulmonary framework, and peripheral neuropathy. Secondarily, it explores the potential effect of available therapy, including Enzyme Replacement Therapy (ERT) and chaperone therapy (migalastat), in reducing exercise intolerance while considering the potential impact of physical activity and exercise training as adjunctive treatments. Conclusion: Exercise intolerance has a major impact on the well-being of people with Fabry disease. Exercise training can play an important role in addition to drug therapy.

BackgroundPneumonectomy is a radical surgical procedure associated with significant morbidity and mortality. Its application in the context of pulmonary neuroendocrine tumours, including carcinoid tumours, requires meticulous preoperative planning and intraoperative precision. This study aims to assess the safety and efficacy of pneumonectomy in the management of these rare and challenging neoplasms.MethodsA retrospective analysis of patients who underwent pneumonectomy for pulmonary carcinoid tumours at our institution over a specified period was conducted. Data regarding patient demographics, tumour characteristics, surgical techniques, intraoperative complications, perioperative management, and long-term outcomes were collected and analysed.ResultsBetween March 2001 and October 2022, 21 patients (7 male, 14 female) with carcinoid tumours underwent pneumonectomy on a total of 459 surgical operations for carcinoid. Preoperative bronchoscopic procedures were conducted in 90.4% of cases, leading to histological diagnoses for most. The median hospital stay was eight days, with no reported perioperative deaths. Median follow-up after surgery was 73 months, with a five-year overall survival of 65.4 months. Recurrences occurred in 28.6% of cases, primarily in atypical carcinoids.ConclusionDespite the rarity of bronchial carcinoids, pneumonectomy is effective for low-grade malignancies, demonstrating positive short—and long-term outcomes. Radical lymph node dissection is fundamental in pathological staging and overall survival.

We study the coupling between time-dependent Darcy–Brinkman and the Darcy equations at the microscale subjected to inhomogeneous body forces and initial conditions to describe a double porosity problem. We derive the homogenized governing equations for this problem using the asymptotic homogenization technique, and as macroscopic results, we obtain a coupling between two Darcy equations, one of which with memory effects, with mass exchange between phases. The memory effects are a consequence of considering the time dependence in the Darcy–Brinkman equation, and they allow us to study in more detail the role of time in the problem under consideration. After the formulation of the model, we solve it in a simplified setting and we use it to describe the movement of fluid within a vascularized lymph node.

Purpose: The purpose of this study is to study the evolution of quality of life (QoL) in the first 5 years following Intensity-modulated radiation therapy (IMRT) for prostate cancer (PCa) and to determine possible associations with clinical/treatment data. Material and methods: Patients were enrolled in a prospective multicentre observational trial in 2010-2014 and treated with conventional (74–80 Gy, 1.8–2 Gy/fr) or moderately hypofractionated IMRT (65–75.2 Gy, 2.2–2.7 Gy/fr). QoL was evaluated by means of EORTC QLQ-C30 at baseline, at radiation therapy (RT) end, and every 6 months up to 5 years after IMRT end. Fourteen QoL dimensions were investigated separately. The longitudinal evaluation of QoL was analysed by means of Analysis of variances (ANOVA) for multiple measures. Results: A total of 391 patients with complete sets of questionnaires across 5 years were available. The longitudinal analysis showed a trend toward the significant worsening of QoL at RT end for global health, physical and role functioning, fatigue, appetite loss, diarrhoea, and pain. QoL worsening was recovered within 6 months from RT end, with the only exception being physical functioning. Based on ANOVA, the most impaired time point was RT end. QoL dimension analysis at this time indicated that acute Grade ≥ 2 gastrointestinal (GI) toxicity significantly impacted global health, physical and role functioning, fatigue, appetite loss, diarrhoea, and pain. Acute Grade ≥ 2 genitourinary (GU) toxicity resulted in lower role functioning and higher pain. Prophylactic lymph-nodal irradiation (WPRT) resulted in significantly lower QoL for global health, fatigue, appetite loss, and diarrhoea; lower pain with the use of neoadjuvant/concomitant hormonal therapy; and lower fatigue with the use of an anti-androgen. Conclusions: In this prospective, longitudinal, observational study, high radiation IMRT doses delivered for PCa led to a temporary worsening of QoL, which tended to be completely resolved at six months. Such transient worsening was mostly associated with acute GI/GU toxicity, WPRT, and higher prescription doses.

Background: Sleeve lobectomy with bronchoplasty is a safe surgical technique for the management of lung cancer and endobronchial localization of extrapulmonary cancers. However, anastomotic complications can occur, and treatment strategies are not standardized. Methods: Data from 280 patients subjected to bronchoplasty were retrospectively analyzed, focusing on surgical techniques, anastomotic complications, and their management. Multivariate analysis was performed, and Kaplan–Meier curves were used to determine survival. Results: Ninety percent of 280 surgeries were for lung cancer. Anastomotic complications occurred in 6.42% of patients: late stenosis in 3.92% and broncho-pleural fistula in 1.78%. The median survival was 65.90 months (95% CI = 41.76–90.97), with no difference (p = 0.375) for patients with (51.28 months) or without (71.03 months) anastomotic complications. Mortality at 30 days was higher with anastomotic complications (16.7% vs. 3%, p = 0.014). Multivariable analysis confirmed pathological stage (N+) as a risk factor for anastomotic complications (p = 0.016). Our mortality (3.93%) and morbidity rate (41.78%) corresponded to recent series results. Conclusions: In our experience, surgery is preferred to avoid life-threatening complications in bronchopleural fistulas. Bronchoscopic balloon dilatation is preferred for benign strictures. The nodal stage is related to complications (p = 0.0014), reflecting the aggressiveness of surgery, which requires extended radical lymphadenectomy.

The present study, based on data concerning 2328 immigrant children attending a representative sample of 561 schools, investigates the impact of various group, family and individual characteristics as well as proficiency in the national language on acceptance and friendship among classmates, while controlling for measurement errors by means of a structural equation modelling approach. As regards group characteristics, the results indicate that only immigrant density in the classroom has a positive impact on social inclusion, which seems to be limited to peer acceptance. As regards family and individual characteristics, low-SES and female immigrants appear to be doubly vulnerable in class, which specifically affects their friendships. One of our main findings is that proficiency in the national language predicts the social inclusion of immigrant children, while controlling for all the other variables considered. A moderation analysis reveals that this factor also applies to second-generation immigrants. In conclusion, we suggest that interventions aiming to facilitate the social inclusion of immigrant children should take into account the fact that proficiency in the national language appears to be much more important than group, family and individual characteristics, and that low-SES and female immigrants require particular attention, since they are doubly vulnerable.

Anemia is common in cancer patients and impacts on quality of life and prognosis. It is typically multifactorial, often involving different pathophysiological mechanisms, making treatment a difficult task. In patients undergoing active anticancer treatments like chemotherapy, decreased red blood cell (RBC) production due to myelosuppression generally predominates, but absolute or functional iron deficiency frequently coexists. Current treatments for chemotherapy-related anemia include blood transfusions, erythropoiesis-stimulating agents, and iron supplementation. Each option has limitations, and there is an urgent need for novel approaches. After decades of relative immobilism, several promising anti-anemic drugs are now entering the clinical scenario. Emerging novel classes of anti-anemic drugs recently introduced or in development for other types of anemia include activin receptor ligand traps, hypoxia-inducible factor-prolyl hydroxylase inhibitors, and hepcidin antagonists. Here, we discuss their possible role in the treatment of anemia observed in patients receiving anticancer therapies.