L'evoluzione della nozione di "sicurezza alimentare": dalla normativa italiana a quella comunitaria.

INTRODUZIONE Questa tesi si propone di esaminare l’evoluzione degli ambiti giuridici su cui si basa l’applicazione della nozione di “sicurezza alimentare” partendo dalla normativa italiana per arrivare a quella comunitaria. L’analisi è stata condotta partendo da un excursus storico relativo alle prime fonti sulla materia soffermandosi, in particolare, sul periodo medioevale, per arrivare all’Unità d’Italia. L’analisi è proseguita sulla normativa italiana degli anni Settanta, Ottanta e Novanta ed infine ai giorni nostri. Si sono poi esaminate le modalità di creazione degli standard, pubblici e privati, e il motivo della loro diffusione, così come quelli delle certificazioni e delle ragioni che hanno portato il legislatore pubblico ad emanare il Reg. 765/08 per il loro controllo. Contemporaneamente, si sono messi in luce gli effetti di tale evoluzione sull’attività di controllo della sicurezza gli alimenti in relazione al ruolo del veterinario ispettore. Quello che si evince dall’analisi svolta è che il controllo della sicurezza alimentare è passato da un sistema di accertamento di tipo prefettizio, da parte del Ministero dell’Interno, al Ministero della Salute, inquadrandosi poi con la legge 283/62 sotto un profilo di diritto pubblico-amministrativistico con rilevanza penale. Successivamente, l’ingresso nel sistema legislativo alimentare europeo con l’adozione del Regolamento 178/02 e del Pacchetto Igiene ha portato ad uno spostamento delle responsabilità, lungo tutta la filiera (From farm to table), dal controllore pubblico all’OSA. Lo studio ha portato ad evidenziare che la governance del settore alimentare è un sistema multilivello in cui oltre ad intrecciarsi il livello nazionale con quello globale, si collegano una molteplicità di interessi coinvolti, il che porta ad un “disordine normativo” con la coesistenza di attori privati e pubblici e strumenti di tutela hard e soft law. Infine, si è arrivati ad affermare che con la predominanza del mercato globale e le implicazioni socioeconomiche ad esso legate, si è fatto sempre maggior ricorso alle certificazioni private. Questo ha causato uno spostamento del concetto di sicurezza alimentare da un contesto normativo di diritto pubblico amministrativistico ad uno di diritto privato amministrativistico. Abstracts This work aims to analyze the evolution of the notion of "food safety" in the Italian and European legislative framework. The analysis begins with a historical perspective starting from the first legal sources on the topic. In particular, the first part of the study spanned from the medieval period to the Unification of Italy. Then, the analysis continued by examining the Italian legislation during the Seventies, Eighties and Nineties, and in the present days. We examined how public and private standards and certification have been produced and the reason of their spread together with the reason that led the legislature to enact the Reg. 765/08 for their control. At the same time, we highlighted the effects of this development on the figure of the Veterinary Inspector. What emerged from the analysis is that the control of food safety, has changed from an inspection system based on a prefectural control, under the Ministry of Interior, to a system of public-regulatory matter with penal relevance under the law 283/62 of the Ministry of Health. Subsequently, the entrance in the European food law system with the adoption of Regulation 178/02 and of the Hygiene Package has led to a shift of responsibilities, throughout the supply chain (From farm to table), from the public controller to FBOs. The study highlighted that the governance of the food industry is a multi-level system. In addition to the overlap of the national and the global level, multiple interests are interconnected, leading to a "regulatory disorder" with the coexistence of private and public actors, and hard and soft law protection tools. Finally, we affirm that with the dominance of the global market and its socio-economic implications, the use of private certifications has increasingly grown. In this context the concept of food safety has moved from a public to a private regulatory matter

SARS-CoV-2 vertical transmission in a twin-pregnant woman. A case report

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS- CoV-2) has affected millions of people around the world in the last years. Among susceptible patients, pregnant women seem to be prone to have serious complications. The possibility of SARS-CoV-2 vertical transmission represents one of the most debated topics in the literature, providing inconclusive results. We present a case of a confirmed vertical transmission in a monochorial diamniotic twin pregnancy complicated by a selective intrauterine growth restriction (sIUGR) and gestational diabetes. The analysis of different biological specimens identifies the presence of SARS-CoV2 genome in the umbilical cord blood of both twins and the placental histologic examination confirmed indirect signs of viral infection, supporting the hypothesis that a transplacental infection can occur. Despite the devastating impact that SARS-CoV2 has worldwide, neonatal infections have been infrequently reported but they can occur under certain biologic conditions. A deep knowledge of the biological mechanisms underlying the risk of SARS-CoV-2 vertical transmission might be useful to understand the pathophysiological bases and the possible long-term implication of a mother-to-child vertical transmission

SARS-CoV-2 infection in pregnancy. Clues and proof of adverse outcomes

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) represents one of the most threatening viral infections in the last decade. Amongst susceptible individuals, infected pregnant women might be predisposed to severe complications. Despite the extensive interest in SARS-CoV-2 research, the clinical course of maternal infection, the vertical transmission and the neonatal outcomes have not been completely understood yet. The aim of our study was to investigate the association between SARS-CoV-2 infection, obstetric outcomes and vertical transmission. Methods: A prospective observational study was performed, enrolling unvaccinated pregnant patients positive for SARS-CoV-2 (cases) and matched with uninfected pregnant women (controls). Maternal and neonatal nasopharyngeal swabs, maternal and cord blood, amniotic fluid and placenta tissue samples were collected; blood samples were tested for anti-S and anti-N antibodies, and histologic examination of placental tissues was performed. Results: The cases showed a significant association with the development of some obstetric complications, such as intrauterine growth restriction and pregnancy-associated hypothyroidism and diabetes, as compared to controls; their newborns were more likely to have a low birth weight and an arterial umbilical pH less than 7. The viral genome was detected in maternal and cord blood and placental samples in six cases. Conclusions: Pregnant women positive for SARS-CoV-2 infection are more likely to develop severe obstetric outcomes; their newborns could have a low birth weight and arterial pH. Vertical transmission seems a rare event, and further investigation is strongly needed

ESMO management and treatment adapted recommendations in the COVID-19 era: gynaecological malignancies

The rapid spread of severe acute respiratory syndrome coronavirus 2 infection and its related disease (COVID-19) has required an immediate and coordinate healthcare response to face the worldwide emergency and define strategies to maintain the continuum of care for the non-COVID-19 diseases while protecting patients and healthcare providers. The dimension of the COVID-19 pandemic poses an unprecedented risk especially for the more vulnerable populations. To manage patients with cancer adequately, maintaining the highest quality of care, a definition of value-based priorities is necessary to define which interventions can be safely postponed without affecting patients’ outcome. The European Society for Medical Oncology (ESMO) has endorsed a tiered approach across three different levels of priority (high, medium, low) incorporating information on the value-based prioritisation and clinical cogency of the interventions that can be applied for different disease sites. Patients with gynaecological cancer are at particular risk of COVID-19 complications because of their age and prevalence of comorbidities. The definition of priority level should be based on tumour stage and histology, cancer-related symptoms or complications, aim (curative vs palliative) and magnitude of benefit of the oncological intervention, patients’ general condition and preferences. The decision-making process always needs to consider the disease-specific national and international guidelines and the local healthcare system and social resources, and a changing situation in relation to COVID-19 infection. These recommendations aim to provide guidance for the definition of deferrable and undeferrable interventions during the COVID-19 pandemic for ovarian, endometrial and cervical cancers within the context of the ESMO Clinical Practice Guidelines

Hypothermic oxygenated perfusion in extended criteria donor liver transplantation-A randomized clinical trial

Hypothermic Oxygenated Perfusion (HOPE) of the liver can reduce the incidence of early allograft dysfunction (EAD) and failure in extended criteria donors (ECD) grafts, although data from prospective studies are very limited. In this monocentric, open-label study, from December 2018 to January 2021, 110 patients undergoing transplantation of an ECD liver graft were randomized to receive a liver after HOPE or after static cold storage (SCS) alone. The primary endpoint was the incidence of EAD. The secondary endpoints included graft and patient survival, the EASE risk score, and the rate of graft or other graft-related complications. Patients in the HOPE group had a significantly lower rate of EAD (13% vs. 35%, p = .007) and were more frequently allocated to the intermediate or higher risk group according to the EASE score (2% vs. 11%, p = .05). The survival analysis confirmed that patients in the HOPE group were associated with higher graft survival one year after LT (p = .03, log-rank test). In addition, patients in the SCS group had a higher re-admission and overall complication rate at six months, in particular cardio-vascular adverse events (p = .04 and p = .03, respectively). HOPE of ECD grafts compared to the traditional SCS preservation method is associated with lower dysfunction rates and better graft survival

Direct-acting antivirals and hepatocellular carcinoma in chronic hepatitis C: A few lights and many shadows

With the introduction of direct-acting antiviral agents (DAA), the rate of sustained virological response (SVR) in the treatment of hepatitis C virus (HCV) has radically improved to over 95%. Robust scientific evidence supports a beneficial role of SVR after interferon therapy in the progression of cirrhosis, resulting in a decreased incidence of hepatocellular carcinoma (HCC). However, a debate on the impact of DAAs on the development of HCC is ongoing. This review aimed to analyse the scientific literature regarding the risk of HCC in terms of its recurrence and occurrence after the use of DAAs to eradicate HCV infection. Among 11 studies examining HCC occurrence, the de novo incidence rate ranged from 0 to 7.4% (maximum follow-up: 18 mo). Among 18 studies regarding HCC recurrence, the rate ranged from 0 to 54.4% (maximum "not well-defined" followup: 32 mo). This review highlights the major difficulties in interpreting data and reconciling the results of the included studies. These difficulties include heterogeneous cohorts, potential misclassifications of HCC prior to DAA therapy, the absence of an adequate control group, short follow-up times and different kinds of follow-up. Moreover, no clinical feature-based scoring system accounts for the molecular characteristics and pathobiology of the tumours. Nonetheless, this review does not suggest that there is a higher rate of de novo HCC occurrence or recurrence after DAA therapy in patients with previous HCV infection. \ua9 2018 The Author(s). Published by Baishideng Publishing Group Inc. All rights reserved

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 > 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 < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 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

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Automated Analysis of Proliferating Cells Spatial Organisation Predicts Prognosis in Lung Neuroendocrine Neoplasms

SIMPLE SUMMARY: Lung neuroendocrine neoplasms (lung NENs) are categorised by morphology, defining a classification sometimes unable to reflect ultimate clinical outcome, particularly for the intermediate domains of adenocarcinomas and large-cell neuroendocrine carcinomas. Moreover, subjectivity and poor reproducibility characterise diagnosis and prognosis assessment of all NENs. The aim of this study was to design and evaluate an objective and reproducible approach to the grading of lung NENs, potentially extendable to other NENs, by exploring a completely new perspective of interpreting the well-recognised proliferation marker Ki-67. We designed an automated pipeline to harvest quantitative information from the spatial distribution of Ki-67-positive cells, analysing its heterogeneity in the entire extent of tumour tissue—which currently represents the main weakness of Ki-67—and employed machine learning techniques to predict prognosis based on this information. Demonstrating the efficacy of the proposed framework would hint at a possible path for the future of grading and classification of NENs. ABSTRACT: Lung neuroendocrine neoplasms (lung NENs) are categorised by morphology, defining a classification sometimes unable to reflect ultimate clinical outcome. Subjectivity and poor reproducibility characterise diagnosis and prognosis assessment of all NENs. Here, we propose a machine learning framework for tumour prognosis assessment based on a quantitative, automated and repeatable evaluation of the spatial distribution of cells immunohistochemically positive for the proliferation marker Ki-67, performed on the entire extent of high-resolution whole slide images. Combining features from the fields of graph theory, fractality analysis, stochastic geometry and information theory, we describe the topology of replicating cells and predict prognosis in a histology-independent way. We demonstrate how our approach outperforms the well-recognised prognostic role of Ki-67 Labelling Index on a multi-centre dataset comprising the most controversial lung NENs. Moreover, we show that our system identifies arrangement patterns in the cells positive for Ki-67 that appear independently of tumour subtyping. Strikingly, the subset of these features whose presence is also independent of the value of the Labelling Index and the density of Ki-67-positive cells prove to be especially relevant in discerning prognostic classes. These findings disclose a possible path for the future of grading and classification of NENs