Le metriche di monitoraggio e valutazione dell’implementazione del PNRR

Il capitolo approfondisce la governance e gli strumenti di monitoraggio del PNRR in Sanità, con riferimento specifico alla Missione 6. Lo studio presenta un'analisi delle dimensioni oggetto di attenzione e degli indicatori forniti a supporto dell'implementazione dei progetti PNRR che riguardano le aziende sanitarie italiane

Regioselective Synthesis, Structural Characterization, and Antiproliferative Activity of Novel Tetra-Substituted Phenylaminopyrazole Derivatives

A small library of highly functionalized phenylaminopyrazoles, bearing different substituents at position 1, 3 and 4 of the pyrazole ring, was prepared by the one pot condensation of active methylene reagents, phenylisothiocyanate and substituted hydrazine (namely, methyl- and benzyl-hydrazine). The identified reaction conditions proved to be versatile and efficient. Fur-thermore, the evaluation of alternative stepwise protocols affected the chemo- and re-gio-selectivity outcome of the one-pot procedure. The chemical identity of two N-methyl pyrazole isomers, selected as prototypes of the whole series, was unambiguously identified by means of NMR and mass spectrometry studies. Additionally, semiempirical calculations provided a structural rationale for the different chromatographic behaviour of the two isomers. The prepared tetra-substituted phenylaminopyrazoles were tested in cell-based assays on a panel of cancer and normal cell lines. The tested compounds did not show any cytotoxic effect on the selected cell lines, thus supporting their pharmaceutical potentials

Left pneumonectomy for rapidly growing lung metastasis from phyllodes tumor

Distant metastases occur in 10-25% of malignant phyllodes tumors of the breast, heralding fatal outcome within few months. Only four cases of successful resection of solitary pulmonary metastases from phyllodes tumor are described in the literature. We report the case of a 67-year-old woman who developed rapidly growing metastases (volume doubling time: 25 days) in the left lung, two years after mastectomy for malignant phyllodes tumor. The left lung was the only site of 18-FDG uptake at total-body PET scan and the patient was successfully treated by left pneumonectomy

Peri-operative complications of video-assisted thoracoscopic surgery (VATS)

AbstractVideo-assisted thoracoscopic surgery (VATS) has multiple indications for diagnosis and treatment of many different thoracic diseases; the commonest are lung wedge resection, pleural and mediastinal biopsy, treatment of pneumothorax, and pleurectomy. Moreover, in recent years a few surgeons have performed routinely major lung anatomic resections by VATS approach, including segmentectomy, lobectomy and pneumonectomy.In our experience VATS constitutes about one-third of all thoracic surgical procedures. In the reviewed literature as in the most frequent complications after VATS procedures are: prolonged air leak, bleeding, infection, postoperative pain, port site recurrence and the need to convert the access in thoracotomy. The complication and mortality rates are generally very low and VATS procedures are considered safe and effective.It is recommended that all thoracic surgery departments audit their VATS procedures for peri-operative morbidity and mortality to compare results and outcomes

Skip metastases to lateral cervical lymph nodes in differentiated thyroid cancer: A systematic review

Papillary thyroid carcinoma is a slow-growing cancer with a generally good prognosis that sometimes have an aggressive behaviour. Metastases to neck lymph nodes is the first step of the diffusion. The central neck compartment is involved most commonly. The ipsilateral lateral neck compartments are usually involved afterwards, and the involvement of the contralateral one is considered a quite rare occurrence. In more rare cases, metastases to lateral neck compartment without central lymph node metastasis (so called skip metastases) could be observed. Aim of this literature review study is to analyse the average incidence, pattern and risk factors of this occurrence.This study was performed according to PRISMA criteria. A final selection of 13 articles published in English language from 1997 to 2017 was performed. Any research article, review or meta-analysis was taken into consideration. Research was expanded considering the related references of articles.The incidence of skip metastases ranged from 1.6 to 21.8%. Risk factors such as age>45years, size <5mm and tumor located in the upper pole or isthmus of thyroid gland were found.Due to the frequency of skip metastases in thyroid cancer, a careful preoperative examination of lateral lymph nodes should be necessary

Combining Fuzzy Logic and Formal Argumentation for Legal Interpretation

International audienceThe interpretation of a norm is often uncertain and connicting. In this paper we propose a model for arguing about legal interpretation , which considers the problems of vagueness. After motivating our adoption of graded categories as a tool to tackle the problem of open texture in legal interpretation, we introduce a model based on fuzzy logic and argumentation. Then, we conduct a case study by using an example from medically assisted reproduction

Lenalidomide normalizes tumor vessels in colorectal cancer improving chemotherapy activity

BACKGROUND: Angiogenesis inhibition is a promising approach for treating metastatic colorectal cancer (mCRC). Recent evidences support the seemingly counterintuitive ability of certain antiangiogenic drugs to promote normalization of residual tumor vessels with important clinical implications. Lenalidomide is an oral drug with immune-modulatory and anti-angiogenic activity against selected hematologic malignancies but as yet little is known regarding its effectiveness for solid tumors. The aim of this study was to determine whether lenalidomide can normalize colorectal cancer neo-vessels in vivo, thus reducing tumor hypoxia and improving the benefit of chemotherapy. METHODS: We set up a tumorgraft model with NOD/SCID mice implanted with a patient-derived colorectal cancer liver metastasis. The mice were treated with oral lenalidomide (50 mg/Kg/day for 28 days), intraperitoneal 5-fluorouracil (5FU) (20 mg/Kg twice weekly for 3 weeks), combination (combo) of lenalidomide and 5FU or irrelevant vehicle. We assessed tumor vessel density (CD146), pericyte coverage (NG2; alphaSMA), in vivo perfusion capability of residual vessels (lectin distribution essay), hypoxic areas (HP2-100 Hypoxyprobe) and antitumor activity in vivo and in vitro. RESULTS: Treatment with lenalidomide reduced tumor vessel density (p = 0.0001) and enhanced mature pericyte coverage of residual vessels (p = 0.002). Perfusion capability of tumor vessels was enhanced in mice treated with lenalidomide compared to controls (p = 0.004). Accordingly, lenalidomide reduced hypoxic tumor areas (p = 0.002) and enhanced the antitumor activity of 5FU in vivo. The combo treatment delayed tumor growth (p = 0.01) and significantly reduced the Ki67 index (p = 0.0002). Lenalidomide alone did not demonstrate antitumor activity compared to untreated controls in vivo or against 4 different mCRC cell lines in vitro. CONCLUSIONS: We provide the first evidence of tumor vessel normalization and hypoxia reduction induced by lenalidomide in mCRC in vivo. This effect, seemingly counterintuitive for an antiangiogenic compound, translates into indirect antitumor activity thus enhancing the therapeutic index of chemotherapy. Our findings suggest that further research should be carried out on synergism between lenalidomide and conventional therapies for treating solid tumors that might benefit from tumor vasculature normalization

Handling Norms in Multi-Agent System by Means of Formal Argumentation

International audienceFormal argumentation is used to enrich and analyse normative multi-agent systems in various ways. In this chapter, we discuss three examples from the literature of handling norms by means of formal argumentation. First, we discuss how existing ways to resolve conflicts among norms using priorities can be represented in formal argumentation, by showing that the so-called Greedy and Reduction approaches can be represented using the weakest and the last link principles respectively. Based on such representation results, formal argumentation can be used to explain the detachment of obligations and permissions from hierarchical normative systems in a new way. Second, we discuss how formal argumentation can be used as a general theory for developing new approaches for normative reasoning, using a dynamic ASPIC-based legal argumentation theory. We show how existing logics of normative systems can be used to analyse such new argumentation systems. Third, we show how argumentation can be used to reason about other challenges in the area of normative multiagent systems as well, by discussing a model for arguing about legal interpretation. In particular, we show how fuzzy logic combined with formal argumentation can be used to reason about the adoption of graded categories and thus address the problem of open texture in normative interpretation. Our aim to discuss these three examples is to inspire new applications of formal argumentation to the challenges of normative reasoning in multiagent systems

Systematic review and critique of circulating miRNAs as biomarkers of stage I-II non-small cell lung cancer

Selected circulating microRNAs (miRNAs) have been suggested for non-invasive screening of non-small cell lung cancer (NSCLC), however the numerous proposed miRNA signatures are inconsistent. Aiming to identify miRNAs suitable specifically for stage I-II NSCLC screening in serum/plasma samples, we searched the databases \u201cPubmed\u201d, \u201cMedline\u201d, \u201cScopus\u201d, \u201cEmbase\u201d and \u201cWOS\u201d and systematically reviewed the publications reporting quantitative data on the efficacy [sensitivity, specificity and/or area under the curve (AUC)] of circulating miRNAs as biomarkers of NSCLC stage I and/or II. The 20 studies fulfilling the search criteria included 1110 NSCLC patients and 1009 controls, and were of medium quality according to Quality Assessment of Diagnostic Accuracy Studies checklist. In these studies, the patient cohorts as well as the control groups were heterogeneous for demographics and clinicopathological characteristics; moreover, numerous pre-analytical and analytical variables likely influenced miRNA determinations, and potential bias of hemolysis was often underestimated. We identified four circulating miRNAs scarcely influenced by hemolysis, each featuring high sensitivity (> 80%) and AUC (> 0.80) as biomarkers of stage I-II NSCLC: miR- 223, miR-20a, miR-448 and miR-145; four other miRNAs showed high specificity (> 90%): miR-628-3p, miR-29c, miR-210 and miR-1244. In a model of two-step screening for stage I-II NSCLC using first the above panel of serum miRNAs with high sensitivity and high AUC, and subsequently the panel with high specificity, the estimated overall sensitivity is 91.6% and overall specificity is 93.4%. These and other circulating miRNAs suggested for stage I-II NSCLC screening require validation in multiple independent studies before they can be proposed for clinical application

Interplay between COVID-19, pollution, and weather features on changes in the incidence of acute coronary syndromes in early 2020

Coronavirus disease 2019 (COVID-19) has caused an unprecedented change in the apparent epidemiology of acute coronary syndromes (ACS). However, the interplay between this disease, changes in pollution, climate, and aversion to activation of emergency medical services represents a challenging conundrum. We aimed at appraising the impact of COVID-19, weather, and environment features on the occurrence of ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) in a large Italian region and metropolitan area