Silvio d’Amico e la nascita del Burcardo

Silvio d’Amico played a central role in the birth and development of the Theatrical Collection of the Italian Society of Authors and Publishers (S.I.A.E.), named ‘Burcardo Library and Theatre Collection’, and in the acquisition of Luigi Rasi’s Theatrical Collection

Futuristas na ribalta: dos joelhos para baixo

Artigo sobre o teatro do movimento Futurista italiano

A sex-informed approach to improve the personalised decision making process in myelodysplastic syndromes: a multicentre, observational cohort study

Background Sex is a major source of diversity among patients and a sex-informed approach is becoming a new paradigm in precision medicine. We aimed to describe sex diversity in myelodysplastic syndromes in terms of disease genotype, phenotype, and clinical outcome. Moreover, we sought to incorporate sex information into the clinical decision-making process as a fundamental component of patient individuality. Methods In this multicentre, observational cohort study, we retrospectively analysed 13 284 patients aged 18 years or older with a diagnosis of myelodysplastic syndrome according to 2016 WHO criteria included in the EuroMDS network (n=2025), International Working Group for Prognosis in MDS (IWG-PM; n=2387), the Spanish Group of Myelodysplastic Syndromes registry (GESMD; n=7687), or the Dusseldorf MDS registry (n=1185). Recruitment periods for these cohorts were between 1990 and 2016. The correlation between sex and genomic features was analysed in the EuroMDS cohort and validated in the IWG-PM cohort. The effect of sex on clinical outcome, with overall survival as the main endpoint, was analysed in the EuroMDS population and validated in the other three cohorts. Finally, novel prognostic models incorporating sex and genomic information were built and validated, and compared to the widely used revised International Prognostic Scoring System (IPSS-R). This study is registered with ClinicalTrials.gov, NCT04889729. Findings The study included 7792 (58middot7%) men and 5492 (41middot3%) women. 10 906 (82middot1%) patients were White, and race was not reported for 2378 (17middot9%) patients. Sex biases were observed at the single-gene level with mutations in seven genes enriched in men (ASXL1, SRSF2, and ZRSR2 p<0middot0001 in both cohorts; DDX41 not available in the EuroMDS cohort vs p=0middot0062 in the IWG-PM cohort; IDH2 p<0middot0001 in EuroMDS vs p=0middot042 in IWG-PM; TET2 p=0middot031 vs p=0middot035; U2AF1 p=0middot033 vs p<0middot0001) and mutations in two genes were enriched in women (DNMT3A p<0middot0001 in EuroMDS vs p=0middot011 in IWG-PM; TP53 p=0middot030 vs p=0middot037). Additionally, sex biases were observed in co-mutational pathways of founding genomic lesions (splicing-related genes, predominantly in men, p<0middot0001 in both the EuroMDS and IWG-PM cohorts), in DNA methylation (predominantly in men, p=0middot046 in EuroMDS vs p<0middot0001 in IWG-PM), and TP53 mutational pathways (predominantly in women, p=0middot0073 in EuroMDS vs p<0middot0001 in IWG-PM). In the retrospective EuroMDS cohort, men had worse median overall survival (81middot3 months, 95% CI 70middot4-95middot0 in men vs 123middot5 months, 104middot5-127middot5 in women; hazard ratio [HR] 1middot40, 95% CI 1middot26-1middot52; p<0middot0001). This result was confirmed in the prospective validation cohorts (median overall survival was 54middot7 months, 95% CI 52middot4-59middot1 in men vs 74middot4 months, 69middot3-81middot2 in women; HR 1middot30, 95% CI 1middot23-1middot35; p<0middot0001 in the GEMSD MDS registry; 40middot0 months, 95% CI 33middot4-43middot7 in men vs 54middot2 months, 38middot6-63middot8 in women; HR 1middot23, 95% CI 1middot08-1middot36; p<0middot0001 in the Dusseldorf MDS registry). We developed new personalised prognostic tools that included sex information (the sex-informed prognostic scoring system and the sex-informed genomic scoring system). Sex maintained independent prognostic power in all prognostic systems; the highest performance was observed in the model that included both sex and genomic information. A five-to-five mapping between the IPSS-R and new score categories resulted in the re-stratification of 871 (43middot0%) of 2025 patients from the EuroMDS cohort and 1003 (42middot0%) of 2387 patients from the IWG-PM cohort by using the sex-informed prognostic scoring system, and of 1134 (56middot0%) patients from the EuroMDS cohort and 1265 (53middot0%) patients from the IWG-PM cohort by using the sex-informed genomic scoring system. We created a web portal that enables outcome predictions based on a sex-informed personalised approach. Interpretation Our results suggest that a sex-informed approach can improve the personalised decision making process in patients with myelodysplastic syndromes and should be considered in the design of clinical trials including low-risk patients. Copyright (c) 2022 Published by Elsevier Ltd. All rights reserved

A Rare Case of Duodenal Metastasis from Lobular Breast Cancer: From Diagnosis to Surgery

Gastrointestinal tract breast cancer (BC) metastases represent a rare event and generally originate from the lobular subtype. Duodenal involvement was rarely described in previous case series. Abdominal symptoms are extremely unspecific and misleading. Diagnosis is challenging, and it consists of a few mandatory steps from radiological examinations to histological and immunohistochemical analyses. Here, we presented the clinical case of a 54-year-old postmenopausal woman who was hospitalized for vomiting and jaundice, presenting increased level of liver enzymes and minimal main bile duct and choledocus dilatation at abdominal ultrasonography. She underwent breast-conserving surgery and axillary lymph node dissection for stage IIIB lobular BC, 5 years before. Metastatic infiltration of the duodenal bulb originating from lobular BC was proven histologically, through fine-needle aspiration during endoscopic ultrasonography. Treatment was established after multidisciplinary team evaluation, based on the clinical status and prognosis of the patient. Pancreaticoduodenectomy was performed, and final histological examination confirmed the secondary localization of lobular BC, infiltrating the duodenal and gastric wall, pancreas parenchyma, and surrounding tissues. No metastatic lymph nodes were found. After surgery, the patient underwent first line of adjuvant systemic treatment with fulvestrant and ribociclib. After a follow-up of 21 months, the patient was in good clinical condition, without signs of locoregional or distant recurrence. This report stressed on the importance of a tailored therapeutic approach. Although systemic therapy generally represents the preferred option, surgery should not be excluded if an oncological radical resection can be performed achieving acceptable locoregional disease control

Diagnosis and Clinical Management of Neuroendocrine Tumor of the Breast: Report of Six Cases and Systematic Review of Existing Literature

ntroduction: Neuroendocrine neoplasm of the breast (bNENs) are considered a rare disease, even if in WHO data they represent about 2-5 % of all breast cancer. The last WHO classification includes: well-differentiated neuroendocrine tumor (bNET), neuroendocrine carcinoma (NEC) and invasive carcinoma with neuroendocrine differentiation. The current knowledge on clinical management of bNENs is poor and patients are usually treated according to non-endocrine tumor components guidelines. Materials and Methods: We presented our experience of six cases of bNENs. Moreover, we conducted a systematic review of published data on diagnosis, treatment and outcome of this kind of tumors. Results: bNENS usually presented as palpable breast masses, classically appearing as irregular hypoechoic lesions at US examination and as hyperdense masses at mammography. Usually pre-operative tumor biopsy is not able to recognize the neuroendocrine components and the final diagnosis is performed only on definitive histopathological assessment. The most frequent subtype seems to be neuroendocrine carcinoma and synaptophysin is positive in most specimens. Treatment strategies, including surgical treatment, radiotherapy and medical treatment are nowadays based on current non-endocrine breast cancer guidelines, independently from neuroendocrine components, even if some studies have proposed the use of somatostatin analogues for bNET and cisplatin-etoposide for NEC. Prognosis of all bNENs, especially of poorly differentiated neoplasia, seems worse compared to non-neuroendocrine breast cancer and stage and morphology seem the best predictor of tumor outcome. Conclusions: We provide an algorithm for clinical management of bNETs, basing on available data. More studies are necessary for confirming the best treatment strategy for these patients, in order to improve clinical outcome

sustainability of a historical building renovation design through the application of leed rating system

Abstract This paper presents a case study of a sustainable certification of a building renovation. The new LEED® rating system, GBC Historic BuildingTM protocol, proposed by Green Building Council Italy and addressed to Italian historical heritage, was applied to the High School "A. Canova" in Treviso, chosen because it was built before 1945 and it required a restoration work. The aim of this paper is to present a retrofit design based on strategies according to three objectives: energy saving, preservation of historical architecture, improvement of indoor environmental quality for users. The application of GBC Historic BuildingTM protocol has been carried out according to the protocol guidebook. The novelty of this paper is that GBC Historic BuildingTM has been used as a design tool, not as assessment tool, in order to develop a design strategy. At first a building survey of the building has been performed to define the state of art in terms of structural instability and deterioration of surfaces and architectural elements in order to propose the most important renovation measures; the dynamic simulation was performed to calculate the building envelope thermal losses and the building energy demand for heating. Different energy efficiency measures have been proposed and an optimal solution has been defined according to simulation data and cost analysis evaluation. Three main goals have been achieved: the reduction of building energy consumptions up to 39%, the conservation of the historical parts of the building and the attainment of good thermal comfort in school classrooms. A Silver LEED level of certification has been gained

Elaboration of a nomogram to predict nonsentinel node status in breast cancer patients with positive sentinel node, intraoperatively assessed with one step nucleic amplification: Retrospective and validation phase

Background: Tumor-positive sentinel lymph node (SLN) biopsy results in a risk of non sentinel node metastases in micro-and macro-metastases ranging from 20 to 50%, respectively. Therefore, most patients underwent unnecessary axillary lymph node dissections. We have previously developed a mathematical model for predicting patient-specific risk of non sentinel node (NSN) metastases based on 2460 patients. The study reports the results of the validation phase where a total of 1945 patients were enrolled, aimed at identifying a tool that gives the possibility to the surgeon to choose intraoperatively whether to perform or not axillary lymph node dissection (ALND).Methods: The following parameters were recorded: Clinical: hospital, age, medical record number; Bio pathological: Tumor (T) size stratified in quartiles, grading (G), histologic type, lymphatic/vascular invasion (LVI), ER-PR status, Ki 67, molecular classification (Luminal A, Luminal B, HER-2 Like, Triple negative); Sentinel and non-sentinel node related: Number of NSNs removed, number of positive NSNs, cytokeratin 19 (CK19) mRNA copy number of positive sentinel nodes stratified in quartiles. A total of 1945 patients were included in the database. All patient data were provided by the authors of this paper.Results: The discrimination of the model quantified with the area under the receiver operating characteristics (ROC) curve (AUC), was 0.65 and 0.71 in the validation and retrospective phase, respectively. The calibration determines the distance between predicted outcome and actual outcome. The mean difference between predicted/observed was 2.3 and 6.3% in the retrospective and in the validation phase, respectively. The two values are quite similar and as a result we can conclude that the nomogram effectiveness was validated. Moreover, the ROC curve identified in the risk category of 31% of positive NSNs, the best compromise between false negative and positive rates i.e. when ALND is unnecessary ( 31%).Conclusions: The results of the study confirm that OSNA nomogram may help surgeons make an intraoperative decision on whether to perform ALND or not in case of positive sentinel nodes, and the patient to accept this decision based on a reliable estimation on the true percentage of NSN involvement. The use of this nomogram achieves two main gools: 1) the choice of the right treatment during the operation, 2) to avoid for the patient a second surgery procedure