Pensare come una città

Il n.1 della Serie City Lab raccoglie i contributi di due cicli di seminari che si sono confrontati con la necessità di considerare la città e il territorio alla luce della molteplicità di soggetti che li abitano, alla costante ricerca di un equilibrio di potere tra le molte e diverse strutture di autorità. Organizzati nell’ambito del Cluster di ricerca CityLab all’Università Iuav di Venezia nell’arco del 2021, i seminari hanno raccolto contributi plurali provenienti da un articolato insieme di contesti ed esperienze. Pensare come una città discute di diversità in campo urbano, di pratiche di innovazione e rigenerazione stimolate dalla messa in forma del progetto, di spazi di educazione e di apprendimento nella e attraverso la città

Promoter methylation of tumor suppressor genes in pre-neoplastic lesions; Potential marker of disease recurrence

Background: Epigenetic alterations of specific genes have been reported to be related to colorectal cancer (CRC) transformation and would also appear to be involved in the early stages of colorectal carcinogenesis. Little data are available on the role of these alterations in determining a different risk of colorectal lesion recurrence. The aim of the present study was to verify whether epigenetic alterations present in pre-neoplastic colorectal lesions detected by colonoscopy can predict disease recurrence. Methods. A retrospective series of 78 adenomas were collected and classified as low (35) or high-risk (43) for recurrence according to National Comprehensive Cancer Network guidelines. Methylation alterations were analyzed by the methylation-specific multiplex ligation probe assay (MS-MLPA) which is capable of quantifying methylation levels simultaneously in 24 different gene promoters. MS-MLPA results were confirmed by pyrosequencing and immunohistochemistry. Results: Higher levels of methylation were associated with disease recurrence. In particular, MLH1, ATM and FHIT gene promoters were found to be significantly hypermethylated in recurring adenomas. Unconditional logistic regression analysis used to evaluate the relative risk (RR) of recurrence showed that FHIT and MLH1 were independent variables with an RR of 35.30 (95% CI 4.15-300.06, P = 0.001) and 17.68 (95% CI 1.91-163.54, P = 0.011), respectively. Conclusions: Histopathological classification does not permit an accurate evaluation of the risk of recurrence of colorectal lesions. Conversely, results from our methylation analysis suggest that a classification based on molecular parameters could help to define the mechanisms involved in carcinogenesis and prove an effective method for identifying patients at high risk of recurrence

Confirmed Activity and Tolerability of Weekly Paclitaxel in the Treatment of Advanced Angiosarcoma

Background. In several prospective and retrospective studies, weekly paclitaxel showed promising activity in patients with angiosarcoma. Patients and Methods. Our study was originally designed as a prospective, phase II multicenter trial for patients younger than 75, with ECOG performance status 0–2, affected by locally advanced or metastatic angiosarcoma. Patients received paclitaxel 80 mg/m2 intravenously, at days 1, 8, and 15 every 4 weeks, until disease progression or unacceptable toxicity. Primary endpoint was objective response. Results. Eight patients were enrolled but, due to very slow accrual, the trial was prematurely stopped and further 10 patients were retrospectively included in the analysis. Out of 17 evaluable patients, 6 patients obtained an objective response (5 partial, 1 complete), with an objective response rate of 35% (95% confidence interval 17%–59%). Of note, five responses were obtained in pretreated patients. In the paper, details of overall survival, progression-free survival, and tolerability are reported. Conclusions. In this small series of patients with locally advanced or metastatic angiosarcoma, weekly paclitaxel was confirmed to be well tolerated and active even in pretreated patients

Are Nutraceuticals Effective in COVID‐19 and Post‐COVID Prevention and Treatment?

The beginning of the end or the end of the beginning? After two years mastered by coronavirus disease 19 (COVID‐19) pandemic, we are now witnessing a turnaround. The reduction of severe cases and deaths from COVID‐19 led to increasing importance of a new disease called post‐COVID syndrome. The term post‐COVID is used to indicate permanency of symptoms in patients who have recovered from severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Immune, antiviral, antimicrobial therapies, as well as ozone therapy have been used to treat COVID‐19 disease. Vaccines have then become available and administered worldwide to prevent the insurgence of the disease. However, the pandemic is not over yet at all given the emergence of new omicron variants. New therapeutic strategies are urgently needed. In this view, great interest was found in nutraceutical products, including vitamins (C, D, and E), minerals (zinc), melatonin, probiotics, flavonoids (quercetin), and curcumin. This review summarizes the role of nutraceuticals in the prevention and/or treatment of COVID‐19 disease and post‐COVID syndrome

Non-pegylated liposomal doxorubicin in older adjuvant early breast cancer patients: cardiac safety analysis and final results of the COLTONE study

Aims: To explore the cardiac safety of adjuvant Non-Pegylated Liposomal Doxorubicin (NPL-DOX) plus Cyclophosphamide (CTX) followed by weekly Paclitaxel, in elderly women (≥ 65 years) with high-risk breast cancer. Previously, we described no symptomatic cardiac events within the first 12 months from starting treatment. We now reported the updated results after a median follow-up 76 months. Methods: The cardiac activity was evaluated with left ventricular ejection fraction (LVEF) echocardiograms assessments, before starting chemotherapy and every 6 months, until 30 months from baseline, then yearly for at least 5 years. Results: Forty-seven women were recruited by two Units of Medical Oncology (Ethics Committee authorization CESM-AOUP, 3203/2011; EudraCT identification number: 2010-024067-41, for Pisa and Pontedera Hospitals). An episode of grade 3 CHF (NCI-CTCAE, version 3.0) occurred after 18 months the beginning of chemotherapy. The echocardiograms assessments were performed comparing the LVEF values of each patient evaluated at fixed period of time, compared to baseline. We observed a slight changed in terms of mean values at 48, 60, 72 and 84 months. At these time points, a statistically significant reduction of - 3.2%, - 4.6%, - 6.4% and - 7.1%, respectively, was observed. However, LVEF remained above 50% without translation in any relevant clinical signs. No other cardiac significant episodes were reported. To this analysis, in 13 patients (28%) occurred disease relapse and,  of them, 11 (23%) died due to metastatic disease. Eight patients died of cancer-unrelated causes. Conclusions: The combination including NPL-DOX in elderly patients revealed low rate of cardiac toxic effects. Comparative trials are encouraged

Comparing T Cell Subsets in Broncho-Alveolar Lavage (BAL) and Peripheral Blood in Patients with Advanced Lung Cancer

Background: Lung cancer (LC) tissue for immunological characterization is often scarce. We explored and compared T cell characteristics between broncho-alveolar lavage from tumor affected (t-BAL) and contralateral lung (cl-BAL), with matched peripheral blood (PB). Methods: BAL and PB were collected during bronchoscopy for diagnostic and/or therapeutic purposes in patients with monolateral primary lesion. Results: Of 33 patients undergoing BAL and PB sampling, 21 had histologically-confirmed LC. Most cases were locally-advanced or metastatic non-small cell LC. T cell characteristics were not significantly different in t-BAL vs. cl-BAL. Compared to PB, CD8 T cells in BAL presented features of immune activation and exhaustion (high PD-1, low IFN-g production). Accordingly, regulatory CD4 T cells were also higher in BAL vs. PB. When dichotomizing T cell density in t-BAL in high and low, we found that PD-L1 expression in LC was associated with T cell density in t-BAL. T-BAL with high T cell density had higher %IFN-g+CD8 T cells and lower %T-regs. Conclusion: In BAL from advanced LC patients, T cells present features of exhaustion. T cells in t-BAL could be the best surrogate of tumor-infiltrating T cell, and future studies should evaluate T cell phenotype and density as potential biomarkers for cancer immunotherapy outcome

Dal collezionismo privato alle istituzioni pubbliche

Il progetto, nato all\u2019interno di corso di Museologia e collezionismo della Scuola di Specializzazione in Beni storico-artistici \u2013 DAR, riguarda la schedatura di opere conservate in istituzioni molto diverse l'una dall'altra e costituiscono una testimonianza della variet\ue0 di approcci e di fonti relative alla storia del collezionismo. Con introduzione di M. Pigozzi e schede di A. Barbanti, G. Cali, I. Carozza, I. Chia, L. Coppa, A. Di Maio, Cristina Elia, C. Forconi, F. Gamba, A. Lisbona, M. Mariano, S. Mauro, F. Passerini, L. Regano, G.M. Sassoli de\u2019 Bianchi Strozzi, I. Siboni, S. Zugni

Association of Upfront Peptide Receptor Radionuclide Therapy With Progression-Free Survival Among Patients With Enteropancreatic Neuroendocrine Tumors

open57noIMPORTANCE Data about the optimal timing for the initiation of peptide receptor radionuclide therapy (PRRT) for advanced, well-differentiated enteropancreatic neuroendocrine tumors are lacking. OBJECTIVE To evaluate the association of upfront PRRT vs upfront chemotherapy or targeted therapy with progression-free survival (PFS) among patients with advanced enteropancreatic neuroendocrine tumors who experienced disease progression after treatment with somatostatin analogues (SSAs). DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study analyzed the clinical records from 25 Italian oncology centers for patients aged 18 years or older who had unresectable, locally advanced or metastatic, well-differentiated, grades 1 to 3 enteropancreatic neuroendocrine tumors and received either PRRT or chemotherapy or targeted therapy after experiencing disease progression after treatment with SSAs between January 24, 2000, and July 1, 2020. Propensity score matching was done to minimize the selection bias. EXPOSURES Upfront PRRT or upfront chemotherapy or targeted therapy. MAIN OUTCOMES AND MEASURES The main outcome was the difference in PFS among patients who received upfront PRRT vs among those who received upfront chemotherapy or targeted therapy. A secondary outcome was the difference in overall survival between these groups. Hazard ratios (HRs) were fitted in a multivariable Cox proportional hazards regression model to adjust for relevant factors associated with PFS and were corrected for interaction with these factors. RESULTS Of 508 evaluated patients (mean ([SD] age, 55.7 [0.5] years; 278 [54.7%] were male), 329 (64.8%) received upfront PRRT and 179 (35.2%) received upfront chemotherapy or targeted therapy. The matched group included 222 patients (124 [55.9%] male; mean [SD] age, 56.1 [0.8] years), with 111 in each treatment group. Median PFS was longer in the PRRT group than in the chemotherapy or targeted therapy group in the unmatched (2.5 years [95%CI, 2.3-3.0 years] vs 0.7 years [95%CI, 0.5-1.0 years]; HR, 0.35 [95%CI, 0.28-0.44; P < .001]) and matched (2.2 years [95% CI, 1.8-2.8 years] vs 0.6 years [95%CI, 0.4-1.0 years]; HR, 0.37 [95%CI, 0.27-0.51; P < .001]) populations. No significant differences were shown in median overall survival between the PRRT and chemotherapy or targeted therapy groups in the unmatched (12.0 years [95%CI, 10.7-14.1 years] vs 11.6 years [95%CI, 9.1-13.4 years]; HR, 0.81 [95%CI, 0.62-1.06; P = .11]) and matched (12.2 years [95% CI, 9.1-14.2 years] vs 11.5 years [95%CI, 9.2-17.9 years]; HR, 0.83 [95%CI, 0.56-1.24; P = .36]) populations. The use of upfront PRRT was independently associated with improved PFS (HR, 0.37; 95%CI, 0.26-0.51; P < .001) in multivariable analysis. After adjustment of values for interaction, upfront PRRT was associated with longer PFS regardless of tumor functional status (functioning: adjusted HR [aHR], 0.39 [95%CI, 0.27-0.57]; nonfunctioning: aHR, 0.29 [95%CI, 0.16-0.56]), grade of 1 to 2 (grade 1: aHR, 0.21 [95%CI, 0.12-0.34]; grade 2: aHR, 0.52 [95%CI, 0.29-0.73]), and site of tumor origin (pancreatic: aHR, 0.41 [95%CI, 0.24-0.61]; intestinal: aHR, 0.19 [95%CI, 0.11-0.43]) (P < .001 for all). Conversely, the advantage was not retained in grade 3 tumors (aHR, 0.31; 95%CI, 0.12-1.37; P = .13) or in tumors with a Ki-67 proliferation index greater than 10% (aHR, 0.73; 95%CI, 0.29-1.43; P = .31). CONCLUSIONS AND RELEVANCE In this cohort study, treatment with upfront PRRT in patients with enteropancreatic neuroendocrine tumors who had experienced disease progression with SSA treatment was associated with significantly improved survival outcomes compared with upfront chemotherapy or targeted therapy. Further research is needed to investigate the correct strategy, timing, and optimal specific sequence of these therapeutic options.openPusceddu, Sara; Prinzi, Natalie; Tafuto, Salvatore; Ibrahim, Toni; Filice, Angelina; Brizzi, Maria Pia; Panzuto, Francesco; Baldari, Sergio; Grana, Chiara M.; Campana, Davide; Davì, Maria Vittoria; Giuffrida, Dario; Zatelli, Maria Chiara; Partelli, Stefano; Razzore, Paola; Marconcini, Riccardo; Massironi, Sara; Gelsomino, Fabio; Faggiano, Antongiulio; Giannetta, Elisa; Bajetta, Emilio; Grimaldi, Franco; Cives, Mauro; Cirillo, Fernando; Perfetti, Vittorio; Corti, Francesca; Ricci, Claudio; Giacomelli, Luca; Porcu, Luca; Di Maio, Massimo; Seregni, Ettore; Maccauro, Marco; Lastoria, Secondo; Bongiovanni, Alberto; Versari, Annibale; Persano, Irene; Rinzivillo, Maria; Pignata, Salvatore Antonio; Rocca, Paola Anna; Lamberti, Giuseppe; Cingarlini, Sara; Puliafito, Ivana; Ambrosio, Maria Rosaria; Zanata, Isabella; Bracigliano, Alessandra; Severi, Stefano; Spada, Francesca; Andreasi, Valentina; Modica, Roberta; Scalorbi, Federica; Milione, Massimo; Sabella, Giovanna; Coppa, Jorgelina; Casadei, Riccardo; Di Bartolomeo, Maria; Falconi, Massimo; de Braud, FilippoPusceddu, Sara; Prinzi, Natalie; Tafuto, Salvatore; Ibrahim, Toni; Filice, Angelina; Brizzi, Maria Pia; Panzuto, Francesco; Baldari, Sergio; Grana, Chiara M.; Campana, Davide; Davì, Maria Vittoria; Giuffrida, Dario; Zatelli, Maria Chiara; Partelli, Stefano; Razzore, Paola; Marconcini, Riccardo; Massironi, Sara; Gelsomino, Fabio; Faggiano, Antongiulio; Giannetta, Elisa; Bajetta, Emilio; Grimaldi, Franco; Cives, Mauro; Cirillo, Fernando; Perfetti, Vittorio; Corti, Francesca; Ricci, Claudio; Giacomelli, Luca; Porcu, Luca; Di Maio, Massimo; Seregni, Ettore; Maccauro, Marco; Lastoria, Secondo; Bongiovanni, Alberto; Versari, Annibale; Persano, Irene; Rinzivillo, Maria; Pignata, Salvatore Antonio; Rocca, Paola Anna; Lamberti, Giuseppe; Cingarlini, Sara; Puliafito, Ivana; Ambrosio, Maria Rosaria; Zanata, Isabella; Bracigliano, Alessandra; Severi, Stefano; Spada, Francesca; Andreasi, Valentina; Modica, Roberta; Scalorbi, Federica; Milione, Massimo; Sabella, Giovanna; Coppa, Jorgelina; Casadei, Riccardo; Di Bartolomeo, Maria; Falconi, Massimo; de Braud, Filipp