Ricostruire 2. Architettura - Storia - Rappresentazione

Dall'editoriale di Marco Rosario Nobile: "Il 2014 è stato l’anniversario (bicentenario della nascita) di un grande architetto come Eu- gène Viollet-le-Duc. Per noi, associarsi al ricordo significa anche rilevarne le scomode pre- ferenze (espresse da un ventenne), che farebbero indispettire molti colleghi: «Je le dis peut-être à ma honte, mais je trouve Palladio, Sansovino, Vignole, plus qu’ennuyeux» (lettera da Venezia, estate 1837). Forse questo impietoso giudizio si giustifica con la perfezione delle opere del Cinquecento del centro-nord Italia, nell’assenza di stimoli a rielaborare mentalmente e poi graficamente completamenti, ricostruzioni che comportino qualche difficolta' suppletiva, opere che nella migliore circostanza delineano di per sé la soluzione di un rebus troppo facile, “noioso” per un esperto enigmista. Ricostruire racconta, per esempi di studio, il ridisegno per la storia, ovvero presenta contributi che contemplano il desiderio di prefigurare i casi falliti, quelli sospesi, le vicende in- 5 terrotte o sommerse dai detriti del tempo. Negli ultimi anni, i campi di attività che comportano l’intreccio tra ipotesi storiche e la loro verifica di attendibilità si sono amplificati grazie a strumenti di rappresentazione sempre più sofisticati. Naturalmente si tratta di esercizi, il cui valore non è comunque da derubricare semplicemente alla voce “speculazioni”. Questo gioco ha coinvolto anche storici del Cinquecento di altissima levatura, da Arnaldo Bruschi a Manfredo Tafuri, e con precedenti di questa portata, cercare giustificazioni non serve. Esistono però spiegazioni: si tratta forse di un fascino che gli architetti conoscono bene, quel processo mentale che in passato poteva debordare anche in opere di comple- tamento, mentre, per chi come noi ha assimilato la passione di Ruskin, consente la soprav- vivenza di un angolo per continuare a coltivare le logiche complesse di Viollet-le Duc. Questo numero è stato curato dai dottori Giuseppe Antista e Mirco Cannella"

Systemic Treatment of Patients With Gastrointestinal Cancers During the COVID-19 Outbreak: COVID-19-adapted Recommendations of the National Cancer Institute of Milan

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak poses a major challenge in the treatment decision-making of patients with cancer, who may be at higher risk of developing a severe and deadly SARS-CoV-2 infection compared with the general population. The health care emergency is forcing the reshaping of the daily assessment between risks and benefits expected from the administration of immune-suppressive and potentially toxic treatments. To guide our clinical decisions at the National Cancer Institute of Milan (Lombardy region, the epicenter of the outbreak in Italy), we formulated Coronavirus-adapted institutional recommendations for the systemic treatment of patients with gastrointestinal cancers. Here, we describe how our daily clinical practice has changed due to the pandemic outbreak, with the aim of providing useful suggestions for physicians that are facing the same challenges worldwide

Systemic Treatment of Patients With Gastrointestinal Cancers During the COVID-19 Outbreak : COVID-19-adapted Recommendations of the National Cancer Institute of Milan

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak poses a major challenge in the treatment decision-making of patients with cancer, who may be at higher risk of developing a severe and deadly SARS-CoV-2 infection compared with the general population. The health care emergency is forcing the reshaping of the daily assessment between risks and benefits expected from the administration of immune-suppressive and potentially toxic treatments. To guide our clinical decisions at the National Cancer Institute of Milan (Lombardy region, the epicenter of the outbreak in Italy), we formulated Coronavirus-adapted institutional recommendations for the systemic treatment of patients with gastrointestinal cancers. Here, we describe how our daily clinical practice has changed due to the pandemic outbreak, with the aim of providing useful suggestions for physicians that are facing the same challenges worldwide

Maintenance Therapy with Panitumumab Alone vs Panitumumab Plus Fluorouracil-Leucovorin in Patients with RAS Wild-Type Metastatic Colorectal Cancer: A Phase 2 Randomized Clinical Trial

Key PointsQuestionIs maintenance therapy with single-agent panitumumab noninferior to panitumumab plus fluorouracil and leucovorin after a 4-month induction treatment with panitumumab plus FOLFOX-4 in patients with previously untreated RAS wild-type metastatic colorectal cancer? FindingsIn this open-label, phase 2 randomized clinical trial of 229 patients, maintenance therapy with single-agent panitumumab alone was inferior to panitumumab plus fluorouracil-leucovorin in terms of 10-month progression-free survival (49.0% vs 59.9%). MeaningThe continuation of single-agent anti-epidermal growth factor receptor treatment in the maintenance setting will likely achieve inferior progression-free survival compared with the continuation of chemotherapy plus an anti-epidermal growth factor receptor agent in a phase 3 confirmation trial. This open-label, phase 2 randomized clinical trial assesses whether maintenance therapy with single-agent panitumumab was noninferior to panitumumab plus combined fluorouracil and leucovorin calcium among patients with RAS wild-type metastatic colorectal cancer. ImportanceFew studies are available on the role of maintenance strategies after induction treatment regimens based on anti-epidermal growth factor receptors, and the optimal regimen for an anti-epidermal growth factor receptors-based maintenance treatment in patients with RAS wild-type metastatic colorectal cancer is still to be defined. ObjectiveTo determine whether maintenance therapy with single-agent panitumumab was noninferior to panitumumab plus fluorouracil and leucovorin after a 4-month induction treatment regimen. Design, Setting, and ParticipantsThis open-label, randomized phase 2 noninferiority trial was conducted from July 7, 2015, through October 27, 2017, at multiple Italian centers. Patients with RAS wild-type, unresectable metastatic colorectal adenocarcinoma who had not received previous treatment for metastatic disease were eligible. Induction therapy consisted of panitumumab plus FOLFOX-4 (panitumumab, 6 mg/kg, oxaliplatin, 85 mg/m(2) at day 1, leucovorin calcium, 200 mg/m(2), and fluorouracil, 400-mg/m(2) bolus, followed by 600-mg/m(2) continuous 24-hour infusion at days 1 and 2, every 2 weeks). Cutoff date for analyses was July 30, 2018. InterventionsPatients were randomized (1:1) to first-line panitumumab plus FOLFOX-4 for 8 cycles followed by maintenance therapy with panitumumab plus fluorouracil-leucovorin (arm A) or panitumumab (arm B) until progressive disease, unacceptable toxic effects, or consent withdrawal. The minimization method was used to stratify randomization by previous adjuvant treatment and number of metastatic sites. Main Outcomes and MeasuresThe prespecified primary end point was 10-month progression-free survival (PFS) analyzed on an intention-to-treat basis with a noninferiority margin of 1.515 for the upper limit of the 1-sided 90% CI of the hazard ratio (HR) of arm B vs A. ResultsOverall, 229 patients (153 male [66.8%]; median age, 64 years [interquartile range (IQR), 56-70 years]) were randomly assigned to arm A (n=117) or arm B (n=112). At a median follow-up of 18.0 months (IQR, 13.1-23.3 months]), a total of 169 disease progression or death events occurred. Arm B was inferior (upper limit of 1-sided 90% CI of the HR,1.857). Ten-month PFS was 59.9% (95% CI, 51.5%-69.8%) in arm A vs 49.0% (95% CI, 40.5%-59.4%) in arm B (HR,1.51; 95% CI, 1.11-2.07; P=.01). During maintenance, arm A had a higher incidence of grade 3 or greater treatment-related adverse events (36 [42.4%] vs 16 [20.3%]) and panitumumab-related adverse events (27 [31.8%] vs 13 [16.4%]), compared with arm B. Conclusions and RelevanceIn patients with RAS wild-type metastatic colorectal cancer, maintenance therapy with single-agent panitumumab was inferior in terms of PFS compared with panitumumab plus fluorouracil-leucovorin, which slightly increased the treatment toxic effects. Trial RegistrationClinicalTrials.gov identifier: NCT0247604

Assessment of Ramucirumab plus paclitaxel as switch maintenance versus continuation of first-line chemotherapy in patients with advanced HER-2 negative gastric or gastroesophageal junction cancers: the ARMANI phase III trial

Background: Platinum/fluoropyrimidine regimens are the backbone of first-line chemotherapy for advanced gastric cancer (AGC). However response rates to first line chemotherapy range from 30 to 50% and disease progression occurs after 4\u20136 cycles. The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only about 40% of AGC pts. are eligible for second-line treatment. Methods: This is a randomized, open-label, multicenter phase III trial. It aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after 3 months of a first-line with a platinum/fluoropyrimidine regimen (either FOLFOX4, mFOLFOX6 or XELOX). The primary endpoint is to compare Progression-Free Survival (PFS) of patients in ARM A (switch maintenance to ramucirumab and placlitaxel) versus ARM B (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of patients that will receive a second line therapy according to arm treatment, safety, quality of life. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues are planned in order to identify potential biomarkers of primary resistance and prognosis. (Continued on next page) Discussion: The ARMANI study estimates if patients treated with early swich with ramucirumab plus paclitaxel received benefit when compared to those treated with continuation of first line therapy. The hypothesis is that the early administration of an active, non-cross resistant second-line regimen such as ramucirumab plus paclitaxel may prolong the time in which patients are progression-free, and consequently have a better quality of life. Moreover, this strategy may rescue all those subjects that become ineligible for second-line therapy due to the rapid deterioration of health status after the first disease progression. Trial registration: ARMANI is registered at ClinicalTrials.gov (NCT02934464, October 17, 2016) and EudraCT(2016\u2013001783-12, April 202,016)

Al-Bustān. Las fincas aristocráticas y la construcción de los paisajes periurbanos de al-Ándalus y Sicilia

Navarro Palazón, Julio, editorLa presente publicación se enmarca en el Proyecto I+D+i «Almunias medievales en el Mediterráneo: Historia y conservación de los paisajes culturales periurbanos» (PID2019-111508GB-I00, dirigido por Julio Navarro Palazón), del Ministerio de Ciencia e Innovación. Agencia Estatal de Investigación. Proyectos de I+D+i, de los Programas Estatales de Generación de Conocimiento y fortalecimiento Científico y Tecnológico del Sistema de I+D+i y de I+D+i Orientada a los Retos de la Sociedad, del Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020. Esta obra es también un fruto destacado del trabajo realizado en el marco de la Unidad Asociada de I+D+i Patrimonio Cultural Árabe e Islámico, Consejo Superior de Investigaciones Científicas-Universidad de Granada, a través de la Escuela de Estudios Árabes de Granad

Metronomic (M), capecitabine (C), and oxaliplatin (O) plus bevacizumab (B) as treatment of advanced colorectal cancer (ACRC) in very elderly people (M-COB): Efficacy and safety (E&S) evaluation—A 2-year monitoring

Background: A limit to delivery of cytotoxic chemotherapy in elderly people with cancer, is severe toxicity as principal side effect of treatment. We designed in 2009 a treatment schedule to evaluate E&S of combination of three drugs O, C plus B in ACRC very old patients in a metronomic mode (M-COB) Methods: 75 (37 f -38 m) very elderly patients with advanced colorectal cancer (median age:76; range: 70-82) were enrolled. Comprehensive Geriatric Assessment (CGA) was performed to all pts to assess eligibility for chemotherapy. Treatment schedule was: O (65 mg/m2) + B (7.5 mg/Kg) on day 1 (O doses was adjusted by Kintzel-Dorr formula). C (fixed dose of 1,000 mg bid) was delivered from day 2 to day 15 every 3 weeks for 12 cycles. Primary endpoints: toxicity profile (NCI-CTC v2.0) and QoL score (EORTC QLQ-C30). Secondary endpoints:. Clinical Response Rate (CRR) by WHO ‘s criteria. All patients were evaluated for main toxicity (Hemat, G.I., HFS, N&V) by ECOG Common Toxicity Criteria. Results: 76 patients were included into groups I Balducci's classification, for frailty assessement. A 50.1% tumor response rate(TRR) was observed both with a 86.7% Clinical Benefit (CB). No one pts experienced grade 4 toxicity. QoL score improvement was noted in all pts after treatment. Median PFS was 12.3 months with a 6 months PFS rate of 82%. Median OS was 23.5 months with a 12 months survival probability of 78.8%. Conclusions: We choose fixed dose of C in order to reduce main toxicity as shown in std treatment of aged pts with ACRC. Nevertheless this don’t impact on efficacy of treatment. Finally the high rate of clinical benefit encourage further enrollement of patients.In conclusion this schedule seem to be active and safe because improves tolerability without any decrease of efficacy in this kind of patients

Effects of anti-aldosteronic agents in resistant hypertension

Hypertension is defined resistant (or refractory) when it is not possible to reach the target values of blood pressure despite the contemporary use of three antihypertensive drugs at optimised dosage (1). Today difficult control of hypertension is more and more frequent in clinical practice. In recent years the role of anti-aldosteronic agents has appeared useful in the treatment of resistant hypertension; this condition seems to be related to the increase of the mean age. Subjects suffering from resistant hypertension mostly show an isolated high systolic pressure. In addition to advanced age, factors commonly associated are: increased levels of aldosterone and intravascular volume, chronic kidney disease, diabetes mellitus, obesity; and therefore these subjects are more exposed to organ damage (2). In some recent trials anti-aldosteronic agents have demonstrated positive effects in ruling hypertension and in reducing organ damage (3) and among the different antialdosteronic agents canrenone showed a smaller occurrence of side effects (impotence and gynaecomastia in males, menstrual pains in females) and so a wider tolerability in comparison with spironolactone and eplerenone (4). However, hyperkalaemia is the most important side effect of all these agents; the principal contraindications are severe renal failure and high levels of serum potassium. Moreover it is necessary to use these drugs with attention if they are combined with ace-inhibitors or angiotensin II receptors blockers, because they can increase kalaemia too. Conclusion In conclusion, scientific data indicate a positive role of these drugs both in the control of resistant hypertension and in the prevention (or at least in the reduction) of organ damage (5,6,7,8). For this reason, it is hoped that there will be a wider use of these agents in clinical practice, of course when they are not contraindicated