Fuori dal canone? Voci della critica e della letteratura femminile contemporanea.

Questo elaborato si propone l’obiettivo di analizzare l’avvento e lo sviluppo di Femminismo, Queer Studies e Postcolonial Studies, le tre metodologie critiche che, sotto la spinta del decostruzionismo di Derrida e del post-strutturalismo, hanno rivoluzionato il canone critico e letterario del ‘900: l’eredità decostruttivista lasciata da Derrida, infatti, mise in moto una serie di meccanismi che condussero verso una specializzazione della letteratura, che, a sua volta, rimise in gioco quelle voci che, fino ad allora, erano state taciute o ignorate dal canone letterario di matrice essenzialmente fallo-logocentrica (cioè patriarcale, eterosessuale ed eurocentrica); nello specifico: la voce femminile, quella omosessuale, e quella post-coloniale. E’ bene precisare che in questo elaborato non si analizzeranno queste tre posizioni critiche e letterature in toto, ma si seguirà piuttosto un percorso guidato da una prospettiva femminile, che, partendo dal femminismo più “puro” delle origini, continuerà all’interno dei Gender and Postcolonial Studies, focalizzandosi rispettivamente sul Lesbian Criticism e sul Black Feminism. Dopo un’introduzione sulla formazione del canone nel corso dell’800, i capitoli dell’elaborato analizzeranno le tre metodologie critiche, focalizzandosi sulle diverse fasi che hanno scandito il loro sviluppo e sulle affinità e differenze che li caratterizzano, riportando i contributi più importanti. Ogni capitolo di matrice teorica sarà seguito da un capitolo dedicato, invece, alla letteratura: in essi verranno riportate, come esempi concreti delle teorie affrontate, tre testi primari, di cui verranno analizzati struttura, impianto narrativo e tematiche, avendo come linea guida le idee di molteplicità, apertura verso l’altro, ibridismo e di rottura delle categorizzazioni e dei binarismi sociali, i concetti cardine su cui si fonda la decostruzione degli “ismi” messa in atto dalle metodologie critiche. Nello specifico, sono stati presi in esame i romanzi The Golden Notebook (1962) di Doris Lessing per la letteratura femminile, The Gracekeepers (2015) di Kirsty Logan per la letteratura lgbt e Small Island (2004) di Andrea Levy per la letteratura femminile “blak”; tutte e tre le opere sono state scelte in quanto realizzazioni positive e costruttive delle istanze teoriche

Early Progression in Non-Small Cell Lung Cancer (NSCLC) with High PD-L1 Treated with Pembrolizumab in First-Line Setting: A Prognostic Scoring System Based on Clinical Features

Background: Pembrolizumab is approved in monotherapy for the first-line (1L) of advanced or metastatic NSCLC patients with high PD-L1 (≥50%). Despite a proportion of patients achieve long-term survival, about one-third of patients experience detrimental survival outcomes, including early death, hyperprogression, and fast progression. The impact of clinical factors on early progression (EP) development has not been widely explored. Methods: We designed a retrospective, multicenter study involving five Italian centers, in patients with metastatic NSCLC with PD-L1 ≥ 50%, treated with Pembrolizumab in a 1L setting. EP was defined as a progressive disease within three months from pembrolizumab initiation. Baseline clinical factors of patients with and without EP were collected and analyzed. Logistic regression was performed to identify clinical factors associated with EP and an EP prognostic score was developed based on the logistic model. Results: Overall, 321 out of 336 NSCLC patients treated with 1L pembrolizumab provided all the data for the analysis. EP occurred in 137 (42.7%) patients; the median PFS was 3.8 months (95% CI: 2.9–4.7), and median OS was not reached in the entire study population. Sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS), steroids, metastatic sites ≥2, and the presence of liver/pleural metastasis were confirmed as independent factors for EP by multivariate analysis. By combining these factors, we developed an EP prognostic score ranging from 0–13, with three-risk group stratification: 0–2 (good prognosis), 3–6 (intermediate prognosis), and 7–13 (poor prognosis). The area under the curve (AUC) of the model was 0.76 (95% CI: 0.70–0.81). Conclusions: We identified six clinical factors independently associated with EP. We developed a prognostic score model for EP-risk to potentially improve clinical practice and patient selection for 1L pembrolizumab in NSCLC with high PD-L1, in the real-world clinical setting

Phase II study of epirubicin, oxaliplatin and docetaxel combination in metastatic gastric or gastroesophageal junction adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>This phase II study was designed to evaluate the activity and safety of a combination of epirubicin, oxaliplatin and docetaxel in metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.</p> <p>Methods</p> <p>Forty patients with measurable distant metastases received epirubicin 50 mg/m², docetaxel 60 mg/m²followed by oxaliplatin 100 mg/m²on day 1 of each 21-day cycle. Primary end point was response rates (RR).</p> <p>Results</p> <p>All patients were evaluable. The overall RR was 47.5% (95% confidence interval (CI) 32–63). The disease control was 80%. Median time for response was 6 weeks. Median time to progression was 6.3 months (95% CI 5.4–7.2) and the median overall survival time was 12.1 months (95% CI 10.7–13.5). Grade 3/4 neutropenia occurred in 50% of patients with two episodes of febrile neutropenia (5%). Other non-hematological grade 3 toxicities included sensory neuropathy in two patiens (5%), vomiting and mucositis in two patients (5%) and diarrhea in one patient (2.5%).</p> <p>Conclusion</p> <p>The combination of epirubicin, oxaliplatin and docetaxel was found to be effective and well tolerated in patiens with metastatic gastric or GEJ adenocarcinoma and maybe an appropriate regimen to be used in the neoadjuvant setting and with molecularly targeted agents.</p

Development and validation of a patient-reported outcome tool to assess cancer-related financial toxicity in Italy

Introduction. Financial toxicity (FT) is a well-recognized problem in oncology. US-based studies have shown that: (a) cancer patients have a 2.7 times risk of bankruptcy; (b) patients who declare bankruptcy have a 79% greater hazard of death; (c) financial burden significantly impairs quality of life (QoL), and (d) reduces compliance and adherence to treatment prescriptions. The aim of the project is to develop and validate a patient-reported-outcome (PRO) measure to assess FT of cancer patients in Italy, where, despite the universal health coverage given by the national health service, FT is an emerging issue. Methods and analysis. Our hypothesis is that a specific FT measure, which considers the relevant socio-cultural context and health care system, would allow to understand the main determinants of cancer-related financial toxicity in Italy and to contrast them. According to the International Society for Pharmaco-economics and Outcomes Research (ISPOR) guidelines on PROs, the project will include the following steps: (1) concept elicitation (from focus groups with patients and caregivers; literature; oncologists; nurses) and analysis, creating a coding library; (2) item generation (using a format that includes a question and a response on a 4-point Likert scale) and analysis through patients’ cognitive interviews of item importance within different coding categories to produce the draft instrument; (3) factor analysis and internal validation (with Cronbach’s alpha and test-retest for reliability) to produce the final instrument; (4) external validation with QoL anchors and depression scales. The use of the FT measure in prospective trials is also planned. Ethics and dissemination. The protocol is approved by the ethical committees of all the participating centres. The project will tentatively produce a validated tool by the spring 2021.The project might also represent a model and the basis for future cooperation with other European countries, with different health care systems and socio-economic conditions

Confirmatory validation analysis of the PROFFIT questionnaire to assess financial toxicity in cancer patients.

BACKGROUND The Patient Reported Outcome for Fighting FInancial Toxicity (PROFFIT) questionnaire was developed to measure financial toxicity (FT) and identify its determinants. The aim of the present study was to confirm its validity in a prospective cohort of patients receiving anticancer treatment. PATIENTS AND METHODS From March 2021 to July 2022, 221 patients were enrolled at 10 Italian centres. Selected items of the EORTC-QLQ-C30 questionnaire represented the anchors, specifically, question 28 (Q-28) on financial difficulties, and questions 29-30 measuring global health status/quality of life (HR-QOL). The study had 80% power to detect a 0.20 correlation coefficient (r) between anchors and PROFFIT-score (items 1-7, range 0-100, 100 indicating maximum FT) with bilateral alpha 0.05 and 80% power. Confirmatory factor analysis was conducted. FT determinants (items 8-16) were described. RESULTS Median age of patients was 65 years, 116 (52.5%) were females, 96 (43.4%) had low education level. Confirmatory factor analysis confirmed goodness of fit of the PROFFIT-score. Significant partial correlation of PROFFIT-score was found with Q-28 (r = 0.51) and HR-QOL (r = -0.23). Mean (SD) PROFFIT-score at baseline was 36.5 (24.9); it was statistically significantly higher for patients living in South Italy, those with lower education level, those who were freelancer/unemployed at diagnosis and those who reported significant economic impact from the COVID-19 pandemic. Mean (SD) scores of determinants ranged from 17.6 (27.1) for item 14 (support from medical staff) to 49.0 (36.3) for item 10 (expenses for medicines or supplements). PROFFIT-score significantly increased with worsening response to determinants. CONCLUSIONS External validation of PROFFIT-score in an independent sample of patients was successful. The instrument is now being used in clinical studies

Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters

IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20

A snow/firn four-century record of polycyclic aromatic hydrocarbons (PAHs) and polychlorobiphenyls (PCBs) at Talos Dome (Antarctica).

A four-century record of fourteen polycyclic aromatic hydrocarbons (PAHs) and seven polychlorobiphenyls (PCBs) was obtained from two snow/firn cores gathered at Talos Dome (Antarctica) in order to assess the contribution of human activities to global environmental pollution. The total concentrations of ΣPAH14 and ΣPCB7 were 0.7ng/l and 0.06ng/l in the deepest firn sample analyzed, and 3.4ng/l and 0.22ng/l in surface snow samples deposited over the last few years, respectively. Our data highlighted the presence of PAH maxima in the concentration depth profile, which correlated with non-sea salt sulphate maxima associated with the major known volcanic eruptions in the period 1600–1930. PAHs showed the highest concentration in the core (4.6ng/l) at a depth of about 27,8m (14,8m water equivalent), here named the “Tambora PAH excess”, in relation to the Tambora eruption (1815A.D.), the largest in recorded history. Surprisingly the data also revealed the presence of synchronous PCB maxima, with a well defined peak (0.14ng/l) at a depth of 27,8m. Between 1930 and 2002, PAHs showed an overall 50% increase, with a slope of about 0.013ngl-1 year-1. This can be predominantly attributed to the emission of incomplete combustion processes of organic matter related to anthropogenic activities. PCBs show a much higher increase (+200%) with a slope of 0.0034ngl-1 year-1 in a very limited period (1930–1980) which is almost totally due to the massive industrial production and use of PCBs, here named “industrial PCB excess”. The slight tendency of PCBs to a constant level from 1980 to 2002 might be attributed to the reduction in the industrial production of PCBs and the restricted use only in totally enclosed systems which started in many countries in the late 1970s

Comparison of two questionnaires on informed consent in "marginal" donor liver

The necessity of liver donors has contributed to overcome the traditional criteria and to propose new ones for the acceptance of livers for transplantation. For this reason expanded or extended donation criteria (ECD) or even overextended criteria for marginal or high risk organ donors have been developed. ELPAT end ELITA-ELTR coordinated the distribution of questionnaire previously reported, that was sent to 53 European liver transplant centers. Criteria were divided based on the response rate. Criteria as Steatosis and Serum sodium > 165 mmol/L in more than 60% of cases are not considered a contraindication to transplantation as well as a previous history of cancer. Criteria as ICU stay, BMI > 30, Serum bilirubin > 3 mg/dL and HIV+ or critically illness are not considered adequate for transplantation from 30% to 59% of cases. On the other hand there is no agreement on other Extended liver donor and recipients criteria such as age up to 80 years, SGOT > 90 U/L, SGPT > 105 U/L and high risk sex practices, drug users, only age > 65 and only age < 65, respectively. Criteria as serum sodium could be not considered ECD criteria. In conclusion the development of more studies as well as the inclusion of more world-wide liver transplantation centers are required to confirm these data