The Vital Habit in Kant’s Philosophy

In this article I focus on the concept of habit in Kant’s philosophy. First of all, I concentrate on the criticisms he delineates against Gewohnheit in his epistemological and moral philosophy. In particular, habit is seen as absence of moral freedom. This conclusion is pretty different from Kant’s position expressed in his Anthropology From the Pragmatic Point of View and in the last part of the Conflict of the Faculties. After a deep insight on the different terms referred to the conceptual field of habit, I focus on the relation between Gewohnheit and desire: in fact, Kant recognized that habit is not the mere repetition of an act, but more precisely it is the desire of repetition. That is why it is not strictly bonded to the deterministic world and it does not refer to machines: only the living beings may have habits. This way, it is possible to understand its role within the theme of health: in the reflections on dietetics, habit is particularly useful. The last part of the article is devoted to the new perspective on Kantian political philosophy opened by this positive view on this concept.En este artículo me centro en el concepto de hábito en la filosofía de Kant. En primer lugar, me enfoco en las críticas que él delinea contra Gewohnheit en su filosofía epistemológica y moral. En particular, el hábito es visto como ausencia de libertad moral. Esta conclusión es bastante diferente a la posición expresada por Kant en su Antropología en sentido pragmático y en la última parte de El conflicto de las facultades. Tras profundizar sobre los diferentes términos referidos al campo conceptual del hábito, me concentro en la relación entre Gewohnheit y deseo: de hecho, Kant reconoció que el hábito no es una mera repetición de un acto, sino, más precisamente, es el deseo de repetición. Es por esto que no está estrictamente ligado al mundo determinista y no se refiere a máquinas: solo los seres vivos podrían tener hábitos. De esta forma, es posible comprender su rol en el tema de la salud: en la reflexión sobre dietética, el hábito es particularmente útil. La última parte del artículo está consagrada a la nueva perspectiva en la filosofía política kantiana abierta por esta visión positiva de este concepto

La frammentazione dell'ordine. Comunità e critica in Friedrich Schlegel

This work is focused on Schlegel’s philosophy, as a thinking which makes possible to affront the problem of the role of subjectivity and philosophy in politics. In particular it deals with the three main spheres elaborated by Schlegel, and so I decided to evolve this text in three chapters: a. history, b. philosophy and critics as production of truth, c. possible interactions between philosophy and political institutions. I made interact these three spheres with the arguments that Schlegel uses to understand the role of philosophy and subjectivity: 1. the effort to rebuild links in the theoretical and political fragmentation which Schlegel sees; 2. the volatility of this effort; 3. the importance of philosophy in the production of an opening or window in established system of theory and politics, to continue in the effort to grasp the absolute, life and to give a key to the interpretation of chaos. These two groups of themes cross each other, and so they mark the weave of the present text, which faces the points 1., 2. and 3. in every field pointed out (a., b., c.). So I focused on Schlegel’s interpretation of the writing of subjective history, which always aims (without success) to objectivity (chap.1); on Schlegel’s conception of truth as a coherent construction (chap. 2); on the possibility of a community (chap.3). In every case the reconstruction is precarious, and can never became objective, universal and stable. From this results the rejection of an a priori history (chap.1), of an objective beauty (chap.2) and of modern natural law. Schlegel turns to the impossibility of the Universal and of a stable system of interpretation of, pointing to a lively and chaotic dimension through opening of those systems to life and changes. From this results the decision of writing fragments and not fixed philosophical systems, to defence of a subjective history and the project of a future not rationally necessary or inferable, but to the realisation of, people should work (chap.1); the importance of irony (chap.2); and the insertion in the State of a class (Stand) of savant not restricted in national borders, whose duty is to help keeping the order inside the States and to keep the attention on the processes of production of truth

Biomarkers of prognosis and toxicity for metastatic melanoma patients treated with ipilimumab.

Background Metastatic melanoma has a dismal prognosis, as a consequence of its intrinsic aggressiveness and the lack of effective treatment options: in fact, until recently, systemic therapies were numbered. Ipilimumab is a fully humanized monoclonal anti-Cytotoxic T-Lymphocyte Antigen 4 antibody that demonstrated a significant improvement of metastatic melanoma patient survival, however toxicity may be severe and life threatening. Clinicians lack reliable prognostic factors for prognosis and toxicity and this makes treatment decisions difficult. Methods An observational prospective study was performed at the Veneto Institute of Oncology (IOV), the main inclusion criteria being the administration of ipilimumab 3mg/kg every 3 weeks for metastatic melanoma. A total of 140 patients were included, clinical features and circulating biomarkers were evaluated for an association with prognosis or adverse events. Out of 140 patients, 113 were evaluated for prognostic factors, and the full cohort was included in a toxicity study. A prognostic model was derived and data from 97 patients from two other Italian Institutes were used to validate this prognostic model. Results Baseline serum lactic dehydrogenase (LDH) concentration and neutrophil count were significantly associated with prognosis. In particular, patients with higher circulating levels of LDH and higher neutrophils before treatment had a shorter survival and increased HR of death (HR=1.36, 95% CI 1.16-1.58, P<.001 and HR=1.76, 95% CI 1.41-2.10, P<.001, respectively). Data were validated on the external cohort and the prognostic model was confirmed. Female patients and patients with lower baseline serum levels of interleukin-6 (IL6) had a higher risk of developing severe toxicity (OR=1.5, 95% CI 1.06-2.16 and OR=2.84 for 1ng/L variation, 95% CI 1.34-6.03, respectively). Conclusions We demonstrated that baseline levels of neutrophils and serum LDH could help clinicians to predict the outcome of melanoma patients treated with ipilimumab and that ipilimumab may not be the best treatment in patients with higher neutrophil count and LDH. Only comparative and translational studies could define if patients with high LDH and neutrophil are refractory to immunotherapy or have a more aggressive variant of melanoma independent from the treatment. Serum baseline IL6 could help in identifying patients with a greater risk of toxicity from ipilimumab and in planning a more specific monitoring during and after the treatment, with the purpose of increasing its safety. In particular, females with low IL6 serum levels should be carefully monitored for AEs

Basal cell carcinoma: 10-year experience with electrochemotherapy

BACKGROUND: Electrochemotherapy (ECT), by combining manageable cytotoxic agents with short electric pulses, represents an effective palliative skin-directed therapy. The accumulated evidence indicates that ECT stands out as a safe and well-tolerated alternative treatment for patients with multiple or large basal cell carcinoma (BCC), who are not suitable for conventional treatments. However, long-term data and shared indications are lacking. METHODS: In this observational study, we retrospectively analyzed 84 prospectively collected patients with multiple, recurrent or locally advanced BCC who were not candidate for standard therapies and received bleomycin-based ECT according to the European Standard Operative Procedures of ECT, from 2006 to 2016. RESULTS: Disease extent was local, locally advanced and metastatic in 40 (48%), 41 (49%) and 3 (3%), respectively. Forty-four (52%) individuals had multiple BCCs. Grade 3 skin toxicity after ECT was observed in 6% of cases. Clearance rate was 50% (95% CI 39-61%). Primary presentation (p = 0.004), tumor size <3 cm (p < 0.001), well-defined borders (p = 0.021), absence of tumor ulceration (p = 0.001), non-aggressive BCC histology (p = 0.046) and age 6469 years were associated with higher complete response rate. In patients with local BCC, the clearance rate was 72.5 and 85% after one or two ECT cycles, respectively. In the laBCC group, 32 patients (78%) achieved an objective response. Five-year recurrence rate for local and laBCC was 20 and 38%, respectively (p 64 0.001). CONCLUSIONS: One or two ECT cycles with bleomycin may be a valuable palliative treatment in well-selected patients with multiple BCCs and favorable tumor features. Validation of predictive factors will be imperative to match patients with optimal ECT treatment modalities. Management of laBCC with ECT warrants further investigation. Trial registration ISRCTN14633165 Registered 24 March 2017 (retrospectively registered)

Local treatment with electrochemotherapy of superficial angiosarcomas: Efficacy and safety results from a multi-institutional retrospective study

Background: Angiosarcoma is an aggressive vascular neoplasm with a high propensity for local recurrence. Electrochemotherapy is an emerging skin-directed therapy, exerting prominent cytotoxic activity, and antivascular effects. Its efficacy in angiosarcoma has not been investigated. Methods: This multicenter retrospective analysis reviewed patients who underwent electrochemotherapy from 2007 to 2014 for superficial advanced angiosarcomas. Bleomycin was administered intravenously and delivered within tumors by means of percutaneously applied electric pulses, according to the European Standard Operating Procedures for Electrochemotherapy. Tumor assessment was performed using RECIST (version 1.1). Toxicity (CTCAE, v4.0) and local progression-free survival (LPFS) were also evaluated. Results: Nineteen patients (13 with locally advanced and 6 with metastatic angiosarcomas) were treated. Tumor sites were: scalp (n¼5), breast(n¼8), other skin sites (n¼3), and soft tissue (n¼3). Target lesions (n¼54) ranged in size from 1.5 to 2.5 cm (median, 2 cm). Treatment was well tolerated. After 2 months, an objective response was observed in 12/19 (63%) patients, complete in 8 (42%). One-year LPFS within treatment field was 68%. Local symptom improvement included palliation of bleeding (5/19 patients) and pain relief (6/19 patients). Conclusions: Electrochemotherapy may represent a new locoregional treatment for selected patients with superficial angiosarcomas

Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients

Introduction Tumour burden is a prognostic biomarker in metastatic melanoma. However, tumour burden is difficult to measure and there are currently no reliable surrogate biomarkers to easily and reliably determine it. The aim of this study was to assess the potential of plasma total cell free DNA as biomarker of tumour burden and prognosis in metastatic melanoma patients. Materials and methods A prospective biomarker cohort study for total plasma circulating cell-free DNA (cfDNA) concentration was performed in 43 metastatic melanoma patients. For 38 patients, paired blood collections and scan assessments were available before treatment and at first response evaluation. Tumour burden was calculated as the sum of volumes from three-dimensional radiological measurements of all metastatic lesions in individual patients. Results Baseline cfDNA concentration correlated with pre-treatment tumour burden (ρ = 0.52, P < 0.001). Baseline cfDNA levels correlated significantly with hazard of death and overall survival, and a cut off value of 89 pg/μl identified two distinct prognostic groups (HR = 2.22 for high cfDNA, P = 0.004). Patients with cfDNA ≥89 pg/μl had shorter OS (10.0 versus 22.7 months, P = 0.009; HR = 2.22 for high cfDNA, P = 0.004) and the significance was maintained when compared with lactic dehydrogenase (LDH) in a multivariate analysis. We also found a correlation between the changes of cfDNA and treatment-related changes in tumour burden (ρ = 0.49, P = 0.002). In addition, the ratio between baseline cfDNA and tumour burden was prognostic (HR = 2.7 for cfDNA/tumour volume ≥8 pg/(μl*cm3), P = 0.024). Conclusions We have demonstrated that cfDNA is a surrogate marker of tumour burden in metastatic melanoma patients, and that it is prognostic for overall survival.Fil: Valpione, S.. University of Manchester; Reino Unido. Christie NHS Foundation Trust; Reino UnidoFil: Gremel, G.. University of Manchester; Reino UnidoFil: Mundra, P.. University of Manchester; Reino UnidoFil: Middlehurst, P.. University of Manchester; Reino UnidoFil: Galvani, E.. Christie NHS Foundation Trust; Reino Unido. University of Manchester; Reino UnidoFil: Girotti, Maria Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. University of Manchester; Reino UnidoFil: Lee, R.J.. University of Manchester; Reino UnidoFil: Garner, G.. University of Manchester; Reino UnidoFil: Dhomen, N.. University of Manchester; Reino UnidoFil: Lorigan, P.C.. Christie NHS Foundation Trust; Reino UnidoFil: Marais, R.. University of Manchester; Reino Unid

The T cell receptor repertoire of tumor infiltrating T cells is predictive and prognostic for cancer survival.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-07-01, epub 2021-07-02Publication status: PublishedFunder: Wellcome Trust; Grant(s): 100282/Z/12/ZFunder: Cancer Research UK; Grant(s): A22902, A27412Tumor infiltration by T cells is paramount for effective anti-cancer immune responses. We hypothesized that the T cell receptor (TCR) repertoire of tumor infiltrating T lymphocytes could therefore be indicative of the functional state of these cells and determine disease course at different stages in cancer progression. Here we show that the diversity of the TCR of tumor infiltrating T cell at baseline is prognostic in various cancers, whereas the TCR clonality of T cell infiltrating metastatic melanoma pre-treatment is predictive for activity and efficacy of PD1 blockade immunotherapy

Recommendations for improving the quality of reporting clinical electrochemotherapy studies based on qualitative systematic review

Background: Electrochemotherapy is becoming a well-established treatment for malignancies of skin and non-skin origin and its use is widening across Europe. The technique was developed and optimized from solid experimental and clinical evidence. A consensus document is now warranted to formalize reporting results, which should strengthen evidence-based practice recommendations. This consensus should be derived from high quality clinical data collection, clinical expertise and summarizing patient feedback. The first step, which is addressed in this paper, aims to critically analyze the quality of published studies and to provide the recommendations for reporting clinical trials on electrochemotherapy. Methods: The quality of reporting in published studies on electrochemotherapy was analyzed in order to produce procedure specific reporting recommendations. A comprehensive literature search of studies published from 2006 to 2015 was performed followed by qualitative analysis of manuscripts assessing for 47 quality criteria grouped into four major clusters: (1) trial design, (2) description of patient population, (3) description of treatment delivery and patient outcome, (4) analysis of results and their interpretation. The summary measure during literature assessment was the proportion of studies fulfilling each manuscript quality criteria. Results: A total of 56 studies were screened, from the period 2006 to 2015, of which 33 were included in the qualitative analysis, with a total of 1215 patients. Overall, the quality of reporting was highly variable. Twenty-four reports (73%) were single-center, non-comparative studies, and only 15 (45%) were prospective in nature (only 2 of them were entered into a clinical trials registry). Electrochemotherapy technique was consistently reported, with most studies (31/33) adhering closely to published standard operating procedures. The quality of reporting the patient population was variable among the analyzed studies, with only between 45% and 100% achieving dedicated quality criteria. Reporting of treatment delivery and patient outcome was also highly variable with studies only fulfilling between 3% and 100%. Finally, reporting study results critically varied, fulfilling from 27% to 100% of the quality criteria. Based on the critical issues emerging from this analysis, recommendations and minimal requirements for reporting clinical data on electrochemotherapy were prepared and summarized into a checklist. Conclusions: There is an increasing body of published clinical data on electrochemotherapy, but more high quality clinical data are needed. Published papers often lack accurate description of study population, treatment delivery as well as patient outcome. Our recommendations, provided in the form of a summary checklist, are intended to ameliorate data reporting in future studies on electrochemotherapy and help researchers to provide a solid evidence basis for clinical practice