La messa alla prova per adulti: riscontri applicativi. Un’indagine empirica sulla prassi della messa alla prova nel Tribunale di Como

Il saggio propone uno studio empirico sulla prassi dell'istituto della messa alla prova nel Tribunale di Como. Introdotta nel segno della lotta al sovraffollamento carcerario, la sospensione del procedimento con messa alla prova per gli adulti ha veicolato nel sistema penale un ampio spettro di istanze politico-criminali, tra le quali spiccano, oltre alla deflazione carceraria, la promozione di dinamiche di risocializzazione del soggetto sottoposto alla prova e di riparazione nei confronti della vittima. Attraverso l’incrocio delle coordinate normative dell’istituto e dei dati empirici relativi alle sentenze di proscioglimento per esito positivo della messa alla prova emesse dalla Sezione Dibattimento Penale del Tribunale di Como negli anni 2016, 2017 e 2018, lo scritto si propone di verificare – nei limiti dei dati disponibili – il grado di effettività dell'istituto, ossia di rispondenza dello stesso agli obiettivi politico-criminali che ne hanno sollecitato l’adozione

Computed tomography based analyses of body mass composition in HER2 positive metastatic breast cancer patients undergoing first line treatment with pertuzumab and trastuzumab

Body composition parameters (BCp) have been associated with outcome in different tumor types. However, their prognostic value in patients with HER2-positive metastatic breast cancer (BC) receiving first line treatment with dual anti-HER2 antibody blockade is unknown. Preclinical evidences suggest that adipocytes adjacent to BC cells can influence response to anti-HER2 treatments. We retrospectively analyzed Computed Tomography (CT)-based BCp from 43 patients with HER2-positive metastatic BC who received first line pertuzumab/trastuzumab-based treatment between May 2009 and March 2020. The impact of baseline CT-based BCp on progression-free survival (PFS) was tested using Kaplan-Meier estimates and univariate and multivariate Cox regression models. We found a significantly worse PFS for patients with high baseline subcutaneous fat index (median 7.9 vs 16.1 months, p = 0.047, HR = 2.04, 95%CI 1-4.17) and for those with high total abdominal fat index (8.1 vs 18.8 months, p = 0.030, HR = 2.17, 95%CI 1.06-4.46). Patients with baseline sarcopenia did not show shorter PFS compared to those without sarcopenia (10.4 vs 9.2 months, p = 0.960, HR = 0.98, 95%CI 0.47-2.03). Total abdominal fat index remained a significant predictor of PFS at multivariate analysis. Our findings suggest that a high quantity of total abdominal fat tissue is a poor prognostic factor in patients receiving trastuzumab/pertuzumab-based first-line treatment for HER2-positive metastatic BC

Ki67 and PR in Patients Treated with CDK4/6 Inhibitors: A Real-World Experience

CDK4/6 inhibitors (CDK4/6i) are recommended in patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer (ABC). Up to now, no prognostic biomarkers have been identified in this setting. We retrospectively analyzed the expression of progesterone receptor (PR) and Ki67, assessed by immunohistochemistry, in 71 ABC patients treated with CDK4/6i and analyzed the impact of these markers on progression-free survival (PFS). The majority of patients 63/71 (88.7%) received palbociclib, 4 (5.6%) received ribociclib, and 4 (5.6%) received abemaciclib. A higher median value of Ki67 was observed in cases undergoing second-line treatment (p= 0.047), whereas the luminal B subtype was more prevalent (p= 0.005). In the univariate analysis of the first-line setting, luminal A subtype showed a trend towards a correlation with a longer PFS (p= 0.053). A higher continuous Ki67 value led to a significantly shorter PFS. When the interaction between pathological characteristics and line of treatment was considered, luminal B subtype showed a significantly (p= 0.043) worse outcome (Hazard Ratio (HR) 2.84; 1.03-7.82 95% Confidence Interval (CI)). PFS in patients undergoing endocrine therapy plus CDK4/6i was inversely correlated with Ki67 expression but not with PR, suggesting that tumor proliferation has a greater impact on cell cycle inhibitors combined with endocrine therapy than PR expression

Clinical trial units and clinical research coordinators: a system facing crisis?

We are currently witnessing an increase in procedural and managerial complexities within the field of clinical research, which require greater human and infrastructural resources as well as imply the need for a greater skill set and expertise on the part of professionals. Within this frame of reference clinical trial units and clinical research coordinators play a vital role in the design and conduct of clinical trials in Italy. There is a current recruitment and retention crisis for this specialist role due to a complex set of factors, most likely to have come to a head due to the lack of recognition at the Italian institutional level, that lead to precarious work contracts, lack of identity, and excessive turnover at experimental sites. This article, led by the Italian Group of Clinical Research Coordinator (GIDMcrc), presents some of the issues and ways in which national stakeholders may be able to address this

CDK4/6-Inhibitors Versus Chemotherapy in Advanced HR+/HER2-Negative Breast Cancer: Results and Correlative Biomarker Analyses of the KENDO Randomized Phase II Trial

Background: The optimal treatment approach for hormone receptor-positive/HER2-negative metastatic breast cancer (HR+/HER2-negative MBC) with aggressive characteristics remains controversial, with lack of randomized trials comparing cyclin-dependent kinase (CDK)4/6-inhibitors (CDK4/6i) + endocrine therapy (ET) with chemotherapy + ET. Materials and methods: We conducted an open-label randomized phase II trial (NCT03227328) to investigate whether chemotherapy + ET is superior to CDK4/6i + ET for HR+/HER2-negative MBC with aggressive features. PAM50 intrinsic subtypes (IS), immunological features, and gene expression were assessed on baseline samples. Results: Among 49 randomized patients (median follow-up: 35.2 months), median progression-free survival (mPFS) with chemotherapy + ET (11.2 months, 95% confidence interval [CI]: 7.7-15.4) was numerically shorter than mPFS (19.9 months, 95% CI: 9.0-30.6) with CDK4/6i + ET (hazard ratio: 1.41, 95% CI: 0.75-2.64). Basal-like tumors under CDK4/6i + ET exhibited worse PFS (mPFS: 11.4 months, 95% CI: 3.00-not reached [NR]) and overall survival (OS; mOS: 18.8 months, 95% CI: 18.8-NR) compared to other subtypes (mPFS: 20.7 months, 95% CI: 9.00-33.4; mOS: NR, 95% CI: 24.4-NR). In the chemotherapy arm, luminal A tumors showed poorer PFS (mPFS: 5.1 months, 95% CI: 2.7-NR) than other IS (mPFS: 13.2 months, 95% CI: 10.6-28.1). Genes/pathways involved in BC cell survival and proliferation were associated with worse outcomes, as opposite to most immune-related genes/signatures, especially in the CDK4/6i arm. CD24 was the only gene significantly associated with worse PFS in both arms. Tertiary lymphoid structures and higher tumor-infiltrating lymphocytes also showed favorable survival trends in the CDK4/6i arm. Conclusions: The KENDO trial, although closed prematurely, adds further evidence supporting CDK4/6i + ET use in aggressive HR+/HER2-negative MBC instead of chemotherapy. PAM50 IS, genomic, and immunological features are promising biomarkers to personalize therapeutic choices

Study on the efficacy of edible coatings on quality of blueberry fruits during shelf-life

Edible films or coatings could be used as an alternative way of conservation, because of their ability to reduce respiration and transpiration rate, maintain firmness and generally delay fruit senescence. The aim of this research was to evaluate the influence of different types of coating: sodium alginate (Al), pectin (Pe) and sodium alginate plus pectin (Al + Pe), on some blueberries quality characteristics, cell viability and microbial growth during 14 days of storage at 4 °C. Blueberry samples differently coated did not show significant differences in weight loss, pH, soluble solid and dry matter content. However, the application of Al, Pe and Al + Pe improved the firmness of blueberry samples as compared to the uncoated one. Changes in the surface reflection properties in the coated blueberries induced a general lower lightness and a more intense blue hue colour than the control sample. The microbiological results indicated that the coating of blueberry, in particular with Al or Pe, significantly reduced the growth kinetics of yeasts and mesophilic aerobic bacteria

Ki67 and PR in Patients Treated with CDK4/6 Inhibitors: A Real-World Experience

CDK4/6 inhibitors (CDK4/6i) are recommended in patients with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer (ABC). Up to now, no prognostic biomarkers have been identified in this setting. We retrospectively analyzed the expression of progesterone receptor (PR) and Ki67, assessed by immunohistochemistry, in 71 ABC patients treated with CDK4/6i and analyzed the impact of these markers on progression-free survival (PFS). The majority of patients 63/71 (88.7%) received palbociclib, 4 (5.6%) received ribociclib, and 4 (5.6%) received abemaciclib. A higher median value of Ki67 was observed in cases undergoing second-line treatment (p = 0.047), whereas the luminal B subtype was more prevalent (p = 0.005). In the univariate analysis of the first-line setting, luminal A subtype showed a trend towards a correlation with a longer PFS (p = 0.053). A higher continuous Ki67 value led to a significantly shorter PFS. When the interaction between pathological characteristics and line of treatment was considered, luminal B subtype showed a significantly (p = 0.043) worse outcome (Hazard Ratio (HR) 2.84; 1.03–7.82 95% Confidence Interval (CI)). PFS in patients undergoing endocrine therapy plus CDK4/6i was inversely correlated with Ki67 expression but not with PR, suggesting that tumor proliferation has a greater impact on cell cycle inhibitors combined with endocrine therapy than PR expression

(Ultra) high pressure homogenization potential on the shelf-life and functionality of kiwifruit juice

The increasing competition within the food industry sector makes the requisite of innovation in processes and products essential, leading to focus the interest on the application of new processing technologies including high pressure homogenization (HPH) and ultra high pressure homogenization (UHPH). In this context, the present research aimed at evaluating the effects of two UHPH treatments performed at 200 MPa for 2 and 3 cycles on quality and functionality of organic kiwifruit juice stored at three different temperatures, i.e., 5, 15, and 25\ub0C. The results showed that only the treatment performed at 200 MPa for 3 cycles was able to significantly increase the shelf-life of organic kiwifruit juices when stored at refrigeration temperature, avoiding also phase separation that occurred in the sample treated at 0.1 MPa (control) after 20 days of refrigerated storage. The obtained data showed also that the highest applied pressure was able to increase some quality parameters of the juice such as viscosity and luminosity (L 17) and increased the availability of total phenol content consequently enhancing the juice total antioxidant activity. The application of a treatment at 200 MPa for 3 cycles allowed to obtain a stable kiwifruit juice for more than 40 days under refrigerated storage. A challenge to implement this technology in food process as full alternative to thermal treatment could be represented by the adoption of pressure level up to 400 MPa followed by the packaging in aseptic conditions

(Ultra) High Pressure Homogenization Potential on the Shelf-Life and Functionality of Kiwifruit Juice

The increasing competition within the food industry sector makes the requisite of innovation in processes and products essential, leading to focus the interest on the application of new processing technologies including high pressure homogenization (HPH) and ultra high pressure homogenization (UHPH). In this context, the present research aimed at evaluating the effects of two UHPH treatments performed at 200 MPa for 2 and 3 cycles on quality and functionality of organic kiwifruit juice stored at three different temperatures, i.e., 5, 15, and 25 degrees C. The results showed that only the treatment performed at 200 MPa for 3 cycles was able to significantly increase the shelf-life of organic kiwifruit juices when stored at refrigeration temperature, avoiding also phase separation that occurred in the sample treated at 0.1 MPa (control) after 20 days of refrigerated storage. The obtained data showed also that the highest applied pressure was able to increase some quality parameters of the juice such as viscosity and luminosity (L*) and increased the availability of total phenol content consequently enhancing the juice total antioxidant activity. The application of a treatment at 200 MPa for 3 cycles allowed to obtain a stable kiwifruit juice for more than 40 days under refrigerated storage. A challenge to implement this technology in food process as full alternative to thermal treatment could be represented by the adoption of pressure level up to 400 MPa followed by the packaging in aseptic conditions