In Situ Raman Analysis of CO\u2082-Assisted Drying of Fruit-Slices

This work explores the feasibility of applying in situ Raman spectroscopy for the online monitoring of the supercritical carbon dioxide (SC-CO\u2082) drying of fruits. Specifically, we investigate two types of fruits: mango and persimmon. The drying experiments were carried out inside an optical accessible vessel at 10 MPa and 313 K. The Raman spectra reveal: (i) the reduction of the water from the fruit slice and (ii) the change of the fruit matrix structure during the drying process. Two different Raman excitation wavelengths were compared: 532 nm and 785 nm. With respect to the quality of the obtained spectra, the 532 nm excitation wavelength was superior due to a higher signal-to-noise ratio and due to a resonant excitation scheme of the carotenoid molecules. It was found that the absorption of CO\u2082 into the fruit matrix enhances the extraction of water, which was expressed by the obtained drying kinetic curve

Microbial inactivation efficiency of supercritical CO2drying process

Conventional drying of spices, as hot air treatment, often needs an additional downstream inactivation step to decrease the microbial load of the dried product and improve its microbial safety and microbial quality. In this regard, the present work explored the possibility to dry and decontaminate food in a single step using supercritical carbon dioxide (scCO(2)) as a drying agent. A case study was focused on the drying of herbs and the antimicrobial effects were evaluated on the naturally present microbiota. For this purpose, experiments were carried out on coriander leaves using a high pressure vessel at 10 MPa, at two different temperatures (40 and 50 degrees C) with drying time of 0 and 150 min to establish the influence of each parameter on the microbial inactivation. Yeasts and molds appeared to be the least resistant to scCO(2) as they could never be detected after the treatment (<2 log CFU/g). Mesophilic bacteria were also significantly reduced, up to 4 log CFU/g, but remained above the limit of quantification. The quality of the dried product was comparable with the quality of air-dried samples in terms of phenolic constituents. Overall, the results indicated that scCO(2) drying was a promising green drying technique combining both drying and microbial inactivation in a single step with a relevant impact on safety and costs

Long-term maintenance of dried acellular matrices

[EN] Dried and sterile acellular esophageal matrix was obtained within a new drying process based on the use of supercritical carbon dioxide (SC-CO2). Experiments were performed coupling a conventional detergent enzymatic treatment with two different drying methods: (i) SC-CO2 drying alone; (ii) dehydration in ethanol and a subsequent SC-CO2 drying. Long term preservation was achieved for several months after drying, demonstrating the maintenance of extracellular matrix (ECM) structure, mechanical properties and biocompatibility within cell repopulation studies in vitro. Overall, the results highlighted the potential of this novel technology to obtain a dry and sterile acellular matrix that can be easily stored for oesophageal regeneration in patients with emergency need.The research leading to these results received funding from Cassa di Risparmio di Trento e Rovereto (CaRiTRo) within the research project "Supercritical decellularization of engineered tissues for clinical application", biomedical science section, 2013. We thanks Lorenza Lazzari for the donation of BM-MSCs from the Cell Factory Bank (Milan-Italy).Zambon, A.; Giobbe, G.; Vetralla, M.; Michelino, F.; Urbani, L.; Pantano, M.; Pugno, N.... (2018). Long-term maintenance of dried acellular matrices. En IDS 2018. 21st International Drying Symposium Proceedings. Editorial Universitat Politècnica de València. 1091-1097. https://doi.org/10.4995/IDS2018.2018.7844OCS1091109

Demographic, tumor and clinical features of clinical trials versus clinical practice patients with HER2-positive early breast cancer: results of a prospective study

Several randomized clinical trials (RCTs) have demonstrated the efficacy of trastuzumab-based adjuvant therapy in HER2-positive breast cancer (BC). However, RCT patients may not invariably be representative of patients routinely seen in clinical practice (CP). To address this issue, we compared the clinical and tumor features of RCT and CP patients with HER2-positive BC

Efficacy and Safety of Trastuzumab Emtansine Plus Capecitabine vs Trastuzumab Emtansine Alone in Patients With Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer A Phase 1 and Randomized Phase 2 Trial

Importance: ERBB2 (HER2)-targeted therapy provides benefits in metastatic breast cancer (mBC) and gastric cancer, but additional treatments are needed to maximize efficacy and quality of life. Objective: To determine maximum tolerated doses (MTDs) of trastuzumab emtansine (T-DM1) plus capecitabine in patients with previously treated ERBB2-positive mBC and locally advanced/metastatic gastric cancer (LA/mGC) (phase 1) and the efficacy and safety of this combination vs T-DM1 alone in patients with mBC (phase 2). Design, setting, and participants: The MTD in phase 1 was assessed using a 3 + 3 design with capecitabine dose modification. Phase 2 was an open-label, randomized, international multicenter study of patients with mBC treated with T-DM1 plus capecitabine or T-DM1 alone. Eligible patients had previously treated ERBB2-positive mBC or LA/mGC with no prior chemotherapy treatment for advanced disease. Interventions: Patients in the phase 1 mBC cohort received capecitabine (750 mg/m2, 700 mg/m2, or 650 mg/m2 twice daily, days 1-14 of a 3-week cycle) plus T-DM1 3.6 mg/kg every 3 weeks. Patients with LA/mGC received capecitabine at the mBC phase 1 MTD, de-escalating as needed, plus T-DM1 2.4 mg/kg weekly. In phase 2, patients with mBC were randomized (1:1) to receive capecitabine (at the phase 1 MTD) plus T-DM1 or T-DM1 alone. Main outcomes and measures: The phase 1 primary objective was to identify the MTD of capecitabine plus T-DM1. The phase 2 primary outcome was investigator-assessed overall response rate (ORR). Results: In phase 1, the median (range) age was 54.0 (37-71) and 57.5 (53-70) years for patients with mBC and patients with LA/mGC, respectively. The capecitabine MTD was identified as 700 mg/m2 in 11 patients with mBC and 6 patients with LA/mGC evaluable for dose-limiting toxic effects. In phase 2, between October 2014 and April 2016, patients with mBC (median [range] age, 52.0 [28-80] years) were randomized to receive combination therapy (n = 81) or T-DM1 (n = 80). The ORR was 44% (36 of 81 patients) and 36% (29 of 80 patients) in the combination and T-DM1 groups, respectively (difference, 8.2%; 90% CI, -4.5 to 20.9; P = .34; clinical cutoff, May 31, 2017). Adverse events (AEs) were reported in 78 of 82 patients (95%) in the combination group, with 36 (44%) experiencing grade 3-4 AEs, and 69 of 78 patients (88%) in the T-DM1 group, with 32 (41%) experiencing grade 3-4 AEs. No grade 5 AEs were reported. Conclusions and relevance: Adding capecitabine to T-DM1 did not statistically increase ORR associated with T-DM1 in patients with previously treated ERBB2-positive mBC. The combination group reported more AEs, but with no unexpected toxic effects

Efficacy and safety of T-DM1 in the 'common-practice' of HER2+ advanced breast cancer setting: a multicenter study

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (mBC). The aim of this 'field-practice' study was to investigate the efficacy and safety of T-DM1, focusing on treatment line, previous lapatinib treatment and patterns of metastasis. Three hundred and three patients with HER2-positive mBC who received T-DM1 were identified by reviewing the medical records of 24 Italian Institutions. One hundred fourty-nine (49%) and 264 (87%) had received prior hormonal treatment and/or anti-HER2 targeted therapy, respectively. Particularly, 149 patients had been previously treated with lapatinib. The objective response rate (ORR) was 36.2%, and 44.5% when T-DM1 was administrated as second-line therapy. Considering only patients with liver metastases, the ORR was 44.4%. The median progression-free survival (PFS) was 7.0 months in the overall population, but it reached 9.0 and 12.0 months when TDM-1 was administered as second- and third-line treatment, respectively.In conclusion, in this 'real-word' study evaluating the effects of T-DM1 in patients with HER2-positive mBC who progressed on prior anti-HER2 therapies, we observed a clinically-relevant benefit in those who had received T-DM1 in early metastatic treatment-line and in subjects previously treated with lapatini

In situ Raman-analysis of supercritical carbon dioxide drying applied to acellular esophageal matrix

Supercritical (SC) carbon dioxide (CO2) drying has shown potential interest on the production of dry decellularized extracellular matrices for tissue engineering. This work explores the feasibility of Raman spectroscopy as in situ analysis for the SC-CO2 drying monitoring of a decellularized esophagus. Esophagus tissue was dried within an optical accessible high pressure CO2 dryer while the Raman signals of the wet tissue were excited at 785 nm. Two different experimental procedures were explored: i) single step process (SC-CO2 drying alone) and ii) two steps process (water exchange by ethanol followed by SC-CO2 drying). The quantification of the removal of water or ethanol from the tissue during the drying was obtained evaluating the variation of the Raman signal intensity ratio during time. The measurement of water or ethanol removal curves during the drying process can be easily/successfully exploited for the in situ monitoring of the drying process of a general matrix/tissue