Association of Upfront Peptide Receptor Radionuclide Therapy With Progression-Free Survival Among Patients With Enteropancreatic Neuroendocrine Tumors

open57noIMPORTANCE Data about the optimal timing for the initiation of peptide receptor radionuclide therapy (PRRT) for advanced, well-differentiated enteropancreatic neuroendocrine tumors are lacking. OBJECTIVE To evaluate the association of upfront PRRT vs upfront chemotherapy or targeted therapy with progression-free survival (PFS) among patients with advanced enteropancreatic neuroendocrine tumors who experienced disease progression after treatment with somatostatin analogues (SSAs). DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study analyzed the clinical records from 25 Italian oncology centers for patients aged 18 years or older who had unresectable, locally advanced or metastatic, well-differentiated, grades 1 to 3 enteropancreatic neuroendocrine tumors and received either PRRT or chemotherapy or targeted therapy after experiencing disease progression after treatment with SSAs between January 24, 2000, and July 1, 2020. Propensity score matching was done to minimize the selection bias. EXPOSURES Upfront PRRT or upfront chemotherapy or targeted therapy. MAIN OUTCOMES AND MEASURES The main outcome was the difference in PFS among patients who received upfront PRRT vs among those who received upfront chemotherapy or targeted therapy. A secondary outcome was the difference in overall survival between these groups. Hazard ratios (HRs) were fitted in a multivariable Cox proportional hazards regression model to adjust for relevant factors associated with PFS and were corrected for interaction with these factors. RESULTS Of 508 evaluated patients (mean ([SD] age, 55.7 [0.5] years; 278 [54.7%] were male), 329 (64.8%) received upfront PRRT and 179 (35.2%) received upfront chemotherapy or targeted therapy. The matched group included 222 patients (124 [55.9%] male; mean [SD] age, 56.1 [0.8] years), with 111 in each treatment group. Median PFS was longer in the PRRT group than in the chemotherapy or targeted therapy group in the unmatched (2.5 years [95%CI, 2.3-3.0 years] vs 0.7 years [95%CI, 0.5-1.0 years]; HR, 0.35 [95%CI, 0.28-0.44; P < .001]) and matched (2.2 years [95% CI, 1.8-2.8 years] vs 0.6 years [95%CI, 0.4-1.0 years]; HR, 0.37 [95%CI, 0.27-0.51; P < .001]) populations. No significant differences were shown in median overall survival between the PRRT and chemotherapy or targeted therapy groups in the unmatched (12.0 years [95%CI, 10.7-14.1 years] vs 11.6 years [95%CI, 9.1-13.4 years]; HR, 0.81 [95%CI, 0.62-1.06; P = .11]) and matched (12.2 years [95% CI, 9.1-14.2 years] vs 11.5 years [95%CI, 9.2-17.9 years]; HR, 0.83 [95%CI, 0.56-1.24; P = .36]) populations. The use of upfront PRRT was independently associated with improved PFS (HR, 0.37; 95%CI, 0.26-0.51; P < .001) in multivariable analysis. After adjustment of values for interaction, upfront PRRT was associated with longer PFS regardless of tumor functional status (functioning: adjusted HR [aHR], 0.39 [95%CI, 0.27-0.57]; nonfunctioning: aHR, 0.29 [95%CI, 0.16-0.56]), grade of 1 to 2 (grade 1: aHR, 0.21 [95%CI, 0.12-0.34]; grade 2: aHR, 0.52 [95%CI, 0.29-0.73]), and site of tumor origin (pancreatic: aHR, 0.41 [95%CI, 0.24-0.61]; intestinal: aHR, 0.19 [95%CI, 0.11-0.43]) (P < .001 for all). Conversely, the advantage was not retained in grade 3 tumors (aHR, 0.31; 95%CI, 0.12-1.37; P = .13) or in tumors with a Ki-67 proliferation index greater than 10% (aHR, 0.73; 95%CI, 0.29-1.43; P = .31). CONCLUSIONS AND RELEVANCE In this cohort study, treatment with upfront PRRT in patients with enteropancreatic neuroendocrine tumors who had experienced disease progression with SSA treatment was associated with significantly improved survival outcomes compared with upfront chemotherapy or targeted therapy. Further research is needed to investigate the correct strategy, timing, and optimal specific sequence of these therapeutic options.openPusceddu, Sara; Prinzi, Natalie; Tafuto, Salvatore; Ibrahim, Toni; Filice, Angelina; Brizzi, Maria Pia; Panzuto, Francesco; Baldari, Sergio; Grana, Chiara M.; Campana, Davide; Davì, Maria Vittoria; Giuffrida, Dario; Zatelli, Maria Chiara; Partelli, Stefano; Razzore, Paola; Marconcini, Riccardo; Massironi, Sara; Gelsomino, Fabio; Faggiano, Antongiulio; Giannetta, Elisa; Bajetta, Emilio; Grimaldi, Franco; Cives, Mauro; Cirillo, Fernando; Perfetti, Vittorio; Corti, Francesca; Ricci, Claudio; Giacomelli, Luca; Porcu, Luca; Di Maio, Massimo; Seregni, Ettore; Maccauro, Marco; Lastoria, Secondo; Bongiovanni, Alberto; Versari, Annibale; Persano, Irene; Rinzivillo, Maria; Pignata, Salvatore Antonio; Rocca, Paola Anna; Lamberti, Giuseppe; Cingarlini, Sara; Puliafito, Ivana; Ambrosio, Maria Rosaria; Zanata, Isabella; Bracigliano, Alessandra; Severi, Stefano; Spada, Francesca; Andreasi, Valentina; Modica, Roberta; Scalorbi, Federica; Milione, Massimo; Sabella, Giovanna; Coppa, Jorgelina; Casadei, Riccardo; Di Bartolomeo, Maria; Falconi, Massimo; de Braud, FilippoPusceddu, Sara; Prinzi, Natalie; Tafuto, Salvatore; Ibrahim, Toni; Filice, Angelina; Brizzi, Maria Pia; Panzuto, Francesco; Baldari, Sergio; Grana, Chiara M.; Campana, Davide; Davì, Maria Vittoria; Giuffrida, Dario; Zatelli, Maria Chiara; Partelli, Stefano; Razzore, Paola; Marconcini, Riccardo; Massironi, Sara; Gelsomino, Fabio; Faggiano, Antongiulio; Giannetta, Elisa; Bajetta, Emilio; Grimaldi, Franco; Cives, Mauro; Cirillo, Fernando; Perfetti, Vittorio; Corti, Francesca; Ricci, Claudio; Giacomelli, Luca; Porcu, Luca; Di Maio, Massimo; Seregni, Ettore; Maccauro, Marco; Lastoria, Secondo; Bongiovanni, Alberto; Versari, Annibale; Persano, Irene; Rinzivillo, Maria; Pignata, Salvatore Antonio; Rocca, Paola Anna; Lamberti, Giuseppe; Cingarlini, Sara; Puliafito, Ivana; Ambrosio, Maria Rosaria; Zanata, Isabella; Bracigliano, Alessandra; Severi, Stefano; Spada, Francesca; Andreasi, Valentina; Modica, Roberta; Scalorbi, Federica; Milione, Massimo; Sabella, Giovanna; Coppa, Jorgelina; Casadei, Riccardo; Di Bartolomeo, Maria; Falconi, Massimo; de Braud, Filipp

Enzyme-aided Wool Dyeing: Influence of Internal Lipids

Dyeing and diffusion properties of dyes into wool fiber are governed by a membranous structure which is formed by a matrix protein and lipid components. External lipids (wool wax) are mainly non-polar, while internal lipids consist mainly of sterols, polar lipids (ceramides), and free fatty acids. These components constitute a real hydrophobic barrier to the diffusion of dye molecules and in fact conventional wool dyeing methods are based on long times at temperature near the boil in order to ensure good levels of dye penetration. To limit the action of this barrier and to achieve higher values of dye bath exhaustion operating at temperatures lower than 98 oC, wool fabric was subjected to three different pre-treatments. The first pre-treatment consisted of the removal of internal lipids by extraction with solvents in order to obtain a higher affinity of the fiber towards the dyes. The second involved hydrolysis with a protease, which leads to the formation of access routes within the fiber to improve the uptake of dyes or other reagents. Finally, the third took into account the combined action of the two previous pre-treatments. The influence of each individual pre-treatment and their combinations on the kinetics and final exhaustion of the dye bath were studied, and assessment of color fastness (to washing and to light) were carried out

Investigation on the explosible properties of textile dusts

The textile industry has encountered in the past some episodes of dust explosion with fatalities, monetary losses and serious damages. In general, the textile industry deals with “nontraditional dusts”, which originate from fibrous materials handled by the companies belonging to textile department. In order to better understand the hazard related to textile-related dusts, the local federation of employers of a northern Italian district funded a research program with the aim to make an extensive survey of the characteristics of the dusts present as by-product in several local manufacturers. One hundred dust samples were collected from several different industrial sites. Some of these were part of the wool manufacturing chain, others operated in the field of natural or synthetic fibers. All the samples were analyzed to determine the particle size distribution. Wet-sieving and/or laser diffraction methods were used depending on the sample. 15 samples were submitted to the speditive explosibility test (SET) developed at Politecnico di Torino (Danzi et. Al. 2016), 14 of these resulted explosible. Some samples, including the one which was negative at the SET, were submitted to test in a 20l sphere. All resulted explosible. In the paper the details of the experimental program and all the results are described

Investigation on the explosible properties of textile dusts

The textile industry has encountered in the past some episodes of dust explosion with fatalities, monetary losses and serious damages. In general, the textile industry deals with “nontraditional dusts”, which originate from fibrous materials handled by the companies belonging to textile department. In order to better understand the hazard related to textile-related dusts, the local federation of employers of a northern Italian district funded a research program with the aim to make an extensive survey of the characteristics of the dusts present as by-product in several local manufacturers. One hundred dust samples were collected from several different industrial sites. Some of these were part of the wool manufacturing chain, others operated in the field of natural or synthetic fibers. All the samples were analyzed to determine the particle size distribution. Wet-sieving and/or laser diffraction methods were used depending on the sample. 15 samples were submitted to the speditive explosibility test (SET) developed at Politecnico di Torino (Danzi et. Al. 2016), 14 of these resulted explosible. Some samples, including the one which was negative at the SET, were submitted to test in a 20l sphere. All resulted explosible. In the paper the details of the experimental program and all the results are described

The concentration and prevalence of ochratoxin A in coffee and coffee-based products : a global systematic review, meta-analysis and meta-regression

The current investigation was aimed to estimate the prevalence and concentration of ochratoxin A (OTA) in different types of coffee and coffee-based products with the aid of a systematic review and meta analysis. Therefore, the recommended databases including PubMed, Scopus, and Embase from Jan 1983 to Oct 2018 were screened to retrieve the related citations. In this regard, among 1041 explored articles in the identification step, thirty six articles with 3182 samples were included in the meta-analysis and meta-regression. According to findings, the global pooled concentration and prevalence of OTA was calculated as 3.21 mu g/kg (95% CI: 3.08-3.34 mu g/kg) and 53.0 % (95% CI: 43.0-62.0), respectively. Also, direct correlations between the increases in poverty as well as the amount of annual precipitation and prevalence of OTA was noted, while with decreasing in HDI the prevalence of OTA in coffee significantly was increased. Moreover, the lowest and highest concentrations of OTA in coffee were observed in Taiwan (0.35 mu g/kg) and Turkey (79.0 mu g/kg), respectively. The outcome of this meta-analysis can be used for the building of risk assessment models aiming to derive data for the development of specific actions to reduce the exposure to this mycotoxin in coffee and coffee-based products23861161

COLD KITS BASED ON PSMA LIGANDS FOR THE PREPARATION OF RADIOPHARMACEUTICALS

The object of the present invention is a novel formulation, based on Prostate Specific Membrane Antigen (PSMA) ligands, for use as radiopharmaceutical precursors (kold kits). The formulation of the invention is designed to allow the radiopharmaceutical to be prepared instantaneously and in a single step by direct addition of radioactive isotopes, to be used both for diagnostic and therapeutic purposes