Capecitabine plus temozolomide in well- or moderately-differentiated primary atypical neuroendocrine tumours — single-centre experience of two cases

Introduction: Neuroendocrine neoplasms (NENs) are a rare and heterogeneous group of tumours, with a variety of primary origins and variable aggressiveness. NENs with an atypical primary origin, such as breast and retroperitoneal NENs, are extremely rare. As a consequence, an established diagnostic and therapeutic strategy in this particular subgroup is lacking. The combination of capecitabine and temozolomide, called CAPTEM regimen, has produced promising response rates in patients with grade 1 or 2 neuroendocrine tumours of multiple origins. Case presentation: The first is a case of a 68-year-old woman with a metastatic primary breast neuroendocrine tumour, treated with cisplatin plus etoposide as first line, followed by CAV scheme (cyclophosphamide, doxorubicin, and vincristine), and subsequently treated, in third line with the CAPTEM regimen, obtaining radiological response and good tolerance. The second is the case of a 66-year-old woman affected by a metastatic primitive retroperitoneal NET G2. The patient progressed after a somatostatin analogue-based first line, whereas the CAPTEM regimen led to a partial and durable response with a favourable safety profile. Conclusions: CAPTEM chemotherapy has been shown to be an active and safe therapeutic option in advanced, metastatic G1/2 atypical primary NENs

Capecitabine plus temozolomide in well- or moderately-differentiated primary atypical neuroendocrine tumours — single-centre experience of two cases

Introduction: Neuroendocrine neoplasms (NENs) are a rare and heterogeneous group of tumours, with a variety of primary origins and variable aggressiveness. NENs with an atypical primary origin, such as breast and retroperitoneal NENs, are extremely rare. As a consequence, an established diagnostic and therapeutic strategy in this particular subgroup is lacking. The combination of capecitabine and temozolomide, called CAPTEM regimen, has produced promising response rates in patients with grade 1 or 2 neuroendocrine tumours of multiple origins. Case presentation: The first is a case of a 68-year-old woman with a metastatic primary breast neuroendocrine tumour, treated with cisplatin plus etoposide as first line, followed by CAV scheme (cyclophosphamide, doxorubicin, and vincristine), and subsequently treated, in third line with the CAPTEM regimen, obtaining radiological response and good tolerance. The second is the case of a 66-year-old woman affected by a metastatic primitive retroperitoneal NET G2. The patient progressed after a somatostatin analogue-based first line, whereas the CAPTEM regimen led to a partial and durable response with a favourable safety profile. Conclusions: CAPTEM chemotherapy has been shown to be an active and safe therapeutic option in advanced, metastatic G1/2 atypical primary NENs

Radiological Protection in Industries Involving NORM: A (Graded) Methodological Approach to Characterize the Exposure Situations

The interest in radiation protection in industrial sectors involving Naturally Occurring Radioactive Materials (NORM) is increasingly growing. This is due also to the recent implementation of the European Council Directive 59/2013/Euratom which in Italy and in the other European Union Member States extends the field of application to industrial sectors never involved before. This paper reports main results of a research project on radiation protection in industries involving NORM carried out in Italy aimed to provide useful tools for stakeholders to comply new legal obligations. The project activities were mainly focused on different aspects relevant to the NORM involving industries, accounting for the positive list reported in the Italian law. Firstly, the inventory of the industries currently operating in Italy in order to identify the industrial sectors with an important radiological impact on population and workers was updated. Based on this information, a general methodology was elaborated taking into account a graded approach. The first phase consists in the identification and characterization of the most critical exposure scenarios and of the radiological content of NORMs involved in the different phases of the industrial processes. In the second phase calculation methods were developed for dose estimation for workers and members of public. These tools require the use of existing and well tested calculation codes, and the development of a dedicated user-friendly software

La radioprotezione applicata alle industrie NORM: sviluppo di un sistema di strumenti metodologici, conoscitivi e formativi a sostegno degli stakeholders. Stato dell’arte del progetto di INAIL

Con il recepimento della Direttiva Europea 59/2013 EURATOM, la normativa italiana di radioprotezione ha introdotto nuovi obblighi per gli esercenti di diversi settori industriali “NORM”. Per sostenere l’assolvimento di tali obblighi che garantiscono la protezione di lavoratori e popolazione, dal 2019 è in corso un progetto di ricerca, nell’ambito del quale sono state realizzate diverse attività. Alcune di esse hanno avuto sviluppi anche in ambito internazionale, a testimonianza di quanto questa tematica sia di grande interesse. Lo scopo del presente lavoro è presentare i nuovi risultati del progetto, dall’aggiornamento del censimento dei settori NORM attualmente attivi in Italia, all’ applicazione e declinazione dell’approccio graduale per l’individuazione di situazioni di particolare interesse dal punto di vista della radioprotezione, fino allo sviluppo di metodologie operative e di calcolo applicate ad alcuni settori

Sviluppo di protocolli di campionamento e di valutazione della dose per settori industriali con presenza di NORM

Nell’ambito delle attività del progetto INAIL - BRIC ID 30 “Protocolli operativi e metodologie di calcolo per l’attuazione della nuova normativa di radioprotezione, recepimento della Direttiva 59/2013/Euratom, in settori industriali NORM di particolare impatto radiologico”, è stato sviluppato un approccio metodologico per gli adempimenti previsti dall’art. 22 del D.lgs. 101/2020. Una proposta di protocollo per la misura della concentrazione di attività delle matrici e per la valutazione della dose efficace per lavoratori e popolazione è stata elaborata per il settore della produzione di cemento e per l’industria dello zircone e zirconio

The multivariate approach identifies relationships between pre-slaughter factors, body lesions, ham defects and carcass traits in pigs.

Abattoir meat inspection has been proposed for the collection of welfare outcomes. The identification of suitable animal-based measures (ABM) is still a critical point that needs to be implemented to avoid collinearity among measures. The present study aims to benchmark the presence of ABM such as skin and tail lesions and ham defects in carcasses from 79 batches of Italian Heavy pigs and to identify possible relationships between the assessed ABM and pre-slaughter factors such as the season and the overnight lairage. Furthermore, the study also considers the effect of pre-slaughter conditions and ABM on carcass traits parameters (cold carcass weight and lean meat percentage). Skin and tail lesions were recorded at the slaughter line. The presence of abscesses, muscle tears and veining defects were assessed in the hams at trimming, according to the Parma Ham Consortium. A multivariate analysis was performed to identify relationships between ABM and pre-slaughter factor; therefore, a linear model was built to assess the effect on carcass weight and lean meat percentage. Main welfare issues were represented by skin and tail lesions and muscle tears (prevalence above 10%). Multivariate analysis evidenced that skin lesions and veining defects were mostly associated with the warm season. Abscesses and muscle tears in the hams were more likely related to overnight lairage, while tail lesions contributed equally to both season and lairage. Moreover, lairage related factors showed to affect lean meat percentage. The findings of the present study suggest that ham defects might be useful indicators of pre-slaughter stress. The validation of these findings with physiological parameters could be of interest for further studies

Main results of the international intercomparison of passive radon detectors under field conditions in Marie Curie's tunnel in Lurisia (Italy)

In recent years a large number of radon intercomparison exercises has been organized; most of them took place in radon chambers, in reference atmosphere of the parameter to control (i.e. radon gas) under temperature, humidity and atmospheric pressure stable conditions. In 2014, in the tunnel belonging to the Lurisia spas complex (Lurisia, Piedmont, Italy), with natural high concentrations of uranium and radon gas, an intercomparison exercise has been held to give to radon measurement services and laboratories the possibility to test their passive systems under field conditions, which are less controlled and much more challenging. The response of laboratories was very positive: 46 participants from 10 European countries and 3 non-European countries. Generally about 80% of results of participants were considered acceptable even if it was observed a global trend of a substantial underestimation of the actual radon concentration

Effects of Air Pollution and Blood Mitochondrial DNA Methylation on Markers of Heart Rate Variability

Background: The mitochondrion is the primary target of oxidative stress in response to exogenous environments. Mitochondrial DNA (mtDNA) is independent from nuclear DNA and uses separate epigenetic machinery to regulate mtDNA methylation. The mtDNA damage induced by oxidative stress can cause mitochondrial dysfunction and is implicated in human diseases; however, mtDNA methylation has been largely overlooked in environmental studies relating to human disease. The purpose of this study was to examine the association between exposure to fine metal‐rich particulates (particulate matter <2.5 µm in diameter [PM2.5]) from welding in a boilermaker union and blood mtDNA methylation in relation to heart rate variability. Methods and Results: Forty‐eight healthy men were recruited on multiple sampling cycles at the Boilermaker Union Local 29, located in Quincy, Massachusetts. We measured personal PM2.5 in the background ambient environment. We measured blood mtDNA methylation in the mtDNA promoter (D‐loop) and genes essential for ATP synthesis (MT‐TF and MT‐RNR1) by bisulfite pyrosequencing. All analyses were adjusted for demographics, type of job, season, welding‐work day, and mtDNA methylation experimental batch effect. The participants’ PM2.5 exposure was significantly higher after a welding‐work day (mean 0.38 mg/m3) than the background personal level (mean 0.15 mg/m3, P<0.001). Blood mtDNA methylation in the D‐loop promoter was associated with PM2.5 levels (β=−0.99%, SE=0.41, P=0.02). MT‐TF and MT‐RNR1 methylation was not associated with PM2.5 exposure (β=0.10%, SE=0.45, P=0.82). Interaction of PM2.5 exposure levels and D‐loop promoter methylation was significantly associated with markers of heart rate variability. Conclusions: Blood mtDNA methylation levels were negatively associated with PM2.5 exposure and modified the adverse relationships between PM2.5 exposure and heart rate variability outcomes

Multidimensional outcome measure of selective dorsal rhizotomy in spastic cerebral palsy

BACKGROUND: One of the treatment option to reduce spasticity in cerebral palsy children is selective dorsal rhizotomy. Several studies have demonstrated short and long term improvements in gait and other activities after rhizotomy but this surgery still remains a controversial procedure and patient outcome indicators measures are not uniform. AIMS: To describe our assessment and outcome evaluation protocol and to verify by this protocol short term results of rhizotomy. METHODS: We recruited 9 cerebral palsy children (mean age 7.9 years ± 3.2) affected by mild to moderate spastic diplegia and operated by rhizotomy. Patients were studied preoperatively and at 12 months after surgery by the following clinical and instrumental measures correlated to the International Classification of Functioning: modified Ashworth Scale, passive Range of Motion, Medical Research Council Scale, Selective Motor Control Scale, 3D-motion analysis and energy cost of locomotion measurements (indicators of "body functions"); Gross Motor Functional Measure and Motor Functional Independence Measure (indicators of "activities and participation"). RESULTS: Our data showed, after rhizotomy, reduction of spasticity specially in plantarflexors muscles (p < 0.01), increase of strength of knee flexors/extensors and foot plantar/dorsiflexion muscles (p < 0.01), improvement of selective motor control (p < 0.05), more similar spatio-temporal parameters of gait analysis to healthy subjects, reduced equinus foot and knees hyperflexion as energy cost. CONCLUSION: The complementary use of multiple indicators may improve the evaluation of the results of dorsal rhizotomy. A beneficial outcome measured by these indicators has been found in our spastic diplegic children one year after rhizotomy