ON THE PLACEMENT OF APRON DOSEMETERS AND DOSE ASSESSMENT IN INTERVENTIONAL CARDIOLOGY PROCEDURES: PRELIMINARY RESULTS.

Personnel involved in interventional practices are likely to be exposed to higher radiation doses than other workers in the medical field. Personnel monitoring and radiation protection measures play a crucial role in keeping these doses below the limits. EURADOS (European Radiation Dosimetry Group) Working Group 12 performed a series of investigations showing how the complexity of the scattered field reaching the operators can influence the doses to the operators. The present work was aimed at determining the possible effects on the registered doses of the scattered field and the actual position of a dosemeter on apron. This study has been performed through Monte Carlo simulations and it was validated through measurements. It does not claim to identify the 'best' position for the dosemeter, but to assess the variability of its response, showing how a variability of the order of +/- 30% to 40 should be taken into account.

Reconstruction of the pelvic ring in iliac or iliosacral resections: allograft or autograft?

BACKGROUND: The necessity to reconstruct the pelvic ring after an iliac or iliosacral resection is still debated. Different reconstructive techniques are available, including autologous and homologous graft and custom-made prosthesis. The aim of this study was to evaluate the functional outcome and complications of patients who underwent resection of iliac bone and part of the sacrum for primary bone tumour and reconstruction with an allograft or autograft. METHODS: We retrospectively evaluated 18 patients (10 males and 8 female) with a mean age of 28 years (range 9-56) who were operated between 1992 and 2015. Six patients were reconstructed with an autograft (Group A) and 12 patients with an allograft (Group B). All complications were recorded. At final follow-up, patients with the original reconstruction still in site were functionally evaluated with MSTS Score. RESULTS: Mean follow-up time was 107 months (range 4-221). Two patients (11.1%) had an external hemipelvectomy for local recurrence, and 3 patients died of the disease. Mean MSTS Score was comparable between the two groups 21.7 (range 20-25) in Group A and 19.9 (range 4-28) in Group B. Patients with partial sacral resection had an increased risk of local recurrence and lower MSTS Score [15.5 (range 7-20) vs. 22.2 (range 4-28)]. CONCLUSIONS: Biological reconstruction of pelvic ring with autologous or homologous bone graft gives acceptable functional results. However, the decision on how to reconstruct the pelvic ring after iliac resection should be taken on a patient-by-patient basis.

Differential changes to splanchnic and peripheral protein metabolism during the diet-induced development of metabolic syndrome in rats.

Little is known about the effects of the development of metabolic syndrome (MS) on protein and amino acid (AA) metabolism. During this study, we took advantage of the variability in interindividual susceptibility to high fat diet-induced MS to study the relationships between MS, protein synthesis, and AA catabolism in multiple tissues in rats. After 4 mo of high-fat feeding, an MS score (ZMS) was calculated as the average of the z-scores for individual MS components [weight, adiposities, homeostasis model for the assessment of insulin resistance (HOMA-IR), and triglycerides]. In the small intestine, liver, plasma, kidneys, heart, and muscles, tissue protein synthesis was measured by 2H2O labeling, and we evaluated the proportion of tissue AA catabolism (relative to protein synthesis) and nutrient routing to nonindispensable AAs in tissue proteins using natural nitrogen and carbon isotopic distances between tissue proteins and nutrients (Δ15N and Δ13C), respectively. In the liver, protein mass and synthesis increased, whereas the proportion of AA catabolism decreased with ZMS. By contrast, in muscles, we found no association between ZMS and protein mass, protein synthesis (except for a weak positive association in the gastrocnemius muscle only), and proportion of AA catabolism. The development of MS was also associated with altered metabolic flexibility and fatty acid oxidation, as shown by less routing of dietary lipids to nonindispensable AA synthesis in liver and muscle. In conclusion, MS development is associated with a greater gain of both fat and protein masses, with higher protein anabolism that mainly occurs in the liver, whereas muscles probably develop anabolic resistance due to insulin resistance.

Inhibitory checkpoints in human natural killer cells: IUPHAR Review 28.

Immune checkpoint inhibitors have revolutionized cancer therapy leading to exceptional success. However, there is still the need to improve their efficacy in non-responder patients. Natural killer (NK) cells represent the first line of defence against tumours, due to their ability to release immunomodulatory cytokines and kill target cells that have undergone malignant transformation. Harnessing NK cell response will open new possibilities to improve control of tumour growth. In this respect inhibitory checkpoints expressed on these innate lymphocytes represents a promising target for next-generation immunotherapy. In this review, we will summarize recent evidences on the expression of NK cells receptors in cancer, with a focus on the inhibitory checkpoint programmed cell death protein 1 (PD-1). We will also highlight the strength and limitations of the blockade of PD-1 inhibitory pathway and suggest new combination strategies that may help to unleash more efficiently NK cell anti-tumour response.

Simulation of H p (10) and effective dose received by the medical staff in interventional radiology procedures.

Interventional radiology and cardiology are widespread employed techniques for diagnosis and treatment of several pathologies because they avoid the majority of the side-effects associated with surgical treatments, but are known to increase the radiation exposure to patient and operators. In recent years many studies treated the exposure of the operators performing cardiological procedures. The aim of this work is to study the exposure condition of the medical staff in some selected interventional radiology procedures. The Monte Carlo simulations have been employed with anthropomorphic mathematical phantoms reproducing the irradiation scenario of the medical staff with two operators and the patient. A personal dosemeter, put on apron, was modelled for comparison with measurements performed in hospitals, done with electronic dosemeters, in a reduced number of interventional radiology practices. Within the limits associated to the use of numerical anthropomorphic models to mimic a complex interventional procedure, the personal dose equivalent, H p (10), was evaluated and normalised to the simulated Kerma-Area Product, KAP, value, indeed the effective dose has been calculated. The H p (10)/KAPvalue of the first operator is about 10 µSv/Gy.cm2, when ceiling shielding is not used. This value is calculated on the trunk and it varies of +/-30% moving the dosemeter to the waist or to the neck. The effective dose, normalised to the KAP value, varies between 0.03 and 0.4 µSv/Gy.cm2. Considering all the unavoidable approximation of this kind of investigations, the comparisons with hospital measurement and literature data showed a good agreement allowing to use of the present results for dosimetric characterisation of interventional radiology procedures.

A novel inhaled phosphodiesterase 4 inhibitor (CHF6001) reduces the allergen challenge response in asthmatic patients.

CHF6001 is an inhaled phosphodiesterase 4 (PDE4) inhibitor in development for the treatment of obstructive lung diseases. The efficacy and safety of CHF6001 were investigated in a double blind, placebo controlled, 3-way cross-over study using the allergen challenge model. Thirty-six atopic asthmatics who were not taking inhaled corticosteroids and who demonstrated a late asthmatic response (LAR) to inhaled allergen at screening were randomised to receive CHF6001 400 µg or 1200 µg or placebo administered once a day using a dry powder inhaler. The three treatment periods were 9 days; allergen challenges were performed on day 9 and induced sputum was obtained after 10 h from challenge. Washout periods between treatments were up to 5 weeks. Both CHF6001 doses significantly attenuated the LAR; the primary endpoint analysis showed that CHF6001 400 µg and 1200 µg caused reductions of 19.7% (p = 0.015) and 28.2% (p < 0.001) respectively of the weighted FEV1 AUC4-10h compared with placebo. The difference between the CHF6001 doses was not statistically significant (p = 0.223). Compared with placebo, CHF6001 caused greater reduction in sputum eosinophil counts, although these changes were not statistically significant. CHF6001 was well tolerated, with similar numbers of adverse events in each treatment period. This inhaled PDE4 inhibitor has the potential to provide clinical benefits in patients with atopic asthma.

First results of an eye lens dosimetry survey in an interventional cardiology department.

The eye lens annual dose limit for exposed personnel to ionizing radiation has recently been revised by the ICRP--International Commission on Radiological Protection and the proposed new limit has been accepted by European legislation through the Council Directive 2013/59/EURATOM 2013. Among medical exposed personnel, the staff performing interventional cardiology are usually affected by relevant doses. For this reason a survey, employing dosemeters characterized in terms of H(p)(3), was performed in order to get the order of magnitude of the doses received by the eye lens, at least as a first guess.The survey showed that the annual dose limit can easily be reached if a proper radiation protection approach is not implemented.

Air kerma to HP(3) conversion coefficients for photons from 10 keV to 10 MeV, calculated in a cylindrical phantom.

In the framework of the ORAMED project (Optimization of RAdiation protection for MEDical staff), funded by the European Union Seventh Framework Programme, different studies were aimed at improving the quality of radiation protection in interventional radiology and nuclear medicine. The main results of the project were presented during a final workshop held in Barcelona in January 2011, the proceedings of which are available in the open literature. One of the ORAMED tasks was focused on the problem of eye-lens photon exposure of the medical staff, a topic that gained more importance especially after the ICRP decision to lower the limiting equivalent dose to 20 mSv per year. The present technical note has the scope, besides briefly summarising the physical reasons of the proposal and the practical implications, to provide, in tabular form, a set of air kerma to Hp(3) conversion coefficients based on the adoption of a theoretical cylindrical model that is well suited for reproduction of the mass and the shape of a human head.

Microbial air monitoring in operating theatres: experience at the University Hospital of Parma.

BACKGROUND: Microbial air monitoring in operating theatres has been a subject of interest and debate. No generally accepted sampling methods and threshold values are available. AIM: To assess microbial air contamination in empty and working conventionally ventilated operating theatres over a three-year period at the University Hospital of Parma, Italy. METHODS: Air sampling was performed in 29 operating theatres. Both active and passive sampling methods were used to assess bacterial and fungal contamination. FINDINGS: In empty theatres, median bacterial values of 12 colony-forming units (cfu)/m(3) [interquartile range (IQR) 4-32] and 1 index of microbial air contamination (IMA) (IQR 0-3) were recorded. In working theatres, these values increased significantly (P < 0.001) to 80 cfu/m(3) (IQR 42-176) and 7 IMA (IQR 4-13). Maximum recorded values were 166 cfu/m(3) and 8 IMA for empty theatres, and 798 cfu/m(3) and 42 IMA for working theatres. Combining active and passive samplings, fungi were isolated in 39.13% of samples collected in empty theatres and 56.95% of samples collected in working theatres. Over the three-year study period, bacterial contamination decreased in both empty and working theatres, and the percentage of samples devoid of fungi increased. In working theatres, a significant correlation was found between the bacterial contamination values assessed using passive and active sampling methods (P < 0.001). CONCLUSION: Microbiological monitoring is a useful tool for assessment of the contamination of operating theatres in order to improve air quality.

A restricted cubic spline approach to assess the association between high fat fish intake and red blood cell EPA + DHA content.

BACKGROUND AND AIMS: Fish, especially fatty fish, are the main contributor to eicosapentaenoic (EPA) and docosahexaenoic (DHA) intake. EPA and DHA concentrations in red blood cells (RBC) has been proposed as a cardiovascular risk factor, with <4% and >8% associated with the lowest and greatest protection, respectively. The relationship between high fat fish (HFF) intake and RBC EPA + DHA content has been little investigated on a wide range of fish intake, and may be non-linear. We aimed to study the shape of this relationship among high seafood consumers. METHODS AND RESULTS: Seafood consumption records and blood were collected from 384 French heavy seafood consumers and EPA and DHA were measured in RBC. A multivariate linear regression was performed using restricted cubic splines to consider potential non-linear associations. Thirty-six percent of subjects had an RBC EPA + DHA content lower than 4% and only 5% exceeded 8%. HFF consumption was significantly associated with RBC EPA + DHA content (P [overall association] = 0.021) adjusted for sex, tobacco status, study area, socioeconomic status, age, alcohol, other seafood, meat, and meat product intakes. This relationship was non-linear: for intakes higher than 200 g/wk, EPA + DHA content tended to stagnate. Tobacco status and fish contaminants were negatively associated with RBC EPA + DHA content. CONCLUSION: Because of the saturation for high intakes, and accounting for the concern with exposure to trace element contaminants, intake not exceeding 200 g should be considered.

Principles for the design and calibration of radiation protection dosemeters for operational and protection quantities for eye lens dosimetry.

The work package two of the ORAMED project--Collaborative Project (2008-2011) supported by the European Commission within its seventh Framework Programme--is devoted to the study of the eye lens dosimetry. A first approach is to implement the use of H(p)(3) by providing new sets of conversion coefficients and well suited calibration and type test procedures. This approach is presented in other papers in the proceedings of this conference. Taking into account that the eye lens is an organ close to the surface of the body, another approach would be to directly estimate the absorbed dose to the eye lens, D(lens,est) through a special calibration procedure although this quantity is not directly measurable. This paper is a methodological paper that tries to identify the critical aspects of a dosimetry in terms of D(lens).

Eye lens dosimetry: task 2 within the ORAMED project.

The ORAMED (Optimization of RAdiation protection for MEDical staff) project is funded by EU-EURATOM within the 7° Framework Programme. Task 2 of the project is devoted to study the dose to the eye lens. The study was subdivided into various topics, starting from a critical revision of the operational quantity H(p)(3), with the corresponding proposal of a cylindrical phantom simulating as best as possible the head in which the eyes are located, the production of a complete set of air kerma to dose equivalent conversion coefficients for photons from 10 keV to 10 MeV, and finally, the optimisation of the design of a personal dosemeter well suited to respond in terms of H(p)(3). The paper presents some preliminary results.

Extremity exposure in nuclear medicine: preliminary results of a European study.

The Work Package 4 of the ORAMED project, a collaborative project (2008-11) supported by the European Commission within its seventh Framework Programme, is concerned with the optimisation of the extremity dosimetry of medical staff in nuclear medicine. To evaluate the extremity doses and dose distributions across the hands of medical staff working in nuclear medicine departments, an extensive measurement programme has been started in 32 nuclear medicine departments in Europe. This was done using a standard protocol recording all relevant information for radiation exposure, i.e. radiation protection devices and tools. This study shows the preliminary results obtained for this measurement campaign. For diagnostic purposes, the two most-used radionuclides were considered: (99m)Tc and (18)F. For therapeutic treatments, Zevalin(®) and DOTATOC (both labelled with (90)Y) were chosen. Large variations of doses were observed across the hands depending on different parameters. Furthermore, this study highlights the importance of the positioning of the extremity dosemeter for a correct estimate of the maximum skin doses.

ENEA extremity dosemeter based on LiF(Mg,Cu,P) to evaluate Hp(3,alpha).

Recent epidemiological studies suggest a rather low-dose threshold (<0.5 Gy) for the induction of a cataract of the eye lens. Some other studies even assume that there is no threshold at all. Therefore, protection measures have to be optimised and current dose limits for the eye lens may be reduced in the future. ICRP Publication 103 on H(p)(d), in §(136), reads that '… a depth d = 3 mm has been proposed for the rare case of monitoring the dose to the lens of the eye. In practice, however, H(p)(3) has rarely been monitored and H(p)(0.07) can be used for the same monitoring purpose… '. As recommended on the EU 'Technical recommendations for monitoring individuals occupationally exposed to external radiation', a test on the ENEA TL extremity dosemeter is herein reported. The results within the actual EU founded Optimization of RAdiation protection for MEDical staff (ORAMED) Project, whose WP2 is aimed at the quantity H(p)(3) and eye lens dosimetry in practice, are taken into account. The paper summarises the main aspects of the study carried out at ENEA-Radiation Protection Institute (Bologna, Italy) to provide practical solutions (in the use and the design) to evaluate the response of the ENEA TL extremity dosemeter in terms of H(p)(3).

Effects of amino acid-derived luminal metabolites on the colonic epithelium and physiopathological consequences.

Depending on the amount of alimentary proteins, between 6 and 18 g nitrogenous material per day enter the large intestine lumen through the ileocaecal junction. This material is used as substrates by the flora resulting eventually in the presence of a complex mixture of metabolites including ammonia, hydrogen sulfide, short and branched-chain fatty acids, amines; phenolic, indolic and N-nitroso compounds. The beneficial versus deleterious effects of these compounds on the colonic epithelium depend on parameters such as their luminal concentrations, the duration of the colonic stasis, the detoxication capacity of epithelial cells in response to increase of metabolite concentrations, the cellular metabolic utilization of these metabolites as well as their effects on colonocyte intermediary and oxidative metabolism. Furthermore, the effects of metabolites on electrolyte movements through the colonic epithelium must as well be taken into consideration for such an evaluation. The situation is further complicated by the fact that other non-nitrogenous compounds are believed to interfere with these various phenomenons. Finally, the pathological consequences of the presence of excessive concentrations of these compounds are related to the short- and, most important, long-term effects of these compounds on the rapid colonic epithelium renewing and homeostasis.

Batch homogeneity of LiF(Mg,Cu,P)-GR200 and LiF(Mg,Cu,P)-MCP-NS TL detectors for use as extremity dosemeters at ENEA personal dosimetry service.

The results of a study of two commercially available LiF(Mg,Cu,P) TL materials, a GR200 detector and a MCP-Ns thin detector, are described in order to use these phosphors for individual monitoring for the extremities. After a dosimetry system has been type tested, the implementation routine is not straightforward. Additional tests and software modification are needed to make the routine system work comply with the type test results. Not often can literature be found on the steps required to implement the results in a routine study. This paper reports the results of the individual calibration of about 15 000 extremity dosemeters, 12 000 containing a GR200 detector and 3000 an MCP-Ns thin detector. It describes the experimental procedure followed in order to assure reproducibility and stability of the results with proper accuracy and reliability. In particular, this is the first time that results on homogeneity of such a large batch of MCP-Ns detectors are reported.

The ENEA neutron personal dosimetry service.

The ENEA Radiation Protection Institute has been operating the only neutron personal dosimetry service in Italy since the 1970s. Since the 1980s the service has been based on PADC (poly allyl diglycol carbonate) for fast neutron dosimetry, while thermal neutron dosimetry has been performed using thermoluminescence (TL) dosemeters. Since the service was started, a number of aspects have undergone evolution. The latest and most important changes are as follows: in 1998 a new PADC material was introduced in routine, since 2001 TL thermal dosimetry has been based on LiF(Mg,Cu,P) [GR-200] and (7)LiF(Mg,Cu,P) [GR-207] detectors and since 2003 a new image analysis reading system for the fast neutron dosemeters has been used. Herein an updated summary of how the service operates and performs today is presented. The approaches to calibration and traceability to estimate the quantity of H(p)(10) are mentioned. Results obtained at the performance test of dosimetric services in the EU member states and Switzerland sponsored by the European Commission and organised by Eurados in 1999 are reported. Last but not least, quality assurance (QA) procedures introduced in the routine operation to track the whole process of dose evaluation (i.e. plastic QA, acceptance test, test etching bath reproducibility and 'dummy customer' (blind test) for each issuing monitoring period) are presented and discussed.

The implementation in routine of the ENEA new personal photon dosemeter.

The ENEA photon dosemeter, introduced in 1995, consisting of two differently filtrated LiF(Mg,Cu,P) detectors, has been modified recently. The ABS (acrylonitrile butadiene styrene) plastic support has been replaced by a new aluminium card supporting the same two detectors (LiF(Mg,Cu,P) GR200). The new card, fully developed at the ENEA-Radiation Protection Institute (which is going to be patented), can now be processed through a Harshaw Model 6600 Automated TLD Reader, a hot gas reader. This paper reports the results of the individual calibration of approximately 60,000 LiF(Mg,Cu,P) GR200 detectors inserted on the new aluminium cards. Before the implementation in routine of the new cards, the reader has been characterised. Steps and tests to be made to use the card in routine (i.e. reader stability, linearity, reproducibility, etc.) are reported. The whole dosimetric system now combines the very good performances of the Harshaw Model 6600 reader and that of LiF(Mg,Cu,P) thermoluminescent material.

Great vessel management for endovascular exclusion of aortic arch aneurysms and dissections.

OBJECTIVES: To evaluate a recent approach for the endovascular repair of thoracic aortic aneurysms and dissections involving the aortic arch in high risk patients (HRP). METHODS: Amongst 102 thoracic aortic aneurysms and dissections, we treated 25 patients for aortic arch endovascular exclusion after transposition of the great vessels, of which 14 (56%) had thoracic aortic arch aneurysms and 11 type A and B chronic aortic dissections. Total transpositions were done in 15 cases (60%) and hemi-arch transpositions in 10. We then used Talent, Excluder and Zenith endografts in 12, seven and six cases, respectively. RESULTS: Surgical transpositions were complicated by one minor stroke, which worsened to a major stroke (4%) after endovascular exclusion. After endovascular exclusions, two patients (8%) died from catheterization related complications. One patient had a delayed minor stroke (4%). The successful exclusion rate was 92%. During follow-up (15+/-5.8 months), one patient (4%) developed unilateral limb palsy, successfully treated by CSF drainage. The late exclusion rate remained 92%. No stent-related complications were seen. CONCLUSIONS: Transposition of supra-aortic vessels allows the endovascular exclusion of the aortic arch in HRP. Aortic endografting after surgical transposition proved to be feasible and offers good mid-term results. Specialized surgical centers with both endovascular and surgical expertise are required to treat these patients.