Real-world effectiveness and safety of Guselkumab for the treatment of psoriasis: a 6-month prospective study in a series of psoriatic patients.

OBJECTIVE: Guselkumab is a fully human monoclonal IgG1 antibody which, by selectively binding to the p19 subunit of IL-23, prevents it from binding to the IL-23 receptor on the cell surfaces. To date, no prospective data are available on the efficacy and safety of this drug in everyday clinical practice in patients with psoriasis (PSO). MATERIALS AND METHODS: This is a longitudinal, single arm, real-world, prospective study to investigate the effect of Guselkumab on PSO and quality of life (DLQI) in 44 PSO patients. Outcomes were PASI, BSA, DLQI at 3 and 6 months. RESULTS: The longitudinal analysis showed that PASI improved from a median value of 24.1 at baseline to 2.0 at 6-months and this was also true for BSA (from 23.0 to 2.0) and DLQI (from 24.0 to 2.5) (all p<0.001). At 6-months, PASI75, PASI90 and PASI100 were 95.5%, 59.1% and 16%, respectively. The PSO improvement related with the increase of DLQI (∆PASI vs. ∆DLQI, r=0.77, p<0.001). No clinically relevant adverse events were observed. CONCLUSIONS: This study demonstrates the effectiveness and safety of Guselkumab on PSO in real world and shows that the reduction of PSO severity due to the drug is directly related with the improvement of quality of life in this patient population.

Improvement of ESR dosimetry for thermal neutron beams through the addition of gadolinium.

In this paper, the addition of gadolinium is proposed as a useful tool to enhance the electron spin resonance (ESR) sensitivity of organic compounds to thermal neutrons. The target of this work is the detection, through the ESR technique, of the thermal neutron fluence in a mixed field of photons and neutrons. Gadolinium was chosen because it has a very high capture cross section to thermal neutrons; its nuclear reaction with thermal neutrons induces complex inner shell transitions that generate, besides other particles, Auger electrons, which in turn release their energy in the neighborhood (only several nanometers) of the place of reaction. Gadolinium was added to two organic molecules: alanine and ammonium tartrate. The main result obtained was a greater neutron sensitivity for dosimeters with gadolinium than for those without gadolinium for both organic molecules used. Since a dosimeter pair is required to discriminate between the two components of a mixed field, we studied the response of each dosimeter pair irradiated in a mixed field. Through a blind test we verified the usefulness of this dosimetric system and we obtained an estimate of the fluence in the mixed field with a relative uncertainty of 3%, when the pair composed of an alanine dosimeter and a dosimeter with alanine and gadolinium is used.

ESR response to gamma-rays of alanine pellets containing B(OH)3 or Gd2O3.

ESR response to gamma-irradiation (1-50 Gy) of blends containing alanine and either B(OH)(3) or Gd(2)O(3) is reported. The sensitivity of the alanine--B(OH)(3) blend is comparable to the sensitivity of pure alanine, although its lowest detectable dose, LDD, is smaller ( approximately 1.3 Gy) than that of pure alanine ( approximately 2.9 Gy). Alanine with Gd(2)O(3) is about two times more sensitive than pure alanine, and its LDD is 0.8 Gy. The better sensitivity and LDD are probably due to the high atomic number (Z=64) of gadolinium, which enhances the interaction probability with photons and, consequently, the radical yield. This study suggests that other high-Z atoms may be useful for increasing the sensitivity of the response of alanine to gamma-radiation.

Study of the glow curves of TLD exposed to thermal neutrons.

The glow curves of thermoluminescent dosimeters (TLD600, TLD700 and MCP), exposed to a mixed field of thermal neutrons and gamma photons are analysed. The fluence values of thermal neutrons used, comparable with those used in radiotherapy, allow one to define the reliability of the TLDs, in particular the most sensitive MCP, in this radiation field and to get information on the dose absorbed values. The glow curves obtained have been deconvoluted using general order kinetics and the observed differences for the different LET components have been analysed. In particular, the ratio of the n(0) parameter of two different peaks seems to allow to discriminate the different contributions of neutrons and gamma photons in the beam.

Alanine blends for ESR measurements of thermal neutron fluence in a mixed radiation field.

In this paper, the results of a study on the electron spin resonance (ESR) dosimetry to measure thermal neutron fluence in a mixed radiation field (neutron and photons) are presented. The ESR responses of alanine dosemeters with different additives are compared. In particular, the (10)B-acid boric and the Gd-oxide were chosen to enhance the sensitivity of alanine dosemeters to thermal neutrons. Irradiations were carried out inside the thermal column of the TAPIRO reactor of the ENEA center, Casaccia Rome. The main results are a greater neutron sensitivity and a smaller lowest detectable fluence for the dosemeters with gadolinium than for dosemeters of alanine with (10)B, which is well known to be much more sensitive to thermal neutrons than simple alanine.

Effects of gamma-irradiation on trehalose-hydroxyethylcellulose microspheres loaded with vancomycin.

Ionizing radiation can be used as a drug sterilization technique, provided that the drug itself is not modified and that no toxic products are produced; moreover, if the irradiated product is a drug delivery system, the drug release characteristics must not be significantly altered by radiation. The aim of this work was to study the effects of sterilization by ionizing radiation on hydroxyethylcellulose/trehalose spherical micromatrices, containing the antibiotic vancomycin. Our experimental results showed that gamma-rays did not alter the chromophore groups of vancomycin (UV measurements), and did not modify the kinetic behavior of drug release from microspheres. Moreover, no significant changes in the shape and in the size distribution of microspheres were found after irradiation. The electron spin resonance (ESR) spectroscopy was proven to be a valid identification method of the executed radiation treatment, even after 5 years. The experimental results showed that the therapeutic application of the pharmacological system investigated was not compromised by irradiation, and that ESR spectroscopy can be used to distinguish irradiated from non-irradiated products.

Response charactterization of ammonium tartrate solid state pellets for ESR dosimetry with radiotherapeutic photon and electron beams.

Solid state pellets (1 mm thick) for electron spin resonance (ESR) dosimetry were made using ammonium tartrate as the radiation-sensitive substance. Their behaviour was experimentally investigated as a function of dose with 60Co gamma rays. The calibration function obtained permits measurements of absorbed dose in the 2-50 Gy range, with a combined uncertainty of +/-4%. The lowest detectable dose was about 0.5 Gy. These properties are comparable with or even better than those of ESR dosimeters made from other materials. The time stability of the ESR signal of ammonium tartrate dosimeters at different storage conditions after irradiation was studied. A rather complex behaviour was observed, which suggests that more species of free radicals are produced by radiation and that migration processes may be effective. No dependence of the response on beam quality was found for high-energy photon and electron beams produced by a linear accelerator used in radiotherapy, whereas dose was underestimated with low-energy x-rays.

The response behaviour of LiF:Mg,Cu,P thermoluminescence dosimeters to high-energy electron beams used in radiotherapy.

To ensure the effectiveness of radiation-therapy treatments, both in-phantom and in-patient reliable dose measurements are required. Thermoluminescence dosimeters are used commonly for both applications. Among the various available materials, the relatively new LiF:Mg,Cu,P phosphor is a suitable candidate for quality control of in vivo dosimetry in electron-beam therapy. The response behaviour of LiF:Mg,Cu,P chips to 6-21 MeV electron beams used in radiotherapy was studied. Batch homogeneity, dose linearity, sensitivity change after use, dose and dose-rate response, energy dependence and fading characteristics were investigated. The contribution from each factor to the overall uncertainty in dose measurement was evaluated. The results of this work show that the LiF:Mg,Cu,P chips are comparable to the commonly used LiF:Mg,Ti ones, and support their use for in vivo electron-beam dosimetry to an accuracy within +/- 10%.

Environmental radioactivity at Stromboli (Aeolian Islands).

HPGe gamma spectrometry, thermoluminescence dosimetry, X-ray diffractometry and fluorescence techniques have been used to analyze the natural radionuclides content of soil and rock samples, air kerma and geochemical features on the island of Stromboli, belonging to the Aeolian Islands, in the Mediterranean Sea. The 214Bi, 238Ac, and 40K contents obtained are in agreement with the magmatic evolution of the rock formation, as shown by the correlations between radionuclide and chemical elements abundacies, depending on the various magmatic differentiation mechanisms. Correlations between radiometric, lithological and geochemical data have been assessed in order to obtain some hints on the geochronology of the magmatic products.

[Comparative calibration of dosimetry methods used around industrial irradiation plants in Italy]. / Intercalibrazione dei metodi dosimetrici utilizzati presso gli impianti di irraggiamento industriale in Italia.

Industrial application of ionizing radiation (sterilization of medical supplies, long lasting food preservation, etc.) is a well established technique all over the world. The efficacy of the treatment depends on an accurate dosimetry assuring both the achievement of irradiation purposes at the lowest cost and the safety of consumers. This is why in 1986 the Istituto Superiore di Sanità (ISS) started an intercomparison program among the industrial plants now working in Italy, aimed to optimize the used dosimetric procedures. The electron spin resonance (ESR) alanine-based dosimetry, set up at ISS, was chosen as reference dosimetry. Each plant received 30 dosimeters to be irradiated in prefixed conditions in order to: a) compare the ESR and the routine dosimetry; b) evaluate the homogeneity factor in the irradiated product; c) test the reproducibility of the irradiation technique. Results support the need of standardized dosimetric procedures for an optimization of the radiation treatment.

EPR dosimetry in a mixed neutron and gamma radiation field.

Suitability of Electron Paramagnetic Resonance (EPR) spectroscopy for criticality dosimetry was evaluated for tooth enamel, mannose and alanine pellets during the 'international intercomparison of criticality dosimetry techniques' at the SILENE reactor held in Valduc in June 2002, France. These three materials were irradiated in neutron and gamma-ray fields of various relative intensities and spectral distributions in order to evaluate their neutron sensitivity. The neutron response was found to be around 10% for tooth enamel, 45% for mannose and between 40 and 90% for alanine pellets according their type. According to the IAEA recommendations on the early estimate of criticality accident absorbed dose, analyzed results show the EPR potentiality and complementarity with regular criticality techniques.

Combined TL and 10B-alanine ESR dosimetry for BNCT.

The dosimetric technique described in this paper is based on electron spin resonance (ESR) detectors using an alanine-boric compound acid enriched with (10)B, and beryllium oxide thermoluminescent (TL) detectors; with this combined dosimetry, it is possible to discriminate the doses due to thermal neutrons and gamma radiation in a mixed field. Irradiations were carried out inside the thermal column of a TRIGA MARK II water-pool-type research nuclear reactor, also used for Boron Neutron Capture therapy (BNCT) applications, with thermal neutron fluence from 10(9) to 10(14) nth cm(-2). The ESR dosemeters using the alanine-boron compound indicated ESR signals about 30-fold stronger than those using only alanine. Moreover, a negligible correction for the gamma contribution, measured with TL detectors, almost insensitive to thermal neutrons, was necessary. Therefore, a simultaneous analysis of our TL and ESR detectors allows discrimination between thermal neutron and gamma doses, as required in BNCT.

Sensitivity of alanine dosimeters with gadolinium exposed to 6 MV photons at clinical doses.

In this study we analyzed the ESR signal of alanine dosimeters with gadolinium exposed to 6 MV linear accelerator photons. We observed that the addition of gadolinium brings about an improvement in the sensitivity to photons because of its high atomic number. The experimental data indicated that the addition of gadolinium increases the sensitivity of the alanine to 6 MV photons. This enhancement was better observed at high gadolinium concentrations for which the tissue equivalence is heavily reduced. However, information about the irradiation setup and of the radiation beam features allows one to correct for this difference. Monte Carlo simulations were carried out to obtain information on the expected effect of the addition of gadolinium on the dose absorbed by the alanine molecules inside the pellets. These results are compared with the experimental values, and the agreement is discussed.

A practical and transferable methodology for dose estimation in irradiated spices, based on thermoluminescence dosimetry.

The thermoluminescence technique is recommended by the European Committee for Standardization for the detection of irradiated food containing silicates as contaminants. In this work, the applicability of the thermoluminescence technique as a quantitative method to assess the original dose in irradiated oregano was studied; the additive-dose method was used, with reirradiation doses up to 600 Gy. The proposed new procedure allows to clearly discriminate irradiated from unirradiated samples, even after one year storage, and it gives an acceptable estimation of the original dose; the overall modified procedure requires only one day to be completed.

Posidonia oceanica as a historical monitor device of lead concentration in marine environment.

We show that Posidonia oceanica is able to reliably monitor the variability of environmental lead (Pb). We analyze lead concentration measured in the scales and rhizomes of Posidonia oceanica collected in seven sites along the coasts of the Sicily island and subsequently fractioned them according to a lepidochronological analysis. We measure lead concentration in Posidonia oceanica tissues by using the flame atomic absorption spectrophotometry technique. We compare the measured lead concentration with the estimated lead emission in air due to the gasoline sold and used for combustion in car engines in Sicily. By computation of the Pearson cross-correlation coefficient, we show that lead concentration, which is measured in the scales of Posidonia oceanica, is statistically correlated to lead emission in air and reflects the level of lead pollution in the coastal marine environment.

ESR spectra of normal human serum after treatment with complement activating agents.

We describe the appearance of a free-radical signal in the ESR spectrum of normal human serum incubated with several complement activating agents. The intensity of this signal is dependent of dose of activating agents, time and temperature. Signals elicited by different complement activators differ in morphology and kinetics. Inhibition by treatment with EDTA and the presence of the signal in activated C 6-deficient rabbit serum suggest that the convertase forming steps of complement activation (C2 to 5) could be the source of free-radical containing molecules.