Efficacy and safety of mycophenolate mofetil and tacrolimus as second-line therapy for patients with autoimmune hepatitis

Background: Predniso(lo)ne, alone or in combination with azathioprine, is the standard of care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate mofetil (MMF) and tacrolimus as second-line therapy for patients with AIH. Patients and methods: We performed a retrospective study of data (from 19 centres in Europe, the United States, Canada, and China) from 201 patients with AIH who received second-line therapy (121 received MMF and 80 received tacrolimus), for a median of 62 months (range, 6–190 months). Patients were categorized according to their response to SOC. Patients in group 1 (n=108) had a complete response to the SOC, but were switched to second line therapy due to side effects of predniso(lo)ne or azathioprine, whereas patients in group 2 (n=93) had not responded to SOC. Results: There was no significant difference in the proportion of patients with a complete response to MMF (69.4%) vs tacrolimus (72.5%) (P=.639). In group 1, MMF and tacrolimus maintained a biochemical remission in 91.9% and 94.1% of patients, respectively (P=.682). Significantly more group 2 patients given tacrolimus compared to MMF had a complete response (56.5 % vs. 34%, P=.029) There were similar proportions of liver-related deaths or liver transplantation among patients given MMF (13.2%) vs tacrolimus (10.3%) (log-rank, P=.472). Ten patients receiving MMF (8.3%) and 10 patients receiving tacrolimus (12.5%) developed side effects that required therapy withdrawal. Conclusions: Long-term therapy with MMF or tacrolimus was generally well tolerated by patients with AIH. The agents were equally effective in previous complete responders who did not tolerate SOC therapy. Tacrolimus led to a complete response in a greater proportion of previous non-responder patients compared to MMF

Efficacy of a new technique - INtubate-RECruit-SURfactant-Extubate - "IN-REC-SUR-E" - in preterm neonates with respiratory distress syndrome: Study protocol for a randomized controlled trial

Background: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria. Methods/design: In this study, 206 spontaneously breathing infants born at 24+0-27+6 weeks' gestation and failing nCPAP during the first 24 h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3 days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30 min after surfactant administration or when they meet the nCPAP failure criteria after extubation. Discussion: From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge. Trial registration: ClinicalTrials.gov identifier: NCT02482766. Registered on 1 June 2015

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P < 0.001), sNox2-dp (r(s), -0.57; P < 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

Evaluation of air photoactivation at linear accelerators for radiotherapy

High-energy x-rays produced by radiotherapy accelerators operating at potentials above 10 MV may activate the air via (γ, n) reactions with both oxygen and nitrogen. While the activation products are relatively short-lived, personnel entering the accelerator room may inhale some radioactive air, which warrants internal dosimetry assessments. This work illustrates a method based on the use of ammonium nitrate solutions for the evaluation of photon-induced air activation and for the estimate of internal doses to radiotherapy personnel. Air activation and internal dosimetry assessments based on our method are presented for some widespread radiotherapy linear accelerator models. Our results indicate that the equivalent dose to the lungs of radiotherapy personnel is negligible for beam energies below 18 MeV

Flexible hybrid coatings with efficient antioxidation properties

In this work, the feasibility of a transparent sol gel coating on polyamide-polyethylene (PA/PE) substrate with antioxidant properties as active food packaging was investigated. Stable water-based silicon alkoxide formulations, containing lipophilic vitamin E as natural antioxidant, were obtained adding ascorbic acid as catalyst. Comparative blank sols were prepared without antioxidant guest molecules. The sol formulations of tetraethyl orthosilicate and a mixture of alcoxysilane containing organic moieties as phenyl and methyl group were stable and easy to process via dip coating on Polyamide/Polyethylene substrates. Organic functionalities were essential to incorporate the lipophilic guests and to achieve an optimal adhesion on the polymeric substrate. The presence of stable coating was evaluated through Electron Microscopy and Optical Emission Spectroscopy analyses, while the surface roughness and optical absorption were measured by noncontact laser profilometry and by UV/vis spectra. The loaded antioxidant amount was estimated right after the coating deposition by spectroscopic UV measurements in ethanol, as its subsequent release within 14 days. The estimated antioxidant release was 10% and 40% of the loaded amount for the hydrochloric-sol and the ascorbic acid catalysed sol, respectively. The antioxidant efficacy of coatings was evaluated through the Ferric Reducing Antioxidant Power (FRAP) assay showing a significant difference in antioxidant efficacy between the vitamin E containing sols and their blank ones. Those results were confirmed by FRAP analysis even four months after the deposition

ESR response of alanine films exposed to low-energy (1-40 keV) X-rays

Introduction L-a-alanine has aroused considerable interest for use in radiation ESR dosimetry. In this work, we examined the energy response of alanine ESR films in the low energy X-photon energy range between 1 keV and 40 keV. Dose measurements through a reference ionization chamber and a semiconductor detection system were also performed to complement ESR measurements. Methods Commercial alanine ESR films were used. All ESR signal measurements were also done using an XBand (9.7 GHz) Bruker spectrometer. The dosimeters were irradiated at the "Livio Scarsi" Laboratory (LAX) of the University of Palermo, where X-ray beams in the 1\u201340 keV energy range are produced using a Seifert SN60 tube. Reference dosimetry measurements were made using a plane parallel chamber with thin polyethylene membranes. X-ray fluxes and energy spectra were measured with an innovative system based on semiconductor detectors (CdTe, Si) and digital pulse processing (DPP) electronics. Results The response of alanine to low-energy X-rays was characterized experimentally. The response as function of dose, the dependence of the ESR signal on the photon energy as well as the stability of the signal with time were investigated. Comparison of the ESR response to high energy photons was also carried out. The relative effectiveness is lower if compared to high-energy photons. Conclusion Alanine dosimeters show very interesting dosimetric features also for these low-energy X-ray beams. To our knowledge, these data have not been previously reported and they may be extremely relevant, e.g., when mapping the high-gradient treatment fields used in microbeam radiation therapy (MRT) with synchrotron radiation

Fricke gel dosimeters with low-diffusion and high-sensitivity based on a chemically cross-linked PVA matrix

Current radiotherapy techniques implement treatment plans based on volumetric distributions of dose with complex shapes and sharp gradients. To verify the agreement between these treatment plans and the dose that is actually delivered, a dosimetric system that is truly three dimensional, sensitive to radiation in each point and tissue equivalent is required. For this purpose, we developed a radio-chromic gel based on polyvinyl alcohol (PVA), that is chemically cross-linked with glutaraldehyde (GTA) and offers high sensitivity and stability, i.e., low diffusion, of the signal. This gel is transparent and therefore it can be read out with optical techniques. The dosimetric characteristics of the PVA-GTA gel were compared to gelatine and to literature data for so called PVA hydrogels and cryogels. The dose response of the PVA-GTA dosimeter is found to be linear between 0 and 30 Gy and its sensitivity higher than any previously reported value for PVA-based gel dosimeters. The diffusion coefficient of the PVA-GTA gel is lower than the diffusion coefficient of gel with matrixes made by natural polymers

Particle anisotropy and crystalline phase transition in one-pot synthesis of nano-zirconia: A causal relationship

Crystalline phase evolution and morphological changes are strictly correlated phenomena during the growth of zirconia nanoparticles. In this work, the effects of synthetic variables, reaction time (up to 24 hours) and precursor concentration (0.16 and 0.5 M), of a one-step non-hydrolytic sol-gel route to zirconia are investigated. Zirconium tetrachloride (ZrCl4) is chosen as a zirconium oxide precursor to react in benzyl alcohol. At a low precursor concentration and a short reaction time, pseudo-spherical particles of size 2 nm with a narrow size distribution are observed by transmission electron microscopy (TEM). At this stage, mainly the tetragonal phase is detected. By increasing both the zirconium precursor concentration and reaction time, a broadening of size distribution is observed resulting from the growth of anisotropic particles. Concurrently, an increasing amount of the monoclinic is detected by X-ray diffraction and Raman spectroscopy. As a novelty, Rietveld investigations on electron diffraction ring patterns obtained by transmission electron microscopy are performed. This procedure allows the collection of comprehensive information about nanostructured particles in one-step analysis. The results derived from this analysis, together with the high resolution transmission electron microscopy (HR-TEM) data, consistently support the structural transition from pseudo-spherical tetragonal particles to rice-shaped monoclinic particles