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Aim To investigate the potential role of a novel spatially fractionated radiation therapy (SFRT) method where heterogeneous dose patterns are created in target areas with virtual rods, straight or curving, of variable position, diameter, separation and alignment personalised to a patient’s anatomy. The images chosen for this study were CT scans acquired for the external beam part of radiotherapy. Methods Ten patients with locally advanced cervical cancer were retrospectively investigated with SFRT. The dose prescription was 30 Gy in 5 fractions to 90% target volume coverage. Peak-and-valley (SFRT_1) and peak-only (SFRT_2) strategies were applied to generate the heterogeneous dose distributions. The planning objectives for the target (CTV) were D90% ≥ 30 Gy, V45Gy ≥ 50–55% and V60Gy ≥ 30%. The planning objectives for the organs at risk (OAR) were: D2cm3 ≤ 23.75 Gy, 17.0 Gy, 19.5 Gy, 17.0 Gy for the bladder, rectum, sigmoid and bowel, respectively. The plan comparison was performed employing the quantitative analysis of the dose-volume histograms. Results The D2cm3 was 22.4 ± 2.0 (22.6 ± 2.1) and 13.9 ± 2.9 (13.2 ± 3.0) for the bladder and the rectum for SFRT_1 (SFRT_2). The results for the sigmoid and the bowel were 2.6 ± 3.1 (2.8 ± 3.0) and 9.1 ± 5.9 (9.7 ± 7.3), respectively. The hotspots in the target volume were V45Gy = 43.1 ± 7.5% (56.6 ± 5.6%) and V60Gy = 15.4 ± 5.6% (26.8 ± 6.6%) for SFRT_1 (SFRT_2). To account for potential uncertainties in the positioning, the dose prescription could be escalated to D90% = 33–35 Gy to the CTV without compromising any constraints to the OARs Conclusion In this dosimetric study, the proposed novel planning technique for boosting the cervix uteri was associated with high-quality plans, respecting constraints for the organs at risk and approaching the level of dose heterogeneity achieved with routine brachytherapy. Based on a sample of 10 patients, the results are promising and might lead to a phase I clinical trial.

The second-phonon ( n ω = 2 ) wobbling band has been established in the nucleus 135Pr. Conclusive evidence for its wobbling nature comes from the Δ I = 1 , E2 character of the transitions between the new band and the previously identified transverse wobbler band ( n ω = 1 ) in this nucleus. Theoretical calculations in the framework of the quasiparticle triaxial rotor and triaxial projected shell models are found to be in good agreement with the experimental results.

Background: Previous studies on oxaliplatin and fluoropyrimidines as adjuvant therapy in older patients with stage III colon cancer (CC) produced conflicting results. Patients and methods: We assessed the impact of age on time to tumour recurrence (TTR), disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) in 2360 patients with stage III CC (1667 aged

Additional file 1.

Despite continuing efforts, compliance rates and knowledge of best practices in hand hygiene remain disappointing. Recognizing that conventional educational tools seem out of touch with young people and that the med and messages contents need refreshing, the Italian Study Group of Hospital Hygiene of the Italian Society of Hygiene, Preventive Medicine and Public Health devised a novel approach to promote the creation of innovative educational tools for improving knowledge of, and compliance with, hand hygiene rules among healthcare and medical students.A contest in creating educational material on hand hygiene practices involved university students of nursing and medicine, and of other healthcare degrees. Students from the universities of the GISIO network were invited to create educational material (e.g., videos, posters, presentations, leaflets, and screensavers) to be presented by May 5th 2019 during the World Hand Hygiene Day / Save Lives: Clean Your Hands Global Annual Initiative of the World Health Organization). A local and a national winners were awarded.Three different local and national contests were performed during 2016, 2017 and 2018. During the three-year period, more than 270 educational tools have been developed: 130 (48%) were judged useful for hand hygiene promotion campaigns. The most frequent projects participating in the contests were videos (39%), posters (29%), leaflets (14%), and others (18%) submitted by more than 1,500 students of nursing (40%), medicine (31%), dentistry (7%), and of other healthcare courses in 14 universities. Products were evaluated by a local committee and, subsequently, local winners represented their University in a national contest.The contest provided a framework for the creation of innovative and potentially effective educational tools via an engaging approach that leveraged student creativity. Given the need to improve compliance rates, this study suggests that new ways can be advantageously explored to teach hand hygiene procedures and increase awareness of the importance of their consistent use among healthcare and medical students.

Teriparatide (TPTD), the amino-terminal parathyroid hormone recombinant peptide [PTH (1–34)], is a drug with a proven anabolic action on the bone, effective in preventing vertebral and non-vertebral fragility fractures. Recent publications have investigated in great detail the TPTD action on the cortical bone, highlighting the increased strength in the critical zone of the hip with high risk of fracture in osteoporotic patients Poole (PLoS ONE 6:e16190, 2011). In November 2002, TPTD was approved by the FDA for use in post-menopausal women and men with osteoporosis at high risk of fracture and in patients with glucocorticoid-induced osteoporosis and, since then, has been used to treat more than 1 million patients worldwide (J Bone Miner Res 27(12):2429-2437, 2012). The unchanged safety profile and the well-known mechanism of action of this drug have led doctors to explore the use of TPTD in other conditions such as delayed fracture healing, non-union, osteonecrosis of the jaw, etc. The positive reports that have resulted from these studies are helping to hypothesize a new perspective on the wider use of this drug, but warrant further clinical investigation to consolidate these results.

Resume Objectifs Cette etude realisee en ouvert est basee sur une approche translationnelle dans le but de detecter les changements cliniques, a l’imagerie et des biomarqueurs synoviaux dans le liquide synovial (LS) et le tissu synovial (TS) dans la spondyloarthropathie peripherique (SpA) apres l’inhibition intra-articulaire (IA) du tumor necrosis factor (TNF)-α par des injections repetees d’etanercept (E). Methodes Vingt-sept patients presentant une synovite resistante du genou ont recu quatre injections IA bihebdomadaires d’E (12,5 mg). Le critere d’evaluation principal etait l’indice du genou de Thompson (THOMP) et les criteres secondaires etaient representes par l’indice articulaire du genou (IAG), la proteine C-reactive (CRP), le health assessment questionnaire-disability index (HAQ-DI), l’epaisseur maximale de la synoviale (EMS) evaluee par echographie et imagerie par resonnance magnetique (IRM) de contraste, le taux serique des cellules mononucleaires dans les TS – CD45+ et – CD31+, le taux dans le LS d’interleukine-1β (IL-1β), le recepteur antagoniste de l’IL-1 (IL-1Ra) et d’IL-6 a l’inclusion et a la fin de l’etude. Resultats A la fin de l’etude, les donnees cliniques, de l’imagerie ainsi que les biomarqueurs ont ete tous significativement reduits et ameliores comparativement aux donnees a l’inclusion. Il y avait une correlation significative entre la clinique, l’imagerie et les biomarqueurs. (la CRP avec le THOMP, l’IAG, le HAQ-DI et le taux d’IL-1Ra ; l’EMS a l’echo avec l’IAG, le TS-CD45+ avec le THOMP, IAG, TS-CD31+ et LS-IL-1β ; le LS-IL-6 avec le THOMP, IAG, LS-IL-1β, ou IL-1Ra). Conclusions Cette etude en « preuve de concept » a demontre une amelioration precoce des scores locaux et systemiques, de l’epaisseur synoviale mesuree par IRM et echographie, et de l’expression des biomarqueurs synoviaux. Le CD45+, CD31+ dans le TS et l’IL-6 et IL-1β dans le LS peuvent etre consideres comme des biomarqueurs potentiels dans la reponse de la SpA peripherique a un agent anti-TNF-α IA.

The aim of this article is to report the dosimetric and clinical findings in the treatment of primary hepatocellular carcinoma (HCC) with volumetric modulated arc therapy (VMAT, RapidArc).A total of 138 patients were investigated. Dose prescription ranged from 45-66 Gy. Most patients (88.4 %) presented AJCC stage III or IV and 83 % were N0-M0. All were classified as Barcelona Clinic Liver Cancer (BCLC) stage A-C. All patients were treated using 10 MV photons with single or multiple, coplanar or non-coplanar arcs, and cone-down technique in case of early response of tumors.The patients' median age was 66 years (range 27-87 years), 83 % were treated with 60 Gy (12 % at 45 Gy, 6 % at 66 Gy), 62 % with cone-down, 98 % with multiple arcs. The mean initial planning target volume (PTV) was 777 ± 632 cm(3); the mean final PTV (after the cone-down) was 583 ± 548 cm(3). High target coverage was achieved. The final PTV was V98% 98 %. Kidneys received on average 5 and 8 Gy (left and right), while the maximum dose to the spinal cord was 22 Gy; mean doses to esophagus and stomach were 23 Gy and 15 Gy, respectively. The average volume of healthy liver receiving more than 30 Gy was 294 ± 145 cm(3). Overall survival at 12 months was 45 %; median survival was 10.3 months (95 % confidence interval 7.2-13.3 months). Actuarial local control at 6 months was 95 % and 93.7 % at 12 months. The median follow-up was 9 months and a maximum of 28 months.This study showed from the dosimetric point of view the feasibility and technical appropriateness of RapidArc for the treatment of HCC. Clinical results were positive and might suggest, with appropriate care, to consider RapidArc as an additional therapeutic opportunity for these patients.

Conventional PET parameters and textural features tabulated according FNA categories and final diagnosis. (DOCX 84Â kb)

Objective To evaluate the efficacy and the feasibility of SBRT for selected patients with isolated local recurrence of pancreatic cancer after radical surgery. Methods A retrospective analysis was performed on patients treated with SBRT for isolated local recurrence from resected pancreatic adenocarcinoma, after multidisciplinary board evaluation. Prescription dose was 45 Gy in 6 fractions for all patients. Primary end-point was freedom from local progression (FFLP). Secondary end-points were overall survival (OS), progression free survival (PFS) and toxicity. Local control was defined according to RECIST criteria. Acute and late toxicity was scored according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Results Between January 2011 and February 2015, 31 patients with isolated local recurrence of resected pancreatic cancer were treated with SBRT. Pancreato-duodenectomy (PD) was performed on 24 patients and distal pancreatectomy (DP) in 7 cases, all with radical resection (R0). Median local recurrence disease free interval (DFI) was 14 months. Median follow-up was 12 months. FFLP was 91% and 82% at 1 and 2-years, respectively. Median PFS was 9 months. Median OS was 18 months. At univariate analysis, OS was correlated with a DFI > 18 months. No cases of acute G3 toxicity or greater occurred. Conclusions SBRT seems to be an effective and safe therapeutic option for isolated local recurrence of pancreatic cancer after surgery. Encouraging local control rate, very low toxicity profile and effective pain control suggest the crucial role of SBRT in the treatment of these long-survivors selected patients.

Purpose: Complex radiotherapy fields delivered using a tertiary multileaf collimator(MLC) often feature small open segments surrounded by large areas of the beam only shielded by the MLC. The aim of this study was to test the ability of two modern dose calculation algorithms to accurately calculate the dose in these fields which would be common, for example, in volumetric modulated arc treatment (VMAT) and study the impact of variations in dosimetric leaf gap (DLG), focal spot size, and MLC transmission in the beam models. Methods: Nine test fields with small fields (0.6–3 cm side length) surrounded by large MLC shielded areas (secondary collimator 12 × 12 cm2) were created using a 6 MV beam from a Varian Clinac iX linear accelerator with 120 leaf MLC. Measurements of output factors and profiles were performed using a diamond detector (PTW) and compared to two dose calculations algorithms anisotropic analytical algorithm [(AAA) and Acuros XB] implemented on a commercial radiotherapytreatment planning system (Varian Eclipse 10). Results: Both calculation algorithms predicted output factors within 1% for field sizes larger than 1 × 1 cm2. For smaller fields AAA tended to underestimate the dose. Profiles were predicted well for all fields except for problems of Acuros XB to model the secondary penumbra between MLC shielded fields and the secondary collimator. A focal spot size of 1 mm or less, DLG 1.4 mm and MLC transmission of 1.4% provided a generally good model for our experimental setup. Conclusions: AAA and Acuros XB were found to predict the dose under small MLC defined field segments well. While DLG and focal spot affect mostly the penumbra, the choice of correct MLC transmission will be essential to model treatments such as VMAT accurately.

Purpose : Flattening filter free (FFF) beams generated by medicallinear accelerators have recently started to be used in radiotherapy clinical practice. Such beams present fundamental differences with respect to the standard filter flattened (FF) beams, making the generally used dosimetric parameters and definitions not always viable. The present study will propose possible definitions and suggestions for some dosimetric parameters for use in quality assurance of FFF beams generated by medicallinacs in radiotherapy. Methods : The main characteristics of the photon beams have been analyzed using specific data generated by a Varian TrueBeam linac having both FFF and FF beams of 6 and 10 MV energy, respectively. Results : Definitions for dose profile parameters are suggested starting from the renormalization of the FFF with respect to the corresponding FF beam. From this point the flatness concept has been translated into one of “unflatness” and other definitions have been proposed, maintaining a strict parallelism between FFF and FF parameter concepts. Conclusions : Ideas for quality controls used in establishing a quality assurance program when introducing FFF beams into the clinical environment are given here, keeping them similar to those used for standard FF beams. By following the suggestions in this report, the authors foresee that the introduction of FFF beams into a clinical radiotherapy environment will be as safe and well controlled as standard beam modalities using the existing guidelines.

Interleukin 1 receptor antagonist (IL-1Ra) is a naturally occurring IL-1 inhibitor, acting as a "receptor antagonist", which blocks IL-1 mediated signal transduction. In 1990 IL-1Ra was cloned and later on, a large numbers of studies led to disclosure of the crucial importance of the imbalance between IL-1 and IL-1Ra in the pathogenesis of rheumatoid arthritis (RA). In 1991, almost 8 years after the initial isolation of IL-1, recombinant IL-1Ra (IL-1ra, Kineret) was introduced in clinical trials involving patients with RA. Between 2001 and 2002 IL-1ra was approved by the US Food and Drug Administration and by the European Agency for the Evaluation of the Medicinal Products and in 2003 it was registered in Italy, too. In RA recombinant IL-1ra has been evaluated in 5 randomized, placebo-controlled clinical trials involving more than 2900 patients. Two of the trials involved the use of IL-1ra as monotherapy versus placebo and two trials in combination with methotrexate (MTX); the last trial explored the use of a fixed 100 mg/day IL-1ra dosage in a RA patient population including a wide array of co-morbid conditions as well as concomitant medications. The studies confirmed both the efficacy and the safety of IL-1ra in patients with active and severe RA. 43% of patients receiving 150 mg/day IL-1ra achieved a 20% response according to the American College of Rheumatology criteria (ACR20), compared to 27% in the placebo group. In the MTX combination therapy study, 42% of the patients receiving 1 mg/Kg/day of IL-1ra achieved an ACR20, 24% an ACR50 and 10% an ACR70. In each study, significant improvements in the Health Assessment Questionnaire scores (HAQ) were observed. There were rapid gains in the number of days at work or domestic activity in the treated patients, and the increases in productivity were dose related. At early 24 weeks, there was significant reduction of both the score for progression of joint space narrowing (JSN) and the Total modified Sharp-Genant score (a combination of erosion and JSN) in all treatment groups (30,75 and 150mg/day). The clinical benefits of treatment with daily subcutaneous injections of IL-1ra in active RA patients were maintained for up to 48 weeks. IL-1ra, a selective inhibitor of the IL-1 pathway, represents an important new biologic approach to treating patients with RA, that significantly reduces clinical signs and symptoms of the disease and joint destruction and has proved safe and well tolerated also in combination with other DMARDs and concomitant medications.

Purpose: A study was carried out to evaluate the robustness and mutual interplay of two variables concurring to generate modulation patterns of the RapidArc (RapidArc) implementation of volumetric modulated arc therapy. Dose rate (DR) and gantry speed (GS) are free parameters optimized alongside field aperture shape by the RapidArc engine; however, they are limited by machine constraints and mutually compensate in order to deliver the proper MU/deg during the gantry rotation. Methods: Four test cases (one geometrical and three clinical) were selected and RapidArc plans were optimized using maximum allowed dose rates from 100 to 600 MU/min. The maximum gantry speed was fixed at 4.8 deg/s. Qualitative analysis of DR and GS patterns from these cases was summarized together with quantitative assessment of delivery parameters. Pretreatment quality assurance measurements and scoring of plan quality aimed to determine whether preferable initial conditions might be identified or the optimization engine might be invariant to those variables and capable of providing adequate plans independently from the limits applied. Results: The results of the study were: (i) High dynamic range in MU/deg is achievable across all dose rates by means of gantry speed modulation; (ii) there is a robust compensation mechanism between the twomore » variables; (iii) from a machine delivery point-of-view, slightly improved accuracy is achieved when lower DRs are applied; however, this does not have practical consequences since measurements and plan evaluation showed a lack of clinically relevant deviation; and (iv) reduced total treatment time is a major advantage of high DR. Conclusions: A trend toward improved plan quality for clinical cases was observed with high DR but cannot be generalized, due to the limited amount of cases investigated and the consequent limited significance of the observed differences. As a minimum benefit, the reduced total treatment time should be considered as well.« less

Purpose: In 2008, a national intensity modulated radiation therapy (IMRT) dosimetry intercomparison was carried out for all 23 radiation oncology institutions in Switzerland. It was the aim to check the treatment chain focused on the planning, dose calculation, and irradiation process. Methods: A thorax phantom with inhomogeneities was used, in which thermoluminescence dosimeter (TLD) and ionization chamber measurements were performed. Additionally, absolute dosimetry of the applied beams has been checked. Altogether, 30 plan-measurement combinations have been used in the comparison study. The results have been grouped according to dose calculation algorithms, classified as ``type a`` or ``type b,`` as proposed by Knoos et al. [``Comparison of dose calculation algorithms for treatment planning in external photon beam therapy for clinical situations,`` Phys. Med. Biol. 51, 5785-5807 (2006)]. Results: Absolute dosimetry check under standard conditions: The mean ratio between the dose derived from the single field measurement and the stated dose, calculated with the treatment planning system, was 1.007 +/- 0.010 for the ionization chamber and 1.002 +/- 0.014 (mean +/- standard deviation) for the TLD measurements. IMRT Plan Check: In the lung tissue of the planning target volume, a significantly better agreement between measurements (TLD, ionization chamber) and calculations is shown for type b algorithms than for type a (p > 0.001). In regions outside the lungs, the absolute differences between TLD measured and stated dose values, relative to the prescribed dose, vertical bar(D-m - D-s) / D-prescribed vertical bar, are 1.9 +/- 0.4% and 1.4 +/- 0.3%, respectively. These data show the same degree of accuracy between the two algorithm types if low-density medium is not present. Conclusions: The results demonstrate that the performed intercomparison is feasible and confirm the calculation accuracies of type a and type b algorithms in a water equivalent and low-density environment. It is now planned to offer the intercomparison on a regular basis to all Swiss institutions using IMRT techniques. (C) 2010 American Association of Physicists in Medicine. [DOT: 10.1118/1.3460795]