Dupilumab efficacy in uncontrolled, moderate-to-severe asthma with self-reported chronic rhinosinusitis

BACKGROUND: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13 signaling, key drivers of type 2 inflammation. In the phase 3 study (NCT02414854), add-on dupilumab 200 mg/300 mg every 2 weeks, versus placebo, significantly reduced severe asthma exacerbations and improved pre-bronchodilator forced expiratory volume in 1 second (FEV OBJECTIVE: To assess the efficacy and safety of dupilumab in patients with uncontrolled, moderate-to-severe asthma with or without self-reported comorbid chronic rhinosinusitis (CRS or non-CRS). METHODS: Comorbid CRS was self-reported by patients using an e-diary. Annualized severe exacerbation rates, changes from baseline in pre- and post-bronchodilator FEV RESULTS: CRS was self-reported by 382 of 1902 (20.1%) patients. Dupilumab 200 mg/300 mg reduced annualized severe exacerbation rates by 63%/61%, respectively, in patients with CRS, and by 42%/40% in patients without CRS (all P \u3c .001 vs placebo). Dupilumab also improved lung function and patient-reported asthma control and quality of life, and suppressed type 2 biomarkers versus placebo in both subgroups. Clinical responses were rapid, with near-maximal responses observed at the earliest measured time points and sustained at week 52. Improvements observed in the CRS subgroup were similar to or numerically greater than those in the non-CRS subgroup. CONCLUSION: Dupilumab showed efficacy and was generally well tolerated in patients with uncontrolled, moderate-to-severe asthma with or without CRS

Assessing mandibular body changes in growing subjects: a comparison of CBCT and reconstructed lateral cephalogram measurements

The aim of this study is to compare cone-beam computed tomography (CBCT) and bi-dimensional reconstructed lateral cephalograms (RLCs) in assessing mandibular body length and growth and to evaluate how mandibular reshaping influences the error in measuring mandibular body growth in bi-dimensional radiographs. Twenty-five patients with two CBCT scans taken at a mean distance of 2.21\u2009\ub1\u20090.5 years were selected. The following measurements were performed: right and left mandibular body length at each point in time, mandibular growth, inter-gonial distance and mandibular symphyseal angle. From each CBCT, an RLC was obtained, and mandibular body length and growth were measured. Data analysis revealed a statistically and clinically significant difference in CBCT and RLC regarding the mandibular length of each patient at each point in time. However, mandibular growth was almost identical. A linear regression was performed to predict growth distortion between RLCs and CBCT depending on the ratio between transverse and sagittal mandibular growth. The expected maximum and minimum distortion, however, appeared not to be significant. In fact, a second linear regression model and a Bland-Altman test revealed a strong correlation between measurements of average mandibular body growth by CBCT and RLCs. As the same distortion occurs in the first and second RLCs, bi-dimensional radiographs remain the method of choice in evaluating mandibular body growth

Orthodontic-surgical treatment: electromyographic and kinesiographic evaluation in follow up period : Experimental study

Introduction. The aim of this study was to investigate muscular function and mandibular kinesiology of patients undergoing orthodontic-surgical treatment by electromyography and kinesiography. Electromyographic evaluation is essential to estimate masticatory forces in patients undergoing combined surgical-orthodontic treatment. Materials and methods. 60 patients referred for orthodontic surgical treatment were included in the study, 43 patients presented a class III while 17 presented a class II. The patients underwent electromyographic and kinesiographic examinations during all the therapeutic orthodontic-surgical phases. Results. The relationship between fundamental electromyographic values and age, weight, asymmetry and activation was weak. A strong and positive relationship was observed between the relaxation percentage after TENS (transcutaneous electrical neuromuscular stimulation), the steepness of the post-surgery rehabilitation curve, the initial POC (percentage overlapping coefficient), and for the values in microvolts of the right and left temporal and masseters at the beginning of treatment. Conclusions. Patients with dentofacial deformities corrected by surgical treatment, have a significant positive treatment outcome in respect of masticatory activity and performance electromyographic evaluation on, before, during and follow up period of the analized patients permit to underline that this examination can predict long term stability

Vapor etching to avoid micro-masking by gas-bubbles in wet release of MEMS

We report on the formation of gas bubbles during the release of MEMS devices using buffered oxide etch. Several approaches to mitigate the problem are proposed and tested together with a qualitative study of the phenomenon. The chemical reaction behind such phenomenon and the influence of defects and topography is discussed. Finally, a comparison with the HF-vapor release technique is shown

Synthesis, Characterization, Fluorescence Properties, and DFT Modeling of Difluoroboron Biindolediketonates

We report a simple and efficient strategy to enhance the fluorescence of biocompatible biindole diketonates (bdks) in the visible spectrum through difluoroboronation (BF2bdks complexes). Emission spectroscopy testifies an increase in the fluorescence quantum yields from a few percent to as much as >0.7. This massive increment is essentially independent of substitutions at the indole (-H, -Cl, and -OCH3) and corresponds to a significant stabilization of the excited state with respect to non-radiative decay mechanisms: the non-radiative decay rates are reduced by as much as an order of magnitude, from 109 s−1 to 108 s−1, upon difluoroboronation. The stabilization of the excited state is large enough to enable sizeable 1O2 photosensitized production. Different time-dependent (TD) density functional theory (DFT) methods were assessed in their ability to model the electronic properties of the compounds, with TD-B3LYP-D3 providing the most accurate excitation energies. The calculations associate the first active optical transition in both the bdks and BF2bdks electronic spectra to the S0 → S1 transition, corresponding to a shift in the electronic density from the indoles to the oxygens or the O-BF2-O unit, respectively

A CBCT based analysis of the correlation between volumetric morphology of the frontal sinuses and the facial growth pattern in caucasian subjects. A cross-sectional study

open7noBackground: The aim of this study was to evaluate the relationship between frontal sinus shape and facial growth pattern. Methods: The three-dimensional examination was carried out by means of 80 CBCT scans selected from a sample of 1247 records of patients treated, for different reason, at the Department of Biomedical Surgical and Dental Sciences at University of Milan, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico Milan. The sample (age ranges between 12 and 40 years) was divided according to gender and age in four groups (12-17, 18-20, 21-30, 31-40). Left and right frontal sinus volume (VOL), surface (SUP) and linear maximum width (XMAX), depth (ZMAX) and height (YMAX) were calculated using Mimics Research 17.0 (Materialise N.V., Leuven, Belgium). Cephalometric analysis has been performed for all subjects to categorize the patients depending on their facial growth pattern. Univariate and multivariate regression analysis were performed to investigate any association of frontal sinuses measurements (height, width, depth, volume and surface) and cephalometric variables. P value < 0.05 was considered statistically significant. Results: A total of 160 frontal sinuses were measures in 80 patients: 40 men and 40 women, average age of 23.5 ±14.6. Globally the frontal sinuses had the following average dimensions: volumes of 9055.8 ± 6505 mm3 and surfaces of 3820.3 ± 2125 mm2. The statistical analysis showed that frontal sinus volume was statistically significant (p=0.003) greater for male (11,425 mm3) than female (6597.5 mm3). Similarly, the surface showed to be greater in men than in women (p=0.005). No correlation between age and frontal sinuses characteristics has been found. A statistically significant (p<0.05) increase of frontal sinus depth, surface and volume was correlated with SNB angle. In addition, frontal sinus volume increased in subjects with greater anterior skeletal dimension values and with a superior length of the cranial base. Furthermore, a decrease of ANB has been found related to an increase in frontal sinus volume (p=0.04). Conclusions: The present study showed a correlation between frontal sinuses dimensions and craniofacial aspects, despite the inter-individual variability of their morphology. The results suggested that young adults in whom the frontal sinuses have reached their maximum size, while vertical growth continues, a larger frontal sinus may be associated with future vertical growth.openAbate A.; Gaffuri F.; Lanteri V.; Fama A.; Ugolini A.; Mannina L.; Maspero C.Abate, A.; Gaffuri, F.; Lanteri, V.; Fama, A.; Ugolini, A.; Mannina, L.; Maspero, C

Correlation between dental vestibular-palatal inclination and alveolar bone remodeling after orthodontic treatment: A CBCT analysis

The aim of this study was to evaluate the correlation between dental vestibular-palatal inclination changes and the cortical bone remodeling after fixed orthodontic treatment using cone beam computed tomography (CBCT). Twenty-two patients with Angle Class I malocclusion, permanent dentition, and mild to moderate dental crowding were included in the present three-dimensional (3D) analysis. Bone dimensions were evaluated by CBCT scans obtained before and after orthodontic treatment, whereas the torque values were calculated by means of digital models using the 3D VistaDent software. A paired t-test was used to compare the changes between the pretreatment and post-treatment measurements. The correlations between variables were analyzed with linear regression analysis. A significant correlation between torque variations and bone thickness changes was observed for the apical buccal level of the anterior side (P < 0.05). Limited and not significant alveolar bone resorption for the apical thickness of anterior teeth occurred at \ub15 degrees of torque variation, while for tooth inclination exceeding +5 or-5 degrees, the bone remodeling was more evident. The present study demonstrated that anterior region was the most affected area by bone remodeling and that torque variation was highly related to apical bone thickness adaptation for maxillary and mandibular incisors and maxillary canines

Relaxation process in a regime of quantum chaos

We show that the quantum relaxation process in a classically chaotic open dynamical system is characterized by a quantum relaxation time scale t_q. This scale is much shorter than the Heisenberg time and much larger than the Ehrenfest time: t_q ~ g^alpha where g is the conductance of the system and the exponent alpha is close to 1/2. As a result, quantum and classical decay probabilities remain close up to values P ~ exp(-sqrt(g)) similarly to the case of open disordered systems.Comment: revtex, 5 pages, 4 figures discussion of the relations between time scale t_q and weak localization correction and between dynamical and disordered systems is adde

Comparison of a tridimensional cephalometric analysis performed on 3T-MRI compared with CBCT : a pilot study in adults

OBJECTIVE: Since the introduction of cone-beam computed tomography (CBCT) in dentistry, this technology has enabled distortion-free three-dimensional cephalometric analysis for orthodontic and orthognathic surgery diagnosis. However, CBCT is associated with significantly higher radiation exposure than traditional routine bidimensional examinations for orthodontic diagnosis, although low-dose protocols have markedly reduced radiation exposure over time. The objective of this preliminary feasibility study is to compare the accuracy and diagnostic capabilities of an already-validated three-dimensional cephalometric analysis on CBCT to those of an analysis on 3-T magnetic resonance imaging (3T-MRI) to assess whether the latter can deliver a comparable quality of information while avoiding radiation exposure. MATERIALS AND METHODS: In order to test the feasibility of three-dimensional cephalometry on 3T-MRI, 18 subjects (4 male; 14 female) with mean age 37.8\u2009\ub1\u2009SD 10.2, who had undergone both maxillofacial CBCT and maxillofacial 3T-MRI for various purposes within 1 month, were selected from the archive of the Department of Dentistry and Maxillofacial Surgery of Fondazione Ospedale Policlinico Maggiore, IRCCS, Milano, Italy. A three-dimensional cephalometric analysis composed of ten midsagittal and four bilateral landmarks and 24 measurements (11 angular, 13 linear) was performed on both scans using Mimics Research\uae v. 17.0 (NV, Technologielaan 15, 3001 Leuven, Belgium). Cephalometric analysis was performed twice by two independent orthodontists for each scan, and each orthodontist repeated the measurements 3 weeks later. Statistical analysis was performed with SPSS\uae 20.00 for Windows (IBM\uae Corporation, Sommers, NY, USA). A Bland-Altman test for each cephalometric value was performed to assess the agreement between the procedures. The intraclass correlation coefficient (ICC) was used to assess interobserver and intraobserver reliability. The coefficient of variation was used to evaluate precision. RESULTS: Both procedures showed good reliability, with mean intraobserver ICCs of 0.977/0.971 for CBCT and 0.881/0.912 for MRI. The average interobserver ICCs were 0.965 for CBCT and 0.833 for MRI. A Bland-Altman analysis for the cephalometric tracing revealed a similar range of agreement between the two modalities; the bias range (mean\u2009\ub1\u2009SD) was -\u20090.25-0.66\u2009mm (0.174\u2009\ub1\u20090.31) for distances and -\u20090.41-0.54\ub0 (0.12\u2009\ub1\u20090.33) for angles. CONCLUSIONS: Within the main limitation of this pilot study, that is, the small sample, it is possible to state that cephalometric measurements on 3T-MRI seem to possess adequate reliability and repeatability and that they show satisfying agreement with values measured on CBCTs. An MRI examination does not expose patients to ionizing radiation and could provide an alternative to CBCT for three-dimensional cephalometrics in the future