Risk factors associated with fatal pulmonary hemorrhage in locally advanced non-small cell lung cancer treated with chemoradiotherapy

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to identify the risk factors associated with fatal pulmonary hemorrhage (PH) in patients with locally advanced non-small cell lung cancer (NSCLC), treated with chemoradiotherapy.</p> <p>Methods</p> <p>The medical records of 583 patients with locally advanced NSCLC, who were treated with chemoradiotherapy between July 1992 and December 2009 were reviewed. Fatal PH was defined as PH leading to death within 24 h of its onset. Tumor cavitation size was defined by the cavitation diameter/tumor diameter ratio and was classified as minimum (< 0.25), minor (≥ 0.25, but < 0.5), and major (≥ 0.5).</p> <p>Results</p> <p>Of the 583 patients, 2.1% suffered a fatal PH. The numbers of patients with minimum, minor, and major cavitations were 13, 11, and 14, respectively. Among the 38 patients with tumor cavitation, all 3 patients who developed fatal PH had major cavitations. On multivariate analysis, the presence of baseline major cavitation (odds ratio, 17.878), and a squamous cell histology (odds ratio, 5.491) proved to be independent significant risk factors for fatal PH. Interestingly, all patients with fatal PH and baseline major cavitation were found to have tumors with squamous cell histology, and the occurrence of fatal PH in patients having both risk factors was 33.3%.</p> <p>Conclusions</p> <p>Patients at high risk of fatal PH could be identified using a combination of independent risk factors.</p

Energy dissipation via acoustic emission in ductile crack initiation

The final publication is available at Springer via http://dx.doi.org/10.1007/s10704-016-0096-8.This article presents a modeling approach to estimate the energy release due to ductile crack initiation in conjunction to the energy dissipation associated with the formation and propagation of transient stress waves typically referred to as acoustic emission. To achieve this goal, a ductile fracture problem is investigated computationally using the finite element method based on a compact tension geometry under Mode I loading conditions. To quantify the energy dissipation associated with acoustic emission, a crack increment is produced given a pre-determined notch size in a 3D cohesive-based extended finite element model. The computational modeling methodology consists of defining a damage initiation state from static simulations and linking such state to a dynamic formulation used to evaluate wave propagation and related energy redistribution effects. The model relies on a custom traction separation law constructed using full field deformation measurements obtained experimentally using the digital image correlation method. The amount of energy release due to the investigated first crack increment is evaluated through three different approaches both for verification purposes and to produce an estimate of the portion of the energy that radiates away from the crack source in the form of transient waves. The results presented herein propose an upper bound for the energy dissipation associated to acoustic emission, which could assist the interpretation and implementation of relevant nondestructive evaluation methods and the further enrichment of the understanding of effects associated with fracture

Evaluation of polyoxyethylene homopolymers for buccal bioadhesive drug delivery device formulations

Our objective was to evaluate the application of polyoxyethylene homopolymers in buccal bioadhesive drug (BBD) delivery device formulations. The bioadhesive strength of four different molecular weight (MW) polyoxyethylene polymers was measured by Instronâ tensile tester using glass plate and bovine sublingual tissue as substrate surfaces. Several BBD device formulations containing polyoxyethylene polymer (MW 7,000,000) were prepared by direct compression and compression molding processes. The prepared BBD devices were evaluated for their elasticity, in vitro adhesion and drug release characteristics. The in vivo bioadhesion characteristics of a placebo compression molded device were examined in 3 adult healthy male beagle dogs. The bioadhesive strength of polyoxyethylene polymers appeared to be directly related to their molecular weights. When bovine sublingual mucosa or a glass plate was used as model mucosal substrate surface, the rank order of bioadhesive strength of different molecular weight polyoxyethylene polymers was similar. The bioadhesive strength of devices prepared by the compression molding process was greater than those prepared by direct compression, but the kinetics of drug release were independent of the process used for the preparation of the devices. The drug release and the bioadhesive strength of the similarly prepared device formulations appeared to be dependent on the drug:polymer ratios. The elasticity of the BBD devices prepared by compression molding was improved by the inclusion of polyisobutylene polymer in the formulations. When adhered to the oral cavity of the dogs, the compression molded placebo BBD device exhibited adhesion for at least 4 hours and appeared to show no signs of local irritation. In conclusion, BBD devices containing polyoxyethylene polymer (MW 7,000,000) can be prepared by direct compression or compression molding process in order to provide controlled drug release to the oral cavity while maintaining appropriate bioadhesive characteristics