Does operative fixation of isolated fractures of ulna shaft results in different outcomes than non-operative management by long arm cast?

Objective

The optimal treatment for isolated fractures of ulnar shaft is debatable. The purpose of this study was to compare functional outcomes and radiological union in patients treated for isolated fractures of the ulnar shaft by open reduction and internal fixation and a long arm cast.

Performance of diffusion-weighted imaging,perfusion imaging,and texture analysis in predicting tumoral response to neoadjuvant chemoradiotherapy in rectal cancer patients studied with 3T MR: initial experience

Purpose

To determine the performance of texture analysis (TA), diffusion-weighted imaging, and perfusion MR (pMRI) in predicting tumoral response in patients treated with neoadjuvant chemoradiotherapy (CRT).

Methods

12 consecutive patients (8 females, 4 males, 63.2 ± 13.4 years) with rectal cancer were prospectively enrolled, and underwent pre-treatment 3T MRI. Treatment protocol consisted of neoadjuvant CRT with oxaliplatin and 5-fluorouracile. Unenhanced T2-weighted images TA (kurtosis), apparent diffusion coefficient (ADC), and pMRI parameters (Ktrans, Kep, Ve, IAUGC) were quantified by manually delineating a region of interest around the tumor outline. After CRT, all patients underwent complete surgical resection and the surgical specimen served as the gold standard. Receiver operating characteristic (ROC) curve analysis was performed to assess the discriminatory power of each quantitative parameter to predict complete response.

Results

Pathological complete response (pCR) was reported in six patients and partial response (PR) in three patients. Three patients were classified as non-responders (NR). Pre-treatment kurtosis was significantly lower in the pCR sub-group in comparison with PR + NR (p = .01). Among ADC and pMRI parameters, only Ve was significantly lower in the pCR sub-group compared with PR + NR (p = .01). A significant negative correlation between kurtosis and ADC (r = ?0.650, p = .022) was observed. Pre-treatment area under the ROC curves (AUC), to discriminate between pCR and PR + NR, was significantly higher for kurtosis (0.861, p = .001) and Ve (0.861, p = .003) compared to all other parameters. The optimal cutoff value for pre-treatment kurtosis and Ve was ≤0.19 (100% sensitivity, 67% specificity) and ≤0.311 (83% sensitivity, 83% specificity), respectively.

Conclusion

Pre-treatment kurtosis derived from T2w images and Ve from pMRI have the potential to act as imaging biomarkers of rectal cancer response to neoadjuvant CRT.

     

MRI texture analysis parameters of contrast-enhanced T1-weighted images of Crohn’s disease differ according to the presence or absence of histological markers of hypoxia and angiogenesis

Purpose

To investigate if texture analysis parameters of contrast-enhanced MRI differ according to the presence of histological markers of hypoxia and angiogenesis in Crohn’s disease (CD).

Methods

Seven CD patients (mean age 38 (19–75), 3 male)) undergoing ileal resection underwent 3T MR enterography including axial ultrafast spoiled gradient-echo T1 post IV gadolinium chelate. Regions of interest were placed in bowel destined for resection and registered to trans-mural histological sections (n = 28 across 7 bowel sections) via MRI of the resected specimen. Microvessel density (MVD) and staining for markers of hypoxia (HIF 1α) and angiogenesis (VEGF) were performed. Texture analysis features were derived utilizing an image filtration-histogram technique at spatial scaling factor (SSF) 0–6 mm, including mean, standard deviation, mean of positive pixels, entropy, kurtosis and skewness and compared according to the presence or absence of histological markers of hypoxia/angiogenesis using Mann–Whitney U/Kruskal–Wallis tests and with the log of MVD using simple linear regression.

Results

Mean, standard deviation and mean of positive pixels were significantly lower in sections expressing VEGF. For example at SSF 6 mm, median (inter-quartile range) of mean, standard deviation and mean of positive pixels in those with VEGF expression were 150.1 (134.7), 132.4 (49.2) and 184.0 (91.4) vs. 362.5 (150.2), 216.3 (100.1) and 416.6 (80.0) in those without (p = 0.001, p = 0.004 and p = 0.001), respectively. There was a significant association between skewness and MVD (ratio 1.97 (1.15–3.41)) at SSF = 2 mm.

Conclusions

Contrast-enhanced MRI texture analysis features significantly differ according to the presence or absence of histological markers of hypoxia and angiogenesis in CD.

     

Mechanistic relationships between polymer microstructure and drug release kinetics in bioerodible polyanhydrides.

This work investigates the relationship between polymer microstructure and drug release kinetics in the bioerodible polyanhydride system, poly[(1,6-bis-p-carboxyphenoxy hexane)-co-(sebacic anhydride)] (CPH-SA). Model drugs, p-nitroaniline (PNA) and disperse yellow 3 (DY), were selected based on compatibility with CPH and SA, respectively. The polymer microstructure and compatibility of the drug with the constituent monomers were determined to have significant influence over the release kinetics of the drugs studied. Polymer systems with homogeneous microstructure, poly(SA) and 50:50 CPH-SA, showed simultaneous polymer degradation and drug release, although the solubility of the drug in the polymer influenced the shape of the release profiles. For the heterogeneous copolymers, 20:80 and 80:20 CPH-SA, individual monomer release kinetics demonstrated the effects of drug partitioning within a phase-separated microstructure. The PNA molecules partition preferentially into the CPH microdomains in the 20:80 CPH-SA copolymer while the DY molecules partition preferentially into the SA microdomains in the 80:20 CPH-SA copolymer. These studies suggest that the drug release mechanism is driven by polymer microstructure, compatibility of the drug with the constituent polymer phases, and solubility of the drug within the polymer. A thorough understanding of drug-polymer interactions as well as the polymer microstructure will pave the way for more accurate predictions of drug release from bioerodible polyanhydrides.     

Mathematical modeling of polymer erosion: consequences for drug delivery

Bioerodible polymers have been extensively used as carriers for drug delivery and as scaffolds for tissue engineering. The ability to model and predict erosion behavior can enable the rational design and optimization of biomaterials for various biomedical applications in vivo. This review examines critically the current approaches in mathematical modeling of the erosion of synthetic polymers. The models are classified broadly based on whether they use phenomenological, probabilistic, or empirical approaches. An analysis of the various physical, chemical, and biological factors affecting polymer erosion and the classes of bioerodible polymers to which these analyses have been applied are discussed. The key features and assumptions associated with each of the models are described, and information is provided on the limitations of the models and the various approaches. The review concludes with several directions for future models of polymer erosion.     

Delivery of Brain-Derived Neurotrophic Factor via Nose-to-Brain Pathway

Purpose  

To investigate the plausibility of delivering brain-derived neurotrophic factor (BDNF) to brain via nose-to-brain pathway using chitosan as barrier-modulating agent.