Does the presence of chondral lesions negatively affect patient-determined outcomes after arthroscopic rotator cuff repair?

Background: There are limited data available to guide patients to their prognosis when glenohumeral chondral lesions are found during arthroscopic rotator cuff repair. Hypothesis: The primary hypothesis was that patients with glenohumeral chondral lesions will have inferior outcomes after arthroscopic rotator cuff repair compared with patients without chondral lesions. The secondary hypothesis was that patients with concomitant chondral lesions will have more severe preoperative symptoms compared with those without chondral lesions. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective analysis was performed of patients who underwent arthroscopic rotator cuff repair between 2008 and 2012. We examined the effects of chondral lesions on patient-determined outcomes, which included the Western Ontario Rotator Cuff Index (WORC), American Shoulder and Elbow Surgeons (ASES) score, Simple Shoulder Test (SST), Single Assessment Numeric Evaluation (SANE), and the Shoulder Activity Level (SAL). Shoulders without chondral lesions were compared with shoulders with chondral lesions to determine whether differences in severity of preoperative symptoms as well as postoperative improvements were statistically significant. Results: A total of 281 shoulders were included from 273 patients, with a mean follow-up of 3.7 years. In total, 90 shoulders (32%) had concomitant chondral lesions in the glenohumeral joint. The presence and degree of chondral damage were not associated with the severity of preoperative symptoms or the amount of improvement after arthroscopic rotator cuff repair, as determined by patient outcome scores. Shoulders with bipolar chondral lesions had less postoperative improvement in their outcome scores compared with shoulders with unipolar lesions, with significant differences found in the SST ( Conclusion: At a mean 3.7-year follow-up, the presence of chondral damage did not appear to negatively affect the improvement in patient-determined outcomes after arthroscopic rotator cuff repair. However, improvement in outcomes was negatively affected by the presence of bipolar chondral lesions

Experimental demonstration of improved magnetorelaxometry imaging performance using optimized coil configurations

Background Magnetorelaxometry imaging is an experimental imaging technique capable of reconstructing magnetic nanoparticle distributions inside a volume noninvasively and with high specificity. Thus, magnetorelaxometry imaging is a promising candidate for monitoring a number of therapeutical approaches that employ magnetic nanoparticles, such as magnetic drug targeting and magnetic hyperthermia, to guarantee their safety and efficacy. Prior to a potential clinical application of this imaging modality, it is necessary to optimize magnetorelaxometry imaging systems to produce reliable imaging results and to maximize the reconstruction accuracy of the magnetic nanoparticle distributions. Multiple optimization approaches were already applied throughout a number of simulation studies, all of which yielded increased imaging qualities compared to intuitively designed measurement setups. Purpose None of these simulative approaches was conducted in practice such that it still remains unclear if the theoretical results are achievable in an experimental setting. In this study, we demonstrate the technical feasibility and the increased reconstruction accuracy of optimized coil configurations in two distinct magnetorelaxometry setups. Methods The electromagnetic coil positions and radii of a cuboidal as well as a cylindrical magnetorelaxometry imaging setup are optimized by minimizing the system matrix condition numbers of their corresponding linear forward models. The optimized coil configurations are manufactured alongside with two regular coil grids. Magnetorelaxometry measurements of three cuboidal and four cylindrical magnetic nanoparticle phantoms are conducted, and the resulting reconstruction qualities of the optimized and the regular coil configurations are compared. Results The computed condition numbers of the optimized coil configurations are approximately one order of magnitude lower compared to the regular coil grids. The reconstruction results show that for both setups, every phantom is recovered more accurately by the optimized coil configurations compared to the regular coil grids. Additionally, the optimized coil configurations yield better signal qualities. Conclusions The presented experimental study provides a proof of the practicality and the efficacy of optimizing magnetorelaxometry imaging systems with respect to the condition numbers of their system matrices, previously only demonstrated in simulations. From the promising results of our study, we infer that the minimization of the system matrix condition number will also enable the practical optimization of other design parameters of magnetorelaxometry imaging setups (e.g., sensor configuration, coil currents, etc.) in order to improve the achievable reconstruction qualities even further, eventually paving the way towards clinical application of this imaging modality

Optimizing excitation coil currents for advanced magnetorelaxometry imaging

Magnetorelaxometry imaging is a highly sensitive technique enabling noninvasive, quantitative detection of magnetic nanoparticles. Electromagnetic coils are sequentially energized, aligning the nanoparticles’ magnetic moments. Relaxation signals are recorded after turning off the coils. The forward model describing this measurement process is reformulated into a severely ill-posed inverse problem that is solved for estimating the particle distribution. Typically, many activation sequences employing different magnetic fields are required to obtain reasonable imaging quality. We seek to improve the imaging quality and accelerate the imaging process using fewer activation sequences by optimizing the applied magnetic fields. Minimizing the Frobenius condition number of the system matrix, we stabilize the inverse problem solution toward model uncertainties and measurement noise. Furthermore, our sensitivity-weighted reconstruction algorithms improve imaging quality in lowly sensitive areas. The optimization approach is employed to real measurement data and yields improved reconstructions with fewer activation sequences compared to non-optimized measurements

Quantitative 2D magnetorelaxometry imaging of magnetic nanoparticles using optically pumped magnetometers

For biomagnetical applications exploiting physical properties of magnetic nanoparticles (MNP), e.g., magnetic hyperthermia, knowledge about the quantitative spatial MNP distribution is crucial, which can be extracted by magnetorelaxometry (MRX) imaging. In this paper, we present quantification, quantitative 1D reconstruction, and quantitative 2D imaging of MNP by exploiting optically pumped magnetometers for MRX. While highlighting the potential of commercially available optically pumped magnetometers (OPM) for MRXI, we discuss current limitations of the used OPM. We show, that with our OPM setup, MNP can be precisely quantified with iron amounts down to ≈6 μg, which can be improved easily. With a 1D-reconstruction setup, point-like and complex MNP phantoms can be reconstructed quantitatively with high precision and accuracy. We show that with our developed 2D MRX imaging setup, which measures 12 cm by 8 cm, point-like MNP distributions with clinically relevant iron concentrations can be reconstructed precisely and accurately. Our 2D setup has the potential to be easily extended to a tomography styled (and thus slice-selective) 3D scanner, by adding a mechanical axis to the phantom

A functional yeast survival screen of tumor-derived cDNA libraries designed to identify anti-apoptotic mammalian oncogenes

Yeast cells can be killed upon expression of pro-apoptotic mammalian proteins. We have established a functional yeast survival screen that was used to isolate novel human anti-apoptotic genes overexpressed in treatment-resistant tumors. The screening of three different cDNA libraries prepared from metastatic melanoma, glioblastomas and leukemic blasts allowed for the identification of many yeast cell death-repressing cDNAs, including 28% of genes that are already known to inhibit apoptosis, 35% of genes upregulated in at least one tumor entity and 16% of genes described as both anti-apoptotic in function and upregulated in tumors. These results confirm the great potential of this screening tool to identify novel anti-apoptotic and tumor-relevant molecules. Three of the isolated candidate genes were further analyzed regarding their anti-apoptotic function in cell culture and their potential as a therapeutic target for molecular therapy. PAICS, an enzyme required for de novo purine biosynthesis, the long non-coding RNA MALAT1 and the MAST2 kinase are overexpressed in certain tumor entities and capable of suppressing apoptosis in human cells. Using a subcutaneous xenograft mouse model, we also demonstrated that glioblastoma tumor growth requires MAST2 expression. An additional advantage of the yeast survival screen is its universal applicability. By using various inducible pro-apoptotic killer proteins and screening the appropriate cDNA library prepared from normal or pathologic tissue of interest, the survival screen can be used to identify apoptosis inhibitors in many different systems