Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.     

The role of endoscopic ultrasound for portal hypertension in liver cirrhosis

Journal of Medical Ultrasonics - Chronic liver disease is still a major problem because disease progression will ultimately lead to liver cirrhosis. Portal hypertension is the hallmark in advanced...     

Biomechanical comparison of stemless humeral components in total shoulder arthroplasty

BackgroundThe purpose of this study was to compare initial fixation strength between various stemless and stemmed humeral components and to correlate implant fixation strength with bone mineral density (BMD).MethodsFive humeral stem designs were investigated: Stemless-A (four hollow fins), Stemless-B (central body, three solid fins), Stemless-C (central screw, peripheral rim-fit), Short stem (50 mm), and Standard stem (130 mm). Fifty cadaveric human humerii were obtained and divided into five groups. BMD within the humeral head was determined for all samples. The mean BMD was similar between groups. The 25 samples with the lowest and highest BMDs were categorized as “Low” and “High,” respectively, with a BMD threshold of 0.35 g/cm², creating BMD subgroups. After implantation, each sample underwent a standardized biomechanical testing protocol, with axial loading followed by torsional loading. Sensors attached to the specimen recorded micromotion throughout testing. Axial loading consisted of cyclic loading for 100 cycles at 3 peak forces (220, 520, and 820 N). Torsional loading consisted of 100 cycles of internal/external rotation at 0.1 Hz at 6 peak torques, or until failure (±2.5, 5, 7.5, 10, 12.5, and 15 Nm). Failure was defined as the torque at which any bone fracture, implant detachment from anchor/stem, or an excess of 50° internal/external rotation occurred. Groups and BMD subgroups were compared.ResultsAt maximal axial loading, Stemless-B demonstrated greater micromotion (540 μm) than Stemless-C (192 μm) (P = .003). Stemless-B and Stemless-A (387 μm) also had greater micromotion than Short stem (118 μm, P < .001, P = .03) and Standard stem (85 μm, P < .001, P = .01). When comparing low-BMD samples at maximal axial loading, these differences were accentuated, but comparison of high-BMD samples showed no significant differences between groups. Torsional testing demonstrated that Standard stem failed at greater torque (7.2 Nm) than Stemless-B (2.3 Nm, P < .001), Stemless-A (1.9 Nm, P < .001), and Stemless-C (3.9 Nm, P = .01). When comparing torsional testing results of low-BMD samples, both Standard stem and Short stem failed at greater torque than Stemless-B (P = .02, P = .003) and Stemless-A (P = .03, P = .004) but failed at a similar torque to Stemless-C. Torsional testing of high-BMD samples showed that Standard stem failed at a greater torque than all stemless designs.ConclusionStemless humeral implants should be used with caution in low-BMD settings (<0.35 g/cm²). A central screw and peripheral rim-fit stemless anchor design demonstrated greater fixation strength at low BMD when compared with other designs, while all stemless designs performed similarly at high BMD.Level of evidenceBasic Science Study; Cadaveric Study     

Two-year results after combined phacoemulsification and iris-fixated phakic intraocular lens removal

Graefe's Archive for Clinical and Experimental Ophthalmology - To describe and present results after a technique for cataract surgery combined with explantation of an iris-fixated phakic...