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.     

Transjugular intrahepatic portosystemic shunting (TIPS) with balloon-expandable and self-expanding stents: Technical and clinical aspects after 3 1/2 years’ experience

Purpose To evaluate prospectively our experience with transjugular intrahepatic portosystemic shunt (TIPS) using four different metallic stents. Methods Between November 1991 and April 1995, 57 patients (41 men and 16 women; age 35–72 years, mean 54 years) underwent the TIPS procedure. Techniques for portal vein localization before and during TIPS were fluoroscopy, computed tomography (CT) studies, wedged hepatic venography, arterial portography, and ultrasound. After predilation we deployed balloon-expandable (n=48) and self-expanding (n=45) metallic stents. Fifteen patients underwent variceal embolization. Initial follow-up angiograms (mean 6.9 months, range 3–24 months) were obtained in 39 of these patients. Results Fifty-three patients (93%) had successful TIPS placement. The mean decrease in portal pressure was 42.7%. Besides fluoroscopy, the most helpful techniques for portal vein localization were venography and CT. Residual stenosis (n=1) and late shortening (n=4) of Wallstents resulted in shunt dysfunction. The technical problems encountered with the Palmaz stent resulted from its lack of flexibility. We combined balloon-expandable and self-expanding stents in 12 patients. The 30-day and late follow-up (mean 11.9 months) percutaneous reintervention rates were 11.3% and 64.2%, respectively. There were no clinically significant complications related to the TIPS insertions. Conclusion An ideal stent does not exist for TIPS, and the authors recommend combining a Palmaz stent with a flexible self-expanding stent.     

Nonsurgical treatment of a massive macrohematuria following kidney biopsy

In the treatment of massive hematuria after renal biopsy, selective percutaneous vaso-occlusion with detachable balloons is an effective alternative to urological surgery, as demonstrated in the case of a 39-year-old man. A review of the literature, which records success rate of more than 90% in nonmalignant renal hemorrhage, confirms the therapeutic value of the various parenchyma-sparing embolization techniques.     

Interleukin-2, its soluble receptor,and soluble T8 antigen in acute ischemic stroke

The treatment of neoplasia with interleukin-2 (IL-2) can be complicated by neurological deficits resembling transient Ischemic attack and stroke. We investigated whether interleukin-2 contributes to the natural course of cerebrovascular ischemia and particularly to the pathogenesis of infection-associated stroke. Plasma levels of interleukin-2 were below the level of detectability in almost all measurements. Patients with and without previous infection (n = 11, 805 ±445 U/ml vs n = 19, 824 ± 501 U/ml) did not have significantly higher levels of soluble interleukin-2 receptors than control subjects with (n = 14, 667 ± 229 U/ml) or without vascular risk factors (n = 17, 567 ± 176 U/ml). Receptor levels increased in patients during the first week after stroke (n = 15, 1157 ± 1013, p < 0.02). Levels of soluble T8 antigen (sT8) were higher in patients (n – 26, 320 ± 112 U/ml) than in healthy control subjects (n = 15, 246 ± 92 U/ml; p < 0.05) and sT8 levels increased during the first week after stroke (p < 0.05). These results reflect an immunological response to the cerebral infarct; they do not indicate a general role of the IL-2 system in the pathogenesis of ischemic stroke with or without previous infection.     

Sex differences of human trabecular bone microstructure in aging are site-dependent.

In this study, we characterize bone microstructure, specifically sex differences, at multiple skeletal sites in 165 subjects >52 yr of age, using microCT technology in vitro. Significant sex differences are observed at the distal radius, femoral neck, and femoral trochanter, but not at the iliac crest, calcaneus, and lumbar vertebral body. Correlations in BV/TV between sites ranged from r = 0.13 to 0.56. INTRODUCTION: The goals of this study were (1) to assess potential sex differences of bone microstructure and their difference between skeletal sites and (2) to explore the relationship of trabecular microstructural properties between relevant skeletal sites. MATERIALS AND METHODS: Trabecular bone microstructural properties were measured in vitro in 165 subjects 52-99 yr of age using microCT. Defined volumes of interest (cylinders with 6 mm diameter and 6 mm length) were scanned at a resolution of 26 microm (isotropic) in six different anatomical sites: distal radius, femoral neck and trochanter, iliac crest, calcaneus, and second lumbar vertebral body. RESULTS: At the radius and femoral neck, trabecular bone displayed a more plate-like structure, thicker trabeculae, smaller separation/higher trabecular number, higher connectivity, and a higher degree of anisotropy in men than in women (p < 0.05). At the trochanter, men displayed more plate-like structure and thicker trabeculae (p < 0.05), but no differences in trabecular separation or other parameters compared with the women. At the calcaneus, iliac crest, and second lumbar vertebra none of the bone parameters displayed significant differences between sexes. The BV/TV at one site explained a range of only 2-32% of the variability at other sites. CONCLUSIONS: These results suggest that trabecular bone microstructural properties are remarkably heterogeneous throughout the skeleton. Significant differences between men and women are observed at some, but not at all, sites. The magnitude of sex differences in trabecular microstructure coincides with that of fracture incidence observed for some of the sites in epidemiological studies.     

Minimally Invasive Coracoclavicular Ligament Augmentation With a Flip Button/Polydioxanone Repair for Treatment of Total Acromioclavicular Joint Dislocation

Treatment of complete acromioclavicular joint disruption remains controversial and ranges from rehabilitation to extensive surgical reconstruction. However, high-grade injuries (type IV, V, and VI) are typically treated surgically. Most reconstruction techniques addressing these injuries selectively focus on coracoclavicular ligament augmentation because it has been shown to be the primary stabilizer of the acromioclavicular joint. The conventional coracoclavicular polydioxanone (PDS) loop, which is widely performed, has been detected to have some pivotal disadvantages, including anterior subluxation of the clavicle, extensive preparation of the coracoid, and bony avulsion of the clavicle as a result of rotational clavicle movement. Therefore we present an augmentation technique that reduces these complications by replicating the orientation of the native coracoclavicular ligament complex and providing a minimally invasive subcoracoid and clavicular fixation of a double PDS loop by use of 2 flip buttons, typically used for extracortical anterior cruciate ligament graft fixation. The key step of the procedure includes the anatomic, secure, and stable placement of the double PDS cerclage under the coracoid base transferring a flip button through a coracoid bone tunnel. Our clinical experience shows that the presented technique is easy to perform and has a comparable invasiveness to recently presented arthroscopic techniques.     

Analysis of selenium content in commercial dietetic products

Selenium (Se) is largely associated with the protein component of foods. The processing of elemental feeds and artificial formulations used in clinical dietetic practice can, therefore, result in significant losses of Se from these products and the Se status of patients consuming these feeds may be compromised. A selection of commercial formulas typically used for enteral feeding, and for patients with cystic fibrosis, phenylketonuria and maple syrup urine disease were analysed for Se micro-fluorimetrically. Low Se contents were found in all food supplements except for Peptisorbon (0.09 mg Se/2000 kcal) and Clinifeed Protein Rich (0.08 mg Se/2000 kcal) which contained adequate daily Se levels according to the American RDI. The results show that a number of feeds are low in Se, especially those used for patients with cystic fibrosis and maple syrup urine disease. An investigation of the Se status of patients on these formulations may indicate the need for Se supplementation.