External validation of a model to predict the survival of patients presenting with a spinal epidural metastasis

The surgical treatment of spinal metastases is evolving. The major problem is the selection of patients who may benefit from surgical treatment. One of the criteria is an expected survival of at least 3 months. A prediction model has been previously developed. The present study has been performed in order to validate externally the model and to demonstrate that this model can be generalized to other institutions and other countries than the Netherlands. Data of 356 patients from five centers in Germany, Spain, Sweden, and the Netherlands who were treated for metastatic epidural spinal cord compression were collected. Hazard ratios in the test population corresponded with those of the developmental population. However, the observed and the expected survival were different. Analysis revealed that the baseline hazard function was significantly different. This tempted us to combine the data and develop a new prediction model. Estimating iteratively, a baseline hazard was composed. An adapted prediction model is presented. External validation of a prediction model revealed a difference in expected survival, although the relative contribution of the specific hazard ratios was the same as in the developmental population. This study emphasized the need to check the baseline hazard function in external validation. A new model has been developed using an estimated baseline hazar

Interobserver reliability and diagnostic performance of Chiari II malformation measures in MR imaging—part 2

PURPOSE: Brain MR imaging is essential in the assessment of Chiari II malformation in clinical and research settings concerning spina bifida. However, the interpretation of MR images of the malformation is not always straightforward. Morphometric analyses of the extent of Chiari II malformation may improve the assessment. In an attempt to select appropriate morphometric measures for this purpose, we investigated the interobserver reliability and diagnostic performance of several morphometric measures of Chiari II malformation on MR images. METHODS: Brain MR images of 79 children [26 with open spinal dysraphism, 17 with closed spinal dysraphism, and 36 without spinal dysraphism; mean age 10.6 (SD 3.2; range, 6-16) years] were evaluated. All children had been assessed for Chiari II malformation (defined as cerebellar herniation in combination with open spinal dysraphism; n = 23). Three observers blindly and independently reviewed the MR images for 21 measures of the cerebellum, brainstem, and posterior fossa in three planes. The interobserver reliability was assessed by an agreement index (AI = 1 - RRE) and the diagnostic performance by receiver operating characteristic analyses. RESULTS: Reliability was good for most measures, except for the degree of herniation of the vermis and tonsil. Most values differed statistically significantly between children with and without Chiari II malformation. The measures mamillopontine distance and cerebellar width showed excellent diagnostic performance. CONCLUSIONS: Morphometric measures may reliably quantify the morphological distortions of Chiari II malformation on MR images and provide additional tools to assess the severity of Chiari II malformation in clinical and research settings

Evaluation of bone mineralization in former preterm born children: Phalangeal quantitative ultrasound cannot replace dual-energy X-ray absorptiometry

Background: Preterm infants are at risk of impaired bone health in later life. Dual-energy X-ray absorptiometry-scan (DXA) is the gold standard to determine bone mineralization. Phalangeal quantitative ultrasound (pQUS) is an alternative technique that is inexpensive, easy to use and radiation-free. The aim of this study was to investigate whether both techniques reveal equivalent results. Materials and methods: Sixty former preterm infants (31 boys; 29 girls) received a DXA and pQUS at age 9 to 10 years. DXA measured bone mineral content (BMC) and bone mineral density (BMD) for total body and lumbar spine (L1-4), while pQUS measured the amplitude dependent speed of sound (AD-SoS) and bone transit time (BTT) at metacarpals II-IV providing continuous values and Z-scores based on age and sex. Four statistical methods evaluated the association between both techniques: Pearson's correlation coefficients, partial correlation coefficients adjusted for gestational age, height and BMI, Bland-Altman analysis and cross tabulation. Results: Both techniques showed a statistically significant weak correlation for continuous values as well as Z-scores (0.291–0.462, p < 0.05). Boys had significant and relatively high correlations (0.468–0.585, p < 0.05). In comparison, the correlations for girls were not significant. Correlation coefficients further decreased while calculating the partial correlations. The Bland-Altman plots showed poor agreement. Sensitivity ranged from 33% to 92% and specificity from 16% to 68%. Positive and negative predictive values ranged from 4% to 38% and 82% to 97%, respectively. Conclusions: We found statistically significant weak correlations and poor agreement between DXA and pQUS measurements. DXA is not equivalent to pQUS and therefore not replaceable by this technique in former preterm born children at the age of 9 to 10 years

External validation of a model to predict the survival of patients presenting with a spinal epidural metastasis

The surgical treatment of spinal metastases is evolving. The major problem is the selection of patients who may benefit from surgical treatment. One of the criteria is an expected survival of at least 3 months. A prediction model has been previously developed. The present study has been performed in order to validate externally the model and to demonstrate that this model can be generalized to other institutions and other countries than the Netherlands. Data of 356 patients from five centers in Germany, Spain, Sweden, and the Netherlands who were treated for metastatic epidural spinal cord compression were collected. Hazard ratios in the test population corresponded with those of the developmental population. However, the observed and the expected survival were different. Analysis revealed that the baseline hazard function was significantly different. This tempted us to combine the data and develop a new prediction model. Estimating iteratively, a baseline hazard was composed. An adapted prediction model is presented. External validation of a prediction model revealed a difference in expected survival, although the relative contribution of the specific hazard ratios was the same as in the developmental population. This study emphasized the need to check the baseline hazard function in external validation. A new model has been developed using an estimated baseline hazar

Decreased Levels of Circulating IL17-Producing CD161(+)CCR6(+) T Cells Are Associated with Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation

Contains fulltext : 110799.pdf (publisher's version ) (Open Access)The C-type lectin-like receptor CD161 is a well-established marker for human IL17-producing T cells, which have been implicated to contribute to the development of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (allo-SCT). In this study, we analyzed CD161(+) T cell recovery, their functional properties and association with GVHD occurrence in allo-SCT recipients. While CD161(+)CD4(+) T cells steadily recovered, CD161(hi)CD8(+) T cell numbers declined during tapering of Cyclosporine A (CsA), which can be explained by their initial growth advantage over CD161(neg/low)CD8(+) T cells due to ABCB1-mediated CsA efflux. Interestingly, occurrence of acute and chronic GVHD was significantly correlated with decreased levels of circulating CD161(+)CD4(+) as well as CD161(hi)CD8(+) T cells. In addition, these subsets from transplanted patients secreted high levels of IFNgamma and IL17. Moreover, we found that CCR6 co-expression by CD161(+) T cells mediated specific migration towards CCL20, which was expressed in GVHD biopsies. Finally, we demonstrated that CCR6(+) T cells indeed were present in these CCL20(+) GVHD-affected tissues. In conclusion, we showed that functional CD161(+)CCR6(+) co-expressing T cells disappear from the circulation and home to GVHD-affected tissue sites. These findings support the hypothesis that CCR6(+)CD161-expressing T cells may be involved in the immune pathology of GVHD following their CCL20-dependent recruitment into affected tissues

Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome.

Item does not contain fulltextWe show that haploinsufficiency of KANSL1 is sufficient to cause the 17q21.31 microdeletion syndrome, a multisystem disorder characterized by intellectual disability, hypotonia and distinctive facial features. The KANSL1 protein is an evolutionarily conserved regulator of the chromatin modifier KAT8, which influences gene expression through histone H4 lysine 16 (H4K16) acetylation. RNA sequencing studies in cell lines derived from affected individuals and the presence of learning deficits in Drosophila melanogaster mutants suggest a role for KANSL1 in neuronal processes.01 juni 201