Aim

Prosthetic joint infections (PJI) and fracture related infections (FRI) are the most challenging complications in orthopaedic surgery. An interdisciplinary approach is mandatory not only to correctly diagnose and treat major musculoskeletal infections but also to address the comorbidities and impairments these patients are not rarely suffering from. Since, little data exists on cardiac complications following PJI and FRI revision surgery, this study aimed to investigate the risk of perioperative myocardial injury (PMI) and mortality.

Ewing Tumors (ET) are highly malignant, localized in bone or soft tissue and are molecularly defined by ews/ets translocations. DNA microarray analysis revealed a relationship of ET to both endothelium and fetal neural crest. We identified expression of histone methyl-transferase Enhancer of Zeste, Drosophila, Homolog 2 (EZH2) to be increased in ET. EZH2’s suppressive activity maintains stemness in normal and malignant cells.

Here, we found EWS/FLI1 bound to the EZH2 promoter in vivo and induced EZH2 expression in ET and mesenchymal stem cells. Down-regulation of EZH2 by RNA interference in ET suppressed oncogenic transformation by inhibiting clonogenicity in vitro. Similarly, tumor development and metastasis was suppressed in immunodeficient Rag2−/−γC−/− mice. EZH2-mediated gene silencing was shown to be dependent on histone deacetylase (HDAC) activity. Subsequent microarray analysis of EZH2 knock down, HDAC-inhibitor treatment and confirmation in independent assays revealed an undifferentiated phenotype maintained by EZH2 in ET. EZH2 regulated stemness genes such as nerve growth factor receptor (NGFR) as well as genes involved in neuroectodermal and endothelial differentiation (EMP1, EPHB2, GFAP, GAP43).

These data suggest that EZH2 might play a central role in Ewing Tumor pathology by shaping the oncogenicity and stem cell phenotype of this tumor.

Several studies report a diminished BMD as a consequence of childhood cancer treatment. The aim of this study was to investigate the effects of an exercise intervention on BMD during treatment, since limited mobility is characteristic for cancer therapy and is a major determinant for bone loss.

We analysed DXA scans (Lunar Prodigy, GE Healthcare) of 53 patients (range 8 to 21 years at time of diagnosis) perioperatively (n=49), six (n=38) and twelve months (n=18) after surgery. Scans were performed for the established sites of the lumbar spine and both femora, as well as experimentally for both calcanei. Areal BMD was corrected to obtain volumetric BMD using the model of Kröger.

For both groups, areal and calculated volumetric BMD values were similar at the lumbar spine at time of surgery, as were the differences between affected and not affected femur and calcaneus. The six and twelve months postoperative measurements revealed higher volumetric and areal BMD at the lumbar spine for the intervention group, although significant differences were only found for volumetric BMD values six months postoperatively.

Furthermore, a comparison of both groups showed that the loss in bone density of the affected lower extremity was less pronounced for the intervention group: differences between affected and not affected femur were 9% to 73% higher in the femur and 20% to 29% higher in the calcaneus for the control group.

Previous reports dealing with diminished BMD in pediatric cancer patients were confirmed in this study. However, differences found in BMD between both groups indicate that an exercise intervention during treatment, consisting primarily of strength and endurance training, may inhibit bone loss in pediatric sarcoma patients. Furthermore, the calcaneal site may be an alternative when the determination of femur BMD is not feasible.