A review of the current literature shows that there is a lack of consensus regarding the treatment of spondylolysis and spondylolisthesis in children and adolescents. Most of the views and recommendations provided in various reports are weakly supported by evidence. There is a limited amount of information about the natural history of the condition, making it difficult to compare the effectiveness of various conservative and operative treatments. This systematic review summarises the current knowledge on spondylolysis and spondylolisthesis and attempts to present a rational approach to the evaluation and management of this condition in children and adolescents.

Distraction forces increase significantly after repeated lengthening of growing-rod constructs, and the length obtained at each procedure exhibits a decreasing trend.

We describe the results of a prospective case series of patients with spondylolysis, evaluating a technique of direct stabilisation of the pars interarticularis with a construct that consists of a pair of pedicle screws connected by a U-shaped modular link passing beneath the spinous process. Tightening the link to the screws compresses bone graft in the defect in the pars, providing rigid intrasegmental fixation. We have carried out this procedure on 20 patients aged between nine and 21 years with a defect of the pars at L5, confirmed on CT. The mean age of the patients was 13.9 years (9 to 21). They had a grade I or less spondylolisthesis and no evidence of intervertebral degeneration on MRI. The mean follow-up was four years (2.3 to 7.3). The patients were assessed by the Oswestry Disability Index (ODI) and a visual analogue scale (VAS). At the latest follow-up, 18 patients had an excellent clinical outcome, with a significant (p < 0.001) improvement in their ODI and VAS scores. The mean ODI score at final follow-up was 8%. Assessment of the defect by CT showed a rate of union of 80%. There were no complications involving the internal fixation. The strength of the construct removes the need for post-operative immobilisation.

SummaryActivating mutations in the K-Ras small GTPase are extensively found in human tumors. Although these mutations induce the generation of a constitutively GTP-loaded, active form of K-Ras, phosphorylation at Ser181 within the C-terminal hypervariable region can modulate oncogenic K-Ras function without affecting the in vitro affinity for its effector Raf-1. In striking contrast, K-Ras phosphorylated at Ser181 shows increased interaction in cells with the active form of Raf-1 and with p110a, the catalytic subunit of PI 3-kinase. Because the majority of phosphorylated K-Ras is located at the plasma membrane, different localization within this membrane according to the phosphorylation status was explored. Density-gradient fractionation of the plasma membrane in the absence of detergents showed segregation of K-Ras mutants that carry a phosphomimetic or unphosphorylatable serine residue (S181D or S181A, respectively). Moreover, statistical analysis of immunoelectron microscopy showed that both phosphorylation mutants form distinct nanoclusters that do not overlap. Finally, induction of oncogenic K-Ras phosphorylation -by activation of protein kinase C (PKC) -increased its co-clustering with the phosphomimetic KRas mutant, whereas (when PKC is inhibited) non-phosphorylated oncogenic K-Ras clusters with the non-phosphorylatable K-Ras mutant. Most interestingly, PI 3-kinase (p110a) was found in phosphorylated K-Ras nanoclusters but not in non-phosphorylated K-Ras nanoclusters. In conclusion, our data provide -for the first time -evidence that PKC-dependent phosphorylation of oncogenic K-Ras induced its segregation in spatially distinct nanoclusters at the plasma membrane that, in turn, favor activation of Raf-1 and PI 3-kinase.