Multi-center, retrospective review. Identify age associated clinical and radiographic features correlating with AS treatment. Little information exists about factors determining treatment for adult scoliosis (AS). Existing studies have not evaluated age stratified differences. Multicenter, retrospective review of 290 patients treated for AS. Patients divided into operative (OP) or nonoperative (NON), and age stratified into 3 groups (G1 = 65 years). Demographic and spinopelvic radiographic parameters evaluated. Health-related quality of life (HRQL) measures included SRS-22, Oswestry Disability Index (ODI), visual analog pain scale. Treatment groups (OP, n = 137; NON, n = 153) demonstrated similar age (OP = 52.7 years; NON = 55.5 years; P > 0.05) and cormorbidities. OP had larger thoracic curves than NON (OP = 51°, NON = 45°; P < 0.05). OP had worse HRQL scores than NON (SRS = 2.95 vs. 3.12, P < 0.05; ODI = 33.4 vs. 28.7, P < 0.05; visual analog pain scale = 6.9 vs. 5.6, P < 0.05, respectively). Age stratification of OP demonstrated larger curves in G1 and G2 versus G3, progressively worsening sagittal imbalance in older age groups, and worse HRQL scores in G3 versus G1 and G2. Age stratification of NON demonstrated worsening sagittal imbalance with age, however, other radiographic values and HRQL scores were similar between all NON age groups. Treatment stratification of age groups demonstrated G1-OP had greater deformity than G1-NON (mean thoracic curve: G1-OP = 53°, G1-NON = 43°; P < 0.05) but similar HRQL values. Whereas G2 and G3-OP had similar radiographic coronal and sagittal values as G2 and G3-NON, but worse HRQL scores. Counter to previous reports, age, cormorbidities, and sagittal balance did not influence treatment modality for AS. Operative treatment for younger patients was driven by increased coronal plane deformity. Conversely, pain and disability mandated treatment for olderpatients, independent of radiographic measures. These findings suggest that AS patients do not become uniformly disabled with age, and that disability can not be solely predicted by radiographic findings. These data should be considered when considering treatment for AS.

Edictive model. Methods We retrospectively reviewed the charts of all 249 patients with idiopathic scoliosis who underwent surgery from 1996 to 2008. We compared those who developed PJK to those who did not. We identified risk factors for PJK and performed univariate and multivariate analyses to determine independent risk factors. We then used a Cox proportional-hazards model to evaluate the time to the development of PJK. The minimum followup time was 1.5 years (mean, 4 years; range, 1.5-9 years). Results The incidence of PJK in our series of patients with idiopathic scoliosis was 17%. There was no difference in Scoliosis Research Society-22 scores between patients without and with junctional kyphosis. Independent risk factors included proximal fusion to T1 through T3 and sagittal sacral vertical line, while in the Cox model a combined anterior-posterior approach surgery was the most important risk factor. Conclusions Patients with a T1 through T3 upper instrumented level, combined anterior-posterior surgery, and increased sagittal sacral vertical line difference had a higher likelihood of developing PJK. Of these risk factors, anterior-posterior surgery was the strongest risk factor. Level of Evidence Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence....

Many receptor tyrosine kinases possess an “activation loop” containing three similarly placed tyrosine autophosphorylation sites. To examine their roles in the TRK NGF receptor, these residues (Tyr-670, Tyr-674, and Tyr-675) were mutated singly and in all combinations to phenylalanine and stably expressed in Trk-deficient PC12nnr5 cells. All mutant receptors showed significantly diminished nerve growth factor (NGF)-stimulated autophosphorylation, indicating impaired catalytic activity. NGF-induced neurite outgrowth exhibited dose-responsive behavior when transfectants were compared by relative receptor expression and exhibited a functional hierarchy: wild type > Y670F ≥ Y674F ≫ Y675F ≥ YY670/674FF = YY670/675FF ≫ YY674/675FF > YYY670/674/675FFF. NGF-induced tyrosine phosphorylation of Shc, ERKs, and SNT and immediate early gene inductions generally paralleled neurogenic potential. However, activation of phosphatidylinositol 3′-kinase and tyrosine phosphorylation of phospholipase Cγ-1 was essentially abolished. The latter effect appears due to selective inability of the mutated TRKs to autophosphorylate the tyrosine residue (Tyr-785) required for binding phospholipase Cγ-1 and indicates that the “activation loop” tyrosines participate in NGF-dependent changes in receptor conformation. Our findings stress the importance that expression levels play in assessing the consequences of receptor mutations and that all three activation loop tyrosines have roles regulating both overall and specific NGF-mediated signaling through TRK.

KIT receptor kinase activity is repressed, prior to stem cell factor binding, by unknown structural constraints. Using site-directed mutagenesis, we examined the role of KIT intracellular juxtamembrane residues Met-552 through Ile-563 in controlling receptor autophosphorylation. Alanine substitution for Tyr-553, Trp-557, Val-559, or Val-560, all sitting along the hydrophobic side of an amphipathic α-helix (Tyr-553–Ile-563) predicted by the Chou-Fasman algorithm, resulted in substantially increased spontaneous receptor phosphorylation, revealing inhibitory roles for these residues. Alanine substitution for other residues, most of which are on the hydrophilic side of the helix, caused no or slightly increased basal receptor phosphorylation. Converting Tyr-553 or Trp-557 to phenylalanine generated slight or no elevation, respectively, in basal KIT phosphorylation, indicating that the phenyl ring of Tyr-553 and the hydrophobicity of Trp-557 are critical for the inhibition. Although alanine substitution for Lys-558 had no effect on receptor phosphorylation, its substitution with proline produced high spontaneous receptor phosphorylation, suggesting that the predicted α-helical conformation is involved in the inhibition. A synthetic peptide comprising Tyr-553 through Ile-563 showed circular dichroism spectra characteristic of α-helix, supporting the structural prediction. Thus, the KIT intracellular juxtamembrane region contains important residues which, in a putative α-helical conformation, exert inhibitory control on the kinase activity of ligand-unoccupied receptor.

Degenerative lumbar spinal stenosis is caused by mechanical factors and/or biochemical alterations within the intervertebral disk that lead to disk space collapse, facet joint hypertrophy, soft-tissue infolding, and osteophyte formation, which narrows the space available for the thecal sac and exiting nerve roots. The clinical consequence of this compression is neurogenic claudication and varying degrees of leg and back pain. Degenerative lumbar spinal stenosis is a major cause of pain and impaired quality of life in the elderly. The natural history of this condition varies; however, it has not been shown to worsen progressively. Nonsurgical management consists of nonsteroidal anti-inflammatory drugs, physical therapy, and epidural steroid injections. If nonsurgical management is unsuccessful and neurologic decline persists or progresses, surgical treatment, most commonly laminectomy, is indicated. Recent prospective randomized studies have demonstrated that surgery is superior to nonsurgical management in terms of controlling pain and improving function in patients with lumbar spinal stenosis.