Index radiographic measurements in the prediction of progression in infantile idiopathic scoliosis: a comparative analysis and description of a novel predictive model.

PURPOSE: To assess the comparative accuracy of commonly utilised index radiological measurements in the prognosis of infantile idiopathic scoliosis (IIS) and build a parsimonious prognostic model utilising these measurements. METHODS: This was a retrospective analysis of a UK population of patients with IIS. Index radiological parameters were analysed, and outcome of their condition was determined over long-term follow-up. Comparative accuracy of each radiological measurement category was determined by logistic regression analyses and the corresponding receiver operating characteristic (ROC) curve. A predictive model of IIS progression using these measurements was then created. RESULTS: All three radiological measurement categories were predictive of IIS progression. However, on pairwise comparison of ROC curves and multivariate analysis, the index Cobb angle proved the most significant predictor of curve progression. Using the index Cobb angle only, a predictive model of curve progression achieved an accuracy of 81.18% with a cut-off Cobb angle of 34.5° found to be the optimal threshold to discriminate a progressive from resolving curve. CONCLUSION: Of the three analysed index radiological parameters commonly used by surgeons in the prognosis of IIS, we found that the Cobb angle is the most accurate predictive measure. Further, neither addition of the RVAD nor convex RVA provided significant further prognostic value in a multivariate model of progression. However, not even the Cobb angle model was accurate in all cases; emphasising caution should be applied when relying on index radiological measurements to predict IIS outcomes.

Long-term follow-up of patients with infantile idiopathic scoliosis: is the rib vertebra angle difference (RVAD) a reliable indicator of evolution?

PURPOSE: Since its original description by Mehta, the rib vertebra angle difference (RVAD) and, in particular, a threshold of 20° have become an accepted and widely utilised prognostic indicator in the assessment of patients presenting with an infantile idiopathic scoliosis (IIS). However, uncertainty in the utility of the RVAD in the prognosis of IIS remains. The aims of this study were to investigate the prognostic significance of the RVAD and to describe the changes in RVAD over long-term follow-up of patients with progressive and resolving IIS. METHODS: This was a retrospective analysis of patients presenting with IIS at a tertiary spinal deformity unit in the UK. Serial patient radiographs were reviewed and a logistic regression model using the patients index RVAD was created to predict the likelihood of curve progression. RESULTS: At both index presentation and over long-term follow-up, patients with a progressive curve had significantly greater mean Cobb angle and RVAD measurements than those with resolving curves. The RVAD and Cobb were found to correlate positively in both groups, reflecting the underlying costovertebral pathoanatomy. The logistic regression model demonstrated that the optimal RVAD threshold in predicting IIS progression was lower at 17.1° than the 20° cut-off previously advocated. CONCLUSION: This study describes the utility of the RVAD in predicting IIS evolution. From this analysis, we would advise caution in predicting outcomes based on the index RVAD at presentation. LEVEL OF EVIDENCE: II.

The Effect of Vancomycin and Gentamicin Antibiotics on Human Osteoblast Proliferation, Metabolic Function, and Bone Mineralization.

STUDY DESIGN: The present study investigates the effect of vancomycin and gentamicin antibiotics on primary human osteoblasts. Osteoblasts were incubated with vancomycin, gentamicin, or with povidone-iodine (PVI), at concentrations advocated for wound irrigation. Osteoblast proliferation, metabolic function, and bone mineralization were measured. OBJECTIVE: The aim of the study was to model gentamicin and vancomycin wound irrigation in vitro and to examine the effect on osteoblast viability and cellular function in comparison to 0.35% PVI. SUMMARY OF BACKGROUND DATA: Vancomycin, gentamicin, and dilute PVI are employed as wound irrigants in spinal surgery to reduce infection. We have, however, recently demonstrated that 0.35% PVI has a detrimental effect on osteoblast cellular function and bone mineralization. Studies to determine the effects of antibiotic wound irrigation solutions on osteoblasts and bone mineralization are therefore warranted. METHODS: Primary human osteoblasts were exposed for 20 minutes to phosphate buffered saline (PBS) control, vancomycin (35 or 3.5 mmol/L), gentamicin (34 or 3.4 mmol/L), or 0.35% PVI for 3 minutes. Cellular proliferation was measured during 7 days by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Osteoblast metabolic function was determined using a Seahorse XFe24 Bioanalyzer. Mineralized bone nodules were quantified using Alizarin red. RESULTS: At concentrations advocated for wound irrigation, both gentamicin (3.4 mmol/L) and vancomycin (3.5 mmol/L) induced a transient 15% to 20% reduction in osteoblast proliferation, which returned to control values within 72 hours. This was in marked contrast to the effect of 0.35% PVI, which resulted in a sustained reduction in osteoblast proliferation of between 40% and 50% during 7 days. Neither gentamicin nor vancomycin at concentrations up to 10× clinical dose had any effect on osteoblast oxygen consumption rate, or significantly affected mineralized bone nodule formation. CONCLUSION: Vancomycin and gentamicin solutions, at concentrations advocated for intrawound application in spinal surgery, have a small but transient effect on osteoblast proliferation, and no effect on either osteoblast metabolic function or bone nodule mineralization. LEVEL OF EVIDENCE: N/A.

Povidone-Iodine Has a Profound Effect on In Vitro Osteoblast Proliferation and Metabolic Function and Inhibits Their Ability to Mineralize and Form Bone.

STUDY DESIGN: A study examining the clinical protocol of scoliosis wound irrigation, demonstrating povidone-iodine's (PVI) effect on human osteoblast cells. Primary and immortal cell line osteoblasts were treated with 0.35% PVI for 3 minutes, and analyzed for proliferation rate, oxidative capacity, and mineralization. OBJECTIVE: To model spinal wound irrigation with dilute PVI in vitro, in order to investigate the effect of PVI on osteoblast proliferation, metabolism, and bone mineralization. SUMMARY OF BACKGROUND DATA: Previously PVI irrigation has been proposed as a safe and effective practice to avoid bacterial growth after spinal surgery. However, recent evidence in multiple cell types suggests that PVI has a deleterious effect on cellular viability and cellular function. METHODS: Primary and immortal human osteoblast cells were exposed to either phosphate buffered saline control or with 0.35% PVI for 3 minutes. Cellular proliferation was measured over the duration of 7 days by MTS assay. Oxygen consumption rate, extracellular acidification rate, and proton production rate were analyzed using a Seahorse XF24 Bioanalyzer. Protein expression of the electron transport chain subunits CII-SDHB, CIII-UQRCR2, and CV-ATP5A was measured via Western blotting. Mineralized bone nodules were stained with alizarin red. RESULTS: Expressed as a percentage of normal osteoblast proliferation, osteoblasts exposed to 0.35% PVI exhibited a significant 24% decrease in proliferation after 24 hours. This was a sustained response, resulting in a 72% decline in cellular proliferation at 1 week. There was a significant reduction in oxygen consumption rate, extracellular acidification rate, and proton production rate (P < 0.05), in osteoblasts that had been exposed to 0.35% PVI for 3 minutes, coupled with a marked reduction in the protein expression of CII-SDHB. Osteoblasts exposed to 0.35% PVI exhibited reduced bone nodule mineralization compared to control phosphate buffered saline exposed osteoblasts (P < 0.01). CONCLUSION: PVI has a rapid and detrimental effect on human osteoblast cellular proliferation, metabolic function, and bone nodule mineralization. LEVEL OF EVIDENCE: NA.

The challenges of cartilage repair and the potential of stem cell applications.

Articular cartilage injuries pose a treatment challenge. These injuries are a direct cause of pain and loss of function and may precipitate osteoarthritis in the affected joint. Typically affecting a younger, more active population whose expectations of treatment and need for long term joint preservation are high. Articular cartilage poses a treatment challenge in that its capacity for satisfactory healing is limited. The common endpoint of conservative management and traditional surgical interventions is the generation of biomechanically inferior fibrocartilage. Regenerative techniques using human stem cells would appear to represent an exciting modality for the production of true hyaline cartilage with material and biological properties suited for lasting function. This review article summarises the current research regarding the use of human stem cells in the treatment of such injuries.