How well do Radiologic Assessments of Truncal and Shoulder Balance Correlate With Cosmetic Assessment Indices in Lenke 1C Adolescent Idiopathic Scoliosis?

STUDY DESIGN: A correlation study. OBJECTIVE: The primary objective was to determine the correlation between radiologic and cosmetic indices of trunk and shoulder balance before and after scoliosis surgery in Lenke 1C adolescent idiopathic scoliosis and to determine whether postoperative trunk shift is affiliated with worsening of the patients' cosmesis. SUMMARY OF BACKGROUND DATA: Achieving a symmetrical appearance with truncal and shoulder balance is of prime importance to adolescent idiopathic scoliosis patients and their surgeons. However, surgeons prefer radiographic indices rather than measures of patients' clinical appearance. If radiographic indices are to be considered accurate depictions of the patient's cosmesis, radiologic and cosmetic indices must necessarily exhibit high association. METHODS: Radiographic and cosmetic indices of trunk and shoulder balance, along with posterior trunk symmetry index, were measured preoperatively and 3 months postoperatively in 33 Lenke 1C scoliosis patients. Pearson correlation analysis was performed. Paired t test was used to determine significant changes in radiographic and cosmetic indices after surgery. Independent-sample t test was used for all intergroup analyses in trunk shift and no-trunk-shift groups. RESULTS: Correlation coefficients between radiologic and cosmetic indices ranged between -0.63 and 0.70 with thoracic apical vertebra-central sacral vertical line (AV-CSVL) distance and first rib angle showing consistent correlations with cosmetic trunk and cosmetic shoulder balance indices. Trunk shift, a postoperative iatrogenic phenomenon, was seen in 19 (58%) patients. These patients had higher preoperative thoracic AV-CSVL translation, thoracic apical vertebra-first thoracic vertebra (AV-T1) translation, thoracic deformity correction rate, AV-T1 correction rates, and shorter fusions compared with the no-trunk-shift group. Posterior trunk symmetry index worsened in trunk shift group and improved significantly (-7.94 vs. 16.53) in no-trunk-shift group. Significant association (P=0.004) was seen between radiographic and cosmetic trunk shift. CONCLUSIONS: Radiographic indices can only minisculely (r≤0.7) reflect cosmetic deformity in Lenke 1C scoliosis, which emphasizes not only the vulnerability of overreliance on radiographic indices but also the vital importance of clinical cosmetic evaluations. In particular, cosmetic shoulder height and angle are not represented by radiographic indices. However, radiograph trunk shift was significantly associated with cosmetic trunk shift in cosmetic pictures.

Improved patient selection by stratified surgical intervention: Aarhus Spinal Metastases Algorithm.

BACKGROUND CONTEXT: Choosing the best surgical treatment for patients with spinal metastases remains a significant challenge for spine surgeons. There is currently no gold standard for surgical treatments. The Aarhus Spinal Metastases Algorithm (ASMA) was established to help surgeons choose the most appropriate surgical intervention for patients with spinal metastases. PURPOSE: The purpose of this study was to evaluate the clinical outcome of stratified surgical interventions based on the ASMA, which combines life expectancy and the anatomical classification of patients with spinal metastases to inform surgical decision making. STUDY DESIGN/SETTING: This is a retrospective study based on a prospective database. PATIENT SAMPLE: A consecutive series of 515 spinal metastatic patients who underwent surgically treatment from December 1992 to June 2012 in Aarhus University Hospital were included prospectively and analyzed in detail retrospectively. OUTCOME MEASURES: Survival time after surgery was determined for all patients. Neurological function was assessed using the Frankel score preoperatively and postoperatively (at the time of discharge). Complete outcome data were retrieved in 97.5% of this cohort. METHODS: Patients with spinal metastases were identified from an institutional database that prospectively collected data since 1992. Survival status data were obtained from a national registry. Neurological function was determined from the same institutional database or local Electronic Patient Journal system. Surgeons evaluated and classified patients into five surgical groups preoperatively by using the revised Tokuhashi score (TS) and the Tomita anatomical classification (TC). RESULTS: The overall median survival time of the cohort was 6.8 (95% confidence interval: 6.1-7.9) months. The median survival times in the five surgical groups determined by the ASMA were 2.1 (TS 0-4, TC 1-7), 5.1 (TS 5-8, TC 1-7), 12.1 (TS 9-11, TC 1-7 or TS 12-15, TC 7), 26.0 (TS 12-15, TC 4-6), and 36.0 (TS 12-15, TC 1-3) months. The 30-day mortality rate was 7.5%. Postoperative neurological function was maintained or improved in 469 patients (92.3%). Overall reoperation rate was 13.5%, commonly because of postoperative hematoma and new limb weakness. CONCLUSIONS: The ASMA recommends at least two surgical options for a particular patient by determining the preoperative life expectancy and anatomical classification of the spinal metastases. This algorithm could help spine surgeons to discriminate the risks of surgeries. The ASMA provides a tool to guild surgeons to evaluate the spinal metastases patients, select potential optimal surgery, and avoid life-threatening risks.

Early versus late initiation of rehabilitation after lumbar spinal fusion: economic evaluation alongside a randomized controlled trial.

STUDY DESIGN: Economic evaluation conducted alongside a randomized controlled trial with 1-year follow-up. OBJECTIVE: To examine the cost-effectiveness of initiating rehabilitation 6 weeks after surgery as opposed to 12 weeks after surgery. SUMMARY OF BACKGROUND DATA: In a previously reported randomized controlled trial, we assessed the impact of timing of rehabilitation after a lumbar spinal fusion and found that a fast-track strategy led to poorer functional ability. Before making recommendations, it seems relevant to address the societal perspective including return to work, quality of life, and costs. METHODS: A cost-effectiveness analysis and a cost-utility analysis were conducted. Eighty-two patients undergoing instrumented lumbar spinal fusion due to degenerative disc disease or spondylolisthesis (grade I or II) were randomized to an identical protocol of 4 sessions of group-based rehabilitation and were instructed in home exercises focusing on active stability training. Outcome parameters included functional disability (Oswestry Disability Index) and quality-adjusted life years. Health care and productivity costs were estimated from national registries and reported in euros. Costs and effects were transformed into net benefit. Bootstrapping was used to estimate 95% confidence intervals (95% CI). RESULTS: The fast-track strategy tended to be costlier by €6869 (95% CI, -4640 to 18,378) while at the same time leading to significantly poorer outcomes of functional disability by -9 points (95% CI, -18 to -3) and a tendency for a reduced gain in quality-adjusted life years by -0.04 (95% CI, -0.13 to 0.01). The overall probability for the fast-track strategy being cost-effective does not reach 10% at conventional thresholds for cost-effectiveness. CONCLUSION: Initiating rehabilitation at 6 weeks as opposed to 12 weeks after surgery is on average more costly and less effective. The uncertainty of this result did not seem to be sensitive to methodological issues, and clinical managements who have already adapted fast-track rehabilitation strategies have reason to reconsider their choice. .

The effect of timing of rehabilitation on physical performance after lumbar spinal fusion: a randomized clinical study.

BACKGROUND: The number of patients undergoing lumbar spinal fusion procedures (LSF) has risen in recent years, but only few studies have examined different rehabilitation strategies for this patient group. PURPOSE: To evaluate the impact of initiating rehabilitation either 6 or 12 weeks after a LSF based on the patients' physical performance using the 6-min walking test (6MWT) and the Åstrand Fitness test (AF-test) as measurement. METHODS: A multicentre RCT including 82 patients with degenerative disc diseases undergoing LSF randomly assigned to initiate rehabilitation either 6 or 12 weeks after surgery. Both groups received the same group-based rehabilitation. The main outcome measures were the 6MWT and the AF-test, secondarily questionnaire-based measures. Follow-up at baseline as well as at 3, 6 and 12 months after surgery. RESULTS: Comparing the two groups no statistically significant difference was found in walking distance or fitness over time. In both groups, the patients achieved an overall increase in walking distance (p < 0.01), but no improvement in fitness. The 6MWT showed significant correlation (-0.37 to -0.59) with the questionnaire-based outcome measures (p < 0.01). The AF-test did not correlate to either the 6MWT or any of the questionnaire-based outcome measures. CONCLUSION: No difference was found in the effect of initiating rehabilitation either 6 or 12 weeks after LSF on the patients' physical performance in terms of fitness and walking distance. The 6MWT showed fair to moderate correlation to the questionnaire-based outcome measures. The AF-test showed no significant independent value, and we question its use in LSF patients.

The effect of early initiation of rehabilitation after lumbar spinal fusion: a randomized clinical study.

STUDY DESIGN: A multicenter randomized clinical trial including 82 patients. OBJECTIVE: To examine the effect of early initiation of rehabilitation after instrumented lumbar spinal fusion. SUMMARY OF BACKGROUND DATA: Lumbar spinal fusion has been performed for more than 70 years. Yet, few studies have examined patients' subsequent rehabilitation. Group-based rehabilitation is both efficient and cost-effective in rehabilitation of lumbar spinal fusion patients. METHODS: Patients with degenerative disc diseases undergoing instrumented lumbar spinal fusion were randomly assigned to initiate their rehabilitation 6 weeks (6-wk group) or 12 weeks after lumbar spinal fusion (12-wk group). Both groups received the same group-based rehabilitation. Primary outcome was the Oswestry Disability Index. Secondary outcome was the Dallas Pain Questionnaire, the Low Back Pain Rating Scale, and absence from work. Wilcoxon rank-sum test was used to compare the groups in terms of differences from baseline to 6 months and 1-year follow-up. Results are presented in median with 25th and 75th percentiles. RESULTS: According to the Oswestry Disability Index, at 1-year follow-up, the 6-week-group had a median reduction of -6 (-19; 4) compared with -20 (-30;-7) in the 12-week group (P, 0.05). The Dallas Pain Questionnaire showed overall the same tendency, and within daily activities were significantly reduced in favor of the 12-week group (P, 0.05). For back pain, the 6-week group had a median reduction of -2.2 (-3.0; -0.7) similar with -3.3 (-4.7; -1.7) in the 12-week group (P, 0.05). The results at 6 months of follow-up were similar. No difference was found according to return to work 1 year postsurgery. CONCLUSION: Early start of rehabilitation (6 wk vs. 12 wk) after lumbar spinal fusion resulted in inferior outcomes. The improvements in the 12-week group were 4 times better than that in the 6-week group, indicating that the start-up time of rehabilitation is an important contributing factor for the overall outcome.

Postoperative spinal alignment remodeling in Lenke 1C scoliosis treated with selective thoracic fusion.

BACKGROUND CONTEXT: Selective thoracic fusion may cause spinal imbalance in certain patients; how the spinal alignment changes over time after surgery is highly correlated with the final spinal balance. PURPOSE: To investigate how spinal alignment changes over time after selective thoracic fusion and how spinal alignment remodeling affects spinal balance. METHODS: All adolescent idiopathic scoliosis (AIS) cases surgically treated in our institution between 2002 and 2008 were reviewed. Inclusion criteria were as follows: Lenke 1C scoliosis patients treated with posterior pedicle screw-only constructs; the lowest instrumented vertebra (LIV) ended at L1 level or above; and 2-year radiographic follow-up. Standing anteroposterior and lateral digital radiographs from four different time points (preoperatively, immediately, 3 months, and 2 years postoperatively) were reviewed. In each standing anteroposterior radiograph, the center sacral vertical line (CSVL, the vertical line that bisects the proximal sacrum) was first drawn, and the translation (deviation from the CSVL) of some key vertebrae was measured, such as the LIV, LIV+1 (the first vertebra below LIV), LIV+2 (the second vertebra below LIV), LIV+3 (the third vertebra below LIV), lumbar apical vertebra (AV), thoracic AV, and T1. Additionally, the Cobb angles of the major thoracic and lumbar curves were measured at different time points, and the correction rates were calculated. Furthermore, clinical photographs of the patients from the back were taken preoperatively and postoperatively. RESULTS: Of 278 AIS patients reviewed, 29 met the inclusion criteria. The continuous follow-up of our present study revealed an interesting phenomenon: postoperative spinal alignment remodeling. A hypothetical criterion was established to determine the onset of the phenomenon. By means of a series of analyses, the criterion was validated. The results of our present study showed that selective thoracic fusion tended to cause leftward spinal imbalance in these Lenke 1C AIS patients. Twenty of the 29 patients had leftward spinal imbalance immediately after surgery. Although some patients regained spinal balance through postoperative spinal alignment remodeling, 11 patients remained imbalanced at 2-year follow-up. CONCLUSIONS: Selective thoracic fusion is prone to cause leftward spinal imbalance in Lenke 1C scoliosis patients. Postoperative spinal alignment remodeling can facilitate recovery of spinal balance in some patients. Postoperative spinal imbalance in Lenke 1C scoliosis patients could be prevented by selecting stable vertebra or the vertebrae above as LIV, checking the balance condition during surgery, or considering ratio criteria when selecting candidates for selective thoracic fusion.

Sagittal spinal balance after lumbar spinal fusion: the impact of anterior column support results from a randomized clinical trial with an eight- to thirteen-year radiographic follow-up.

STUDY DESIGN: Randomized clinical trial. OBJECTIVE: To analyze the long-term clinical impact of anterior column support on sagittal balance after lumbar spinal fusion. SUMMARY OF BACKGROUND DATA: Several investigators have stressed the importance of maintaining sagittal balance in relation to spinal fusion to avoid lumbar 'flat back,' accelerated adjacent segment degeneration, pain, and inferior functional outcome. Only limited evidence exists on how sagittal alignment affects clinical outcome. Anterior lumbar interbody fusion combined with posterolateral fusion has been proved superior to posterolateral fusion alone regarding outcome and cost-effectiveness. No randomized controlled trial has been published analyzing the effect of anterior support on radiographic measurements of sagittal balance. METHODS: Between 1996 and 1999, 148 patients with severe chronic low back pain were randomly selected for posterolateral lumbar fusion plus anterior support (PLF + ALIF) or posterolateral lumbar fusion. A total of 92 patients participated. Sagittal balance parameters were examined on full lateral radiographs of the spine: pelvic incidence (PI), pelvic tilt (PT), sacral slope, thoracic kyphosis, lumbar lordosis, and positioning of C7 plumb line. The type of lumbar lordosis was evaluated and outcome assessed by Oswestry Disability Index (ODI). RESULTS: Follow-up rate was 74%. Sagittal balance parameters were similar between randomization groups. None of the parameters differed significantly between patients with an ODI from 0 to 40 and patients with ODI over 40. Balanced patients had a significantly superior outcome as measured by ODI (P < 0.05) compared with unbalanced patients. CONCLUSION: No difference in the investigated sagittal balance parameters was seen between patients treated with PLF + ALIF or posterolateral fusion alone. Lumbar lordosis and type of lordosis correlated with outcome but could not explain the superior outcome in the group with anterior support. Whether sagittal balance and anterior support during fusion provide a protective effect on adjacent motion segments remains unclear.

Adjacent segment degeneration after lumbar spinal fusion: the impact of anterior column support: a randomized clinical trial with an eight- to thirteen-year magnetic resonance imaging follow-up.

STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To analyze long-term adjacent segment degeneration (ASD) after lumbar fusion on magnetic resonance imaging and compare randomization groups with and without anterior column support. SUMMARY OF BACKGROUND DATA: ASD can be a long-term complication after fusion. The prevalence and the cause of ASD are not well documented, but ASD are one of the main arguments for introducing the use of motion-preserving techniques as an alternative to fusion. Anterior lumbar interbody fusion combined with posterolateral lumbar fusion (ALIF+PLF) has been proved superior to posterolateral fusion alone regarding outcome and cost-effectiveness. METHODS: Between 1996 and 1999, 148 patients with severe chronic low back pain were randomly selected for ALIF+PLF or for PLF alone. Ninety-five patients participated. ASD was examined on magnetic resonance imaging with regard to disc degeneration, disc herniation, stenosis, and endplate changes. Disc heights on radiographs taken at index surgery and at long-term follow-up were compared. Outcome was assessed by validated questionnaires. RESULTS: The follow-up rate was 76%. ASD was similar between randomization groups. In the total cohort, endplate changes were seen in 26% of the participants and correlated significantly with the presence of disc degeneration and disc herniation. Disc degeneration and dorsal disc herniation were the parameters registered most frequently and were significantly more pronounced at the first adjacent level than at the second and the third adjacent levels. Patients without disc height reduction over time were significantly younger than patients with disc height reduction. Disc degeneration and stenosis correlated significantly with outcome at the first adjacent level. CONCLUSION: The cause of the superior outcome in the group with anterior support is still unclear. Compared with the findings reported in the literature, the prevalence of ASD is likely to be in concordance with the expected changes in a nonoperated symptomatic population and therefore not accelerated by fusion.

Different mechanisms of spinal fusion using equine bone protein extract, rhBMP-2 and autograft during the process of anterior lumbar interbody fusion.

To elucidate the molecular mechanisms of spinal fusion with different graft materials during an anterior lumbar interbody fusion, we examined the gene-expression profiles after implantation of equine bone protein extract, rhBMP-2 and autograft using microarray technology and data analysis, including hierarchical clustering, self-organizing maps (SOM), KEGG pathway and Biological process GO analyses in a porcine model. The results suggest that equine bone protein extract exhibited a more similar expression pattern with autograft than that of rhBMP-2. rhBMP-2 recruits progenitor cells, proliferation and differentiation possibly by inducing various factors including PGHS-2, IFGBP-2, VEGF and chemokines and then leads to preferable membranous ossification and bone remodeling. Conversely, equine bone protein extract results in endochondral ossification via upregulation of cartilage-related genes. Ossification by inducing direct osteoblastic differentiation and obviating the cartilaginous intermediate phases may increase spinal fusion rate.

Flow perfusion culture of human mesenchymal stem cells on silicate-substituted tricalcium phosphate scaffolds.

Autologous bone grafts are currently the gold standard for treatment of large bone defects, but their availability is limited due to donor site morbidity. Different substitutes have been suggested to replace these grafts, and this study presents a bone tissue engineered alternative using silicate-substituted tricalcium phosphate (Si-TCP) scaffolds seeded with human bone marrow-derived mesenchymal stem cells (hMSC). The cells were seeded onto the scaffolds and cultured either statically or in a perfusion bioreactor for up to 21 days and assessed for osteogenic differentiation by alkaline phosphatase activity assays and by quantitative real-time RT-PCR on bone markers. During culture, cells from the flow cultured constructs demonstrated improved proliferation and osteogenic differentiation verified by a more pronounced expression of several bone markers, e.g. alkaline phosphatase, osteopontin, Runx2, bone sialoprotein II, and bone morphogenetic protein 2. Cells and matrix were distributed homogeneously throughout the entire scaffold in flow culture, whereas only a peripheral layer was obtained after static culture. A viable and homogenous ex vivo bone construct with superior osteogenic properties was produced in dynamic culture and may provide a replacement for autologous grafts.

Cost-effectiveness evaluation of an RCT in rehabilitation after lumbar spinal fusion: a low-cost, behavioural approach is cost-effective over individual exercise therapy.

Recently, Christensen et al. reported the clinical effects of a low-cost rehabilitation program equally efficient to a relatively intensive program of individual, physiotherapist-guided exercise therapy. Yet, the low-cost approach is not fully supported as an optimal strategy until a full-scale economic evaluation, including extra-hospital effects such as service utilization in the primary health care sector and return-to-work, is conducted. The objective of this study was to conduct such evaluation i.e. investigate the cost-effectiveness of (1) a low-cost rehabilitation regimen with a behavioural element and (2) a regimen of individual exercise therapy, both in comparison with usual practice, from a health economic, societal perspective. Study design was a cost-effectiveness evaluation of an RCT with a 2-year follow-up. Ninety patients having had posterolateral or circumferential fusion (indicated by chronic low back pain and localized pathology) were randomized 3 months after their spinal fusion. Validated pain- and disability index scales were applied at baseline and at 2 years postoperative. Costs were measured in a full-scale societal perspective. The probability of the behavioural approach being cost-effective was close to 1 given pain as the prioritized effect measure, and 0.8 to 0.6 (dependent on willingness to pay per effect unit) given disability as the prioritized effect measure. The probability of the exercise therapy approach being cost-effective was modest due to inferior effectiveness. Results proved robust to relevant sensitivity analysis although a differentiated cost-effectiveness ratio between males and females was suspected. In conclusion, a simple behavioural extension, of setting up group meetings for patients, to a regimen with a strict physiotherapeutic focus was found cost-effective, whereas the cost-effectiveness of increasing frequency and guidance of a traditional physiotherapeutic regimen was unlikely in present trial setting.

Circumferential fusion is dominant over posterolateral fusion in a long-term perspective: cost-utility evaluation of a randomized controlled trial in severe, chronic low back pain.

STUDY DESIGN: Cost-utility evaluation of a randomized, controlled trial with a 4- to 8-year follow-up. OBJECTIVE: To investigate the incremental cost per quality-adjusted-life-year (QALY) when comparing circumferential fusion to posterolateral fusion in a long-term, societal perspective. SUMMARY OF BACKGROUND DATA: The cost-effectiveness of circumferential fusion in a long-term perspective is uncertain but nonetheless highly relevant as the ISSLS prize winner 2006 in clinical studies reported the effect of circumferential fusion superior to the effect of posterolateral fusion. A recent trial found no significant difference between posterolateral and circumferential fusion reporting cost-effectiveness from a 2-year viewpoint. METHODS: A total of 146 patients were randomized to posterolateral or circumferential fusion and followed 4 to 8 years after surgery. The mean age of the cohort was 46 years (range, 20-65 years); 61% were females, 49% were smokers, 30% had primary diagnosis of isthmic spondylolisthesis, 35% had disc degeneration and no previous surgery, and 35% had disc degeneration and previous surgery. Eighty-two percent of patients have had symptoms for more than 2 years and 50% were out of the labor market due to sickness. The EQ-5D instrument was applied for the measurement of health-related quality of life and costs (2004 U.S. dollars) were measured in a full-scale societal perspective. Productivity costs were valued by the Friction Cost method, and both costs and effects were discounted. Arithmetic means and 95% bias-corrected, bootstrapped confidence intervals were reported. Nonparametric statistics were used for tests of statistical significance. Comprehensive sensitivity analysis was conducted and reported using cost-effectiveness acceptability curves. RESULTS: The circumferential group demonstrated clinical superiority over the posterolateral fusion group in functional outcome (P < 0.01), fusion rate (P < 0.04), and number of reoperations (P < 0.01) among others. Cost-utility analysis demonstrated circumferential fusion dominant over posterolateral fusion, that is, for each QALY gained performing circumferential fusion, the incremental saving was estimated at U.S. $49,306 (95% confidence interval, $27,183-$2,735,712). Results proved to be strong to various sensitivity analyses; only a differentiated underestimation of patients' need for postoperative household help against the circumferential approach could alter the dominance; however, still the probability of cost-effectiveness was >0.85 given a threshold for willingness to pay of U.S. $50,000 per QALY. CONCLUSION: Circumferential fusion is dominant over instrumented posterolateral fusion, that is, both being significantly cheaper and significantly better in a long-term, societal perspective.

Determinants of cost-effectiveness in lumbar spinal fusion using the net benefit framework: a 2-year follow-up study among 695 patients.

Up to one third of patients undergoing lumbar spinal fusion show no improvement after the procedure and thus, despite evidence from RCTs, there might be a rationale for observational studies clarifying indications. Similarly, selection of the right patients for the right procedure could have significant impact on cost-effectiveness, which in some countries, in turn, affects whether procedures are to be available through the National Health Service. The aim of this study was to investigate determinants of cost-effectiveness in lumbar spinal fusion. An observational cohort study with 2-year follow-up was conducted: 695 patients who underwent lumbar spinal fusion from 1996 to 2002 were included and followed for 2 years. Patients had a localized segmental pathology and were diagnosed with MRI-verified isthmic spondylolisthesis (26%) or disc degeneration (74%). The surgical techniques were non-instrumented posterolateral fusion (14%), instrumented posterolateral fusion (54%), and circumferential fusion (32%). Societal costs and improvement in functional disability (Dallas Pain Questionnaire) were transformed into a net benefit measure. Classical linear regression of the net benefit was conducted using predictors of age, sex, diagnosis, duration of pain, smoking habits, occupational status, severity of disability, emotional distress, surgical technique, and number of levels fused. The main results were that two determinants were found to negatively influence net benefit: smoking and diagnosis, whereas two others were found to be positively associated with the net benefit: severe disability and emotional distress. In conclusion, predicting net benefit reverses the picture usually seen in studies predicting clinical outcomes, because the response variable is based on improvement over time rather than end-point measures alone. Smoking habits, diagnosis, pre-operative disability, and pre-operative emotional distress were found to be significantly associated with the net benefit of spinal fusion.

Circumferential fusion improves outcome in comparison with instrumented posterolateral fusion: long-term results of a randomized clinical trial.

STUDY DESIGN: Prospective randomized clinical study with a 5- to 9-year follow-up period. OBJECTIVE: The aim of the present study was to analyze the long-term outcome with respect to functional disability, pain, and general health of patients treated by means of circumferential lumbar fusion in comparison with those treated by means of instrumented posterolateral lumbar fusion. SUMMARY OF BACKGROUND DATA: Circumferential fusion has become a common procedure in lumbar spinal fusion both as a primary and salvage procedure. However, the claimed advantages of circumferential fusion over conventional posterolateral fusion lack scientific documentation. (The primary report with a 2-year follow-up has been published in Spine in 2002.) METHODS: From April 1996 to November 1999, a total of 148 patients (mean age, 45 years) with severe chronic low back pain were randomly selected for either posterolateral lumbar fusion (titanium Cotrel-Dubousset) or circumferential lumbar fusion (instrumented posterolateral fusion with anterior intervertebral support by a Brantigan cage). The primary outcome measure was the Dallas Pain Questionnaire (DPQ). The secondary outcome measures were the Oswestry Disability Index, the SF-36 instrument, and the Low Back Pain Rating Scale. All measures assessed the endpoint outcomes at 5 to 9 years after surgery. RESULTS: The available response rate was 93%. The circumferential group showed a significantly better improvement (P < 0.05) in comparison with the posterolateral group with respect to all four DPQ categories: daily activities, work/leisure, anxiety/depression, and social interest. The Oswestry Disability Index supported these results (P < 0.01). General health, as assessed by means of the SF-36, also showed significantly better physical health (P < 0.01) in the circumferential group, whereas no significant difference was found with respect to mental health compared with the posterolateral group. The circumferential group experienced significantly less back pain (P < 0.05) in comparison with the posterolateral group. In regard to leg pain, no significant difference was found. CONCLUSION: Circumferential lumbar fusion demands more extensive operative resources compared with posterolateral lumbar fusion. However, 5 to 9 years after surgery, the circumferentially fused patients had a significantly improved outcome compared with those treated by means of posterolateral fusion. These new results not only emphasize the superiority of circumferential fusion in the complex pathology of the lumbar spine but are also strongly supported in all of the validated questionnaires used in the study.

Optimizing viral and non-viral gene transfer methods for genetic modification of porcine mesenchymal stem cells.

INTRODUCTION: Mesenchymal stem cells (MSCs) provide an excellent source of pluripotent progenitor cells for tissue-engineering applications due to their proliferation capacity and differentiation potential. Genetic modification of MSCs with genes encoding tissue-specific growth factors and cytokines can induce and maintain lineage-specific differentiation. Due to anatomical and physiological similarities to humans, porcine research models have been proven valuable for the preclinical testing of tissue engineering protocols in large animals. The aim of this study was to evaluate optimized viral and non-viral ex vivo gene delivery systems with respect to gene transfer efficiency, maintenance of transgene expression, and safety issues using primary porcine MSCs as target cells. MATERIALS AND METHODS: MSCs were purified from bone marrow aspirates from the proximal tibiae of four 3-month-old Danish landrace pigs by Ficoll step gradient separation and polystyrene adherence technique. Vectors expressing enhanced green fluorescent protein (eGFP) and human bone morphogenetic protein-2 (BMP-2) were transferred to the cells by different non-viral methods and by use of recombinant adeno-associated virus (rAAV)-mediated and retroviral gene delivery. Each method for gene delivery was optimized. Gene transfer efficiency was compared on the basis of eGFP expression as assessed by fluorescence microscopy and fluorescence-activated flow cytometry. BMP-2 gene expression and osteogenic differentiation were evaluated by realtime quantitative RT-PCR and histochemical detection of alkaline phosphatase activity, respectively. RESULTS: Non-viral gene delivery methods resulted in transient eGFP expression by less than 2% of the cells. Using high titer rAAV-based vector up to 90% of the cells were transiently transduced. The efficiency of rAAV-mediated gene delivery was proportional to the rAAV vector titer applied. Retroviral gene delivery resulted in long-term transgene expression of porcine MSCs. A 26-fold increase in percentage of eGFP expressing cells (1.7%+/-0.2% versus 44.1% +/-5.0%, mean +/-SD) and a 68-fold increase in mean fluorescence intensity (327.4+/-56.6 versus 4.8+/-1.3) was observed by centrifugation of retroviral particles onto the target cell layer. Porcine MSCs that were BMP-2 transduced by optimized retroviral gene delivery demonstrated a significant increase in BMP-2 gene expression and showed increased osteogenic differentiation. Retrovirally transduced porcine MSCs were furthermore tested free of replication-competent viruses. DISCUSSION: The non-viral gene transfer methods applied were significantly less efficient compared to the viral methods tested. However, due to advantages with respect to safety issues and ease of handling, improvement of non-viral gene delivery to primary MSCs deserves further attention. The high efficiency of rAAV-mediated gene delivery observed at high titers can be explained by the ability of rAAV vector to transduce nondividing cells and by its tropism towards porcine MSCs. rAAV-mediated gene delivery resulted in transient transgene expression due to lack of stable AAV genome integration. MLV-mediated retroviral gene delivery can be considered a safe method for long-term transgene expression by porcine MSCs, and is therefore particularly attractive for advanced tissue engineering strategies requiring extended transgene expression.

Lumbar spinal fusion patients' demands to the primary health sector: evaluation of three rehabilitation protocols. A prospective randomized study.

Very few studies have investigated the effects or costs of rehabilitation regimens following lumbar spinal fusion. The effectiveness of in-hospital rehabilitation regimens has substantial impact on patients' demands in the primary health care sector. The aim of this study was to investigate patient-articulated demands to the primary health care sector following lumbar spinal fusion and three different in-hospital rehabilitation regimens in a prospective, randomized study with a 2-year follow-up. Ninety patients were randomized 3 months post lumbar spinal fusion to either a 'video' group (one-time oral instruction by a physiotherapist and patients were then issued a video for home exercise), or a 'café' group (video regimen with the addition of three café meetings with other fusion-operated patients) or a 'training' group (exercise therapy; physiotherapist-guided; two times a week for 8 weeks). Register data of service utilization in the primary health care sector were collected from the time of randomization through 24 months postsurgery. Costs of in-hospital protocols were estimated and the service utilization in the primary health care sector and its cost were analyzed. A significant difference (P=0.023) in number of contacts was found among groups at 2-year follow-up. Within the periods of 3-6 months and 7-12 months postoperatively, the experimental groups required less than half the amount of care within the primary health care sector as compared to the video group (P=0.001 and P=0.008). The incremental costs of the café regimen respectively, the training regimen were compensated by cost savings in the primary health care sector, at ratios of 4.70 (95% CI 4.64; 4.77) and 1.70 (95% CI 1.68; 1.72). This study concludes that a low-cost biopsychosocial rehabilitation regimen significantly reduces service utilization in the primary health care sector as compared to the usual regimen and a training exercise regimen. The results stress the importance of a cognitive element of coping in a rehabilitation program.

Importance of the back-café concept to rehabilitation after lumbar spinal fusion: a randomized clinical study with a 2-year follow-up.

STUDY DESIGN: A prospective, randomized, clinical study with a 2-year follow-up. OBJECTIVES: To analyze the effect of three different rehabilitation strategies for lumbar spinal fusion patients. SUMMARY OF BACKGROUND DATA: Fifteen percent to 40% of lumbar spinal fusion patients are not expected to improve significantly over a 2-year period. Optimization of present forms of rehabilitation could possibly further improve the outcome. MATERIALS AND METHODS: Between 1996 and 1999, 90 patients who had undergone lumbar spinal fusion were 3 months after surgery randomized to one of three different rehabilitation groups. Video group participants watched a video of exercises for training and were subsequently and only once provided instruction regarding their use. The back-café group was provided the same program as the video group, but as a supplement met with a back-café with other fusion-operated patients three times over an 8-week period. The training group was provided physical therapy training twice weekly for 8 weeks. Functional outcome was evaluated at 6, 12, and 24 months after surgery by use of the low back pain rating scale and a questionnaire covering daily functions, work status, and a patient's contact with the primary sector. RESULTS: By 2-year follow-up, the back-café and video groups had less pain compared with the training group (P < 0.03). The back-café group was better at performing daily functions such as carrying bags of market items (P < 0.01), getting up from a chair (P < 0.01), and ascending staircases (P < 0.01) compared with the video and training groups. More in the back-café group resumed working after surgery compared with the two other groups (P < 0.04). The video group had significantly more contacts with general practitioners, physical therapists, and so on compared with the back-café and training groups (P < 0.001). CONCLUSION: The patients in the back-café group were significantly better at accomplishing a succession of daily tasks compared with the video and training groups 2 years after lumbar spinal fusion. At the 2-year follow-up the training group had a significant pain problem compared with the video and back-café groups. The video group had significantly more treatment demands outside the hospital system. This study demonstrates the relevance of the inclusion of coping schemes and questions the role of intensive exercises in a rehabilitation program for spinal fusion patients.

Spinal blood flow in 24-hour megadose glucocorticoid treatment in awake pigs.

OBJECT: Because of the controversy regarding the benefits of 24-hour administration of methylprednisolone in patients with spinal cord injury (SCI), it is important to investigate its mechanism of action and side effects. This study was conducted to determine if high-dose methylprednisolone modulates neural and vertebral blood flow in an awake large-sized animal model without SCI. METHODS: From a group of 18 immature female domestic pigs born to nine different litters, nine animals were randomly allocated to receive methylprednisolone treatment, whereas their nine female siblings served as controls. Drug or placebo was applied in a blinded fashion by a third person not involved in the study. The following treatment for SCI, as suggested by the North American Spinal Cord Injury Study, was administered to the awake pig: methylprednisolone (30 mg/kg of body weight) was infused into the jugular vein during a 15-minute period, followed by a 45-minute pause, and the infusion was maintained over a 23-hour period at a dose of 5.4 mg/kg body weight/hour. By means of the radioactive tracer microsphere technique, spinal cord blood flow (SCBF) was measured in the awake standing pig in the cerebrum, and in spinal gray and white matter, nerve roots, endplates, cancellous bone, cortical shell, and T12-L2 discs. Blood flow was measured before, 1 hour after initiation of infusion, and 24 hours postinfusion. Examination of blood flow in the neural and vertebral tissue samples, as well as of central hemodynamics, revealed no significant difference between the experimental and control groups, and this parity was maintained throughout the experimental phases. CONCLUSIONS: In the awake pig model, 24-hour methylprednisolone treatment does not modulate cerebral or SCBF, nor does it increase the risk for vertebral osteonecrosis by producing vertebral ischemia.

Circumferential lumbar spinal fusion with Brantigan cage versus posterolateral fusion with titanium Cotrel-Dubousset instrumentation: a prospective, randomized clinical study of 146 patients.

STUDY DESIGN: A prospective randomized clinical study with a 2-year follow-up period was conducted. OBJECTIVE: To analyze the effects of circumferential fusion using ALIF radiolucent carbon fiber cages and titanium posterior instrumentation on functional outcome, fusion rate, complications, and lumbar lordosis. SUMMARY OF BACKGROUND DATA: Circumferential fusion has become a common procedure in lumbar spine fusion, both as a primary and salvage procedure. However, the claimed advantages of ALIF plus PLF over conventional PLF lack scientific documentation. METHODS: From April 1996 through November 1999, a total of 148 patients with severe chronic low back pain were randomly selected for either posterolateral lumbar fusion with titanium CD-Horizon (posterolateral group) or circumferential fusion with a ALIF Brantigan cage plus posterior instrumentation. The Dallas Pain Questionnaire (DPQ), the Low Back Pain Rating Scale (LBPR), and a questionnaire concerning work status assessed their outcomes. RESULTS: Both groups showed highly significant improvement in all four categories of life quality (DPQ) as well as in the back pain and leg pain index (LBPR), as compared with preoperative status. There was a clear tendency toward better overall functional outcome for patients with the circumferential procedure ( < 0.08), and this patient group also showed significantly less leg pain at the 1-year follow-up evaluation ( < 0.03) and less peak back pain at 2 years ( < 0.04). Sagittal lordosis was restored and maintained in the circumferential group ( < 0.01). The circumferential fusion patients showed a higher posterolateral fusion rate (92%) than the posterolateral group (80%)( < 0.04). The repeat operation rate including implant removal was significantly lower in the circumferential group (7%) ( < 0.009) than in the posterolateral group (22%). CONCLUSIONS: Circumferential lumbar fusion restored lordosis, provided a higher union rate with significantly fewer repeat operations, showed a tendency toward better functional outcome, and resulted in less peak back pain and leg pain than instrumented posterolateral fusion. The clinical perspective of the current study implies a recommendation to favor circumferential fusion as a definitive surgical procedure in complex lumbar pathology involving major instability, flatback, and previous disc surgery in younger patients, as compared with posterolateral fusion with pedicle screws alone.