Decompression with or without Fusion in Degenerative Lumbar Spondylolisthesis.

BACKGROUND: In patients with lumbar spinal stenosis and degenerative spondylolisthesis, it is uncertain whether decompression surgery alone is noninferior to decompression with instrumented fusion. METHODS: We conducted an open-label, multicenter, noninferiority trial involving patients with symptomatic lumbar stenosis that had not responded to conservative management and who had single-level spondylolisthesis of 3 mm or more. Patients were randomly assigned in a 1:1 ratio to undergo decompression surgery (decompression-alone group) or decompression surgery with instrumented fusion (fusion group). The primary outcome was a reduction of at least 30% in the score on the Oswestry Disability Index (ODI; range, 0 to 100, with higher scores indicating more impairment) during the 2 years after surgery, with a noninferiority margin of -15 percentage points. Secondary outcomes included the mean change in the ODI score as well as scores on the Zurich Claudication Questionnaire, leg and back pain, the duration of surgery and length of hospital stay, and reoperation within 2 years. RESULTS: The mean age of patients was approximately 66 years. Approximately 75% of the patients had leg pain for more than a year, and more than 80% had back pain for more than a year. The mean change from baseline to 2 years in the ODI score was -20.6 in the decompression-alone group and -21.3 in the fusion group (mean difference, 0.7; 95% confidence interval [CI], -2.8 to 4.3). In the modified intention-to-treat analysis, 95 of 133 patients (71.4%) in the decompression-alone group and 94 of 129 patients (72.9%) in the fusion group had a reduction of at least 30% in the ODI score (difference, -1.4 percentage points; 95% CI, -12.2 to 9.4), showing the noninferiority of decompression alone. In the per-protocol analysis, 80 of 106 patients (75.5%) and 83 of 110 patients (75.5%), respectively, had a reduction of at least 30% in the ODI score (difference, 0.0 percentage points; 95% CI, -11.4 to 11.4), showing noninferiority. The results for the secondary outcomes were generally in the same direction as those for the primary outcome. Successful fusion was achieved with certainty in 86 of 100 patients (86.0%) who had imaging available at 2 years. Reoperation was performed in 15 of 120 patients (12.5%) in the decompression-alone group and in 11 of 121 patients (9.1%) in the fusion group. CONCLUSIONS: In this trial involving patients who underwent surgery for degenerative lumbar spondylolisthesis, most of whom had symptoms for more than a year, decompression alone was noninferior to decompression with instrumented fusion over a period of 2 years. Reoperation occurred somewhat more often in the decompression-alone group than in the fusion group. (NORDSTEN-DS ClinicalTrials.gov number, NCT02051374.).

Dural Sac Cross-sectional area change from preoperatively and up to 2 years after decompressive surgery for central lumbar spinal stenosis: investigation of operated levels, data from the NORDSTEN study.

PURPOSE: The aim of the present study was to investigate how canal area size changed from before surgery and up to 2 years after decompressive lumbar surgery lumbar spinal stenosis. Further, to investigate if an area change postoperatively (between 3 months to 2 years) was associated with any preoperative demographic, clinical or MRI variables or surgical method used. METHODS: The present study is analysis of data from the NORDSTEN- SST trial where 437 patients were randomized to one of three mini-invasive surgical methods for lumbar spinal stenosis. The patients underwent MRI examination of the lumbar spine before surgery, and 3 and 24 months after surgery. For all operated segments the dural sac cross-sectional area (DSCA) was measured in mm2. Baseline factors collected included age, gender, BMI and smoking habits. Furthermore, surgical method, index level, number of levels operated, all levels operated on and baseline Schizas grade were also included in the analysis. RESULTS: 437 patients were enrolled in the NORDSTEN-SST trial, whereof 310 (71%) had MRI at 3 months and 2 years. Mean DSCA at index level was 52.0 mm2 (SD 21.2) at baseline, at 3 months it increased to 117.2 mm2 (SD 43.0) and after 2 years the area was 127.7 mm2 (SD 52.5). Surgical method, level operated on or Schizas did not influence change in DSCA from 3 to 24 months follow-up. CONCLUSION: The spinal canal area after lumbar decompressive surgery for lumbar spinal stenosis increased from baseline to 3 months after surgery and remained thereafter unchanged 2 years postoperatively.

The association between lumbar lordosis preoperatively and changes in PROMs for lumbar spinal stenosis patients 2 years after spinal surgery: radiological and clinical results from the NORDSTEN-spinal stenosis trial.

BACKGROUND: Patients with lumbar spinal stenosis (LSS) sometimes have lower lumbar lordosis (LL), and the incidence of LSS correlates closely with the loss of LL. The few studies that have evaluated the association between LL and clinical outcomes after non-instrumented surgery for LSS show conflicting results. This study investigates the association between preoperative LL and changes in PROMs 2 years after decompressive surgery. METHOD: This prospective cohort study obtained preoperative and postoperative data for 401 patients from the multicenter randomized controlled spinal stenosis trial as part of the NORwegian degenerative spondylolisthesis and spinal STENosis (NORDSTEN) study. Before surgery, the radiological sagittal alignment parameter LL was measured using standing X-rays. The association between LL and 2-year postoperative changes was analyzed using the oswestry disability index (ODI), a numeric rating scale (NRS) for low back and leg pain, the Zurich claudication questionnaire (ZCQ), and the global perceived effect (GPE) score. The changes in PROMs 2 years after surgery for quintiles of lumbar lordosis were adjusted for the respective baseline PROMs: age, sex, smoking, and BMI. The Schizas index and the Pfirrmann index were used to analyze multiple regressions for changes in PROMs. RESULTS: There were no associations in the adjusted and unadjusted analyses between preoperative LL and changes in ODI, ZCQ, GPE, and NRS for back and leg pain 2 years after surgery. CONCLUSION: LL before surgery was not associated with changes in PROMs 2 years after surgery. Lumbar lordosis should not be a factor when considering decompressive surgery for LSS.

Preoperative fatty infiltration of paraspinal muscles assessed by MRI is associated with less improvement of leg pain 2 years after surgery for lumbar spinal stenosis.

PURPOSE: Fatty infiltration (FI) of the paraspinal muscles may associate with pain and surgical complications in patients with lumbar spinal stenosis (LSS). We evaluated the prognostic influence of MRI-assessed paraspinal muscles' FI on pain or disability 2 years after surgery for LSS. METHODS: A muscle fat index (MFI) was calculated (by dividing signal intensity of psoas to multifidus and erector spinae) on preoperative axial T2-weighted MRI of patients with LSS. Pain and disability 2 years after surgery were assessed using the Oswestry disability index, the Zurich claudication questionnaire and numeric rating scales for leg and back pain. Multivariate linear and logistic regression analyses (adjusted for preoperative outcome scores, age, body mass index, sex, smoking status, grade of spinal stenosis, disc degeneration and facet joint osteoarthritis) were used to assess the associations between MFI and patient-reported clinical outcomes. In the logistic regression models, odds ratios (OR) and 95% confidence intervals (CI) were calculated for associations between the MFI and ≥ 30% improvement of the outcomes (dichotomised into yes/no). RESULTS: A total of 243 patients were evaluated (mean age 66.6 ± 8.5 years), 49% females (119). Preoperative MFI and postoperative leg pain were significantly associated, both with leg pain as continuous (coefficient - 3.20, 95% CI - 5.61, - 0.80) and dichotomised (OR 1.51, 95% CI 1.17, 1.95) scores. Associations between the MFI and the other outcome measures were not statistically significant. CONCLUSION: Preoperative FI of the paraspinal muscles on MRI showed statistically significant association with postoperative NRS leg pain but not with ODI or ZCQ.

Responsiveness of the Oswestry Disability Index and Zurich Claudication Questionnaire in patients with lumbar spinal stenosis: evaluation of surgically treated patients from the NORDSTEN study.

PURPOSE: To evaluate the responsiveness of the original low back pain specific Oswestry Disability Index (ODI) and the spinal stenosis specific Zürich Claudication Questionnaire (ZCQ), and to investigate cut-off values for clinical "success" for ODI and ZCQ in surgically treated patients with lumbar spinal stenosis (LSS). METHODS: We included 601 LSS patients (218 with, 383 without degenerative spondylolisthesis) from the NORDSTEN trials. Outcome measures included ODI and ZCQ (symptom severity and physical function scales) with three alternative response parameters: scores at follow-up, absolute and relative changes from baseline to two-year follow-up. Effect size and standardised response mean evaluated internal responsiveness. External responsiveness was assessed by the Spearman rank correlation between patient-reported global perceived effect scale (GPE) and ODI and ZCQ, and receiver operating characteristics (ROC). We evaluated which cut-off values could maximise the percentage of correctly classified patients according to the GPE-anchor "completely recovered" / "much improved" for each parameter. RESULTS: Internal and external responsiveness were high for all three indices with effect sizes, standardized response means, ROC and corresponding area under the curve > 0.8. Correlations with GPE responses were moderate (> 0.50) for absolute change and strong (> 0.67) for relative change and follow-up scores. The 30% ODI relative change cut-off correctly classified 81% of patients to "success", within a range of accurate cut-offs according to the GPE-anchor. CONCLUSION: ODI and ZCQ demonstrate comparable responsiveness in evaluating outcomes for surgically treated LSS patients. The 30% ODI threshold was consistent with treatment "success" in NORDSTEN trials. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02007083 10/12/2013, NCT02051374 31/01/2014 and NCT03562936 20/06/2018.

Glucoregulatory Properties of a Protein Hydrolysate from Atlantic Salmon (Salmo salar): Preliminary Characterization and Evaluation of DPP-IV Inhibition and Direct Glucose Uptake In Vitro.

Metabolic disorders are increasingly prevalent conditions that manifest pathophysiologically along a continuum. Among reported metabolic risk factors, elevated fasting serum glucose (FSG) levels have shown the most substantial increase in risk exposure. Ultimately leading to insulin resistance (IR), this condition is associated with notable deteriorations in the prognostic outlook for major diseases, including neurodegenerative diseases, cancer risk, and mortality related to cardiovascular disease. Tackling metabolic dysfunction, with a focus on prevention, is a critically important aspect for human health. In this study, an investigation into the potential antidiabetic properties of a salmon protein hydrolysate (SPH) was conducted, focusing on its potential dipeptidyl peptidase-IV (DPP-IV) inhibition and direct glucose uptake in vitro. Characterization of the SPH utilized a bioassay-guided fractionation approach to identify potent glucoregulatory peptide fractions. Low-molecular-weight (MW) fractions prepared by membrane filtration (MWCO = 3 kDa) showed significant DPP-IV inhibition (IC50 = 1.01 ± 0.12 mg/mL) and glucose uptake in vitro (p ≤ 0.0001 at 1 mg/mL). Further fractionation of the lowest MW fractions (<3 kDa) derived from the permeate resulted in three peptide subfractions. The subfraction with the lowest molecular weight demonstrated the most significant glucose uptake activity (p ≤ 0.0001), maintaining its potency even at a dilution of 1:500 (p ≤ 0.01).

Pharmacological evaluation of the effects of enzymatically liberated fish oil on eosinophilic inflammation in animal models.

The inappropriate activation of eosinophils is a well-recognized driver of various human inflammatory diseases including asthma, chronic rhinitis, and various gastrointestinal diseases, including eosinophilic esophagitis. Steroids, both topical and systemic, remain a cornerstone of treatment and can be highly effective. However, some individuals suffer side effects, unresolved symptoms, or both. OmeGo, an enzymatically liberated fish oil, has demonstrated anti-inflammatory and antioxidant properties as well the reduction of the activation, migration, and survival of eosinophils. Two animal models of eosinophilic inflammation were used to further assess OmeGo's profile. A house dust mite model of induced asthma showed a significant reduction in eosinophilic lung inflammation compared to the negative control, linoleic acid. The CRTH2 antagonist fevipiprant showed a similar eosinophilic inhibitory profile to OmeGo. In contrast, cod liver oil had no impact on any measure of inflammation. A guinea pig model of mild intraperitoneal eosinophilia showed a significant reduction in eosinophil activity by OmeGo, assessed by chemotaxis and chemokinesis. Apolipoprotein A-IV, an endogenous human protein with anti-inflammatory actions, showed a similar but numerically lower effect. OmeGo therefore combines a consistent antieosinophilic action with the known anti-inflammatory effects of polyunsaturated fatty acids. Proof-of-concept studies in asthma are warranted.

The Norwegian degenerative spondylolisthesis and spinal stenosis (NORDSTEN) study: study overview, organization structure and study population.

PURPOSE: To provide an overview of the The Norwegian Degenerative spondylolisthesis and spinal stenosis (NORDSTEN)-study and the organizational structure, and to evaluate the study population. METHODS: The NORDSTEN is a multicentre study with 10 year follow-up, conducted at 18 public hospitals. NORDSTEN includes three studies: (1) The randomized spinal stenosis trial comparing the impact of three different decompression techniques; (2) the randomized degenerative spondylolisthesis trial investigating whether decompression surgery alone is as good as decompression with instrumented fusion; (3) the observational cohort tracking the natural course of LSS in patients without planned surgical treatment. A range of clinical and radiological data are collected at defined time points. To administer, guide, monitor and assist the surgical units and the researchers involved, the NORDSTEN national project organization was established. Corresponding clinical data from the Norwegian Registry for Spine Surgery (NORspine) were used to assess if the randomized NORDSTEN-population at baseline was representative for LSS patients treated in routine surgical practice. RESULTS: A total of 988 LSS patients with or without spondylolistheses were included from 2014 to 2018. The clinical trials did not find any difference in the efficacy of the surgical methods evaluated. The NORDSTEN patients were similar to those being consecutively operated at the same hospitals and reported to the NORspine during the same time period. CONCLUSION: The NORDSTEN study provides opportunity to investigate clinical course of LSS with or without surgical interventions. The NORDSTEN-study population were similar to LSS patients treated in routine surgical practice, supporting the external validity of previously published results. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02007083 10/12/2013, NCT02051374 31/01/2014 and NCT03562936 20/06/2018.

The Salmon Oil OmeGo Reduces Viability of Colorectal Cancer Cells and Potentiates the Anti-Cancer Effect of 5-FU.

Colorectal cancer (CRC) is one of the most common cancer types worldwide. Chemotherapy is toxic to normal cells, and combinatory treatment with natural well-tolerated products is being explored. Some omega-3 polyunsaturated fatty acids (n-3 PUFAs) and marine fish oils have anti-cancer effects on CRC cells. The salmon oil OmeGo (Hofseth BioCare) contains a spectrum of fatty acids, including the n-3 PUFAs docosahexaenoic acid (DHA) and eicosahexaenoic acid (EPA). We explored a potential anti-cancer effect of OmeGo on the four CRC cell lines DLD-1, HCT-8, LS411N, and LS513, alone and in combination with the chemotherapeutic agent 5-Fluorouracil (5-FU). Screening indicated a time- and dose-dependent effect of OmeGo on the viability of the DLD-1 and LS513 CRC cell lines. Treatment with 5-FU and OmeGo (IC20-IC30) alone indicated a significant reduction in viability. A combinatory treatment with OmeGo and 5-FU resulted in a further reduction in viability in DLD-1 and LS513 cells. Treatment of CRC cells with DHA + EPA in a concentration corresponding to the content in OmeGo alone or combined with 5-FU significantly reduced viability of all four CRC cell lines tested. The lowest concentration of OmeGo reduced viability to a higher degree both alone and in combination with 5-FU compared to the corresponding concentrations of DHA + EPA in three of the cell lines. Results suggest that a combination of OmeGo and 5-FU could have a potential as an alternative anti-cancer therapy for patients with CRC.

Is the presence of foraminal stenosis associated with outcome in lumbar spinal stenosis patients treated with posterior microsurgical decompression.

BACKGROUND: We aim to investigate associations between preoperative radiological findings of lumbar foraminal stenosis with clinical outcomes after posterior microsurgical decompression in patients with predominantly central lumbar spinal stenosis (LSS). METHODS: The study was an additional analysis in the NORDSTEN Spinal Stenosis Trial. In total, 230 men and 207 women (mean age 66.8 (SD 8.3)) were included. All patients underwent an MRI including T1- and T2-weighted sequences. Grade of foraminal stenosis was dichotomized into none to moderate (0-1) and severe (2-3) category using Lee's classification system. The Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ), and numeric rating scale (NRS) for back and leg pain were collected at baseline and at 2-year follow-up. Primary outcome was a reduction of 30% or more on the ODI score. Secondary outcomes included the mean improvement on the ODI, ZCQ, and NRS scores. We performed multivariable regression analyses with the radiological variates foraminal stenosis, Pfirrmann grade, Schizas score, dural sac cross-sectional area, and the possible plausible confounders: patients' gender, age, smoking status, and BMI. RESULTS: The cohort of 437 patients presented a high degree of degenerative changes at baseline. Of 414 patients with adequate imaging of potential foraminal stenosis, 402 were labeled in the none to moderate category and 12 in the severe category. Of the patients with none to moderate foraminal stenosis, 71% achieved at least 30% improvement in ODI. Among the patients with severe foraminal stenosis, 36% achieved at least 30% improvement in ODI. A significant association between severe foraminal stenosis and less chance of reaching the target of 30% improvement in the ODI score after surgery was detected: OR 0.22 (95% CI 0.06, 0.83), p=0.03. When investigating outcome as continuous variables, a similar association between severe foraminal stenosis and less improved ODI with a mean difference of 9.28 points (95%CI 0.47, 18.09; p=0.04) was found. Significant association between severe foraminal stenosis and less improved NRS pain in the lumbar region was also detected with a mean difference of 1.89 (95% CI 0.30, 3.49; p=0.02). No significant association was suggested between severe foraminal stenosis and ZCQ or NRS leg pain. CONCLUSION: In patients operated with posterior microsurgical decompression for LSS, a preoperative severe lumbar foraminal stenosis was associated with higher proportion of patients with less than 30% improvement in ODI. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov (22.11.2013) under the identifier NCT02007083.

The association between preoperative MRI findings and clinical improvement in patients included in the NORDSTEN spinal stenosis trial.

PURPOSE: To investigate potential associations between preoperative MRI findings and patient reported outcome measures (PROMs) after surgery for lumbar spinal stenosis (LSS). METHODS: The NORDSTEN trial included 437 patients. We investigated the association between preoperative MRI findings such as morphological grade of stenosis (Schizas grade), quantitative grade of stenosis (dural sac cross-sectional area), disc degeneration (Pfirrmann score), facet joint tropism and fatty infiltration of the multifidus muscle, and improvement in patient reported outcome measures (PROMs) 2 years after surgery. We dichotomized each radiological parameter into a moderate or severe category. PROMs i.e., Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ) and Numeric rating scale (NRS) for back and leg pain were collected before surgery and at 2 year follow-up. In the primary analysis, we investigated the association between MRI findings and ODI score (dichotomized to ≥ 30% improvement or not). In the secondary analysis, we investigated the association between MRI findings and the mean improvement on the ODI-, ZCQ- and NRS scores. We used multivariable regression models adjusted for patients' gender, age, smoking status and BMI. RESULTS: The primary analysis showed that severe disc degeneration (Pfirrmann score 4-5) was significantly associated with less chance of achieving a 30% improvement on the ODI score (OR 0.54, 95% CI 0.34, 0.88). In the secondary analysis, we detected no clinical relevant associations. CONCLUSION: Severe disc degeneration preoperatively suggest lesser chance of achieving 30% improvement in ODI score after surgery for LSS. Other preoperative MRI findings were not associated with patient reported outcome.

Clinical and MRI findings in lumbar spinal stenosis: baseline data from the NORDSTEN study.

PURPOSE: The aim was to describe magnetic resonance imaging findings in patients planned for lumbar spinal stenosis surgery. Further, to describe possible associations between MRI findings and patient characteristics with patient reported disability or pain. METHODS: The NORDSTEN spinal stenosis trial included 437 patients planned for surgical decompression of LSS. The following MRI findings were evaluated before surgery: morphological (Schizas) and quantitative (cross-sectional area) grade of stenosis, disk degeneration (Pfirrmann), facet joint tropism and fatty infiltration of the multifidus muscle. Patients were dichotomized into a moderate or severe category for each radiological parameter classification. A multivariable linear regression analysis was performed to investigate the association between MRI findings and preoperative scores for Oswestry Disability Index, Zurich Claudication Questionnaire and Numeric rating scale for back and leg pain. The following patient characteristics were included in the analysis: gender, age, smoking and weight. RESULTS: The percentage of patients with severe scores was as follows: Schizas (C + D) 71.3%, cross-sectional area (< 75 mm2) 86.8%, Pfirrmann (4 + 5) 58.1%, tropism (≥ 15°) 11.9%, degeneration of multifidus muscle (2-4) 83.7%. Regression coefficients indicated minimal changes in severity of symptoms when comparing the groups with moderate and severe MRI findings. Only gender had a significant and clinically relevant association with ODI score. CONCLUSION: In this cross-sectional study, the majority of the patients had MRI findings classified as severe LSS changes, but the findings had no clinically relevant association with patient reported disability and pain at baseline. Patient characteristics have a larger impact on disability and pain than radiological findings. TRIAL REGISTRATION: www. CLINICALTRIALS: gov identifier: NCT02007083, registered December 2013.

Salmon Protein Hydrolysate Potentiates the Growth Inhibitory Effect of Bicalutamide on Human Prostate Cancer Cell Lines LNCaP and PC3 by Modulating Iron Homeostasis.

Prostate cancer is a common cause of cancer death in men. In advanced stages of prostate cancer, androgen deprivation therapy (ADT) is initiated. Despite ADT, prostate cancers invariably progress to become androgen independent. A growing body of evidence implicates iron dysmetabolism in prostate cancer progression. A bioactive peptide-rich salmon protein hydrolysate (SPH) has previously been demonstrated to modulate iron homeostatic mechanisms. In the present study, the anticancer effect of SPH and bicalutamide co-treatment on LNCaP and PC3 prostate cancer cell proliferation was investigated. Our results found that SPH potentiates the anti-proliferative effect of bicalutamide in a dose-dependent manner for both cell lines. In the presence of 160 µg/mL SPH, co-treatment with 1.0 µM bicalutamide decreased LNCaP cells' relative colony survival from 25% (1.0 µM bicalutamide monotreatment) to 2% after culturing for 12 days. For PC3 cells, the relative colony survival diminished from 52% (10.0 µM bicalutamide) to 32% at an SPH concentration of 160 µg/mL. Gene expression profiling, employing quantitative real-time PCR, revealed that the inhibitory effects were related to significant FTH1 up-regulation with a concomitant TFRC down-regulation. In conclusion, our results provide in vitro evidence that SPH potentiates the growth inhibitory effect of bicalutamide on prostate cancer cells by modulating iron homeostasis mechanisms.

Reliability of preoperative MRI findings in patients with lumbar spinal stenosis.

BACKGROUND: Magnetic Resonance Imaging (MRI) is an important tool in preoperative evaluation of patients with lumbar spinal stenosis (LSS). Reported reliability of various MRI findings in LSS varies from fair to excellent. There are inconsistencies in the evaluated parameters and the methodology of the studies. The purpose of this study was to evaluate the reliability of the preoperative MRI findings in patients with LSS between musculoskeletal radiologists and orthopaedic spine surgeons, using established evaluation methods and imaging data from a prospective trial. METHODS: Consecutive lumbar MRI examinations of candidates for surgical treatment of LSS from the Norwegian Spinal Stenosis and Degenerative Spondylolisthesis (NORDSTEN) study were independently evaluated by two musculoskeletal radiologists and two orthopaedic spine surgeons. The observers had a range of experience between six and 13 years and rated five categorical parameters (foraminal and central canal stenosis, facet joint osteoarthritis, redundant nerve roots and intraspinal synovial cysts) and one continuous parameter (dural sac cross-sectional area). All parameters were re-rated after 6 weeks by all the observers. Inter- and intraobserver agreement was assessed by Gwet's agreement coefficient (AC1) for categorical parameters and Intraclass Correlation Coefficient (ICC) for the dural sac cross-sectional area. RESULTS: MRI examinations of 102 patients (mean age 66 ± 8 years, 53 men) were evaluated. The overall interobserver agreement was substantial or almost perfect for all categorical parameters (AC1 range 0.67 to 0.98), except for facet joint osteoarthritis, where the agreement was moderate (AC1 0.39). For the dural sac cross-sectional area, the overall interobserver agreement was good or excellent (ICC range 0.86 to 0.96). The intraobserver agreement was substantial or almost perfect/ excellent for all parameters (AC1 range 0.63 to 1.0 and ICC range 0.93 to 1.0). CONCLUSIONS: There is high inter- and intraobserver agreement between radiologists and spine surgeons for preoperative MRI findings of LSS. However, the interobserver agreement is not optimal for evaluation of facet joint osteoarthritis. TRIAL REGISTRATION: www.ClinicalTrials.gov identifier: NCT02007083 , registered December 2013.

Comparable increases in dural sac area after three different posterior decompression techniques for lumbar spinal stenosis: radiological results from a randomized controlled trial in the NORDSTEN study.

PURPOSE: To investigate changes in dural sac area after three different posterior decompression techniques in patients undergoing surgery for lumbar spinal stenosis. Decompression of the nerve roots is the main surgical treatment for lumbar spinal stenosis. The aim of this study was to radiologically investigate three commonly used posterior decompression techniques. METHODS: The present study reports data from one of two multicenter randomized trials included in the NORDSTEN study. In the present trial, involving 437 patients undergoing surgery, we report radiological results after three different midline retaining posterior decompression techniques: unilateral laminotomy with crossover (UL) (n = 146), bilateral laminotomy (BL) (n = 142) and spinous process osteotomy (SPO) (n = 149). MRI was performed before and three months after surgery. The increase in dural sac area and Schizas grade at the most stenotic level was evaluated. Three different predefined surgical indicators of substantial decompression were used: (1) postoperative dural sac area of > 100 mm2, (2) increase in the dural sac area of at least 50% and (3) postoperative Schizas grade A or B. RESULTS: No differences between the three surgical groups were found in the mean increase in dural sac area. Mean values were 66.0 (SD 41.5) mm2 in the UL-group, 71.9 (SD 37.1) mm2 in the BL-group and 68.1 (SD 41.0) mm2 in the SPO-group (p = 0.49). No differences in the three predefined surgical outcomes between the three groups were found. CONCLUSION: For patients with lumbar spinal stenosis, the three different surgical techniques provided the same increase in dural sac area. CLINICAL TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov reference on November 22th 2013 under the identifier NCT02007083.

Clinical outcome after surgery for lumbar spinal stenosis in patients with insignificant lower extremity pain. A prospective cohort study from the Norwegian registry for spine surgery.

BACKGROUND: Spinal stenosis is a clinical diagnosis in which the main symptom is pain radiating to the lower extremities, or neurogenic claudication. Radiological spinal stenosis is commonly observed in the population and it is debated whether patients with no lower extremity pain should be labelled as having spinal stenosis. However, these patients is found in the Norwegian Registry for Spine Surgery, the main object of the present study was to compare the clinical outcomes after decompressive surgery in patients with insignificant lower extremity pain, with those with more severe pain. METHODS: This study is based on data from the Norwegian Registry for Spine Surgery (NORspine). Patients who had decompressive surgery in the period from 7/1-2007 to 11/3-2013 at 31 hospitals were included. The patients was divided into four groups based on preoperative Numeric Rating Scale (NRS)-score for lower extremity pain. Patients in group 1 had insignificant pain, group 2 had mild or moderate pain, group 3 severe pain and group 4 extremely severe pain. The primary outcome was change in the Oswestry Disability Index (ODI). Successfully treated patients were defined as patients reporting at least 30% reduction of baseline ODI, and the number of successfully treated patients in each group were recorded. RESULTS: In total, 3181 patients were eligible; 154 patients in group 1; 753 in group 2; 1766 in group 3; and 528 in group 4. Group 1 had significantly less improvement from baseline in all the clinical scores 12 months after surgery compared to the other groups. However, with a mean reduction of 8 ODI points and 56% of patients showing a reduction of at least 30% in their ODI score, the proportion of patients defined as successfully treated in group 1, was not significantly different from that of other groups. CONCLUSION: This national register study shows that patients with insignificant lower extremity pain had less improvement in primary and secondary outcome parameters from baseline to follow-up compared to patients with more severe lower extremity pain.

Decompression alone versus decompression with instrumental fusion the NORDSTEN degenerative spondylolisthesis trial (NORDSTEN-DS); study protocol for a randomized controlled trial.

BACKGROUND: Fusion in addition to decompression has become the standard treatment for lumbar spinal stenosis with degenerative spondylolisthesis (DS). The evidence for performing fusion among these patients is conflicting and there is a need for further investigation through studies of high quality. The present protocol describes an ongoing study with the primary aim of comparing the outcome between decompression alone and decompression with instrumented fusion. The secondary aim is to investigate whether predictors can be used to choose the best treatment for an individual. The trial, named the NORDSTEN-DS trial, is one of three studies in the Norwegian Degenerative Spinal Stenosis (NORDSTEN) study. METHODS: The NORDSTEN-DS trial is a block-randomized, controlled, multicenter, non-inferiority study with two parallel groups. The surgeons at the 15 participating hospitals decide whether a patient is eligible or not according to the inclusion and exclusion criteria. Participating patients are randomized to either a midline preserving decompression or a decompression followed by an instrumental fusion. Primary endpoint is the percentage of patients with an improvement in Oswestry Disability Index version 2.0 of more than 30% from baseline to 2-year follow-up. Secondary outcome measurements are the Zürich Claudication Questionnaire, Numeric Rating Scale for back and leg pain, Euroqol 5 dimensions questionnaire, Global perceived effect scale, complications and several radiological parameters. Analysis and interpretation of results will also be conducted after 5 and 10 years. CONCLUSION: The NORDSTEN/DS trial has the potential to provide Level 1 evidence of whether decompression alone should be advocated as the preferred method or not. Further on the study will investigate whether predictors exist and if they can be used to make the appropriate choice for surgical treatment for this patient group. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02051374 . First Posted: January 31, 2014. Last Update Posted: February 14, 2018.

Follow-up score, change score or percentage change score for determining clinical important outcome following surgery? An observational study from the Norwegian registry for Spine surgery evaluating patient reported outcome measures in lumbar spinal stenosis and lumbar degenerative spondylolisthesis.

BACKGROUND: Assessment of outcomes for spinal surgeries is challenging, and an ideal measurement that reflects all aspects of importance for the patients does not exist. Oswestry Disability Index (ODI), EuroQol (EQ-5D) and Numeric Rating Scales (NRS) for leg pain and for back pain are commonly used patients reported outcome measurements (PROMs). Reporting the proportion of individuals with an outcome of clinical importance is recommended. Knowledge of the ability of PROMs to identify clearly improved patients is essential. The purpose of this study was to search cut-off criteria for PROMs that best reflect an improvement considered by the patients to be of clinical importance. METHODS: The Global Perceived Effect scale was utilized to evaluate a clinically important outcome 12 months after surgery. The cut-offs for the PROMs that most accurately distinguish those who reported 'completely recovered' or 'much improved' from those who reported 'slightly improved', unchanged', 'slightly worse', 'much worse', or 'worse than ever' were estimated. For each PROM, we evaluated three candidate response parameters: the (raw) follow-up score, the (numerical) change score, and the percentage change score. RESULTS: We analysed 3859 patients with Lumbar Spinal Stenosis [(LSS); mean age 66; female gender 50%] and 617 patients with Lumbar Degenerative Spondylolisthesis [(LDS); mean age 67; 72% female gender]. The accuracy of identifying 'completely recovered' and 'much better' patients was generally high, but lower for EQ-5D than for the other PROMs. For all PROMs the accuracy was lower for the change score than for the follow-up score and the percentage change score, especially among patients with low and high PROM scores at baseline. The optimal threshold for a clinically important outcome was ≤24 for ODI, ≥0.69 for EQ-5D, ≤3 for NRS leg pain, and ≤ 4 for NRS back pain, and, for the percentage change score, ≥30% for ODI, ≥40% for NRS leg pain, and ≥ 33% for NRS back pain. The estimated cut-offs were similar for LSS and for LDS. CONCLUSION: For estimating a 'success' rate assessed by a PROM, we recommend using the follow-up score or the percentage change score. These scores reflected a clinically important outcome better than the change score.

Does surgical technique influence clinical outcome after lumbar spinal stenosis decompression? A comparative effectiveness study from the Norwegian Registry for Spine Surgery.

INTRODUCTION: The aim of this study was to compare the clinical outcome of spinal process osteotomy with two other midline-retaining methods, bilateral laminotomy and unilateral laminotomy with crossover, among patients undergoing surgery for lumbar spinal stenosis. METHODS: This cohort study was based on data from the Norwegian Registry for Spine Surgery (NORspine). Patients were operated on between 2009 and 2013 at 31 Norwegian hospitals. The patients completed questionnaires at admission for surgery, and after 3 and 12 months. The Oswestry Disability Index (ODI) was the primary outcome. Secondary outcomes were duration of surgery and hospital stay, Numeric Rating Scale (NRS) for back pain and leg pain, and EQ-5D and EQ-VAS. The patients were classified into one of three treatment groups according to the surgery they had received, and a propensity score was utilized to minimize bias. The three treatment groups were divided into subgroups based on Propensity Scores, and the statistical analyses were performed with and within the Propensity Score stratified subgroups. RESULTS: 103 patients had spinal process osteotomy, 966 patients had bilateral laminotomy, and 462 patients had unilateral laminotomy with crossover. Baseline clinical scores were similar in the three groups. There were no differences in improvement after 3 and 12 months between treatment groups. At 12 months, mean ODI improvement was 15.2 (SD 16.7) after spinous process osteotomy, 16.9 (SD 17.0) after bilateral laminotomy, and 16.7 (SD 16.9) after unilateral laminotomy with crossover. There were no differences in the secondary clinical outcomes or complication rates. Mean duration of surgery was greatest for spinal process osteotomy (p < 0.05). Length of stay was 2.1 days (SD 2.1) in the bilateral laminotomy group, 3.5 (SD 2.4) days for unilateral laminotomy, and 6.9 days (SD 4.1) for spinous process osteotomy group (p < 0.05). CONCLUSION: In a propensity scored matched cohort, there were no differences in the clinical outcome 12 months after surgery for lumbar spinal stenosis performed using the three different posterior decompression techniques. Bilateral laminotomy had shortest duration of surgery and shortest length of hospital stay. Surgical technique does not seem to affect clinical outcome after three different midline-retaining posterior decompression techniques.

The effectiveness of decompression alone compared with additional fusion for lumbar spinal stenosis with degenerative spondylolisthesis: a pragmatic comparative non-inferiority observational study from the Norwegian Registry for Spine Surgery.

PURPOSE: To evaluate the effect of adding fusion to decompression in patients operated for lumbar spinal stenosis with a concomitant lumbar degenerative spondylolisthesis. METHODS: After propensity score matching, 260 patients operated with decompression and fusion and 260 patients operated with decompression alone were compared. Primary outcome measures were leg and back pain [Numeric Rating Scale (NRS), 0-10] and Oswestry Disability Index (ODI, 0-100) at 12 months. RESULTS: At 12-month follow-up, the fusion group rated their pain significantly lower than the decompression alone group [leg pain 3.0 and 3.6, respectively, mean difference -0.6, 95 % confidence interval (CI) -1.2 to -0.05, p = 0.03 and back pain 3.3 and 3.9, respectively, mean difference -0.6, 95 % CI -1.1 to -0.1, p = 0.02]. ODI was not significantly different between the groups (21.0 versus 23.3, mean difference -2.3, 95 % CI -5.8 to 1.1, p = 0.18). Seventy-four percent of the fusion group and 63 % of the decompression alone group achieved a clinically important improvement in back pain (difference in proportion of responders = 11 %, 95 % CI 2-20 %, p = 0.01), corresponding to a number needed to treat of 9 patients (95 % CI 5-50). There was no significant difference in responder rate for leg pain (74 and 67 %, respectively, difference 7 %, 95 % CI -1 to 16 %, p = 0.09) or for ODI (67 and 59 %, respectively, difference 8 %, 95 % CI 0-18 %, p = 0.06). The duration of surgery and hospital stay was longer for the fusion group (mean difference 68 min, 95 % CI 58-78, p < 0.01 and mean difference 4.2 days, 95 % CI 3.5-4.8, p < 0.01). CONCLUSION: In the present non-inferiority study, we cannot conclude that decompression alone is as good as decompression with additional fusion. However, the small differences in the groups' effect sizes suggest that a considerable number of patients can be treated with decompression alone. A challenge in future studies will be to find the best treatment option for each patient.