Change in Lumbar Lordosis after Decompressive Surgery in Lumbar Spinal Stenosis Patients and Associations with Patient Related Outcomes 2 Years after Surgery. Radiological and Clinical Results from the NORDSTEN Spinal Stenosis Trial.

STUDY DESIGN: A prospective cohort study. OBJECTIVE: The aim was to investigate changes in lumbar lordosis (LL) and its association to changes in patient reported outcome measures (PROMs) after decompressive surgery for lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND: Few studies have addressed change in LL after decompression surgery for LSS in relation to outcomes. METHOD: Pre- and postoperative data from 310 patients having standing x-ray both before and 2 years after surgery were included. The patients were grouped based on the change in LL preoperatively to 2 years after surgery; group 1: <5 degrees (n=196), group 2: ≥5 <10 degrees (n=55) or group 3: ≥10 degrees (n=59) of change in LL. The changes in function, disability and pain were assessed by the Oswestry Disability Index (ODI), Numeric Rating Scale (NRS), and the Zurich claudication questionnaire (ZCQ). The three groups were compared regarding baseline variables using the ANOVA test for continuous variables and the chi-square test for categorical variables. The groups were further compared with a likelihood ratio test in relation to changes in PROMs 2 year after surgery and outcomes were adjusted for respective baseline PROMs, age, sex, smoking, BMI, Schizas and Pfirrmann scores. RESULTS: LL was significantly changed at group level 2 years after surgery with a mean difference of 2.2 (SD 9.4) degrees ( P =0.001). The three LL change groups did not show any significant differences in patient characteristics, function, disability, and pain at baseline. The two groups with a change of more than 5 degrees in LL 2 year after surgery (group 2 and 3) had significantly greater improvements in ODI ( P =0.022) and ZCQ function ( P =0.016) in the adjusted analyses, but was not significant for back and leg pain. CONCLUSION: Changed LL after decompressive surgery for LSS was associated with improved ODI and physical function.

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).

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.

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.

The Influence of Spinous Process Union on Clinical Outcomes After Spinous Process Osteotomy for Lumbar Spinal Stenosis After 2 Years: A Secondary Analysis From the NORDSTEN-Study.

BACKGROUND: Lumbar spinal stenosis is a prevalent and increasingly important cause of low back pain, leg pain, and walking impairment. Minimally invasive decompressive techniques such as spinous process (SP) osteotomy have become more common in recent years. The main aim of this study was to investigate the proportion of complete SP union and whether complete radiological healing after the osteotomy is associated with superior clinical outcome after 2 years. METHODS: In this retrospective cohort study, 149 patients were included from the Spinal Stenosis Trial, a part of the NORwegian Degenerative spondylolisthesis and spinal STENosis study. Computed tomography imaging was performed 2 years postoperatively. The number of osteotomies and the number of SP unions were recorded. Patients were divided into groups based on the degree of union: nonunion, partial union, and complete union. Rate of success (>30% improvement in Oswestry Disability Index [ODI]) and mean change in ODI were the primary outcome measures. We compared the differences between baseline and follow-up between the Degree of Union groups. RESULTS: The study included 102 of 149 eligible patients. Ten patients (9.8%) were classified as having nonunion, 15 (14.7%) as having partial union, and 77 (75.5%) as having complete union. Of the 155 osteotomies, there were 122 classified as union (77%). The success rate was 74%, with no influence of SP union. The mean change in the ODI was -20.1 (95% CI -37.0, 14.2) with no influence of SP union. CONCLUSIONS: We found no influence of SP union, classified by computed tomography, on clinical outcome 2 years after SP osteotomy in patients with lumbar spinal stenosis. CLINICAL RELEVANCE: Supplying useful information about SPO to assist surgeons in the choice of decompressive technique.

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.

Do patients with lumbar spinal stenosis benefit from decompression of levels with adjacent moderate stenosis? A prospective cohort study from the NORDSTEN study.

BACKGROUND: Lumbar spinal stenosis (LSS) is characterized by pain that radiates to the buttocks and/or legs, aggravated by walking and relieved by forward flexion. There is poor correlation between clinical symptoms and severity of stenosis on MRI, and multilevel stenosis has not been described to present worse symptoms or treatment outcomes, compared with patients with single-level stenosis. In patients with one level with severe stenosis combined with an adjacent level with moderate stenosis, the surgeon must decide whether to decompress only the narrowest level or both, to achieve the best possible outcome. The potential benefits of performing surgery on an adjacent moderate stenosis is debated, and the scientific evidence in scarce. PURPOSE: The aim of the present study was to investigate whether patients with a level of adjacent moderate stenosis, along with an index stenosis, benefitted from a dual-level decompression (DLD) compared with a single-level decompression (SLD). Furthermore, to investigate whether DLD patients had longer duration of surgery and hospital stay, higher rates of complications and/or lower rate of reoperations compared with SLD patients. STUDY DESIGN: Prospective cohort study. PATIENT SAMPLE: We analyzed data from the Norwegian Degenerative Spondylisthesis and Spinal Stenosis study- Spinal Stenosis Trial (NORDSTEN-SST). In this randomized multicenter study, 437 patients were included, evaluating clinical outcomes of three different surgical treatment options for LSS. Patients with degenerative spondylolisthesis were excluded. METHOD: Based on preoperative MRI, the present analysis included all patients who had a moderate stenosis (defined as Schizas B or C) in addition to a predefined index stenosis (the level with the smallest cross-sectional area). We compared patients who, based on the surgeons` choice, received a dual-level decompression, with those receiving a single-level decompression. OUTCOME MEASURES: The primary outcome was mean change in the Oswestry Disability Index (ODI) score from baseline to 2-year follow up. Secondary outcomes were proportion of success (30% reduction in ODI score), the Numeric Rating Scales for back and leg pain (NRS), the EuroQol 5-dimensional questionnaire utility index (EQ-5D), the Zurich Claudication Questionnaire (ZCQ), the Global Perceived Effect (GPE)-scale, duration of surgery, duration of hospital stay, perioperative complications and reoperation rates. RESULTS: Among the 222 patients, included in the analysis, 108 underwent DLD and 114 underwent SLD. There was no difference in change scores for any of the investigated patient-reported outcomes between the groups after 2 years. However, the DLD group had longer duration of surgery and longer length of hospital stay. There was no difference in reoperation rates or perioperative complications. CONCLUSION: This study, alongside the NORDSTEN-LSS trial on patients with adjacent moderate stenosis as well as an index stenosis, showed no superior clinical effectiveness for dual-level surgery compared with single-level surgery.

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.

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.

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.

Surgery in degenerative spondylolisthesis: does fusion improve outcome in subgroups? A secondary analysis from a randomized trial (NORDSTEN trial).

BACKGROUND CONTEXT: Patients with spinal stenosis and degenerative spondylolisthesis are treated surgically with decompression alone or decompression with fusion. However, there is debate regarding which subgroups of patients may benefit from additional fusion. PURPOSE: To investigate possible treatment effect modifiers and prognostic variables among patients operated for spinal stenosis and degenerative spondylolisthesis. DESIGN: A secondary exploratory study using data from the Norwegian Degenerative Spondylolisthesis and Spinal Stenosis (NORDSTEN-DS) trial. Patients were randomized to decompression alone or decompression with instrumented fusion. PATIENT SAMPLE: The sample in this study consists of 267 patients from a randomized multicenter trial involving 16 hospitals in Norway. Patients were enrolled from February 12, 2014, to December 18, 2017. The study did not include patients with degenerative scoliosis, severe foraminal stenosis, multilevel spondylolisthesis, or previous surgery. OUTCOME MEASURES: The primary outcome was an improvement of ≥ 30% on the Oswestry Disability Index score (ODI) from baseline to 2-year follow-up. METHODS: When investigating possible variables that could modify the treatment effect, we analyzed the treatment arms separately. When testing for prognostic factors we analyzed the whole cohort (both treatment groups). We used univariate and multiple regression analyses. The selection of variables was done a priori, according to the published trial protocol. RESULTS: Of the 267 patients included in the trial (183 female [67%]; mean [SD] age, 66 [7.6] years), complete baseline data for the variables required for the present analysis were available for 205 of the 267 individuals. We did not find any clinical or radiological variables at baseline that modified the treatment effect. Thus, none of the commonly used criteria for selecting patients for fusion surgery influenced the chosen primary outcome in the two treatment arms. For the whole cohort, less comorbidity (American Society of Anesthesiologists Classification [ASA], OR = 4.35; 95% confidence interval (CI [1.16-16.67]) and more preoperative leg pain (OR = 1.23; CI [1.02-1.50]) were significantly associated with an improved primary outcome. CONCLUSIONS: In this study on patients with degenerative spondylolisthesis, neither previously defined instability criteria nor other pre-specified baseline variables were associated with better clinical outcome if fusion surgery was performed. None of the analyzed variables can be applied to guide the decision for fusion surgery in patients with degenerative spondylolisthesis. For both treatment groups, less comorbidity and more leg pain were associated with improved outcome 2 years after surgery. TRIAL REGISTRATION: NORDSTEN-DS ClinicalTrials.gov, NCT02051374.

Is Repeated Preoperative Magnetic Resonance Imaging Necessary Before Planned Decompressive Surgery for Lumbar Spinal Stenosis?

BACKGROUND: Currently, there are different routines in Norwegian hospitals regarding how recent magnetic resonance imaging (MRI) of the lumbar spine should be performed before surgery. Patients with lumbar spinal stenosis from the Norwegian degenerative spondylolisthesis and spinal stenosis study, who had 2 preoperative MRIs performed within the year before surgery, were included. The aim of the present study was to evaluate the utility of repeated preoperative MRI for patients undergoing decompressive spine surgery for degenerative spinal stenosis. METHODS: For all included patients, the changes between the 2 preoperative MRIs were investigated for disc degeneration (Pfirrmann's classification), foraminal stenosis (Lee's classification), spondylolisthesis, and central canal stenosis (Schizas score and dural sac cross-sectional area). RESULTS: A total of 65 patients (78 levels) were included. Thirty-seven patients were women, and the mean age was 67 (range 48-79) years. Schizas score showed a clinically meaningful change of ±2 or 3 grades in 5 levels, and dural sac cross- sectional area was reduced in 47 levels with a mean change of -2.3 mm2. Three levels had a clinically relevant change in grade of foraminal stenosis of ±2. For disc degeneration, 53 of the levels had no change, and the rest of the levels had a change of ±1 grade. Increased spondylolisthesis was measured at 21 levels, and the mean slip was <2 mm. Also, 4 levels had >2 mm slip. CONCLUSION: For patients undergoing surgery for lumbar spinal stenosis, repeated MRI within the year before planned surgery showed few significant changes in common radiological parameters. The benefit for the surgeon of repeat MRI is therefore limited.

Postoperative Dural Sac Cross-Sectional Area as an Association for Outcome After Surgery for Lumbar Spinal Stenosis: Clinical and Radiological Results From the NORDSTEN-Spinal Stenosis Trial.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: The aim was to investigate the association between postoperative dural sac cross-sectional area (DSCA) after decompressive surgery for lumbar spinal stenosis and clinical outcome. Furthermore, to investigate if there is a minimum threshold for how extensive a posterior decompression needs to be to achieve a satisfactory clinical result. SUMMARY OF BACKGROUND DATA: There is limited scientific evidence for how extensive lumbar decompression needs to be to obtain a good clinical outcome in patients with symptomatic lumbar spinal stenosis. MATERIALS AND METHODS: All patients were included in the Spinal Stenosis Trial of the NORwegian Degenerative spondylolisthesis and spinal STENosis (NORDSTEN)-study. The patients underwent decompression according to three different methods. DSCA measured on lumbar magnetic resonance imaging at baseline and at three months follow-up, and patient-reported outcome at baseline and at two-year follow-up were registered in a total of 393 patients. Mean age was 68 (SD: 8.3), proportion of males were 204/393 (52%), proportion of smokers were 80/393 (20%), and mean body mass index was 27.8 (SD: 4.2).The cohort was divided into quintiles based on the achieved DSCA postoperatively, the numeric, and relative increase of DSCA, and the association between the increase in DSCA and clinical outcome were evaluated. RESULTS: At baseline, the mean DSCA in the whole cohort was 51.1 mm 2 (SD: 21.1). Postoperatively the area increased to a mean area of 120.6 mm 2 (SD: 46.9). The change in Oswestry disability index in the quintile with the largest DSCA was -22.0 (95% CI: -25.6 to -18), and in the quintile with the lowest DSCA the Oswestry disability index change was -18.9 (95% CI: -22.4 to -15.3). There were only minor differences in clinical improvement for patients in the different DSCA quintiles. CONCLUSION: Less aggressive decompression performed similarly to wider decompression across multiple different patient-reported outcome measures at two years following surgery.

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.

Assessing the Anti-Inflammatory Effects of an Orally Dosed Enzymatically Liberated Fish Oil in a House Dust Model of Allergic Asthma.

Eosinophils are a major driver of inflammation in a number of human diseases, including asthma. Biologic therapies targeting IL-5 have enabled better control of severe eosinophilic asthma, but no such advances have been made for enhancing the control of moderate asthma. However, a number of moderate asthma sufferers remain troubled by unresolved symptoms, treatment side effects, or both. OmeGo, an enzymatically liberated fish oil, has demonstrated antioxidant and anti-inflammatory properties including the reduction of eosinophilia. A house dust mite model of induced asthma in mice was utilized in this study, and OmeGo showed a significant reduction in eosinophilic lung and systemic inflammation and reduced lung remodelling compared to cod liver oil. The CRTH2 antagonist fevipiprant showed an anti-inflammatory profile similar to that of OmeGo. OmeGo has the potential to be a pragmatic, cost-effective co-treatment for less severe forms of eosinophilic asthma. Proof-of-concept studies are planned.

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.

A novel MRI index for paraspinal muscle fatty infiltration: reliability and relation to pain and disability in lumbar spinal stenosis: results from a multicentre study.

BACKGROUND: Fatty infiltration of the paraspinal muscles may play a role in pain and disability in lumbar spinal stenosis. We assessed the reliability and association with clinical symptoms of a method for assessing fatty infiltration, a simplified muscle fat index (MFI). METHODS: Preoperative axial T2-weighted magnetic resonance imaging (MRI) scans of 243 patients aged 66.6 ± 8.5 years (mean ± standard deviation), 119 females (49%), with symptomatic lumbar spinal stenosis were assessed. Fatty infiltration was assessed using both the MFI and the Goutallier classification system (GCS). The MFI was calculated as the signal intensity of the psoas muscle divided by that of the multifidus and erector spinae. Observer reliability was assessed in 102 consecutive patients for three independent investigators by intraclass correlation coefficient (ICC) and 95% limits of agreement (LoA) for continuous variables and Gwet's agreement coefficient (AC1) for categorical variables. Associations with patient-reported pain and disability were assessed using univariate and multivariate regression analyses. RESULTS: Interobserver reliability was good for the MFI (ICC 0.79) and fair for the GCS (AC1 0.33). Intraobserver reliability was good or excellent for the MFI (ICC range 0.86-0.91) and moderate to almost perfect for the GCS (AC1 range 0.55-0.92). Mean interobserver differences of MFI measurements ranged from -0.09 to -0.04 (LoA -0.32 to 0.18). Adjusted for potential confounders, none of the disability or pain parameters was significantly associated with MFI or GCS. CONCLUSION: The proposed MFI demonstrated high observer reliability but was not associated with preoperative pain or disability.

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.

Comparison of 3 Different Minimally Invasive Surgical Techniques for Lumbar Spinal Stenosis: A Randomized Clinical Trial.

Importance: Operations for lumbar spinal stenosis is the most often performed surgical procedure in the adult lumbar spine. This study reports the clinical outcome of the 3 most commonly used minimally invasive posterior decompression techniques. Objective: To compare the effectiveness of 3 minimally invasive posterior decompression techniques for lumbar spinal stenosis. Design, Setting, and Participants: This randomized clinical trial used a parallel group design and included patients with symptomatic and radiologically verified lumbar spinal stenosis without degenerative spondylolisthesis. Patients were enrolled between February 2014 and October 2018 at the orthopedic and neurosurgical departments of 16 Norwegian public hospitals. Statistical analysis was performed in the period from May to June 2021. Interventions: Patients were randomized to undergo 1 of the 3 minimally invasive posterior decompression techniques: unilateral laminotomy with crossover, bilateral laminotomy, and spinous process osteotomy. Main Outcomes and Measures: Primary outcome was change in disability measured with Oswestry Disability Index (ODI; range 0-100), presented as mean change from baseline to 2-year follow-up and proportions of patients classified as success (>30% reduction in ODI). Secondary outcomes were mean change in quality of life, disease-specific symptom severity measured with Zurich Claudication Questionnaire (ZCQ), back pain and leg pain on a 10-point numeric rating score (NRS), patient perceived benefit of the surgical procedure, duration of the surgical procedure, blood loss, perioperative complications, number of reoperations, and length of hospital stay. Results: In total, 437 patients were included with a median (IQR) age of 68 (62-73) years and 230 men (53%). Of the included patients, 146 were randomized to unilateral laminotomy with crossover, 142 to bilateral laminotomy, and 149 to spinous process osteotomy. The unilateral laminotomy with crossover group had a mean change of -17.9 ODI points (95% CI, -20.8 to -14.9), the bilateral laminotomy group had a mean change of -19.7 ODI points (95% CI, -22.7 to -16.8), and the spinous process osteotomy group had a mean change of -19.9 ODI points (95% CI, -22.8 to -17.0). There were no significant differences in primary or secondary outcomes among the 3 surgical procedures, except a longer duration of the surgical procedure in the bilateral laminotomy group. Conclusions and Relevance: No differences in clinical outcomes or complication rates were found among the 3 minimally invasive posterior decompression techniques used to treat patients with lumbar spinal stenosis. Trial Registration: ClinicalTrials.gov Identifier: NCT02007083.