"Visualization" of pain using cerebral 18F-FDG PET/CT following surgical treatment of lumbar disc herniation.

PURPOSE: We hypothesized that unilateral leg pain following surgical treatment of lumbar disc herniation (LDH) is associated with an increase in the glucose metabolism of the contralateral thalamus. METHODS: Patients scheduled for surgery due to LDH underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography less than two weeks prior to surgery. Their thalamic FDG uptake was measured and expressed as the mean and partial volume corrected mean standardized uptake values (SUVmean and cSUVmean). These measures were compared with patient-related outcome measures collected pre- and 1-year post-operatively: back and leg pain on a 0-100 VAS scale and health-related quality of life as measured by the EuroQol-5D (EQ-5D). RESULTS: Twenty-six patients (ten females) aged 49.7 ± 7.4 (mean ± SD) years were included. There was a significant correlation between painful body side and increased contralateral thalamic uptake of FDG, with regard to cSUVmean values. Correlation analyses including clinical parameters and cSUVmean indicated some association with 1-year change in EQ-5D. CONCLUSION: These preliminary data sustain the hypothesis that unilateral pain in patients with LDH is associated with increased glucose metabolism in the contralateral thalamus, suggesting a central role of thalamus in chronic pain perception.

Are Modic Changes Associated With Health-related Quality of Life After Discectomy: A Study on 620 Patients With Two-year Follow-up.

STUDY DESIGN: A registry-based comparative cohort study with 2-year follow-up. OBJECTIVE: To assess whether Modic changes (MCs) are associated with health-related quality of life, long-term physical disability, back- or leg pain after discectomy. SUMMARY OF BACKGROUND DATA: Previous studies have failed to show a clinically significant association between MCs and patient-reported outcomes (PROs) after discectomy. METHODS: Data from the Danish National Spine Registry on patients undergoing first-time lumbar discectomy at a single institution from 2014 to 2017 with an accessible preoperative lumbar magnetic resonance imaging, complete preoperative, and 2-year follow-up questionnaires were obtained. PROs including Oswestry disability index (ODI), European Quality of Life-Five Dimensions (EQ-5D), visual analogue scale (VAS) back and leg pain, and patient satisfaction were collected. Patients were stratified based on the presence (+MC) or absence (-MC) of MCs on the preoperative MRI. RESULTS: Of 620 patients included, MCs were present in 290 patients (47%). Of these, MC type 1 (MC-1) was present in 73 (25%) and MC type 2 (MC-2) in 217 (75%) patients. Preoperative data for ODI, EQ-5D, VAS-BP, and VAS-LP were comparable for the +MC and -MC groups. Both groups had a statistically significant improvement in PROs from baseline compared with 2-year follow-up (P < 0.001). At 2-year follow-up, both groups had improved with no significant difference between them in regards to ODI (15.5 vs. 17.2, P = 0.208); EQ-5D (0.75 vs. 0.72, P = 0.167); VAS-BP (27.1 vs. 28.3, P = 0.617); VAS-LP (26.8 vs. 25.0, P = 0.446); and patient satisfaction (74% vs. 76%, P = 0.878). CONCLUSION: MCs were not found to be associated with health-related quality of life, disability, back- or leg pain, or patient satisfaction 2 years after discectomy. LEVEL OF EVIDENCE: 2.

Is the Hospital Anxiety and Depression Scale Associated With Outcomes After Lumbar Spine Surgery?

STUDY DESIGN: Longitudinal cohort. OBJECTIVES: The Hospital Anxiety and Depression Scale (HADS) was developed to provide clinicians a reliable, valid, and practical tool to identify and quantify the anxiety and depression in medical patients. Several studies have shown that patients with chronic low back pain may have subclinical depression and impairments in mental health and that these in turn may lead to less than optimal results after lumbar spine surgery. The purpose of this study is to determine if there are associations between preoperative HADS and differences in pre- and postoperative health-related quality-of-life (HRQOLs) scores after spine surgery. METHODS: From a single center, a consecutive series of patients completed the HADS, Oswestry Disability Index (ODI), Short Form-36 (SF-36), EuroQOL-5D (EQ-5D), and Visual Analog Scale (VAS) for back and leg pain. Except for HADS, the patients completed the same HRQOLs 1 year after surgery. RESULTS: Of 308 eligible cases, 208 (68%) had follow-up data available and were included in the analysis. Patients in the HADS-Anxiety (HADS-A) Abnormal category had the worst preoperative HRQOLs but had the greatest improvement in 1-year postoperative scores. Except for VAS Leg Pain, preoperative HRQOLs were better in patients in the HADS-Depressed (HADS-D) Normal category. Patients in the HADS-D Abnormal category had statistically significantly greater improvement in 1-year postoperative EQ-5D and ODI scores when compared with the other cohorts. CONCLUSION: Worse HADS-A and HADS-D scores are associated with worse preoperative HRQOL scores in patients with lumbar degenerative disorders scheduled for spine surgery. However, similar improvements in HRQOLs can be expected 1 year postoperative regardless of the patients' HADS scores.

Randomized double blind clinical trial of ABM/P-15 versus allograft in noninstrumented lumbar fusion surgery.

BACKGROUND CONTEXT: Due to poor bone stock in the elderly, a noninstrumented fusion is commonly performed in Scandinavia when instability is present. Allograft bone is often used as graft extender with consequent low fusion rates. The use of 15 amino acid residue (ABM/P-15) has shown superior fusion rates in dental and cervical spinal surgery but no clinical studies have been conducted in noninstrumented lumbar fusion surgery. PURPOSE: To evaluate patient reported outcomes (PROs) and the intertransverse fusion rate in noninstrumented posterolateral fusion with either ABM/P-15 or allograft. STUDY DESIGN: Double-blind randomized clinical trial. PATIENT SAMPLE: Patients 60 years or older with degenerative spondylolisthesis undergoing decompression and noninstrumented posterolateral fusion. OUTCOME MEASURES: Visual analog scales for back and leg pain, Oswestry Disability Index and EuroQoL-5D. METHODS: One hundred one patients were enrolled in the study and randomized 1:1 to either ABM/P-15 (mixed 50/50, 5cc/level) or allograft bone (30 g/level), both mixed with local bone graft. PROs were collected at baseline and at 12 and 24 months after surgery. The patients underwent 1-year postoperative fine cut computed tomography-scans (0.9 mm) with reconstructions, independently evaluated by three reviewers. Fusion status was concluded by consensus of two of the three as "fusion" or "no fusion." RESULTS: There were 49 patients available for analysis in both cohorts. The two groups were similar in terms of sex distribution, age, and number of levels fused. The fusion rate was significantly higher in the ABM/P-15 group with 50% fused compared with 20% in the allograft group. PROs at baseline and at all follow-up time points were similar between the two groups. CONCLUSIONS: Patients undergoing noninstrumented posterolateral fusion augmented with ABM/P-15 had a statistically significantly higher fusion rate compared with allograft when evaluated with postoperative fine cut computed tomography-scans (0.9 mm) with reconstructions. However, this did not translate to better clinical outcomes.

Increasing reoperation rates and inferior outcome with prolonged symptom duration in lumbar disc herniation surgery - a prospective cohort study.

BACKGROUND CONTEXT: Lumbar disc herniation (LDH) is associated with great morbidity and significant socioeconomic impact in many parts of the world. Studies have shown that most LDH can be treated effectively with nonoperative management. However, for some patients in whom pain and disability are unacceptable, surgical intervention provides effective clinical relief. Currently, there is little consensus in the medical community on the timing of surgery for patients suffering from radicular pain due to LDH. Multiple studies suggest that prolonged symptom duration adversely affects clinical outcome. PURPOSE: The aim of this study is to evaluate if prolonged symptom duration is correlated with less favorable outcome following surgery for LDH. STUDY DESIGN/SETTING: Consecutive series of patients from a single-center, multisurgeon, tertiary spine practice. PATIENT SAMPLE: Consecutive series of patients who underwent surgery for LDH. OUTCOME MEASURES: Oswestry Disability Index (ODI), EuroQol-5D (EQ-5D), and Visual Analog Scale (VAS) for back and leg pain (0-100). METHODS: Patients with a first-episode LDH were included. Data were prospectively collected in DaneSpine, the Danish National Spine Registry. Subjects were divided into three groups based on their preoperative self-reported duration of leg pain: <3 months, 3 to 12 months, and >12 months. Associations between patient-reported outcomes (PROs), perioperative complications and duration of symptoms were evaluated. Statistical significance level was set at p value <.01. RESULTS: There were 2,144 patients included in the study, with complete 1-year follow-up on 1,694 patients (79%) and a reoperation rate of 8.4%. Incidence of surgical complications, specifically dural tears, was higher with increasing duration of leg pain; however, this did not reach statistical significance (p=.039). Prolonged preoperative symptoms adversely influenced all PROs (EQ-5D, ODI, VAS) 1 year after surgery (p=.001). Furthermore, reoperation rates increased with longer duration of preoperative symptoms. A statistically significant trend (p=.008) of increasing incidence of reoperation was found with increasing length of symptom duration. CONCLUSIONS: Delayed surgical intervention results in inferior outcomes and increased reoperation rates. Patients who had surgery within the first 3 months of leg pain achieved significantly better outcome 1 year after surgery when compared to the other groups.

Smoking Is an Independent Risk Factor of Reoperation Due to Recurrent Lumbar Disc Herniation.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: The purpose of the present study is to determine if age, gender, smoking status, and body mass index (BMI) are significant risk factors of symptomatic recurrent lumbar disc herniation (rLDH) leading to reoperation. METHODS: A cohort of 1378 consecutive patients who underwent discectomy for LDH from June 2010 to January 2015 at our institution were included. Patients who underwent reoperation due to rLDH prior to August 2015 were identified. Data on reoperations, age, gender, smoking status, and BMI were collected from our database. A comparison of age, gender, smoking status, and BMI was made between the controls (non-rLDH) and the cases (rLDH group). Binary logistic regression was performed to determine whether age, gender, smoking status, and BMI were independent risk factors for rLDH. RESULTS: Patients in the non-rLDH group (48.2 years) were older than the rLDH group (44.7 years; P = .013). Gender distribution (54.8% vs 48.5% males; P = .222) and BMI (26.6 vs 26.6; P = .458) were similar between the 2 groups. A significantly higher prevalence of smokers was found in the rLDH group (33.1% vs 51.5%; P < .001). Binary logistic regression analysis showed that smoking was an independent risk factor of rLDH (odds ratio = 2.12; 95% confidence interval = 1.39-3.15; P < .001). CONCLUSIONS: Neither age, BMI, nor gender had any statistical significant association with the risk of rLDH. Smoking was associated with higher risk of reoperation due to rLDH.

[Surgical treatment of lumbar disc herniation].

The Danish Health Authority has recently published a new guideline on the treatment of lumbar disc herniation with radiculopathy. This paper goes through the surgical treatment and considers the evidence behind surgical treatment of these patients, along with the outcome reported in literature. The new guideline recommends referring patients to be assessed by a surgeon within 12 weeks in cases, where severe and debilitating pain persists despite non-surgical treatment. This is found to be well in line with literature, as many studies have shown time to be a predictive factor in surgical treatment of these patients.

Surfactant Protein D Deficiency Aggravates Cigarette Smoke-Induced Lung Inflammation by Upregulation of Ceramide Synthesis.

Cigarette smoke (CS) is the main cause of chronic obstructive pulmonary disease. Surfactant protein D (SP-D) is an important anti-inflammatory protein that regulates host immune defense in the lungs. Here, we investigated the role of SP-D in a murine model of CS-induced inflammation. Pulmonary SP-D localization and abundance was compared between smoker and non-smoker individuals. For in vivo studies, wildtype, and SP-D-deficient mice were exposed to CS for either 12 weeks or 3 days. Moreover, the effect of therapeutic administration of recombinant fragment of human SP-D on the acute CS-induced changes was evaluated. Pulmonary SP-D appeared with heterogenous expression in human smokers, while mouse lung SP-D was uniformly upregulated after CS exposure. We found that SP-D-deficient mice were more susceptible to CS-induced macrophage-rich airway inflammation. SP-D deficiency influenced local pro-inflammatory cytokine levels, with increased CCL3 and interleukin-6 but decreased CXCL1. Furthermore, CS exposure caused significant upregulation of pro-inflammatory ceramides and related ceramide synthase gene transcripts in SP-D-deficient mice compared to wildtype littermates. Administration of recombinant fragment of human SP-D (rfhSP-D) alleviated CS-induced macrophage infiltration and prevented induction of ceramide synthase gene expression. Finally, rfhSP-D treatment attenuated CS-induced human epithelial cell apoptosis in vitro. Our results indicate that SP-D deficiency aggravates CS-induced lung inflammation partly through regulation of ceramide synthesis and that local SP-D enrichment rescues CS-induced inflammation.

[Non-surgical treatment of lumbar radiculopathy].

The objective of this paper is to give insight into evidence-based recommendations on key clinical questions regarding treatment of lumbar disc herniation with radiculopathy. This paper is based on the recently published Danish national clinical guideline for non-operative treatment. Limited evidence is found regarding non-surgical treatment of patients with lumbar radiculopathy. Physiotherapy, in the form of group sessions, seems to have the best level of evidence. However, evidence is still very limited and of poor quality. No evidence has been found with regards to acupuncture or manipulation therapy.

Contractile Changes in the Vasculature After Subchronic Smoking: A Comparison Between Wild Type and Surfactant Protein D Knock-Out Mice.

INTRODUCTION: Cigarette smoking is a well-known risk factor for developing cardiovascular diseases, but the underlying mechanisms are largely unknown. Recent data suggest that vasocontractile receptor modulation could be an important factor. Surfactant protein D (SP-D) is important in the particle clearance in the lungs and knock-out (KO) mice for this protein develop emphysema. SP-D is also weakly expressed in the vasculature. We aimed to investigate whether SP-D was important in the cardiovascular response to cigarette smoke exposure (CSE), by utilizing SP-D KO mice and a myograph setup. METHODS: Wild type (WT) and SP-D KO mice were exposed to cigarette smoke (CS) or room air for 12 weeks. The pulmonary artery, left anterior descending coronary artery, and basilar artery (BA) were isolated and mounted in wire myographs. Contractile concentration response curves to endothelin-1 and UDP were obtained. RESULTS: CSE caused a leftward shift in the concentration response curves for endothelin-1 in the BA for both WT and SP-D KO. UDP, acting on the purinergic P2Y6 receptor, caused reduced contraction in the left descending artery and increased contraction in the BA in the CSE WT mice. SP-D KO mice displayed no smoke induced changes, but were surprisingly similar to the CSE WT. CONCLUSION: The contractility to UDP was altered in the brain and heart vasculature of CSE mice. SP-D KO (both control and CSE) and CSE WT had similar changes in contractility compared to control WT. IMPLICATIONS: These results show that sub-chronic smoking induces vascular changes in the WT, mainly for the purinergic P2Y6 receptor together with minor changes for the endothelin-1 receptor. SP-D KO (both control and CSE) does not show any further changes compared to CSE WT.