Lumbar Bracing for Chronic Low Back Pain: A Randomized Controlled Trial.

PURPOSE: We performed this study to evaluate the effect of back bracing to treat patients with chronic low back pain. METHODS: This was a prospective, unblinded, randomized controlled trial of 61 adults with uncomplicated chronic low back pain (>12 wks) and imaging findings of degenerative spondylosis, to assess the effectiveness of a semirigid back brace. All study participants received back school instruction. The treatment group also received a lumbar orthosis and was instructed to wear it as needed for symptom relief. At baseline, 6 wks, 12 wks, and 6 mos after intervention, we collected: Numerical Rating Scale to measure pain intensity, Pain Disability Questionnaire, Patient-Reported Outcome Measurement Information System, and EuroQol 5-Dimension (EQ-5D) to measure patient-reported function and quality of life. RESULTS: An interim analysis at the halfway point in enrollment (61 of 120 planned participants) revealed the Pain Disability Questionnaire, Patient-Reported Outcome Measurement Information System, and EQ-5D scores in the treatment group to be worse than in the control group, but no significant group differences in Numerical Rating Scale scores. Outcome differences between groups analyzed over time revealed (effect [P]): Pain Disability Questionnaire = 0.84 (0.04); Patient-Reported Outcome Measurement Information System = 0.78 (0.005); EQ-5D = 0.06 (0.01); and Numerical Rating Scale = 0.02 (0.6). We halted the study because continuation was unlikely to produce significant changes to the results. CONCLUSIONS: In patients with uncomplicated chronic low back pain, a back brace when combined with education and exercise instruction did not provide any pain relief compared with education and exercise instruction alone. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Describe the effect of lumbar back bracing on pain intensity in patients with chronic low back pain; (2) Discuss the effects of lumbar back bracing on pain-related disability, function, and quality of life in patients with chronic low back pain; and (3) Understand the role of lumbar back bracing in the treatment of patients with chronic low back pain. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Motor Unit Number Index in Evaluating Patients With Lumbar Spinal Stenosis.

OBJECTIVE: Motor unit number index is a quantitative electrophysiological measure that provides an index of the number of motor neurons supplying a muscle. The aim of this exploratory study was to assess the utility of motor unit number index in the evaluation of patients with lumbar spinal stenosis. DESIGN: Participants were assigned to three groups: clinical and radiological lumbar stenosis (lumbar spinal stenosis with neurogenic intermittent claudication), group A; radiological lumbar spinal stenosis without neurogenic intermittent claudication, group B; and a control group, group C. Patients self-rated their pain and functional disability using the numerical rating scale and a series of functional questionnaires. An electromyographer performed nerve conduction tests, electromyography, and motor unit number index testing. RESULTS: Seventeen patients completed the study. There were 9, 5, and 3 patients in groups A, B, and C, respectively. There were no discernable differences in motor unit number index values of any individual muscle or combined motor unit number index score between the three groups. Motor unit number index values did not correlate to pain/functional measures. CONCLUSIONS: In this exploratory study, motor unit number index did not demonstrate discriminatory ability between patients with lumbar spinal stenosis and was not correlated with pain and functional measures. Further study is needed to explore motor unit number index's role in longitudinal evaluation of patients with the clinical syndrome of lumbar spinal stenosis.

Anti-CD40 Antibody Fused to CD40 Ligand Is a Superagonist Platform for Adjuvant Intrinsic DC-Targeting Vaccines.

CD40 is a potent activating receptor expressed on antigen-presenting cells (APCs) of the immune system. CD40 regulates many aspects of B and T cell immunity via interaction with CD40L expressed on activated T cells. Targeting antigens to CD40 via agonistic anti-CD40 antibody fusions promotes both humoral and cellular immunity, but current anti-CD40 antibody-antigen vaccine prototypes require co-adjuvant administration for significant in vivo efficacy. This may be a consequence of dulling of anti-CD40 agonist activity via antigen fusion. We previously demonstrated that direct fusion of CD40L to anti-CD40 antibodies confers superagonist properties. Here we show that anti-CD40-CD40L-antigen fusion constructs retain strong agonist activity, particularly for activation of dendritic cells (DCs). Therefore, we tested anti-CD40-CD40L antibody fused to antigens for eliciting immune responses in vitro and in vivo. In PBMC cultures from HIV-1-infected donors, anti-CD40-CD40L fused to HIV-1 antigens preferentially expanded HIV-1-specific CD8+ T cells versus CD4+ T cells compared to analogous anti-CD40-antigen constructs. In normal donors, anti-CD40-CD40L-mediated delivery of Influenza M1 protein elicited M1-specific T cell expansion at lower doses compared to anti-CD40-mediated delivery. Also, on human myeloid-derived dendritic cells, anti-CD40-CD40L-melanoma gp100 peptide induced more sustained Class I antigen presentation compared to anti-CD40-gp100 peptide. In human CD40 transgenic mice, anti-CD40-CD40L-HIV-1 gp140 administered without adjuvant elicited superior antibody responses compared to anti-CD40-gp140 antigen without fused CD40L. In human CD40 mice, compared to the anti-CD40 vehicle, anti-CD40-CD40L delivery of Eα 52-68 peptide elicited proliferating of TCR I-Eα 52-68 CD4+ T cells producing cytokine IFNγ. Also, compared to controls, only anti-CD40-CD40L-Cyclin D1 vaccination of human CD40 mice reduced implanted EO771.LMB breast tumor cell growth. These data demonstrate that human CD40-CD40L antibody fused to antigens maintains highly agonistic activity and generates immune responses distinct from existing low agonist anti-CD40 targeting formats. These advantages were in vitro skewing responses towards CD8+ T cells, increased efficacy at low doses, and longevity of MHC Class I peptide display; and in mouse models, a more robust humoral response, more activated CD4+ T cells, and control of tumor growth. Thus, the anti-CD40-CD40L format offers an alternate DC-targeting platform with unique properties, including intrinsic adjuvant activity.

Predicting Response to Epidural Steroid Injections for Lumbar Spinal Stenosis with Biomarkers and Electromyography.

BACKGROUND: Epidural steroid injections (ESIs) may be beneficial for lumbar spinal stenosis (LSS) symptoms. Past studies found interferon-gamma, fibronectin-aggrecan complex, and electromyography (EMG) to predict patients' response to ESIs for other spinal pathologies, but no similar studies have been done for LSS. OBJECTIVE: To explore the ability of biomarkers and EMG to help predict outcome after ESI in LSS. DESIGN: Prospective observational cohort. SETTING: The physical medicine & rehabilitation spine clinic at a tertiary care center. PARTICIPANTS: Eleven patients with LSS were recruited from the spine clinic at a Veterans Affairs Medical Center. INTERVENTIONS: Participants underwent one interlaminar ESI. Before ESI, the following data were collected: pain intensity on visual analog scale (VAS), disability via the Pain Disability Questionnaire (PDQ) and LSS symptoms via the Swiss Spinal Stenosis Questionnaire (SSSQ), serum high-sensitivity C-reactive protein level, standard diagnostic EMG, assay of epidural lavasate (epidural saline lavage performed immediately prior to ESI) and serum cytokine biomarkers indicative of inflammation. OUTCOME MEASURES: Leg pain intensity (VAS), disability (PDQ), LSS symptoms (SSSQ) and satisfaction (SSSQ satisfaction subscale) were assessed at 1 and 2 months following ESI. Pearson correlational coefficients were calculated between independent variables and outcome measures. RESULTS: Serum monocyte chemoattractant protein-1 (MCP-1) level positively correlated with improvement on 2-month satisfaction. Abnormal EMG finding of radiculopathy positively correlated with improvement in PDQ score at 1 month. Epidural cytokine levels were not detectable in most samples, except for scattered marginally elevated levels in a few cytokines such as MCP-1, RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted) and interleukin-1b. CONCLUSIONS: This exploratory pilot study revealed that some biomarkers and EMG findings indicative of inflammation and nerve root injury may be predictive of improvement following ESI in patients with LSS. The results of this study will be used to inform a fully powered study to further evaluate these relationships in LSS patients.

MEK Inhibitors Reverse Growth of Embryonal Brain Tumors Derived from Oligoneural Precursor Cells.

Malignant brain tumors are the leading cause of cancer-related deaths in children. Primitive neuroectodermal tumors of the CNS (CNS-PNETs) are particularly aggressive embryonal tumors of unknown cellular origin. Recent genomic studies have classified CNS-PNETs into molecularly distinct subgroups that promise to improve diagnosis and treatment; however, the lack of cell- or animal-based models for these subgroups prevents testing of rationally designed therapies. Here, we show that a subset of CNS-PNETs co-express oligoneural precursor cell (OPC) markers OLIG2 and SOX10 with coincident activation of the RAS/MAPK (mitogen-activated protein kinase) pathway. Modeling NRAS activation in embryonic OPCs generated malignant brain tumors in zebrafish that closely mimic the human oligoneural/NB-FOXR2 CNS-PNET subgroup by histology and comparative oncogenomics. The zebrafish CNS-PNET model was used to show that MEK inhibitors selectively eliminate Olig2+/Sox10+ CNS-PNET tumors in vivo without impacting normal brain development. Thus, MEK inhibitors represent a promising rationally designed therapy for children afflicted with oligoneural/NB-FOXR2 CNS-PNETs.