Cervical radiculopathy is a relatively common neurological disorder resulting from nerve root dysfunction, which is often due to mechanical compression; however, inflammatory cytokines released from damaged intervertebral disks can also result in symptoms. Cervical radiculopathy can often be diagnosed with a thorough history and physical examination, but an magnetic resonance imaging or computed tomographic myelogram should be used to confirm the diagnosis. Because of the ubiquity of degenerative changes found on these imaging modalities, the patient's symptoms must correlate with pathology for a successful diagnosis. In the absence of myelopathy or significant muscle weakness all patients should be treated conservatively for at least 6 weeks. Conservative treatments consist of immobilization, anti-inflammatory medications, physical therapy, cervical traction, and epidural steroid injections. Cervical radiculopathy typically is self-limiting with 75%-90% of patients achieving symptomatic improvement with nonoperative care. For patients who are persistently symptomatic despite conservative treatment, or those who have a significant functional deficit surgical treatment is appropriate. Surgical options include anterior cervical decompression and fusion, cervical disk arthroplasty, and posterior foraminotomy. Patient selection is critical to optimize outcome.

Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

No abstract

BACKGROUND CONTEXT Intervertebral disc degeneration (IDD) is a common cause of back pain. Patients who fail conservative management may face the morbidity of surgery. Alternative treatment modalities could have a significant impact on disease progression and patients’ quality of life. PURPOSE To determine if the injection of a virus vector carrying a therapeutic gene directly into the nucleus pulposus improves the course of IDD. STUDY DESIGN Prospective randomized controlled animal study. METHODS Thirty-four skeletally mature New Zealand white rabbits were used. In the treatment group, L2–L3, L3–L4, and L4–L5 discs were punctured in accordance with a previously validated rabbit annulotomy model for IDD and then subsequently treated with adeno-associated virus serotype 2 (AAV2) vector carrying genes for either bone morphogenetic protein 2 (BMP2) or tissue inhibitor of metalloproteinase 1 (TIMP1). A nonoperative control group, nonpunctured sham surgical group, and punctured control group were also evaluated. Serial magnetic resonance imaging (MRI) studies at 0, 6, and 12 weeks were obtained, and a validated MRI analysis program was used to quantify degeneration. The rabbits were sacrificed at 12 weeks, and L4–L5 discs were analyzed histologically. Viscoelastic properties of the L3–L4 discs were analyzed using uniaxial load normalized displacement testing. Creep curves were mathematically modeled according to a previously validated two-phase exponential model. Serum samples obtained at 0, 6, and 12 weeks were assayed for biochemical evidence of degeneration. RESULTS The punctured group demonstrated MRI and histologic evidence of degeneration as expected. The treatment groups demonstrated less MRI and histologic evidence of degeneration than the punctured group. The serum biochemical marker C-telopeptide of collagen type II increased rapidly in the punctured group, but the treated groups returned to control values by 12 weeks. The treatment groups demonstrated several viscoelastic properties that were distinct from control and punctured values. CONCLUSIONS Treatment of punctured rabbit intervertebral discs with AAV2-BMP2 or AAV2-TIMP1 helps delay degenerative changes, as seen on MRI, histologic sampling, serum biochemical analysis, and biomechanical testing. Although data from animal models should be extrapolated to the human condition with caution, this study supports the potential use of gene therapy for the treatment of IDD.

AMP-forming acetyl-CoA synthetase [ACS; acetate:CoA ligase (AMP-forming), EC 6.2.1.1] catalyzes the activation of acetate to acetyl-CoA in a two-step reaction. This enzyme is a member of the adenylate-forming enzyme superfamily that includes firefly luciferase, nonribosomal peptide synthetases, and acyl- and aryl-CoA synthetases/ligases. Although the structures of several superfamily members demonstrate that these enzymes have a similar fold and domain structure, the low sequence conservation and diversity of the substrates utilized have limited the utility of these structures in understanding substrate binding in more distantly related enzymes in this superfamily. The crystal structures of the Salmonella enterica ACS and Saccharomyces cerevisiae ACS1 have allowed a directed approach to investigating substrate binding and catalysis in ACS. In the S. enterica ACS structure, the propyl group of adenosine 5'-propylphosphate, which mimics the acyl-adenylate intermediate, lies in a hydrophobic pocket. Modeling of the Methanothermobacter thermautotrophicus Z245 ACS (MT-ACS1) on the S. cerevisiae ACS structure showed similar active site architecture, and alignment of the amino acid sequences of proven ACSs indicates that the four residues that compose the putative acetate binding pocket are well conserved. These four residues, Ile312, Thr313, Val388, and Trp416 of MT-ACS1, were targeted for alteration, and our results support that they do indeed form the acetate binding pocket and that alterations at these positions significantly alter the enzyme's affinity for acetate as well as the range of acyl substrates that can be utilized. In particular, Trp416 appears to be the primary determinant for acyl chain length that can be accommodated in the binding site.

Background: Perioperative allogeneic red blood cell transfusion is a risk factor for surgical site infection. The purpose of

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Study Design. Retrospective comparative study. Objective. The purpose of this study was to investigate whether preoperative depressive symptoms, measured by mental component score of the Short Form-12 survey (MCS-12), influence patient-reported outcome measurements (PROMs) following an anterior cervical discectomy and fusion (ACDF) surgery for cervical degeneration. Summary of Background Data. There is a paucity of literature regarding preoperative depression and PROMs following ACDF surgery for cervical degenerative disease. Methods. Patients who underwent an ACDF for degenerative cervical pathology were identified. A score of 45.6 on the MCS-12 was used as the threshold for depression symptoms, and patients were divided into two groups based on this value: depression (MCS-12 ≤45.6) and nondepression (MCS-12 >45.6) groups. Outcomes including Neck Disability Index (NDI), physical component score of the Short Form-12 survey (PCS-12), and Visual Analogue Scale Neck (VAS Neck), and Arm (VAS Arm) pain scores were evaluated using independent sample t test, recovery ratios, percentage of patients reaching the minimum clinically important difference, and multiple linear regression – controlling for factors such as age, sex, and BMI. Results. The depression group was found to have significantly worse baseline pain and disability than the nondepression group in NDI (P < 0.001), VAS Neck pain (P < 0.001), and VAS Arm pain (P < 0.001) scores. Postoperatively, both groups improved to a similar amount with surgery based on the recovery ratio analysis. The depression group continued to have worse scores than the nondepression group in NDI (P = 0.010), PCS-12 (P = 0.026), and VAS Arm pain (P = 0.001) scores. Depression was not a significant predictor of change in any PROMs based on regression analysis. Conclusion. Patients who presented with preoperative depression reported more pain and disability symptoms preoperatively and postoperatively; however, both groups achieved similar degrees of improvement. Level of Evidence: 3