Stability of the Subaxial Spine after Penetrating Trauma: Do Classification Systems Apply?

OBJECTIVE: Blunt spinal trauma classification systems are well established and provide reliable treatment algorithms. To date, stability of the spine after civilian gunshot wounds (CGSWS) is poorly understood. Herein, we investigate the validity of trauma classification systems including the Thoracolumbar Injury Classification and Severity Score (TLICS), Subaxial Cervical Spine Injury Classification and Severity Score (SLIC), and Denis' three-column model when applied to spinal penetrating trauma from gunshots, while secondarily evaluating stability of these injuries. METHODS: Gunshot injuries to the spine were identified from an institutional database from ICD-nine codes. Trauma scorings systems were applied using traditional criteria. Neurologic compromise and spinal stability were evaluated using follow-up clinic notes and radiographs. RESULTS: Thirty-one patients with CSGSW were evaluated. There was an equal distribution of injuries amongst the spinal levels and spinal columns. Twenty patients had neurological deficits at presentation. Eight patient had a TLICS score >4. Three patients had a SLIC score >4. One patient had surgical treatment. Nonoperative treatment did not lead to spinal instability or adverse outcomes in any cases. The posterior column had a high correlation with neurologic compromise, though not statistically significant (p=.118). CONCLUSIONS: The TLICS, SLIC, and three-column classification systems cannot be applied to CSGSW to quantify injury severity, predict outcomes, or guide treatment decision-making. Despite significant neurologic injuries and disruption of multiple spinal columns, CSGSW do not appear to result in unstable injuries requiring operative intervention. Further research is needed to identify the rare spinal gunshot injury that would benefit from immediate surgical intervention.

Sphingosine 1-phosphate receptor agonist FTY720-phosphate causes marginal zone B cell displacement.

FTY720 is an immunosuppressive agent that modulates lymphocyte trafficking. It is phosphorylated in vivo to FTY720-phosphate (FTY-P) and binds to a family of G protein-coupled receptors recognizing sphingosine 1-phosphate (S1P) as the natural ligand. It has previously been reported that FTY-P blocks egress of lymphocytes from the thymus and lymph nodes, resulting in peripheral blood lymphopenia. We now report that FTY-P also causes displacement of marginal zone (MZ) B cells to the splenic follicles, an effect that is similar to that observed after in vivo administration of lipopolysaccharide. This effect is specific to B cells in the MZ, as treatment with FTY-P does not cause redistribution of the resident macrophage population. A small but statistically significant decrease in the expression of beta1 integrin on MZ B cells was observed with FTY-P treatment. The redistribution of MZ B cells from the MZ sinuses does not abolish the ability of these cells to respond to the T-independent antigen, trinitrophenol-Ficoll. It has been proposed that the displacement of MZ B cells to the follicles is an indication of cell activation. Consistent with this, FTY-P caused an increase in percentage of MZ B cells expressing activation markers CD9, CD1d, and CD24. These results suggest that S1P receptors on MZ B cells are responsible for their mobilization to follicles.

Concomitant Lumbar Stenosis and Aortic Pseudoaneurysm: A Case Report.

Aortic pseudoaneurysm can create a constellation of symptoms that can mimic lumbar back pain. There are rare but well-documented reports of aortic pathology (aneurysms, pseudoaneurysms, and chronic contained aneurysm ruptures) eroding into the vertebral column causing neural compression. We report a case of a rapidly progressive aortic pseudoaneurysm in a patient with pre-existing lumbar spine pathology which had the potential for catastrophic intraoperative bleeding during a minimally invasive surgery (MIS) using the transforaminal lumbar interbody fusion (TLIF) technique. Postoperatively, the patient's radicular pain resolved but her back pain remained. Further workup identified the pseudoaneurysm and the patient subsequently underwent open vascular repair. In this report, we highlight a lesser known mimicker of lumbar back pain.

Comparison of agreement of cervical spine degenerative pathology findings in magnetic resonance imaging studies.

BACKGROUND CONTEXT: Magnetic resonance imaging (MRI) is often used in the evaluation of degenerative conditions of the cervical spine. However, the agreement of interpreting and reporting varying degenerative findings on cervical MRI has not been well assessed. PURPOSE: This study aimed to compare the inter-rater and intra-rater agreement of MRI findings between common degenerative findings of the cervical spine. STUDY DESIGN: A retrospective diagnostic study was used as study design. PATIENT SAMPLE: The sample consisted of 48 patients who underwent routine cervical spine MRI at our institution between January 2011 and June 2012. OUTCOME MEASURES: Reviewers evaluated each MRI study at each vertebral level for disc hydration, disc space height, central stenosis, foraminal stenosis, end plate changes, spondylolisthesis, and cord signal change. METHODS: A panel of two orthopedic spine surgeons and four musculoskeletal radiologists independently reviewed 48 sets of T2-weighted axial and sagittal MRI sequences for a series of preselected criteria, and their findings were compared with those of the other panelists to determine inter-rater agreement. Each panelist also re-reviewed the first 10 studies to determine intra-rater agreement. Absolute inter-rater and intra-rater agreements were then calculated and compared for different findings. A modified analysis ignored disagreements between the least severe grades of findings to determine the inter-rater and intra-rater agreements of the most clinically important severity grades. RESULTS: Absolute inter-rater agreement ranged from 54.6% to 95.0%. Disc hydration (54.6%), central stenosis (72.7%), and foraminal stenosis (73.1%) demonstrated the lowest inter-rater agreement, whereas spondylolisthesis (95.0%) and cord signal change (92.9%) demonstrated the highest agreement. The modified analysis found better inter-rater agreement, ranging from 80.9% to 95.0%. Absolute intra-rater agreement ranged from 74.2% to 94.7%. The modified analysis again found better agreement, ranging from 85.0% to 94.7%. As would be expected, overall intra-rater agreement (81.6%, 95% CI 78.9%-84.3%) was higher than inter-rater agreement (75.7%, 95% CI 74.4%-77.0%). The clinical specialty of the reviewer had no significant impact on inter- or intra-rater agreement. CONCLUSIONS: MRI findings play an important role in the management of patients with cervical spine conditions. For this reason, consistent descriptions of these findings are essential and physicians should be aware of the relative reliability of these findings. This systematic study developed standardized grading criteria and nomenclature for common clinically significant MRI findings in the cervical spine. Even in this optimized research setting, we found significant ranges in agreement across these MRI findings. In the clinical setting, inter- and intra-rater agreements may be lower, and the range of agreements between findings may be greater. Physicians should be aware of inconsistencies inherent in the interpretation of cervical MRI findings and should be aware that some findings demonstrate lower agreement than others.

Three-Dimensional Isotropic MRI of the Cervical Spine: A Diagnostic Comparison With Conventional MRI.

STUDY DESIGN: Retrospective diagnostic trial. OBJECTIVE: To determine the diagnostic performance of 3-dimensional turbo spin-echo (3D-TSE) isotropic magnetic resonance imaging (MRI) in the assessment of cervical spine pathology. SUMMARY OF BACKGROUND DATA: MRI is the imaging modality of choice for many cervical spine pathologies. However, axial imaging may be suboptimal if the image plane is oriented differently than the plane of interest, due to lordosis, kyphosis, or deformity. 3D-TSE isotropic MRI is a promising novel technology that bypasses this limitation by enabling dynamic image reformation in any desired orientation. METHODS: Forty-eight patients who underwent 3D-TSE and conventional 2-dimensional fast spin-echo (2D-FSE) T2-weighted cervical spine MRI at our institution were randomly selected. 3D-TSE and 2D-FSE sequences from each subject were independently evaluated by 2 orthopedic spine surgeons and 4 musculoskeletal radiologists. Images were assessed using specific pilot-tested criteria for stenosis, herniation, and degenerative changes. Intermethod, interrater, and intrarater agreements for 3D-TSE and 2D-FSE, and Fleiss κ coefficients were determined. RESULTS: The overall intermethod agreement was 80.7%. The interrater agreement was 75.9% for 3D-TSE and 75.7% for 2D-FSE (P=0.47). The intrarater agreement was 82.2% for 3D-TSE and 81.5% for 2D-FSE (P=0.71). Fleiss κ coefficients were 0.42 for 3D-TSE and 0.43 for 2D-FSE (P=0.62), indicating moderate interrater reliability. The intermethod agreement and the 2D-FSE intrarater agreement were statistically similar (P=0.49). CONCLUSIONS: There is a high degree of agreement between 3D-TSE and 2D-FSE MRI in assessing the cervical spine. The intermethod variability was statistically similar to the intrinsic intrarater variability of 2D-FSE MRI. This study demonstrates that 3D-TSE yields at least equivalent diagnostic information as conventional 2D-FSE in the cervical spine. In addition, reviewers noted subjective advantages of 3D-TSE image reprocessing, especially when evaluating greater pathology or deformity, with a simplified image acquisition process.

A rational utilization of high-throughput screening affords selective, orally bioavailable 1-benzyl-3-carboxyazetidine sphingosine-1-phosphate-1 receptor agonists.

Moderately potent, selective S1P(1) receptor agonists identified from high-throughput screening have been adapted into lipophilic tails for a class of orally bioavailable amino acid-based S1P(1) agonists represented by 7. Many of the new compounds are potent S1P(1) agonists that select against the S1P(2), S1P(3), and S1P(4) (although not S1P(5)) receptor subtypes. Analogues 18 and 24 are highly orally bioavailable and possess excellent pharmacokinetic profiles in the rat, dog, and rhesus monkey.

Direct-injection HPLC assay for the determination of a new carbapenem antibiotic in human plasma and urine.

Reversed-phase high-performance liquid chromatography (RP-HPLC) assays using ultraviolet (UV) absorbance detection have been developed for the determination of a new carbapenem antibiotic I in human plasma and urine. A column-switching technique is employed in the HPLC methods to perform on-line extraction and separation for each sample. Each plasma sample is thawed, centrifuged, stabilized, and then injected onto an in-line reversed-phase extraction column using a methanol (8%)/phosphate buffer, pH 6.5. After 3 min, the analytes are back-flushed off the extraction column with a mixture of acetonitrile (5.5%) and methanol (10%)/phosphate buffer (pH 6.5) for 3 min onto a BDS Hypersil 3 microm C18 (100 x 4.6 mm i.d.) analytical column. The sample preparation and HPLC conditions for the urine assay are similar to the plasma assay, except that a CN extraction column is used. Both assays are specific with respect to endogenous material and the major metabolite II, and both are linear over the concentration range of 0.25-50, and 2-200 microg/ml, respectively. The assays were successfully applied to a clinical dose-ranging study. One limitation of the on-line extraction method is that the extraction column needs to be replaced regularly every 100-150 plasma samples and every 200-300 urine samples. Subsequently, the urine method was modified to an ion-pair HPLC assay for the simultaneous determination of both the antibiotic I and its metabolite II.

Minimal tumor volume may provide additional prognostic information in good performance patients after radical prostatectomy.

OBJECTIVES: The significance of tumor volume (TV) as a predictor of biochemical failure after radical prostatectomy (RP) remains debatable. TV determinants can also entail significant time and cost. Estimating TVs using an asymmetric categorical classification system provides an economical alternative to determining this parameter. We evaluated the prognostic value of an estimated TV in patients undergoing RP in predicting for prostate-specific antigen (PSA) failure. METHODS: We retrospectively reviewed the clinical and pathologic features of 865 patients who underwent RP at our institution from 1991 to 1999. The TV, PSA level, final Gleason score, percentage of positive biopsy cores, and clinical stage were evaluated using univariate and multivariate analysis to determine their association with biochemical failure. Patients were also stratified according to PSA level (less than versus greater than 10 ng/mL), Gleason score (less than versus greater than 7), and clinical T stage (Stage T1c or better versus worse than Stage T1c) to analyze the prognostic significance of TV in this subpopulation of patients. RESULTS: Of our 865 evaluable patients, 124 (14.3%) had progression to biochemical failure at a mean follow-up of 60 months. The TV was significantly associated with biochemical failure on univariate analysis (P = 0.024). In the low-risk patients (PSA level less than 10 ng/mL, Gleason score less than 7, and clinical Stage T1c or better), a minimal TV was associated with a lower risk of biochemical failure on multivariate analysis (hazard ratio 2.0, 95% confidence interval 1.09 to 3.68, P = 0.025). CONCLUSIONS: In RP patients with favorable clinical and pathologic characteristics, a minimal TV was associated with a decreased risk of biochemical failure. In carefully selected patients, the estimated TV might provide additional prognostic information for risk stratification for PSA progression and biochemical failure.

Synthesis, stereochemical determination and biochemical characterization of the enantiomeric phosphate esters of the novel immunosuppressive agent FTY720.

The novel immunosuppressive agent FTY720 (1) is phosphorylated in vivo in a variety of species yielding an active metabolite that is an agonist of four of the five known G-protein-coupled sphingosine-1-phosphate (S1P) receptors. A synthesis amenable to producing gram quantities of the stereoisomeric phosphate esters, a determination of their absolute stereochemistry via an enantioselective synthesis and their characterization as S1P receptor agonists and antagonists is reported.

Potent S1P receptor agonists replicate the pharmacologic actions of the novel immune modulator FTY720.

Alteration in lymphocyte trafficking and prevention of graft rejection in rodents observed on exposure to FTY720 (1) or its corresponding phosphate ester 2 can be induced by the systemic administration of potent sphingosine-1-phosphate receptor agonists exemplified by 19. The similar S1P receptor profiles of 2 and 19 coupled with their comparable potency in vivo supports a connection between S1P receptor agonism and immunosuppressive efficacy.