Christopher R. Brown

Proinflammatory cytokine expression profile in degenerated and herniated human intervertebral disc tissues

OBJECTIVE Prior reports document macrophage and lymphocyte infiltration with proinflammatory cytokine expression in pathologic intervertebral disc (IVD) tissues. Nevertheless, the role of the Th17 lymphocyte lineage in mediating disc disease remains uninvestigated. We undertook this study to evaluate the immunophenotype of pathologic IVD specimens, including interleukin-17 (IL-17) expression, from surgically obtained IVD tissue and from nondegenerated autopsy control tissue. METHODS Surgical IVD tissues were procured from patients with degenerative disc disease (n = 25) or herniated IVDs (n = 12); nondegenerated autopsy control tissue was also obtained (n = 8) from the anulus fibrosus and nucleus pulposus regions. Immunohistochemistry was performed for cell surface antigens (CD68 for macrophages, CD4 for lymphocytes) and various cytokines, with differences in cellularity and target immunoreactivity scores analyzed between surgical tissue groups and between autopsy control tissue regions. RESULTS Immunoreactivity for IL-4, IL-6, IL-12, and interferon-gamma (IFNgamma) was modest in surgical IVD tissue, although expression was higher in herniated IVD samples and virtually nonexistent in control samples. The Th17 lymphocyte product IL-17 was present in >70% of surgical tissue fields, and among control samples was detected rarely in anulus fibrosus regions and modestly in nucleus pulposus regions. Macrophages were prevalent in surgical tissues, particularly herniated IVD samples, and lymphocytes were expectedly scarce. Control tissue revealed lesser infiltration by macrophages and a near absence of lymphocytes. CONCLUSION Greater IFNgamma positivity, macrophage presence, and cellularity in herniated IVDs suggests a pattern of Th1 lymphocyte activation in this pathology. Remarkable pathologic IVD tissue expression of IL-17 is a novel finding that contrasts markedly with low levels of IL-17 in autopsy control tissue. These findings suggest involvement of Th17 lymphocytes in the pathomechanism of disc degeneration.

Impact of surgical approach on complications and resource utilization of cervical spine fusion: a nationwide perspective to the surgical treatment of diffuse cervical spondylosis

BACKGROUND CONTEXT Cervical spine fusion is performed for various indications in patient populations ranging from young and healthy to aged and frail. The choice of surgical approach is affected not only by disease pathoanatomy, but also by age, medical comorbidities, and the number of involved levels. Anterior fusion is more common for single-level pathology in relatively young, healthy patients; and posterior fusion is typically performed on older, more comorbid patients with multilevel disease. Consequently, retrospective comparisons of surgical approaches for cervical fusion will be impacted by this bias, and the optimal management of multilevel cervical spine pathology remains ambiguous with surgeon preference and experience playing a significant role in choice of procedures. PURPOSE To define the complications and resource utilization related to multilevel cervical spine fusion surgery, and to evaluate the impact of surgical approach on these outcomes. STUDY DESIGN/SETTING A retrospective nationwide database study of inpatient perioperative complications. PATIENT SAMPLE All patients undergoing multilevel (four to eight levels) cervical spine fusion for degenerative disease between 2003 and 2005 at institutions represented in the Nationwide Inpatient Sample database. OUTCOME MEASURES Measures of patient periprocedural mortality, selected specific morbidities, and resource utilization were evaluated. Resource utilization included length of hospitalization, inflation-adjusted cost, and likelihood of nonroutine discharge to assisted living. METHODS Data for 8,548 patients who underwent cervical fusion of four to eight levels were collected from the Nationwide Inpatient Sample database (2003-2005), and subjects were grouped by surgical approach (anterior vs. posterior). Descriptive statistics compared baseline characteristics, and bivariate analysis and logistic regression modeling evaluated the effect of surgical approach on mortality, selected postoperative complications, length of stay, hospitalization cost, and discharge disposition. All tests were performed at the 0.05 level of significance. RESULTS This observational study indicates that a posterior approach to multilevel cervical fusion is associated with more respiratory complications, postoperative infections, symptomatic hematomas, and transfusions when compared with an anterior approach. Resource utilization was nearly double for those undergoing a posterior approach, including hospital length of stay, inflation-adjusted cost, and likelihood of discharge to an assisted-living facility. Not surprisingly, this study confirms that patients fused posteriorly had a lower incidence of symptomatic postoperative dysphagia. CONCLUSIONS This nationwide study defines the incidence of mortality and the frequency of inpatient complications encountered during multilevel cervical fusion. The results suggest that immediate morbidity from anterior approaches is less than those undergoing posterior fusion. Prospective analysis is required to evaluate if these findings remain significant in a randomized study population. Further, these results represent only perioperative complications. However, based on the data presented herein, when confronted with the patient requiring a four-level cervical fusion, the anterior approach may offer a less risky and less costly option.

Extreme lateral interbody fusion approach for isolated thoracic and thoracolumbar spine diseases: initial clinical experience and early outcomes.

Study Design Retrospective review of prospective collected data on 22 patients. Objective To describe our initial clinical experience and outcomes with the extreme lateral interbody fusion (XLIF) approach for spinal diseases requiring access to the thoracic cavity. Summary of Background Data Minimally invasive anterior approaches to the thoracic spine have traditionally consisted of thoracoscopic and mini-open thoracotomy techniques. We present our initial experience with employing the XLIF technique to treat thoracic spine diseases. Methods Clinical, radiographic, operative, postoperative, and functional outcomes were analyzed. Results A total of 22 patients (15 females, 7 males, average age 64.6 y) with isolated thoracic and thoracolumbar spine diseases were treated between 2005 and 2009. The indications for surgery included degenerative scoliosis (11), pathological fractures from tumors (2), adjacent level disease from prior fusions (5), thoracic disc herniations (3), and discitis/osteomyelitis (1). A total of 47 levels were treated. In the subset of patients treated for degenerative scoliosis, the mean preoperative and postoperative coronal Cobb angles were 22 and 14, respectively. The mean preoperative and postoperative sagittal angles were 39 and 44, respectively. The average estimated blood loss and length of stay were 227.5 mL and 4.8 d, respectively. Three complications consisting of wound infection, subsidence, and adjacent level disease requiring additional procedures were encountered. There were no neural, vascular, visceral injuries, or death. At a mean follow-up of 16.4 months (range, 3-50), we observed a 95.5% substantial clinical benefit. All patients who had reached a minimum of 6 months (95.5%) demonstrated radiographic evidence of fusion. Conclusions The XLIF technique can be expanded to treat diseases in the thoracic spine. Although the magnitude of deformity correction achieved is less than that of the traditional open approaches, the lesser invasiveness of this technique may be tolerable for the elderly and in patients with significant medical comorbidities.

Impact of body habitus on perioperative morbidity associated with fusion of the thoracolumbar and lumbar spine.

OBJECTIVESpinal fusion is performed in patients ranging from young and healthy to aged and frail. Although recent population trends in the United States are toward obesity, no large-scale study has evaluated how body habitus affects mortality, complications, and resource utilization for lumbar spine fusion. Such information is important for patient selection and to confirm the safety of such procedures in this population. METHODSData for 244 170 patients who underwent thoracolumbar or lumbar spine fusion for degenerative disease between 1988 and 2004 were collected from the Nationwide Inpatient Sample database, and subjects were grouped by surgical approach and body habitus. Multivariate logistic regression evaluated group effects on selected postoperative complications, length of stay, resource utilization, and discharge disposition. RESULTSThis study confirms that body habitus affects perioperative morbidity sustained by patients undergoing thoracolumbar or lumbar spine fusion. Demographic heterogeneity exists for race, geography, and number of diseased levels among body habitus groups, prompting application of multivariate logistic regression for outcomes. For all approaches, higher body mass index associated with increased transfusion requirements and likelihood of discharge to assisted living. Furthermore, morbidly obese patients undergoing posterior fusion sustained more wound complications and postoperative infections. CONCLUSIONThis nationwide study describes inpatient complications encountered during fusion surgery in patients who are obese. For a given surgical approach, patients with higher body mass index sustain increased transfusion requirements and utilize more resources during thoracolumbar and lumbar spine fusion. Nevertheless, the findings of equivalent mortality, length of stay, and other complication rates suggest that patients who are obese remain safe surgical candidates.

Impact of preoperative neurological status on perioperative morbidity associated with anterior and posterior cervical fusion

OBJECT Cervical spine fusion is performed for various indications in patient populations ranging from young and healthy to aged and frail. Whereas disease pathoanatomy dictates the surgical approach, preoperative neurological status does not necessarily implicate a specific technique. Although one expects anterior decompression to be performed over fewer segments in healthier patients who experience fewer complications and faster recovery, the impact of pre-operative myelopathy on perioperative complications remains unclear. No large-scale study has evaluated rates of common complications for cervical fusion or their association with surgical approach and neurological status. METHODS Data for 96,773 patients who underwent cervical fusion for degenerative disease between 1988 and 2003 were collected from the Nationwide Inpatient Sample database. Patients were grouped according to surgical approach (anterior versus posterior) and preoperative neurological status (myelopathic versus nonmyelopathic). Multivariate regression was used to evaluate group effects on selected postoperative complications, length of stay, and disposition at the time of hospital discharge. Although this technique can control for the observed covariates, the absence of key information such as the number of fused levels precludes statistical comparison between patients who underwent anterior or posterior approaches. RESULTS In this study the authors confirmed that preoperative neurological status impacts perioperative morbidity. For example, patients who were nonmyelopathic and underwent an anterior approach were 7 years younger than the rest of the cohort, and they had a mortality rate of 0.05%. Transfusion was required in 0.34%, and venous thromboembolism occurred in 0.04%. Conversely, these rates were > 13-fold higher in patients with myelopathy who underwent a posterior approach. Furthermore, independent of approach, preoperative myelopathy is highly prognostic of death, pneumonia, transfusion, infection, length of stay, and posthospital disposition. These outcomes at least doubled, with some increasing > 10-fold. CONCLUSIONS This nationwide study clarifies the frequency and associations of inpatient complications encountered when treating cervical spine disease. Whereas immediate complications due to anterior approaches are limited, patients with myelopathy who undergo a posterior approach have a more sobering outlook. This study shows that clinical myelopathy augments rates of complication during cervical fusion, regardless of the approach. The exclusion of pathoanatomical data from the Nationwide Inpatient Sample database, of key importance in guiding the surgical approach, prevents any conclusions being drawn about the merits and disadvantages of anterior versus posterior surgery.

Experience with intrawound vancomycin powder for spinal deformity surgery.

Study Design. Retrospective cohort study. Objective. To evaluate the ability of local vancomycin powder to prevent deep wound infection after thoracolumbar and lumbar spinal fusion for open deformity cases. Summary of Background Data. Recent studies report that local delivery of vancomycin powder is associated with a decrease in spinal surgical site infection (SSI). This study compares deformity fusion cases before and after the routine application of spinal vancomycin powder. Methods. Posterior spinal deformity surgical procedures by a single institution were reviewed from January 2011 to April 2013. Routine application of vancomycin powder started in April 2012. Inclusion criteria included adult patients who underwent posterior fusion for deformity pathologies, including spondylolisthesis, kyphosis, sagittal imbalance, and scoliosis. Each cohorts baseline characteristics including infection risk factors, operative data, and rates of wound infection were compared. Associations between infection and vancomycin powder, with and without propensity score adjustment for risk factors were determined using logistic regression. Results. A total of 306 patients were included in the study. All measured baseline and operative variables were statistically similar between untreated (n = 150) and those who received vancomycin powder (n = 156). No significant change in deep wound infection rate was seen between the control (5.3%) and intervention group (5.1%, P = 0.936). Logistic regression with and without propensity score adjusted for risk factors demonstrated that the use of vancomycin powder did not impact the development of SSI (odds ratio [95% confidence interval]: 1.01 [0.36–2.79], P = 0.9910) and (odds ratio [95% confidence interval]: 0.87 [0.31–2.42], P = 0.7876), respectively. Conclusion. The local application of powdered vancomycin was not associated with a significant difference in the rate of deep SSI after spinal deformity surgery, and other treatment modalities are necessary to limit infection for this high-risk group. This study is in contrary to prior studies, which have reported a decrease in SSI with vancomycin powder. Level of Evidence: 2

Minimally Invasive Lumbar Interbody Fusion in Patients Older Than 70 Years of Age: Analysis of Peri- and Postoperative Complications

BACKGROUND:The number of spine operations performed in the elderly population is rising. OBJECTIVE:To identify and describe perioperative and postoperative complications in patients 70 years and older who have undergone minimally invasive lumbar interbody spine fusion. METHODS:A retrospective analysis was performed on 66 consecutive patients aged 70 years or older who underwent a minimally invasive interbody lumbar fusion. Electronic medical records were analyzed for patient demographics, procedures, and perioperative and postoperative complications. RESULTS:Between 2000 and 2009, 66 patients with an average age of 74.9 years (range, 70-86 years) underwent 68 lumbar interbody fusions procedures. The mean follow-up was 14.7 months (range, 1.5-50 months). The minimally invasive approaches included 41 cases of extreme lateral interbody fusion and 27 minimally invasive transforaminal lumbar interbody fusions. We observed 5 major (7.4%) and 17 minor (25%) complications. The 5 major complications consisted of 4 cases of interbody graft subsidence and 1 adjacent level disease. There were no intraoperative medical complications. There were no myocardial infarctions, pulmonary embolisms, hardware complications requiring removal, wound infections, major visceral, vascular, neural injuries, or death in the study period. CONCLUSION:Minimally invasive interbody fusions can be performed in the elderly (ages 70 years and older) with an overall low rate of major complications. Graft subsidence in this population when not supplemented with posterior instrumentation is a concern. Age should not be a deterrent to performing complex minimally invasive interbody fusions in the elderly.

Clinical Outcomes of Extreme Lateral Interbody Fusion in the Treatment of Adult Degenerative Scoliosis

Introduction. The use of extreme lateral interbody fusion (XLIF) and other lateral access surgery is rapidly increasing in popularity. However, limited data is available regarding its use in scoliosis surgery. The objective of this study was to evaluate the clinical outcomes of adults with degenerative lumbar scoliosis treated with XLIF. Methods. Thirty consecutive patients with adult degenerative scoliosis treated by a single surgeon at a major academic institution were followed for an average of 14.3 months. Interbody fusion was completed using the XLIF technique with supplemental posterior instrumentation. Validated clinical outcome scores were obtained on patients preoperatively and at most recent follow-up. Complications were recorded. Results. The study group demonstrated improvement in multiple clinical outcome scores. Oswestry Disability Index scores improved from 24.8 to 19.0 (P < 0.001). Short Form-12 scores improved, although the change was not significant. Visual analog scores for back pain decreased from 6.8 to 4.6 (P < 0.001) while scores for leg pain decreased from 5.4 to 2.8 (P < 0.001). A total of six minor complications (20%) were recorded, and two patients (6.7%) required additional surgery. Conclusions. Based on the significant improvement in validated clinical outcome scores, XLIF is effective in the treatment of adult degenerative scoliosis.

Extreme lateral interbody fusion for the treatment of adult degenerative scoliosis

Extreme lateral interbody fusion (XLIF; NuVasive Inc., San Diego, CA, USA) is a minimally invasive lateral transpsoas approach to the thoracolumbar spine. Though the procedure is rapidly increasing in popularity, limited data is available regarding its use in deformity surgery. We aimed to evaluate radiographic correction using XLIF in adults with degenerative lumbar scoliosis. Thirty consecutive patients were followed for an average of 14.3 months. Interbody fusion was completed using the XLIF technique with supplemental posterior instrumentation. Plain radiographs were obtained on all patients preoperatively, postoperatively, and at most recent follow-up. Plain radiographic measurements of coronal Cobb angle, apical vertebral translation, segmental lordosis, global lordosis, disc height, neuroforaminal height and neuroforaminal width were made at each time point. CT scans were obtained for all patients 1 year after surgery to evaluate for fusion. There was significant improvement in multiple radiographic parameters from preoperative to postoperative. Cobb angle corrected 72.3%, apical vertebral translation corrected 59.7%, neuroforaminal height increased 80.3%, neuroforaminal width increased 7.4%, and disc height increased 116.7%. Segmental lordosis at L4-L5 increased 14.1% and global lordosis increased 11.5%. There was no significant loss of correction from postoperative to most recent follow-up. There was an 11.8% pseudoarthrosis rate at levels treated with XLIF. Complications included lateral incisional hernia (n=1), rupture of anterior longitudinal ligament (n=2), wound breakdown (n=2), cardiac instability (n=1), pedicle fracture (n=1), and nonunion requiring revision (n=1). XLIF significantly improves coronal plane deformity in patients with adult degenerative scoliosis. XLIF has the ability to correct sagittal plane deformity, although it is most effective at lower lumbar levels.

Attenuation of Inflammatory Events in Human Intervertebral Disc Cells With a Tumor Necrosis Factor Antagonist

Study Design. The inflammatory responses of primary human intervertebral disc (IVD) cells to tumor necrosis factor &agr; (TNF-&agr;) and an antagonist were evaluated in vitro. Objective. To investigate an ability for soluble TNF receptor type II (sTNFRII) to antagonize TNF-&agr;-induced inflammatory events in primary human IVD cells in vitro. Summary of Background Data. TNF-&agr; is a known mediator of inflammation and pain associated with radiculopathy and IVD degeneration. sTNFRs and their analogues are of interest for the clinical treatment of these IVD pathologies, although information on the effects of sTNFR on human IVD cells remains unknown. Methods. IVD cells were isolated from surgical tissues procured from 15 patients and cultured with or without 1.4 nmol/L TNF-&agr; (25 ng/mL). Treatment groups were coincubated with varying doses of sTNFRII (12.5–100 nmol/L). Nitric oxide (NO), prostaglandin E2 (PGE2), and interleukin-6 (IL6) levels in media were quantified to characterize the inflammatory phenotype of the IVD cells. Results. Across all patients, TNF-&agr; induced large, statistically significant increases in NO, PGE2, and IL6 secretion from IVD cells compared with controls (60-, 112-, and 4-fold increases, respectively; P < 0.0001). Coincubation of TNF-&agr; with nanomolar doses of sTNFRII significantly attenuated the secretion of NO and PGE2 in a dose-dependent manner, whereas IL6 levels were unchanged. Mean IC50 values for NO and PGE2 were found to be 35.1 and 20.5 nmol/L, respectively. Conclusion. Nanomolar concentrations of sTNFRII were able to significantly attenuate the effects of TNF-&agr; on primary human IVD cells in vitro. These results suggest this sTNFR to be a potent TNF antagonist with potential to attenuate inflammation in IVD pathology.