Faculty Bibliography

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. It is characterized by demyelination of neurons and loss of neuronal axons and oligodendrocytes. In MS, auto-reactive T cells and B cells cross the blood-brain barrier (BBB), causing perivenous demyelinating lesions that form multiple discrete inflammatory demyelinated plaques located primarily in the white matter. In chronic MS, cortical demyelination and progressive axonal transections develop. Treatment for MS can be stratified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs aim to decrease circulating immune cells or to prevent these cells from crossing the BBB and reduce the inflammatory response. There are currently 10 DMTs approved for the relapsing forms of MS; these vary with regard to their efficacy, route and frequency of administration, adverse effects, and toxicity profile. Better drug delivery systems are being developed in order to decrease adverse effects, increase drug efficacy, and increase patient compliance through the direct targeting of pathologic cells. Here, we address the uses and benefits of advanced drug delivery systems, including nanoparticles, microparticles, fusion antibodies, and liposomal formulations. By altering the properties of therapeutic particles and enhancing targeting, breakthrough drug delivery technologies potentially applicable to multiple disease treatments may rapidly emerge.

BACKGROUND CONTEXT: In transforminal lumbar interbody fusion (TLIF), bilateral pedicle screw/rod fixation has been shown to increase fusion construct stability and decrease posterior instrumentation stress when compared to unilateral instrumentation. However, unilateral instrumentation is beneficial over bilateral instrumentation due to shorter operative time, less blood loss and reduced implant costs. It is important to note though that comparative studies between unilateral and bilateral instrumentation in TLIF have shown similar patient satisfaction outcomes, they are limited in their evaluation of complications due to small sample size of studies. PURPOSE: The purpose of this meta-analysis was to evaluate complications, and fusion rates between unilateral and bilateral instrumentation in TLIF. STUDY DESIGN/SETTING: Meta-analysis of randomized controlled trials. PATIENT SAMPLE: 549 patients undergoing one- and multi-levels TLIF. OUTCOME MEASURES: Outcome data extracted included fusion rates, health related quality of life (HRQoL) scores and complications including cage migration, dural tear, deep vein thrombosis, surgical site infections and screw failures. METHODS: Randomized controlled trials (RCTs) that compared outcomes between unilateral and bilateral pedicle screw instrumentation in single- and multi-level TLIF were identified. Data extraction was performed by two independent reviewers. Meta-analysis was performed using RevMan 5. Weighted standardized mean difference (SMD) and odds ratio (OR) 95% confidence intervals (CI) were calculated. Jadad scoring was used to assess bias of included studies. RESULTS: Eight RCTs were included, having a total of 549 patients (267 unilateral/282 bilateral). Minimum follow-up ranged from 3 to 24 months. Bias-assessment scores varied between 0 and 3 indicating high-moderate bias-risk. Six involved open TLIF procedures and two involved minimally invasive TLIF. There was no difference between postoperative Health Related Quality of Life scores in the unilateral and bilateral instrumented groups (SMD = 0.29; [-0.77, 0.18]; p=0.69). There was no statistical difference in fusion rates (OR = 0.47; 95% CI [0.21, 1.04], p=0.68), with 88.9% and 95.0% achieving fusion in the unilateral and bilateral groups, respectively. The unilateral cohort had a higher incidence of cage migration (5.6%) when compared to the bilateral cohort (2.5%), approaching statically significant (p=0.07). Other complications which included dural tears, deep vein thrombosis, surgical site infections and screw failures were comparable between the groups. CONCLUSIONS: Fusion rates and complications appear comparable in unilateral and bilateral instrumentation in TLIF. Though not statistically significant, there was higher incidence of cage migration in the unilateral cohort

BACKGROUND CONTEXT: Numerous studies have demonstrated poorer outcomes in patients receiving Workers' Compensation following treatment of various health conditions including spine disorders. It is thus important to consider compensation status when assessing treatment outcomes in spine surgery. However, reported strengths of association have varied significantly (1.31-7.22). PURPOSE: The objective of this study was to evaluate the association of unsatisfactory outcomes on compensation status in spine surgery patients. STUDY DESIGN/SETTING: Meta-analysis. PATIENT SAMPLE: 3567 patients undergoing spine surgery. OUTCOME MEASURES: Demographics, type of surgery, country, follow-up time, patient satisfaction, return to work and non-union events. METHODS: Both prospective and retrospective studies that compared outcomes between compensated and non-compensated patients in spine surgery were included. Outcome data extracted by two independent investigators. The meta-analysis was performed using Revman software. Depending on heterogeneity, a fixed or random effects model was used to calculate risk ratio (RR, 95% confidence interval [CI]) for dichotomous variables. RESULTS: 31 studies (13 prospective; 18 retrospective) with a total of 3,567 patients were included in the analysis. Follow-up time varied from 4 months to 10 years. Twelve studies involved only decompression; the rest were fusion. Overall RR of an unsatisfactory outcome was 2.12 [1.74, 2.58; p<0.001] in compensated patients when compared to noncompensated patients after surgery. RR of an unsatisfactory outcome in compensated patients compared to noncompensated was 2.09 [1.38, 3.17]; p< 0.01 among studies from Europe and Australia and 2.14 [1.48, 2.60]; p< 0.01 among US studies. RR of decompression-only procedures was 2.53 [1.85, 3.47] and 1.79 [1.45, 2.21] for fusion. 52% (182/491) of compensated patients returned to work versus 82% (1034/1250) of non-compensated (RR 0.73 [0.59, 0.90]; p<0.001). 25 % (74/292) and 13.5% (39/ 287) of patients had nonunion in the compensated and noncompensated groups, respectively. This was not statistically significant (RR 1.33 [0.92, 1.91]; p=0.07). CONCLUSIONS: Workers' Compensation patients have a two-fold increased risk of an unsatisfactory outcome compared to noncompensated patients after surgery. This association was consistent when studies were grouped by country or procedure. Compensation status must be considered in all surgical intervention studies

BACKGROUND: Wound drains that are left in place for a prolonged period of time have a higher rate of bacterial contamination. Following spinal surgery, a drain is often left in place for a longer period of time if it maintains a high output. Given the major consequences of an infection following spinal surgery and the lack of data with regard to the use of antibiotics and drains, we performed a study of patients with a drain following spinal surgery to compare infection rates between those who were treated with antibiotics for twenty-four hours and those who received antibiotics for the duration for which the drain was in place. METHODS: We performed a prospective randomized trial of 314 patients who underwent multilevel thoracolumbar spinal surgery followed by use of a postoperative drain. The patients were randomized into two groups, one of which received perioperative antibiotics for twenty-four hours (twenty-four-hour group) and the other of which received antibiotics for the duration that the drain was in place (drain-duration group). Data collected included demographic characteristics, medical comorbidities, type of spinal surgery, and surgical site infection. RESULTS: Twenty-one (12.4%) of the 170 patients in the twenty-four-hour group and nineteen (13.2%) of the 144 in the drain-duration group developed a surgical site infection (p = 0.48). There were no significant differences between the twenty-four-hour and drain-duration groups with respect to demographic characteristics (except for the American Society of Anesthesiologists [ASA] classification), operative time, type of surgery, drain output, or length of hospital stay. CONCLUSIONS: Continuing perioperative administration of antibiotics for the entire duration that a drain is in place after spinal surgery did not decrease the rate of surgical site infections. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

STUDY DESIGN: Cohort. OBJECTIVE: To compare the perioperative morbidity of patients with cardiac stents after spine surgery who continue to take aspirin before and after the operation with a similar group of patients who preoperatively discontinued aspirin. SUMMARY OF BACKGROUND DATA: The preoperative discontinuation of anticoagulant therapy has been the standard of care for orthopedic surgical procedures. However, recent literature has demonstrated significant cardiac risk associated with aspirin withdrawal in patients with cardiac stents. Although it has recently been demonstrated that performing orthopedic surgery while continuing low-dose aspirin therapy seems to be safe, studies focused on spinal surgery have not yet been performed. Because of the risk of intraspinal bleeding and the serious consequences of subsequent epidural hematoma with associated spinal cord compression, spinal surgeons have been reluctant to operate on patients taking aspirin. METHODS: This institutional review board-approved study included 200 patients. Preoperative parameters and postoperative outcome measures were analyzed for 100 patients who underwent spinal surgery after the discontinuation of anticoagulation therapy and 100 patients who continued to take daily aspirin through the perioperative period. The primary outcome measure was serious bleeding-related postoperative complications such as spinal epidural hematoma. The operative time, intraoperative estimated blood loss, hospital length of stay, transfusion of blood products, and 30-day hospital readmission rates were also recorded and compared. RESULTS: The patients who continued taking aspirin in the perioperative period had a shorter hospital length of stay on average (4.1 +/- 2.7 vs. 6.2 +/- 5.8; P < 0.005), as well as a reduced operative time (210 +/- 136 vs. 266 +/- 143; P < 0.01), whereas there was no significant difference in the estimated blood loss (642 +/- 905 vs. 697 +/- 1187), the amount of blood products transfused, overall intra- and postoperative complication rate (8% vs. 11%), or 30-day hospital readmission rate (5% vs. 5%). No clinically significant spinal epidural hematomas were observed in either of the study groups. CONCLUSION: The current study has observed no appreciable increase in bleeding-related complication rates in patients with cardiac stents undergoing spine surgery while continuing to take aspirin compared with patients who discontinued aspirin prior to surgery. Although very large studies will be needed to determine whether aspirin administration results in a small complication rate increase, the current study provides evidence that perioperative aspirin therapy is relatively safe in patients undergoing spinal surgery. LEVEL OF EVIDENCE: 2.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To assess the rate and causes of unplanned readmissions after surgical treatment of common degenerative lumbar pathologies within 90 days. SUMMARY OF BACKGROUND DATA: With pay-for performance and bundled payment compensation models being implemented; there is a growing emphasis to decrease the number of unplanned readmissions after surgery. Reports on degenerative lumbar spine pathology readmission rates are often obtained from national databases that lack clinical detail. Less published are the results from single-center institutions. METHODS: Hospital administrative database from a single-tertiary institution was queried to identify patients who underwent surgery for 6 common lumbar pathologies during a period from 2011 to 2013. All readmissions within 90 days of discharge were reviewed for cause and rate of unplanned readmissions was calculated. RESULTS: A total of 1306 patients were identified who underwent surgery for various lumbar pathologies during a 2-year time period. There were a total of 70 readmissions captured in the database that included 14 planned, 43 unplanned readmissions, and 13 coding errors. The unplanned readmission rate varied between 2.1% and 7.1% depending on pathology, with an overall rate of 3.3% within 90 days of discharge. Index length of stay, discharge disposition, severity of illness scores, and surgical approach were associated with readmission. The addition of fusion to decompression procedures did not seem to increase readmission rates. Surgical site infections and wound complications were the 2 most common reasons for readmissions accounting for 72% of all readmissions during the 90-day postdischarge period. CONCLUSION: The rate of readmission after surgery for common lumbar degenerative pathologies is relatively low. Surgical site infections and wound complications were the most common cause of readmission in this patient cohort. LEVEL OF EVIDENCE: 4.

BACKGROUND: Unplanned hospital readmissions result in significant clinical and financial burdens to patients and the healthcare system. Readmission rates and causes have been investigated using large administrative databases which have certain limitations in data reporting and coding. The objective of this study was to provide a description of 90 day post-discharge readmissions following surgery for common degenerative cervical spine pathologies at a large-volume tertiary hospital. The study also compared the readmission rates of patients who underwent anterior- and posterior-approach procedures. METHODS: The administrative records from a single-center, high-volume tertiary institution were queried using ICD-9 codes for common cervical pathology over a three year period to determine the rate and causes of readmissions within the 90 days following the index surgery. RESULTS: A total of 768 patients underwent degenerative cervical spine surgery during the three year study period. Within 90 days of discharge, 24 (3.13%) patients were readmitted; 16 (2.06%) readmissions were planned for lumbar surgery; 8 (1.04%) readmissions were unplanned. 640 patients underwent procedures involving an anterior approach and 128 patients underwent procedures involving a posterior approach. There were 14 (2.17%) planned readmissions in the anterior group and 2 (1.5%) in the posterior group. The unplanned readmission rate was 0.63% (4 patients) and 3.13% (4 patients) in the anterior and posterior groups, respectively. (p=0.0343). CONCLUSION: The 90 day post-discharge unplanned readmission rate that followed elective degenerative cervical spine surgery was 1.04%. The unplanned readmission rate associated with posterior-approach procedures (3.13%) was significantly higher than that of anterior-approach procedures (0.63%). LEVEL OF EVIDENCE: IV.

BACKGROUND CONTEXT: Intraoperative neuromonitoring (IOM) of spinal cord and nerve root injury through somatosensory evoked potentials (SSEP), transcranial motor evoked potentials (TcMEP), spontaneous electromyography (sEMG), and triggered electromyography (tEMG) modalities is vital during spinal surgery. However, there are currently no practice guidelines or practice patterns for the utilization of unimodal or multimodal IOM (MIOM) for specific spinal surgeries. PURPOSE: This pilot study documents practice patterns of IOM for select spinal procedures. STUDY DESIGN/SETTING: Questionnaire survey. PATIENT SAMPLE: 22 fellowship-trained spine surgeons, both surgeons and neurosurgeons, were queried on use of IOM modality combination in various spine procedures. Surgical experience varied from three to 29 years, with an average of 14.4 years. OUTCOME MEASURES: Percentage of surgeons using IOM modality or MIOM combination was calculated for each procedure. METHODS: Spine surgeons at two hospitals were surveyed on practice patterns of use of intraoperative monitoring for three deformity procedures and 21 non-deformity procedures. RESULTS: Of the 18 (81%) responses received: 15 from orthopaedic surgeons and 3 from neurosurgeons. Deformity Surgery: For both cervical and thoracic deformity surgeries, all surgeons used at least SSEP+TcMEP. For cervical surgeries, 47% of surgeons additionally used sEMG while for thoracic 71% of surgeons additionally used sEMG+tEMG. Most surgeons (44%) used all four modalities for lumbar deformity surgery. Non-Deformity surgery: For patients having radiculopathy undergoing ACDF, SSEP alone was utilized by 29%. However, in patients undergoing ACDF with symptoms of myelopathy, most surgeons (31%) used SSEP+TcMEP with only 13% using SSEP only. Fourty-six percent of surgeons utilized SSEP+TcMEP+sEMG for cervical arthroplasty procedures. SSEP+ TcMEP+sEMG was most commonly used for posterior cervical laminoforaminotomy, posterior cervical laminectomy and posterior cervical laminect!