Senolytic Combination Treatment Is More Potent Than Single Drugs in Reducing Inflammatory and Senescence Burden in Cells from Painful Degenerating IVDs.

BACKGROUND: Low back pain is a global health problem directly related to intervertebral disc (IVD) degeneration. Senolytic drugs (RG-7112 and o-Vanillin) target and remove senescent cells from IVDs in vitro, improving tissue homeostasis. One drawback of using a single senolytic agent is the failure to target multiple senescent antiapoptotic pathways. This study aimed to determine if combining the two senolytic drugs, o-Vanillin and RG-7112, could more efficiently remove senescent cells and reduce the release of inflammatory factors and pain mediators in cells from degenerating human IVDs than either drug alone. METHODS: Preliminary data evaluating multiple concentrations of o-Vanillin and RG-7112 led to the selection of four treatment groups. Monolayer and pellet cultures of cells from painful degenerate IVDs were exposed to TLR-2/6 agonist. They were then treated with the senolytics o-Vanillin and RG7112 alone or combined. p16ink4a, Ki-67, caspase-3, inflammatory mediators, and neuronal sprouting were assessed. RESULTS: Compared to the single treatments, the combination of o-Vanillin and RG-7112 significantly reduced the amount of senescent IVD cells, proinflammatory cytokines, and neurotrophic factors. Moreover, both single and combination treatments significantly reduced neuronal sprouting in rat adrenal pheochromocytoma (PC-12 cells). CONCLUSIONS: Combining o-Vanillin and RG-7112 greatly enhanced the effect of either senolytic alone. Together, these results support the potential of senolytics as a promising treatment for IVD-related low back pain.

o-Vanillin Modulates Cell Phenotype and Extracellular Vesicles of Human Mesenchymal Stem Cells and Intervertebral Disc Cells.

Human mesenchymal stem cell (hMSC) and extracellular vesicle (EV) therapy is a promising treatment for discogenic low back pain (LBP). Although promising, major obstacles remain to be overcome. Cellular senescence reduces self-renewal and multipotent potentials, and the senescence-associated secretory phenotype creates an inflammatory environment negatively affecting tissue homeostasis. Reducing senescence could therefore improve regenerative approaches. Ortho-Vanillin (o-Vanillin) has senolytic activity and anti-inflammatory properties and could be a valuable supplement to MSC and EV therapy. Here, we used direct co-culture experiments to evaluate proteoglycan synthesis, inflammatory mediators, and senescent cells in the presence or absence of o-Vanillin. EV release and transfer between hMSCs and intervertebral disc cells (DCs) was examined, and the effect on hMSC differentiation and DC phenotype was evaluated in the presence and absence of o-Vanillin. This study demonstrates that o-Vanillin affects cell communication, enhances hMSC differentiation and improves DC phenotype. Co-cultures of DCs and hMSCs resulted in increased proteoglycan synthesis, a decreased number of senescent cells and decreased release of the cytokines IL6 and 8. Effects that were further enhanced by o-Vanillin. o-Vanillin profoundly increased EV release and/or uptake by hMSCs and DCs. DC markers were significantly upregulated in both cell types in response to conditioned media of o-Vanillin treated donor cells. Collectively, this study demonstrates that o-Vanillin affects hMSC and DC crosstalk and suggests that combining hMSCs and senolytic compounds may improve the outcome of cell supplementation and EV therapy for LBP.

Pseudotumor after total disc replacement in the lumbar spine: A case report and review of the literature.

Background: Total disc replacement as a treatment for degenerative disc disease is gaining increased popularity. There is limited data in the literature about formation of a pseudotumor as a complication following this procedure. We report a very rare case of a pseudotumor after a lumbar total disc replacement with a review of the literature. Methods: A case study of a 49-year-old lady, who underwent L4-L5 total disc replacement and presented one year later with progressive back pain radiating to both lower extremities. Imaging revealed a soft tissue mass around the prosthesis. A review of the literature for similar cases has been done and reviewed. Results: Imaging revealed a soft tissue mass around the prosthesis and left hydronephrosis. CT venogram for leg swelling showed total occlusion of the left common iliac vein. CT myelogram showed compression of the cauda from the pseudotumor. The prosthesis was removed and replaced by an allograft fusion cage and plate. Intraoperatively both extremities became pulseless and bilateral common iliac arteries thrombectomy was carried out. This occurred again after closure immediately and bilaterally femoral artery exploration and thrombectomy was carried out. Histopathology showed a soft tissue with fibrinous necrosis and lymphohistiocytic inflammation. Conclusion: Soft tissue reaction and pseudotumor formation can be induced by Metal-on-Metal total disc replacement prostheses. Neurologic, vascular, and visceral complications may occur. In this case implant removal can stopped progression of the soft tissue reaction. Most patients in the literature benefit from implant removal followed by spinal fusion.

National adverse event profile after lumbar spine surgery for lumbar degenerative disorders and comparison of complication rates between hospitals: a CSORN registry study.

OBJECTIVE: Previous works investigating rates of adverse events (AEs) in spine surgery have been retrospective, with data collection from administrative databases, and often from single centers. To date, there have been no prospective reports capturing AEs in spine surgery on a national level, with comparison among centers. METHODS: The Spine Adverse Events Severity system was used to define the incidence and severity of AEs after spine surgery by using data from the Canadian Spine Outcomes and Research Network (CSORN) prospective registry. Patient data were collected prospectively and during hospital admission for those undergoing elective spine surgery for degenerative conditions. The Spine Adverse Events Severity system defined minor and major AEs as grades 1-2 and 3-6, respectively. RESULTS: There were 3533 patients enrolled in this cohort. There were 85 (2.4%) individual patients with at least one major AE and 680 (19.2%) individual patients with at least one minor AE. There were 25 individual patients with 28 major intraoperative AEs and 260 patients with 275 minor intraoperative AEs. Postoperatively there were 61 patients with a total of 80 major AEs. Of the 487 patients with minor AEs postoperatively there were 698 total AEs. The average enrollment was 321 patients (range 47-1237 patients) per site. The rate of major AEs was consistent among sites (mean 2.9% ± 2.4%, range 0%-9.1%). However, the rate of minor AEs varied widely among sites-from 7.9% to 42.5%, with a mean of 18.8% ± 9.7%. The rate of minor AEs varied depending on how they were reported, with surgeon reporting associated with the lowest rates (p < 0.01). CONCLUSIONS: The rate of major AEs after lumbar spine surgery is consistent among different sites but the rate of minor AEs appears to vary substantially. The method by which AEs are reported impacts the rate of minor AEs. These data have implications for the detection and reporting of AEs and the design of strategies aimed at mitigating complications.

Toll-like receptor 2 induced senescence in intervertebral disc cells of patients with back pain can be attenuated by o-vanillin.

BACKGROUND: There is an increased level of senescent cells and toll-like teceptor-1, -2, -4, and -6 (TLR) expression in degenerating intervertebral discs (IVDs) from back pain patients. However, it is currently not known if the increase in expression of TLRs is related to the senescent cells or if it is a more general increase on all cells. It is also not known if TLR activation in IVD cells will induce cell senescence. METHODS: Cells from non-degenerate human IVD were obtained from spine donors and cells from degenerate IVDs came from patients undergoing surgery for low back pain. Gene expression of TLR-1,2,4,6, senescence and senescence-associated secretory phenotype (SASP) markers was evaluated by RT-qPCR in isolated cells. Matrix synthesis was verified with safranin-O staining and Dimethyl-Methylene Blue Assay (DMMB) confirmed proteoglycan content. Protein expression of p16INK4a, SASP factors, and TLR-2 was evaluated by immunocytochemistry (ICC) and/or by enzyme-linked immunosorbent assay (ELISA). RESULTS: An increase in senescent cells was found following 48-h induction with a TLR-2/6 agonist in cells from both non-degenerate and degenerating human IVDs. Higher levels of SASP factors, TLR-2 gene expression, and protein expression were found following 48-h induction with TLR-2/6 agonist. Treatment with o-vanillin reduced the number of senescent cells, and increased matrix synthesis in IVD cells from back pain patients. Treatment with o-vanillin after induction with TLR-2/6 agonist reduced gene and protein expression of SASP factors and TLR-2. Co-localized staining of p16INK4a and TLR-2 demonstrated that senescent cells have a high TLR-2 expression. CONCLUSIONS: Taken together our data demonstrate that activation of TLR-2/6 induce senescence and increase TLR-2 and SASP expression in cells from non-degenerate IVDs of organ donors without degeneration and back pain and in cells from degenerating human IVD of patients with disc degeneration and back pain. The senescent cells showed high TLR-2 expression suggesting a link between TLR activation and cell senescence in human IVD cells. The reduction in senescence, SASP, and TLR-2 expression suggest o-vanillin as a potential disease-modifying drug for patients with disc degeneration and back pain.

Preoperative Factors Predict Postoperative Trajectories of Pain and Disability Following Surgery for Degenerative Lumbar Spinal Stenosis.

STUDY DESIGN: Longitudinal analysis of prospectively collected data. OBJECTIVE: Investigate potential predictors of poor outcome following surgery for degenerative lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA: LSS is the most common reason for an older person to undergo spinal surgery, yet little information is available to inform patient selection. METHODS: We recruited LSS surgical candidates from 13 orthopedic and neurological surgery centers. Potential outcome predictors included demographic, health, clinical, and surgery-related variables. Outcome measures were leg and back numeric pain rating scales and Oswestry disability index scores obtained before surgery and after 3, 12, and 24 postoperative months. We classified surgical outcomes based on trajectories of leg pain and a composite measure of overall outcome (leg pain, back pain, and disability). RESULTS: Data from 529 patients (mean [SD] age = 66.5 [9.1] yrs; 46% female) were included. In total, 36.1% and 27.6% of patients were classified as experiencing a poor leg pain outcome and overall outcome, respectively. For both outcomes, patients receiving compensation or with depression/depression risk were more likely, and patients participating in regular exercise were less likely to have poor outcomes. Lower health-related quality of life, previous spine surgery, and preoperative anticonvulsant medication use were associated with poor leg pain outcome. Patients with ASA scores more than two, greater preoperative disability, and longer pain duration or surgical waits were more likely to have a poor overall outcome. Patients who received preoperative chiropractic or physiotherapy treatment were less likely to report a poor overall outcome. Multivariable models demonstrated poor-to acceptable (leg pain) and excellent (overall outcome) discrimination. CONCLUSION: Approximately one in three patients with LSS experience a poor clinical outcome consistent with surgical non-response. Demographic, health, and clinical factors were more predictive of clinical outcome than surgery-related factors. These predictors may assist surgeons with patient selection and inform shared decision-making for patients with symptomatic LSS. LEVEL OF EVIDENCE: 2.

Opioid use trends in patients undergoing elective thoracic and lumbar spine surgery.

Background: Opioid use in North America has increased rapidly in recent years. Preoperative opioid use is associated with several negative outcomes. Our objectives were to assess patterns of opioid use over time in Canadian patients who undergo spine surgery and to determine the effect of spine surgery on 1-year postoperative opioid use. Methods: A retrospective analysis was performed on prospectively collected data from the Canadian Spine Outcomes and Research Network for patients undergoing elective thoracic and lumbar surgery. Self-reported opioid use at baseline, before surgery and at 1 year after surgery was compared. Baseline opioid use was compared by age, sex, radiologic diagnosis and presenting complaint. All patients meeting eligibility criteria from 2008 to 2017 were included. Results: A total of 3134 patients provided baseline opioid use data. No significant change in the proportion of patients taking daily (range 32.3%-38.2%) or intermittent (range 13.7%-22.5%) opioids was found from pre-2014 to 2017. Among patients who waited more than 6 weeks for surgery, the frequency of opioid use did not differ significantly between the baseline and preoperative time points. Significantly more patients using opioids had a chief complaint of back pain or radiculopathy than neurogenic claudication (p < 0.001), and significantly more were under 65 years of age than aged 65 years or older (p < 0.001). Approximately 41% of patients on daily opioids at baseline remained so at 1 year after surgery. Conclusion: These data suggest that additional opioid reduction strategies are needed in the population of patients undergoing elective thoracic and lumbar spine surgery. Spine surgeons can be involved in identifying patients taking opioids preoperatively, emphasizing the risks of continued opioid use and referring patients to appropriate evidence-based treatment programs.

Contexte: En Amérique du Nord, l'utilisation d'opioïdes a augmenté rapidement dans les dernières années. La prise d'opioïdes en période préopératoire est associée à plusieurs issues négatives. Cette étude visait à évaluer l'évolution des tendances dans l'utilisation d'opioïdes des patients canadiens ayant subi une chirurgie spinale, et de déterminer les effets de la chirurgie sur leur utilisation 1 an après l'opération. Méthodes: Une analyse rétrospective a été réalisée à partir de données recueillies de manière prospective par le Canadian Spine Outcomes and Research Network pour les patients ayant subi une chirurgie thoracique ou une chirurgie spinale élective. On a comparé l'utilisation autodéclarée d'opioïdes au début du suivi, avant la chirurgie et 1 an après la chirurgie. L'utilisation d'opioïdes au départ a été comparée selon le sexe, l'âge, le diagnostic radiologique et le motif de consultation. Entre 2008 et 2017, tous les patients satisfaisant aux critères d'admissibilités ont été inclus dans l'étude. Résultats: Au total, 3134 patients ont fourni des données sur leur prise d'opioïdes au début du suivi. Il n'y avait pas de changement significatif dans la proportion de patients utilisant quotidiennement (32,3 % à 38,2 %) ou occasionnellement (13,7 % à 22,5 %) des opioïdes entre les patients à l'étude avant 2014 et ceux à l'étude de 2014 à 2017. Parmi les patients qui ont attendu plus de 6 semaines avant la chirurgie, la fréquence de la prise d'opioïdes n'a pas changé de manière significative entre le début du suivi et la rencontre préopératoire. Une proportion significativement plus grande de patients qui utilisaient des opioïdes consultaient principalement pour des douleurs au dos ou une radiculopathie que pour une claudication neurogène (p < 0,001), et il y avait une proportion significativement plus grande de patients de moins de 65 ans qui utilisaient des opioïdes que de patients de 65 ans ou plus (p < 0,001). Environ 41 % des patients qui prenaient quotidiennement des opioïdes au départ le faisaient aussi 1 an après la chirurgie. Conclusion: Ces données suggèrent que des stratégies supplémentaires de réduction de l'utilisation d'opioïdes sont nécessaires pour les patients qui subissent une chirurgie thoracique ou une chirurgie spinale élective. Il est possible de demander aux chirurgiens spécialisés dans ce domaine de repérer les patients qui prennent des opioïdes avant l'opération, puisque l'utilisation prolongée comporte des risques, et de les aiguiller vers un programme de traitement adéquat et fondé sur des données probantes.

Patients undergoing surgery for lumbar spinal stenosis experience unique courses of pain and disability: A group-based trajectory analysis.

OBJECTIVE: Identify patient subgroups defined by trajectories of pain and disability following surgery for degenerative lumbar spinal stenosis, and investigate the construct validity of the subgroups by evaluating for meaningful differences in clinical outcomes. METHODS: We recruited patients with degenerative lumbar spinal stenosis from 13 surgical spine centers who were deemed to be surgical candidates. Study outcomes (leg and back pain numeric rating scales, modified Oswestry disability index) were measured before surgery, and after 3, 12, and 24 months. Group-based trajectory models were developed to identify trajectory subgroups for leg pain, back pain, and pain-related disability. We examined for differences in the proportion of patients achieving minimum clinically important change in pain and disability (30%) and clinical success (50% reduction in disability or Oswestry score ≤22) 12 months from surgery. RESULTS: Data from 548 patients (mean[SD] age = 66.7[9.1] years; 46% female) were included. The models estimated 3 unique trajectories for leg pain (excellent outcome = 14.4%, good outcome = 49.5%, poor outcome = 36.1%), back pain (excellent outcome = 13.1%, good outcome = 45.0%, poor outcome = 41.9%), and disability (excellent outcome = 30.8%, fair outcome = 40.1%, poor outcome = 29.1%). The construct validity of the trajectory subgroups was confirmed by between-trajectory group differences in the proportion of patients meeting thresholds for minimum clinically important change and clinical success after 12 postoperative months (p < .001). CONCLUSION: Subgroups of patients with degenerative lumbar spinal stenosis can be identified by their trajectories of pain and disability following surgery. Although most patients experienced important reductions in pain and disability, 29% to 42% of patients were classified as members of an outcome trajectory subgroup that experienced little to no benefit from surgery. These findings may inform appropriate expectation setting for patients and clinicians and highlight the need for better methods of treatment selection for patients with degenerative lumbar spinal stenosis.

Effect of preoperative symptom duration on outcome in lumbar spinal stenosis: a Canadian Spine Outcomes and Research Network registry study.

BACKGROUND CONTEXT: Lumbar degenerative stenosis is one of the most common spine pathologies for which surgical intervention is indicated. There is some evidence that a prolonged duration of neurological compression could lead to a failure of surgery to alleviate symptoms. PURPOSE: Determination of whether longer symptom duration was associated with worse postoperative disability outcomes after decompressive surgery for lumbar degenerative stenosis. STUDY DESIGN/SETTING: The Canadian Spine Outcomes and Research Network (CSORN) prospective database includes pre- and postoperative data from 18 tertiary care hospitals. PATIENT SAMPLE: The CSORN database was queried for all cases of degenerative lumbar stenosis receiving surgical decompression for neurogenic claudication or radiculopathy. Patients with tumor, infection, fracture, or previous surgery were excluded. Patients were divided into groups based on symptom duration (<6 weeks, 6-12 weeks, 3-6 months, 6-12 months, 1-2 years, and >2 years). OUTCOME MEASURES: Change between preoperative and 12-month postoperative Oswestry Disability Index (ODI) was compared between symptom duration groups. Secondary outcomes included SF12 physical component score (PCS), and numeric rating scales for leg and back pain. Outcomes were also assessed at 3 months and 24 months postoperatively. METHODS: Change in ODI, and secondary outcome measures, were compared between different symptom duration groups. Multiple regression analysis was used to identify factors interacting with symptom duration to predict change in ODI. RESULTS: Four hundred and seventy-eight cases of lumbar stenosis with 12-month postoperative data were identified. Longer symptom duration correlated with less improvement in ODI (p<.001). Patients with >1 year of symptoms were less likely to achieve a Minimal Clinically Significant Difference in ODI (54.4% vs. 66.1%; p=.03) and were more likely to experience no improvement or worse disability, postoperatively (22.1% vs. 11.3%; p=.008). Similar results were found at 3- and 24-month timepoints. Smaller postoperative improvements in SF12 PCS and leg pain scales were also correlated with longer symptom duration (p<.05). CONCLUSIONS: Multicenter registry data provides important real-world evidence to guide consent, surgical planning, and health resource management. Longer symptom duration was found to correlate with less improvement in pain and disability after lumbar stenosis surgery suggesting that these patients may benefit from earlier treatment.

Curcumin and o-Vanillin Exhibit Evidence of Senolytic Activity in Human IVD Cells In Vitro.

Curcumin and o-Vanillin cleared senescent intervertebral disc (IVD) cells and reduced the senescence-associated secretory phenotype (SASP) associated with inflammation and back pain. Cells from degenerate and non-mildly-degenerate human IVD were obtained from organ donors and from patients undergoing surgery for low back pain. Gene expression of senescence and SASP markers was evaluated by RT-qPCR in isolated cells, and protein expression of senescence, proliferation, and apoptotic markers was evaluated by immunocytochemistry (ICC). The expression levels of SASP factors were evaluated by enzyme-linked immunosorbent assay (ELISA). Matrix synthesis was verified with safranin-O staining and the Dimethyl-Methylene Blue Assay for proteoglycan content. Western blotting and ICC were used to determine the molecular pathways targeted by the drugs. We found a 40% higher level of senescent cells in degenerate compared to non-mildly-degenerate discs from unrelated individuals and a 10% higher level in degenerate compared to non-mildly-degenerate discs from the same individual. Higher levels of senescence were associated with increased SASP. Both drugs cleared senescent cells, and treatment increased the number of proliferating as well as apoptotic cells in cultures from degenerate IVDs. The expression of SASP factors was decreased, and matrix synthesis increased following treatment. These effects were mediated through the Nrf2 and NFkB pathways.

Spontaneous Spinal Epidural Hematoma: Correlation of Timing of Surgical Decompression and MRI Findings with Functional Neurological Outcome.

OBJECTIVE: Spontaneous spinal epidural hematoma (SSEH) is a rare and morbid entity, with the prognosis affected by delayed diagnosis and surgical intervention. The correlation between the timing of the intervention and neurological recovery has not been clearly reported. We present a retrospective study of SSEH to determine the correlation between the timing of surgical intervention and changes in the spinal cord signal on magnetic resonance imaging (MRI) with the neurological outcome. METHODS: The records of 14 patients who had undergone surgical decompression of SSEHs during a 10-year duration were reviewed. The diagnosis was established from the MRI, intraoperative, and histopathological examination findings. RESULTS: We identified 14 patients from both centers, 6 of whom were male. Their mean age was 54.1 years. The onset was spontaneous, and 2 patients were receiving anticoagulant therapy. The most common presentation was paraplegia (n = 8), followed by paraparesis (n = 3) and quadriparesis (n = 2). Spinal cord signal changes were demonstrated on all T2-weighted MRI studies. The response to surgery was favorable for 13 of our patients at the 6-month follow-up examination. The spinal cord changes had persisted in 5 patients on the 6-month postoperative MRI scan. All 14 patients, except for 1, had a favorable neurological outcome at the last follow-up examination. CONCLUSIONS: Significant neurological recovery after surgical decompression of SSEHs can be achieved, despite the significant preoperative neurological deficits, spinal cord changes on MRI, and delayed timing of intervention.

Factors Associated With Clinical Outcomes After Lumbar Interbody Fusion With a Porous Nitinol Implant.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: The aim of this study is to assess the association of demographic and perioperative factors with clinical outcomes of lumbar interbody fusion with a porous nitinol (TiNi) implant for degenerative disc disease. METHODS: Forty-one patients with degenerative lumbar disease were prospectively followed for a mean of 4.8 years. All patients were instrumented with porous TiNi interbody fusion devices. The Oswestry Disability Index (ODI) and return to work were used to assess clinical outcomes. Factors including age, body mass index, smoking status, insurance status, number of comorbidities, duration of surgery, estimated blood loss, number of levels fused, time since surgery, and preoperative ODI score were assessed. A multiple linear regression analysis was performed to look for demographic and perioperative factors associated with clinical outcome. RESULTS: All patients except one (98%) showed complete fusion on radiography at 1 year. Estimated blood loss and duration of surgery were significantly associated with higher postoperative ODI scores (P = .002 and P = .019, respectively). Smoking status, salary insurance status, age, body mass index, number of comorbidities, number of levels fused, time since surgery, and preoperative ODI score were not significantly associated with outcome. CONCLUSIONS: Porous nitinol permitted fusion rates similar to those reported in the literature for alternative fusion cages. Poor functional outcome of patients was strongly associated with intraoperative blood loss and duration of surgery. We believe that estimated blood loss should be carefully evaluated in studies of postoperative outcome, as it may affect midterm outcomes. LEVEL OF EVIDENCE: Level 3.

Prevalence and Complications of Postoperative Transfusion for Cervical Fusion Procedures in Spine Surgery: An Analysis of 11,588 Patients from the American College of Surgeons National Surgical Quality Improvement Program Database.

STUDY DESIGN: Retrospective cohort study. PURPOSE: The purpose of this study was to assess the rate of blood transfusion after cervical fusion surgery, and its effect on complication rates. OVERVIEW OF LITERATURE: Cervical spine fusions have gained interest in the literature since these procedures are now ever more frequently being performed in an outpatient setting with few complications. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients that underwent cervical fusion from 2010 to 2013. Multivariate regression analysis was used to determine postoperative complications associated with transfusion and cervical fusion. RESULTS: We identified 11,588 patients who had cervical fusion between 2010 and 2013. The rate of blood transfusion following cervical fusion found to be 1.47%. All transfused patients were found to have increased risk of venous thromboembolism (TBE) (odds ratio [OR], 3.19; 95% confidence interval [95% CI], 1.16-8.77), myocardial infarction (MI) (OR, 9.12; 95% CI, 2.53-32.8), increased length of stay (LOS) (OR, 28.03; 95% CI, 14.28-55.01) and mortality (OR, 4.14; 95% CI, 1.44-11.93). Single level fusion had increased risk of TBE (OR, 3.37; 95% CI, 1.01-11.33), MI (OR, 10.5; 95% CI, 1.88-59.89), and LOS (OR, 14.79; 95% CI, 8.2-26.67). Multilevel fusion had increased risk of TBE (OR, 5.64; 95% CI, 1.15-27.6), surgical site infection (OR, 16.29; 95% CI, 3.34-79.49), MI (OR, 10.84; 95% CI, 2.01-58.55), LOS (OR, 26.56; 95% CI, 11.8-59.78), and mortality (OR, 10.24; 95% CI, 2.45-42.71). Patients who had anterior cervical discectomy and fusion surgery and received a transfusion had an increased risk of TBE (OR, 4.87; 95% CI, 1.04-22.82), surgical site infection (OR, 9.73; 95% CI, 2.14-44.1), MI (OR, 9.88; 95% CI, 1.87-52.2), increased LOS of more than 2 days (OR, 28.34; 95% CI, 13.79-58.21) and increase in mortality (OR, 6.3; 95% CI, 1.76-22.48). While, transfused patients who had posterior fusion surgery had increased risk of MI (OR, 10.45; 95% CI, 1.42-77.12) and increased LOS of more than 6 days (OR, 4.42; 95% CI, 2.68-7.29). CONCLUSIONS: Our results demonstrate that although cervical fusions can be done as outpatient procedures special precautions and investigations should be done for patients who receive transfusion after cervical fusion. These patients are demonstrated to have higher rate of MI, TBE, wound infection and mortality when compared to those who do not receive transfusion.

Differences between Manufacturers of Computed Tomography-Based Computer-Assisted Surgery Systems Do Exist: A Systematic Literature Review.

STUDY DESIGN: Literature review. OBJECTIVE: Several studies have shown that the accuracy of pedicle screw placement significantly improves with use of computed tomography (CT)-based navigation systems. Yet, there has been no systematic review directly comparing accuracy of pedicle screw placement between different CT-based navigation systems. The objective of this study is to review the results presented in the literature and compare CT-based navigation systems relative only to screw placement accuracy. METHODS: Data sources included CENTRAL, Medline, PubMed, and Embase databases. Studies included were randomized clinical trials, case series, and case-control trials reporting the accuracy of pedicle screws placement using CT-based navigation. Two independent reviewers extracted the data from the selected studies that met our inclusion criteria. Publications were grouped based on the CT-based navigation system used for pedicle screw placement. RESULTS: Of the 997 articles we screened, only 26 met all of our inclusion criteria and were included in the final analysis, which showed a significant statistical difference (p < 0.0001, 95% confidence interval 0.92 to 1.23) in accuracy of pedicle screw placement between three different CT-based navigation systems. The mean (weighted) accuracy of pedicle screws placement based on the CT-based navigation system was found to be 97.20 ± 2.1% in StealthStation (Medtronic, United States) and 96.1 ± 3.9% in VectorVision (BrainLab, Germany). CONCLUSION: This review summarizes results presented in the literature and compares screw placement accuracy using different CT-based navigation systems. Although certain factors such as the extent of the procedure and the experience and skills of the surgeon were not accounted for, the differences in accuracy demonstrated should be considered by spine surgeons and should be validated for effects on patients' outcome.

Spontaneous spinal epidural hematoma management: a case series and literature review.

OBJECTIVE: Spontaneous spinal epidural hematoma (SSEH) manifests from blood accumulating in the epidural space, compressing the spinal cord and leading to acute neurological deficits. Standard therapy is decompressive laminectomy, although spontaneous recoveries have been reported. Sub-optimal therapeutic principles contribute to SSEH's 5.7% mortality-which patient will benefit from surgery remains unclear. This study aims to investigate parameters that affect SSEH's progression, outlining a best-practice therapeutic approach. MATERIALS AND METHODS: Literature review yielded 65 cases from 12 studies. Furthermore, 6 cases were presented from our institution. All data were analyzed under American Spinal Injury Association (ASIA) score guidelines. RESULTS: Fifty percent of SSEH patients do not fully recover. In all, 30% of patients who presented with an ASIA score of A did not improve with surgery, although every SSEH patient who presented at C or D improved. Spontaneous recovery is rare-only 23% of patients were treated conservatively. Seventy-three percent of those made a full recovery, as opposed to the 48% improvement in patients managed surgically. Thirty-three percent of patients managed conservatively had an initial score of A or B, all improving to a score of D or E without surgery. Regardless, conservative management tends toward low-risk presentations. Patients managed conservatively were three times as likely to have an initial score of D than their surgically managed counterparts. DISCUSSION: The degree of pre-operative neural deficit is a major prognostic factor. Conservative management has proven effective, although feasible only if spontaneous recovery is manifested. Decompressive laminectomy should continue to remain readily available, given the inverse correlation between operative interval and recovery.

Nonsurgical management of an extensive spontaneous spinal epidural hematoma causing quadriplegia and respiratory distress in a choledocholithiasis patient: A case report.

RATIONALE: Spontaneous spinal epidural hematoma (SSEH) manifests from blood accumulating in the epidural space, compressing the spinal cord, and leading to acute neurological deficits. The disease's cloudy etiology and rarity contribute to dangerously suboptimal therapeutic principles. These neural deficits can be permanent, even fatal, if the SSEH is not treated in a timely and appropriate manner. Standard therapy is decompressive laminectomy, though nonsurgical management is a viable course of action for patients who meet a criterion that is continuously being refined. PATIENT CONCERNS: A 76-year-old woman on warfarin for a past pulmonary embolism presented to the emergency room with jaundice, myalgia, hematuria, neck pain, and an International Normalized Ratio (INR) of 14. Upon admission, she rapidly developed quadriplegia and respiratory distress that necessitated intubation. DIAGNOSES: T2-weighted magnetic resonance imaging (MRI) revealed an epidural space-occupying hyperintensity from C2 to S5 consistent with a spinal epidural hematoma. An incidental finding of dilated intrahepatic and common bile ducts prompted an endoscopic retrograde cholangiopancreatography, which demonstrated choledocholithiasis. INTERVENTIONS: The patient's INR was normalized with Vitamin K and Beriplex. Upon transfer to the surgical spine team for assessment of a possible intervention, the patient began to demonstrate recovery of neural functions. The ensuing sustained motor improvement motivated the team's preference for close neurologic monitoring and continued medical therapy over surgery. Thirteen hours after the onset of her symptoms, the patient was extubated. A sphincterotomy was later performed, removing 81 common bile duct stones. OUTCOMES: MRI demonstrated complete resorption of the SSEH and the patient maintained full neurological function at final follow-up. LESSONS: Nonsurgical management of SSEH should be considered in the context of early and sustained recovery. Severe initial neural deficit does not necessitate surgical decompression. Choledocholithiasis and subsequent Vitamin K deficiency, particularly when coupled with anticoagulant use, can increase INR and is a novel proposed risk factor for SSEH. Furthermore, coagulopathies should be medically corrected before surgical intervention within a given timeframe, as spontaneous recovery may manifest. This should be favored over surgery in patients demonstrating early and sustained recovery, as nonsurgical management is 25% more effective in achieving full recovery.

Incidence, Predictors, and Postoperative Complications of Blood Transfusion in Thoracic and Lumbar Fusion Surgery: An Analysis of 13,695 Patients from the American College of Surgeons National Surgical Quality Improvement Program Database.

Study Design Retrospective cohort study. Objective To identify predictive factors for blood transfusion and associated complications in lumbar and thoracic fusion surgeries. Methods The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients who underwent lumbar or thoracic fusion from 2010 to 2013. Multivariate analysis was used to determine predictive factors and postoperative complications associated with transfusion. Results Out of 13,695 patients, 13,170 had lumbar fusion and 525 had thoracic fusion. The prevalence of transfusion was 31.8% for thoracic and 17.0% for lumbar fusion. The multivariate analysis showed that age between 50 and 60, age between 61 and 70, age > 70, dyspnea, American Society of Anesthesiologists class 3, bleeding disease, multilevel surgery, extended surgical time, return to operation room, and higher preoperative blood urea nitrogen (BUN) were predictors of blood transfusion for lumbar fusion. Multilevel surgery, preoperative BUN, and extended surgical time were predictors of transfusion for thoracic fusion. Patients receiving transfusions who underwent lumbar fusion were more likely to develop wound infection, venous thromboembolism, pulmonary embolism, and myocardial infarction and had longer hospital stay. Patients receiving transfusions who underwent thoracic fusion were more likely to have extended hospital stay. Conclusion This study characterizes incidence, predictors, and postoperative complications associated with blood transfusion in thoracic and lumbar fusion. Pre- and postoperative planning for patients deemed to be at high risk of requiring blood transfusion might reduce postoperative complications in this population.

Predictors of Discharge Destination After Lumbar Spine Fusion Surgery.

STUDY DESIGN: Retrospective cohort study of the prospective collected American College of Surgeons National Surgical Quality Improvement Program database. OBJECTIVE: The aim of the study was to identify predictive factors for the need of discharging patients to a facility other than home after lumbar spine fusion surgery. SUMMARY OF BACKGROUND DATA: Lumbar spine fusion surgery is a common surgical procedure used to treat a variety of lumbar spine conditions. A great number of patients fail to go home after surgery and require admission to a rehabilitation center. Predictive factors for discharging patients to a facility other than home after lumbar fusion surgery do not exist in the literature. METHODS: A total of 15,092 patients undergoing lumbar spine fusion were dichotomized based on discharge destination to patients who were discharged home (N = 12,339) and others who were discharged to a facility other than home (N = 2753). Outcomes included patient demographics, comorbidities, and clinical characteristics. A multivariate logistic regression was used to identify whether outcomes studied were predictive factors for discharging patients to a facility other than home after lumbar fusion surgery. RESULTS: Majority of patients were discharged home after lumbar fusion surgery (81.76%), with only some discharged to a facility other than home (18.24%). Multivariate analysis identified age, female sex, comorbidities (diabetes, chronic obstructive pulmonary disease, congestive heart failure, hypertension, and obesity), minor and major complications, hospital length of stay, operative time at least 259 minutes, and multilevel surgery as significant predictive factors of discharging patients to a facility other than home after lumbar fusion surgery. CONCLUSION: The identified predictive factors can help the health system in developing an algorithm for early recognition of patients requiring postoperative admission to a facility other than home and possibly decreasing their hospital length of stay. This can significantly decrease the hospital costs for such patients. LEVEL OF EVIDENCE: 3.

The use of computer-assisted surgery as an educational tool for the training of orthopedic surgery residents in pedicle screw placement: a pilot study and survey among orthopedic residents.

BACKGROUND: The training of orthopedic residents in adequate pedicle screw placement is very important. We sought to investigate orthopedic residents' perspectives on the use of computer-assisted surgery (CAS) in a training trial. METHODS: Orthopedic residents were randomly assigned to independently place a screw using the free-hand technique and the CAS technique on 1 of 3 cadavers (Cobb angles 5º, 15º and 67º) at randomly selected thoracolumbar vertebral levels. All residents were blinded to their colleagues' pedicle screw placements and were asked to complete a short questionnaire at the end of the session to evaluate their experience with CAS. We obtained CT images for each cadaver to assess pedicle screw placement accuracy and classified placement as A) screw completely in pedicle, B) screw < 2 mm outside pedicle, C) screw 2-4 mm outside pedicle, or D) screw > 4 mm outside pedicle. RESULTS: Twenty-four orthopedic residents participated in this trial study. In total, 65% preferred using the free-hand technique in an educational setting even though most (60%) said that CAS is safer. The main reason for free-hand technique preference was the difficult technical aspects encountered with CAS. In addition, accuracy of pedicle screw placement in this trial showed that 5 screws were classified as A or B (safe zone) and 19 as grade C or D (unsafe zone) using the free-hand technique compared with 15 and 9, respectively, using CAS (p = 0.008). CONCLUSION: Orthopedic residents perceived CAS as safe and demonstrated improved accuracy in pedicle screw placement in a single setting. However, the residents preferred the free-hand technique in an educational stetting owing to the difficult technical aspects of CAS.

CONTEXTE: Il est très important d'apprendre aux médecins résidents en chirurgie orthopédique comment positionner adéquatement une vis pédiculaire. Notre objectif était d'obtenir l'opinion des médecins résidents sur le recours à la chirurgie assistée par ordinateur (CAO) dans un essai sur la formation. MÉTHODES: Des médecins résidents en chirurgie orthopédique répartis aléatoirement ont placé indépendamment une vis à l'aide d'une technique à main libre basée sur les repères topographiques et la palpation, et de la CAO dans 1 de 3 cadavres (angles de Cobb de 5°, 15° et 67°) dans une vertèbre dorsolombaire sélectionnée aléatoirement. Aucun des médecins résidents n'a pu observer le positionnement de la vis de ses collègues, et les participants ont rempli un court questionnaire à la fin de la séance pour évaluer leur expérience de la CAO. Nous avons obtenu un tomodensitogramme pour chaque cadavre afin d'évaluer la précision du positionnement de la vis pédiculaire, classée selon 4 catégories : A) vis entièrement dans le pédicule, B) vis < 2 mm hors du pédicule, C) vis de 2­4 mm hors du pédicule, ou D) vis > 4 mm hors du pédicule. RÉSULTATS: Vingt-quatre médecins résidents en chirurgie orthopédique ont participé à l'étude clinique. Au total, 65 % d'entre eux ont préféré utiliser la technique à main libre dans un contexte de formation, même si la plupart (60 %) considéraient que la CAO était plus sécuritaire. La principale raison justifiant cette préférence était le degré de difficulté technique associé à la CAO. De plus, une évaluation de la précision du positionnement a montré qu'avec la technique à main libre, 5 des vis posées se classaient dans les catégories A ou B (sécuritaire) et 19 dans les catégories C ou D (non sécuritaire), alors que la CAO a permis de positionner 15 vis dans les catégories A ou B et 9 dans les catégories C ou D (p = 0,008). CONCLUSION: Chez un sous-groupe de patients souffrant de traumatismes abdominaux pénétrants, le traitement conservateur est sécuritaire et se traduit par une durée de séjour inférieure de 1,9 jour. La présence de fluide détectée par tomodensitographie est un indicateur de l'échec du traitement.

The Relationship between Preoperative Expectations and the Short-Term Postoperative Satisfaction and Functional Outcome in Lumbar Spine Surgery: A Systematic Review.

Study Design Systematic review. Objective To examine the relationship between the patient's preoperative expectations and short-term postoperative satisfaction and functional outcome in lumbar spine surgery. Methods The Medline, Embase, and Cochrane databases were queried using a predefined search algorithm to identify all lumbar spine studies analyzing the influence of preoperative expectations on postoperative satisfaction and functional outcome. Two independent reviewers and a third independent mediator reviewed the literature and performed study screening, selection, methodological assessment, and data extraction using an objective protocol. Results Of 444 studies identified, 13 met the inclusion criteria. Methodological quality scores ranged from 59 to 100% with the greatest variability in defining patient characteristics and the methods of assessing patient expectations. Patient expectations were assessed in 22 areas, most frequently back and leg pain expectations and general expectations. Functional outcome was assessed by 13 tools; the most common were the visual analog scale, Oswestry Disability Index (ODI), and Short Form Health Survey (SF-36). Positive expectations for symptomatology, activity, general health, and recovery correlated with satisfaction. General expectations correlated with higher SF-36 Physical Subcomponent scores, better global function, and lower ODI outcome. Conclusions on the influence of the expectations for pain were limited due to the study heterogeneity, but the evidence suggests a positive correlation between the expectation and outcome for back and leg pain. Conclusions Positive expectations correlated significantly with short-term postoperative satisfaction and functional outcome, including higher SF-36 scores, earlier return to work, and decreased ODI scores. Future expectation-based investigations will benefit from implementation of the standardized methods of expectation, satisfaction, and outcome analysis discussed herein.