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.

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.

Methods to determine pedicle screw placement accuracy in spine surgery: a systematic review.

STUDY DESIGN: Systematic review. OBJECTIVES: The aims of this systematic review were: (1) to determine the most commonly used methods for assessing pedicle screw placement accuracy, and (2) assess the difference in pedicle screw placement accuracy between navigation and free-hand techniques according to the classification method. BACKGROUND DATA: Pedicle screw fixation and spine surgery have almost become synonymous. However, there is currently no gold standard method to assess pedicle screw placement accuracy. We reviewed the literature to determine current techniques used by spine surgeons for the assessment of pedicle screw accuracy. METHODS: We systematically reviewed the medical literature (OVID Medline, Embase, PubMed) to identify all articles published between 2010 and 2013 that have assessed pedicle screw placement accuracy in humans. Two independent reviewers with a third independent mediator performed study screening, selection and data extraction using a blinded and objective protocol. RESULTS: A total of 68 relevant articles were included in this systematic review, for a total of 3442 patients, 60 cadavers and 43,305 pedicle screws. The most widely used method (37 articles) was based on 2 mm breach increments measured on computer tomography images. The second most widely used method consisted of an "in" or "out" classification system (16 articles). The remaining 15 articles used variable classification systems. Our result suggests that an average of 91.4% of pedicle screws placed with free-hand or fluoroscopy technique where within the safe zone (<2 mm breach) in comparison to an average of 97.3% of pedicle screws using navigation (p < 0.001) for the 2 mm increment method. Similarly, the in or out classification also showed statistically significant difference between free-hand and navigated techniques (p < 0.001). CONCLUSION: The grading system based on 2 mm increments seems to be the most widely accepted method for determining pedicle screw placement accuracy. All grading systems were based on imaging alone without taking into account the direction of the breach or patient's symptoms.

Maverick total disc replacement in a real-world patient population: a prospective, multicentre, observational study.

PURPOSE: Controlled trials have shown that total disc replacement (TDR) can provide pain and disability relief to patients with degenerative disc disease; however, whether these outcomes can also be achieved for patients treated in normal surgical practice has not been well documented. METHODS: This prospective, international study observed changes in disability and back pain in 134 patients who were implanted with Maverick TDR within the framework of routine clinical practice and followed for 2 years post-surgery. Primary and secondary outcomes were the differences from baseline to 6 months post-surgery in the means of the Oswestry Disability Index and the change in back pain intensity assessed on a 10-cm visual analogue scale, respectively. Mean patient age at surgery was 43 years, but ranged up to 65 years. RESULTS: One hundred twenty-three patients had an implant at one level, 10 patients at two levels, and one patient at three levels. Statistically significant improvements in mean disability (-25.4) and low back pain intensity (-4.0) scores were observed at 6 months postoperatively (P < 0.0001 for both) in the hands of experienced surgeons (>10 TDRs per centre). During the study, 56 patients (42 %) experienced a complication or adverse event. CONCLUSIONS: This is the first international observational study to report outcomes of TDR in real-world clinical settings. We showed statistically significant improvements in disability and pain scores at 6 months following Maverick TDR, which were maintained for 2 years alongside an acceptable rate of perioperative complications. The safety and tolerability shown in this observational study were comparable to those from controlled trials.

3D-Printed ABS and PLA Scaffolds for Cartilage and Nucleus Pulposus Tissue Regeneration.

Painful degeneration of soft tissues accounts for high socioeconomic costs. Tissue engineering aims to provide biomimetics recapitulating native tissues. Biocompatible thermoplastics for 3D printing can generate high-resolution structures resembling tissue extracellular matrix. Large-pore 3D-printed acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA) scaffolds were compared for cell ingrowth, viability, and tissue generation. Primary articular chondrocytes and nucleus pulposus (NP) cells were cultured on ABS and PLA scaffolds for three weeks. Both cell types proliferated well, showed high viability, and produced ample amounts of proteoglycan and collagen type II on both scaffolds. NP generated more matrix than chondrocytes; however, no difference was observed between scaffold types. Mechanical testing revealed sustained scaffold stability. This study demonstrates that chondrocytes and NP cells can proliferate on both ABS and PLA scaffolds printed with a simplistic, inexpensive desktop 3D printer. Moreover, NP cells produced more proteoglycan than chondrocytes, irrespective of thermoplastic type, indicating that cells maintain individual phenotype over the three-week culture period. Future scaffold designs covering larger pore sizes and better mimicking native tissue structure combined with more flexible or resorbable materials may provide implantable constructs with the proper structure, function, and cellularity necessary for potential cartilage and disc tissue repair in vivo.

Painful, degenerating intervertebral discs up-regulate neurite sprouting and CGRP through nociceptive factors.

Intervertebral disc degeneration (IVD) can result in chronic low back pain, a common cause of morbidity and disability. Inflammation has been associated with IVD degeneration, however the relationship between inflammatory factors and chronic low back pain remains unclear. Furthermore, increased levels of nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are both associated with inflammation and chronic low back pain, but whether degenerating discs release sufficient concentrations of factors that induce nociceptor plasticity remains unclear. Degenerating IVDs from low back pain patients and healthy, painless IVDs from human organ donors were cultured ex vivo. Inflammatory and nociceptive factors released by IVDs into culture media were quantified by enzyme-linked immunosorbent assays and protein arrays. The ability of factors released to induce neurite growth and nociceptive neuropeptide production was investigated. Degenerating discs release increased levels of tumour necrosis factor-α, interleukin-1ß, NGF and BDNF. Factors released by degenerating IVDs increased neurite growth and calcitonin gene-related peptide expression, both of which were blocked by anti-NGF treatment. Furthermore, protein arrays found increased levels of 20 inflammatory factors, many of which have nociceptive effects. Our results demonstrate that degenerating and painful human IVDs release increased levels of NGF, inflammatory and nociceptive factors ex vivo that induce neuronal plasticity and may actively diffuse to induce neo-innervation and pain in vivo.

Chondroadherin fragmentation mediated by the protease HTRA1 distinguishes human intervertebral disc degeneration from normal aging.

Chondroadherin, a member of the leucine-rich repeat family, has previously been demonstrated to be fragmented in some juveniles with idiopathic scoliosis. This observation led us to investigate adults with disc degeneration. Immunoblotting analysis demonstrated that non-degenerate discs from three different age groups show no chondroadherin fragmentation. Furthermore, the chondroadherin fragments in adult degenerate disc and the juvenile scoliotic disc were compared via immunoblot analysis and appeared to have a similar size. We then investigated whether or not chondroadherin fragmentation increases with the severity of disc degeneration. Three different samples with different severities were chosen from the same disc, and chondroadherin fragmentation was found to be more abundant with increasing severity of degeneration. This observation led us to the creation of a neoepitope antibody to the cleavage site observed. We then observed that the cleavage site in adult degenerate discs and juvenile scoliotic discs was identical as confirmed by the neoepitope antibody. Consequently, investigation of the protease capable of cleaving chondroadherin at this site was necessary. In vitro digests of disc tissue demonstrated that ADAMTS-4 and -5; cathepsins K, B, and L; and MMP-3, -7, -12, and -13 were incapable of cleavage of chondroadherin at this site and that HTRA1 was indeed the only protease capable. Furthermore, increased protein levels of the processed form of HTRA1 were demonstrated in degenerate disc tissues via immunoblotting. The results suggest that chondroadherin fragmentation can be used as a biomarker to distinguish the processes of disc degeneration from normal aging.

Mitigating spinal cord distraction injuries: the effect of durotomy in decreasing cord interstitial pressure in vitro.

STUDY DESIGN: The present study involved an in vitro examination of spinal cord interstitial pressure (CIP) during distraction before and after durotomy in three spinal cord segments obtained from five pigs. OBJECTIVES: To determine whether durotomy can be used to decrease the elevated CIP associated with spinal cord distraction. SUMMARY OF BACKGROUND DATA: Spinal cord distraction is a known cause of spinal cord injury. Several articles describing the pathophysiology of cord distraction injuries suggest that the underlying mechanism of injury is a microvascular ischemic event. The authors have previously described an increase in CIP with spinal cord distraction, with average pressures of 23 mmHg at loads of 1,000 g. To date, there are no published studies that have evaluated the efficacy of intentional durotomies as a treatment for elevated CIP. METHODS: A total of 15 spinal cord sections were harvested from pigs and distracted while immersed in saline, using a fixed 1,000 g distraction force. The CIP decay was then measured at 30-s intervals for 10 min. The distraction/relaxation maneuver was performed six times with continuous CIP monitoring and was subsequently followed by durotomy. RESULTS: The pressure-decay curves were similar for each specimen, but varied according to individual pigs and anatomical levels. CIP decayed over the first 4 min of distraction and remained constant for the final 6 min. Longitudinal durotomy led to a dramatic drop in CIP toward baseline and appeared to be as effective as transverse durotomy with regard to the normalization of pressure. CONCLUSION: Spinal cord distraction causes elevations in CIP. Durotomy lowers elevated CIP in vitro and may be effective at lowering CIP in vivo. Further study is required to evaluate the usefulness of durotomy in vivo.

Pharmacological Treatment of Degenerative Cervical Myelopathy: A Critical Review of Current Evidence.

Degenerative cervical myelopathy (DCM) is the leading cause of spinal cord dysfunction in adults, representing substantial morbidity and significant financial and resource burdens. Typically, patients with progressive DCM will eventually receive surgical treatment. Nonetheless, despite advancements in pharmacotherapeutics, evidence for pharmacological therapy remains limited. Health professionals from various fields would find interest in pharmacological agents that could benefit patients with mild DCM or enhance surgical outcomes. This review aims to consolidate all clinical and experimental evidence on the pharmacological treatment of DCM. We conducted a comprehensive narrative review that presents all pharmacological agents that have been investigated for DCM treatment in both humans and animal models. Riluzole exhibits effectiveness solely in rat models, but not in treating mild DCM in humans. Cerebrolysin emerges as a potential neuroprotective agent for myelopathy in animals but had contradictory results in clinical trials. Limaprost alfadex demonstrates motor function improvement in animal models and exhibits promising outcomes in a small clinical trial. Glucocorticoids not only fail to provide clinical benefits but may also lead to adverse events. Cilostazol, anti-Fas ligand antibody, and Jingshu Keli display promise in animal studies, while erythropoietin, granulocyte colony-stimulating factor and limaprost alfadex exhibit potential in both animal and human research. Existing evidence mainly rests on weak clinical data and animal experimentation. Current pharmacological efforts target ion channels, stem cell differentiation, inflammatory, vascular, and apoptotic pathways. The inherent nature and pathogenesis of DCM offer substantial prospects for developing neurodegenerative or neuroprotective therapies capable of altering disease progression, potentially delaying surgical intervention, and optimizing outcomes for those undergoing surgical decompression.

The effect of angular mismatch between vertebral endplate and vertebral body replacement endplate on implant subsidence.

STUDY DESIGN: Comparative biomechanical study. OBJECTIVE: To determine whether an angular mismatch between the vertebral body replacement (VBR) endplate and the simulated foam vertebral endplate leads to accelerated subsidence in a cyclic compression model of the VBR-vertebra interface. SUMMARY OF BACKGROUND DATA: One of the main complications of the VBR surgery is postoperative subsidence and collapse of the VBR implant into the adjacent vertebral bodies. Although numerous factors affecting intervertebral cage subsidence have been cited, few studies have proposed factors responsible for VBR cage subsidence. METHODS: Hardwood blocks at 0-30-degree angles and polyurethane foam blocs have been used as base for this experimental setting. One end of the Synex (Synthes) expandable cage was attached to a material testing machine. The endplate of the implant was placed at a similar spot on the block in such a manner that there was an exact match between the Synex endplate and the foam block at 0 degrees, subsequent angled blocks would tilt the foam endplates by the 10-, 20-, and 30-degree increments as needed. Cyclic axial loads were applied in 9 load-unload cycles. RESULTS: Five samples were tested at each mismatch angle (0, 10, 20, and 30 degrees), for a total of 20 trials. Implant subsidence significantly increased for each 10-degree increase in mismatch angle. This effect, however, did not follow a uniform trend at all angles. The curve appeared exponential at 0 degree of angular mismatch, became linear at 10-20 degrees of mismatch, and then demonstrated some ability to resist load at 30 degrees, leading to a plateau at the higher loads. CONCLUSIONS: Increasing mismatch angles are an important factor in leading to increased cage subsidence into polyurethane blocks. Consequently, the incidence of subsidence in the clinical setting could be reduced by paying careful attention to ensuring that both the prosthetic and bony endplates are well apposed at the end of surgery.

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.

Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function.

Chronic pain is associated with reduced brain gray matter and impaired cognitive ability. In this longitudinal study, we assessed whether neuroanatomical and functional abnormalities were reversible and dependent on treatment outcomes. We acquired MRI scans from chronic low back pain (CLBP) patients before (n = 18) and 6 months after (spine surgery or facet joint injections; n = 14) treatment. In addition, we scanned 16 healthy controls, 10 of which returned 6 months after the first visit. We performed cortical thickness analysis on structural MRI scans, and subjects performed a cognitive task during the functional MRI. We compared patients and controls, as well as patients before versus after treatment. After treatment, patients had increased cortical thickness in the left dorsolateral prefrontal cortex (DLPFC), which was thinner before treatment compared with controls. Increased DLPFC thickness correlated with the reduction of both pain and physical disability. Additionally, increased thickness in primary motor cortex was associated specifically with reduced physical disability, and right anterior insula was associated specifically with reduced pain. Left DLPFC activity during an attention-demanding cognitive task was abnormal before treatment, but normalized following treatment. These data indicate that functional and structural brain abnormalities-specifically in the left DLPFC-are reversible, suggesting that treating chronic pain can restore normal brain function in humans.

Balloon kyphoplasty versus non-surgical fracture management for treatment of painful vertebral body compression fractures in patients with cancer: a multicentre, randomised controlled trial.

BACKGROUND: Non-randomised trials have reported benefits of kyphoplasty in patients with cancer and vertebral compression fractures (VCFs). We aimed to assess the efficacy and safety of balloon kyphoplasty compared with non-surgical management for patients with cancer who have painful VCFs. METHODS: The Cancer Patient Fracture Evaluation (CAFE) study was a randomised controlled trial at 22 sites in Europe, the USA, Canada, and Australia. We enrolled patients aged at least 21 years who had cancer and one to three painful VCFs. Patients were randomly assigned by a computer-generated minimisation randomisation algorithm to kyphoplasty or non-surgical management (control group). Investigators and patients were not masked to treatment allocation. The primary endpoint was back-specific functional status measured by the Roland-Morris disability questionnaire (RDQ) score at 1 month. Outcomes at 1 month were analysed by modified intention to treat, including all patients with data available at baseline and at 1 month follow-up. Patients in the control group were allowed to crossover to receive kyphoplasty after 1 month. This study is registered with ClinicalTrials.gov, NCT00211237. FINDINGS: Between May 16, 2005, and March 11, 2008, 134 patients were enrolled and randomly assigned to kyphoplasty (n=70) or non-surgical management (n=64). 65 patients in the kyphoplasty group and 52 in the control group had data available at 1 month. The mean RDQ score in the kyphoplasty group changed from 17·6 at baseline to 9·1 at 1 month (mean change -8·3 points, 95% CI -6·4 to -10·2; p<0·0001). The mean score in the control group changed from 18·2 to 18·0 (mean change 0·1 points; 95% CI -0·8 to 1·0; p=0·83). At 1 month, the kyphoplasty treatment effect for RDQ was -8·4 points (95% CI -7·6 to -9·2; p<0·0001). The most common adverse events within the first month were back pain (four of 70 in the kyphoplasty group and five of 64 in the control group) and symptomatic vertebral fracture (two and three, respectively). One patient in the kyphoplasty group had an intraoperative non-Q-wave myocardial infarction, which resolved and was attributed to anaesthesia. Another patient in this group had a new VCF, which was thought to be device related. INTERPRETATION: For painful VCFs in patients with cancer, kyphoplasty is an effective and safe treatment that rapidly reduces pain and improves function. FUNDING: Medtronic Spine LLC.

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.

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.

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.

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.

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.