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.

Validation of the Critical-Care Pain Observation Tool (CPOT) in pediatric patients undergoing orthopedic surgery.

Background: Postoperative pain cannot be measured accurately among many children with intellectual and developmental disabilities, resulting in underrecognition or delay in recognition of pain. The Critical-Care Pain Observation Tool (CPOT) is a pain assessment tool that has been widely validated in critically ill and postoperative adults. Aims: The objective of this study was to validate the CPOT for use with pediatric patients able to self-report and undergoing posterior spinal fusion surgery. Methods: Twenty-four patients (10-18 years old) scheduled to undergo surgery were consented to this repeated-measure, within-subject study. To examine discriminative and criterion validation, CPOT scores and patients' self-reports of pain intensity were collected prospectively by a bedside rater before, during, and after a nonnociceptive and nociceptive procedure on the day following surgery. Patients' behavioral reactions were video recorded at the bedside and retrospectively viewed by two independent video raters to examine interrater and intrarater reliability of CPOT scores. Results: Discriminative validation was supported with higher CPOT scores during the nociceptive procedure than during the nonnociceptive procedure. Criterion validation was supported with a moderate positive correlation between the CPOT scores and the patients' self-reported pain intensity during the nociceptive procedure. A CPOT cutoff score of ≥2 was associated with the maximum sensitivity (61.3%) and specificity (94.1%). Reliability analyses revealed poor to moderate agreement between bedside and video raters and moderate to excellent consistency within video raters. Conclusions: These findings suggest that the CPOT may be a valid tool to detect pain in pediatric patients in the acute postoperative inpatient care unit after posterior spinal fusion.

Contexte: La douleur postopératoire ne peut pas être mesurée avec précision chez de nombreux enfants atteints de déficience intellectuelle et développementale, entraînant ainsi une méconnaissance ou un retard dans la reconnaissance de la douleur. Le Critical-Care Pain Observation Tool (CPOT) est un outil d'évaluation de la douleur qui a été largement validé chez les adultes gravement malades et postopératoires.Objectifs: L'objectif de cette étude était de valider le CPOT pour une utilisation auprès de patients pédiatriques capables d'autoévaluation et subissant une chirurgie de fusion vertébrale postérieure.Méthodes: Dans le cadre d'une étude intra-sujet, un consentement à cette mesure répétée a été obtenu pour vingt-quatre patients (10­18 ans) devant subir une intervention chirurgicale. Pour examiner la validation discriminante et de critère, les scores CPOT et les autoévaluations des patients concernant l'intensité de la douleur ont été collectés de manière prospective par un évaluateur au chevet du patient avant, pendant et après une procédure non nociceptive et nociceptive le lendemain de la chirurgie. Les réactions comportementales des patients ont été enregistrées sur vidéo au chevet du patient et visionnées rétrospectivement par deux des évaluateurs vidéo indépendants pour examiner la fiabilité des scores CPOT inter-évaluateurs et intra-évaluateurs.Résultats: La validation discriminante a été confirmée par l'obtention de scores plus élevés à l'échelle CPOT pendant la procédure nociceptive que pendant la procédure non nociceptive. La validation de critère a été confirmée par une corrélation positive modérée entre les scores sur l'échelle CPOT et l'intensité de la douleur autoévaluée par les patients pendant la procédure nociceptive. Un score-seuil ≥ 2 sur l'échelle CPOT a été associé à la sensibilité et la spécificité maximales (61,3 % et 94,1 %, respectivement). Les analyses de fiabilité ont révélé une concordance faible à modérée entre les évaluateurs de chevet et les évaluateurs vidéo, et une cocordance modérée à excellente parmi les évaluateurs vidéo.Conclusions: Ces résultats indiquent que le CPOT peut être un outil valide pour détecter la douleur chez les enfants patients de l'unité de soins hospitaliers postopératoires aigus après une fusion rachidienne postérieure.

Breast Hypertrophy: A Real Pain in the Back.

BACKGROUND: Bilateral breast hypertrophy comes with signs and symptoms ranging from mild to debilitating. Bilateral breast reduction (BBR) is one of the most frequently performed plastic surgery procedures, and its effects on parameters such as spinal balance, paraspinal muscle function, and physical performance have not been thoroughly evaluated. The objective of this study was to evaluate the effects of BBR using advanced spine imaging modalities, and pain resolution. METHODS: A prospective, observational, cohort study was carried out at the McGill University Health Centre. The following measures were recorded preoperatively and postoperatively for each patient: patient questionnaires (BREAST-Q and Pain), magnetic resonance imaging, and EOS low-radiation spinal scan. RESULTS: Significant postoperative pain reduction was recorded, and there was up to 148% improvement in physical tests. Improvement in all questionnaire and BREAST-Q categories was documented. Preoperative and postoperative magnetic resonance imaging did demonstrate a statistically significant absence of permanent anatomical skeletal sequelae. Postoperative improvement in thoracic kyphosis was documented. CONCLUSIONS: Quality-of-life scores are uniformly improved following BBR. Key findings following BBR include significant pain reduction and no evidence of spinal skeletal change. This is a finding of major importance in view of the practice of many insurance companies/third-party payer and health care systems that use the Schnur scale. The Schnur scale associates a weight for resection with body size that is not directly predictive of pain relief. This may indicate the need for more precise or different guidelines based on these quantitative findings. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Association between the Use of Quantitative Sensory Testing and Conditioned Pain Modulation and the Prescription of Medication and Interventional Procedures in Children with Chronic Pain Conditions.

The evidence supporting the use of pharmacological treatments in pediatric chronic pain is limited. Quantitative sensory testing (QST) and conditioned pain modulation evaluation (CPM) provide information on pain phenotype, which may help clinicians to tailor the treatment. This retrospective study aimed to evaluate the association between the use of QST/CPM phenotyping on the selection of the treatment for children with chronic pain conditions. We retrospectively analyzed the medical records of 208 female patients (mean age 15 ± 2 years) enrolled in an outpatient interdisciplinary pediatric complex pain center. Pain phenotype information (QST/CPM) of 106 patients was available to the prescribing physician. The records of 102 age- and sex-matched patients without QST/CPM were used as controls. The primary endpoint was the proportion of medications and interventions prescribed. The secondary endpoint was the duration of treatment. The QST/CPM group received less opioids (7% vs. 28%, respectively, p < 0.001), less anticonvulsants (6% vs. 25%, p < 0.001), and less interventional treatments (29% vs. 44%, p = 0.03) than controls. Patients with an optimal CPM result tended to be prescribed fewer antidepressants (2% vs. 18%, p = 0.01), and patients with signs of allodynia and/or temporal summation tended to be prescribed fewer NSAIDs (57% vs. 78%, p = 0.04). There was no difference in the duration of the treatments between the groups. QST/CPM testing appears to provide more targeted therapeutic options resulting in the overall drop in polypharmacy and reduced use of interventional treatments while remaining at least as effective as the standard of care.

A roadmap to surgery in osteogenesis imperfecta: results of an international collaboration of patient organizations and interdisciplinary care teams.

Background and purpose - Involvement of patient organizations is steadily increasing in guidelines for treatment of various diseases and conditions for better care from the patient's viewpoint and better comparability of outcomes. For this reason, the Osteogenesis Imperfecta Federation Europe and the Care4BrittleBones Foundation convened an interdisciplinary task force of 3 members from patient organizations and 12 healthcare professionals from recognized centers for interdisciplinary care for children and adults with osteogenesis imperfecta (OI) to develop guidelines for a basic roadmap to surgery in OI.Methods - All information from 9 telephone conferences, expert consultations, and face-to-face meetings during the International Conference for Quality of Life for Osteogenesis Imperfecta 2019 was used by the task force to define themes and associated recommendations.Results - Consensus on recommendations was reached within 4 themes: the interdisciplinary approach, the surgical decision-making conversation, surgical technique guidelines for OI, and the feedback loop after surgery.Interpretation - The basic guidelines of this roadmap for the interdisciplinary approach to surgical care in children and adults with OI is expected to improve standardization of clinical practice and comparability of outcomes across treatment centers.

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.

Inflammatory interactions between degenerated intervertebral discs and microglia: Implication of sphingosine-1-phosphate signaling.

The etiology of intervertebral disc degeneration is largely unknown, but local neuroinflammation may exert a crucial role through activation of cells as microglia and pro-inflammatory cytokines production. We aimed to compare the effect of degenerated and normal intervertebral disc microenvironment on microglial cells and the potential role of sphingosine-1-phosphate, a pro-inflammatory sphingolipid, in their crosstalk. Human degenerated intervertebral discs (Pfirrmann grade IV) were obtained at surgery for spondylolisthesis. Normal intervertebral discs were collected from cadaveric normal lumbar spines. Normal and degenerated-intervertebral discs were kept in culture to obtain media conditioning. Then, microglial cells were cocultured with conditioned media and viability, proliferation, migration, chemotaxis, and inflammatory gene expression were evaluated. The results demonstrate that conditioned media from degenerated intervertebral discs activate microglial cells, increasing chemotaxis, migration, and pro-inflammatory mediators release to a great extent than normal discs. In addition, we show that the administration of sphingosine-1-phosphate to normal intervertebral disc/microglia coculture mimicked degenerative effects. Interestingly, sphingosine-1-phosphate content in conditioned media from degenerated discs was significantly higher than that from normal ones. In addition, FTY720, a functional antagonist of sphingosine-1-phosphate, potently inhibited the effect of degenerated intervertebral discs on microglial inflammatory factor transcription and migration. Our data report, for the first time, that sphingosine-1-phosphate is involved as signal in the microenvironment of human degenerated intervertebral discs. Sphingosine-1-phosphate signaling modulation by FTY720 may induce beneficial effects in counteracting microglial activation during intervertebral disc degeneration.

Publication rate of abstracts presented at the annual meetings of the AANS/CNS Section on Disorders of the Spine and Peripheral Nerves.

OBJECTIVE: The objective of this study was to determine the publication rate of abstracts presented at the annual meetings of the AANS/CNS Section on Disorders of the Spine and Peripheral Nerves (Spine Summit). METHODS: The authors used a search algorithm in PubMed to determine the publication rate of abstracts presented at the Spine Summit from 2007 to 2012. The variables assessed were presentation modality, topic, meeting year, publication year, destiny journal and its 5-year impact factor (IF), country, and citation count (retrieved from the Scopus database). RESULTS: One thousand four hundred thirty-six abstracts were analyzed; 502 were oral presentations and 934 were digital poster presentations. The publication rate was 53.97% (775/1436). The mean time from presentation to publication was 1.35 ± 1.97 years (95% CI 1.21-1.49 years). The mean citation count of published articles was 40.55 ± 55.21 (95% CI 36.66-44.44). Oral presentations had a higher publication rate (71.51%, 359/502) than digital posters (44.54%, 416/934; OR 3.13, 95% CI 2.48-3.95, p < 0.001). Oral presentations had a higher number of citations (55.51 ± 69.00, 95% CI 48.35-62.67) than digital posters (27.64 ± 34.88, 95% CI 24.28-31.00, p < 0.001). The mean IF of published articles was 3.48 ± 2.91 (95% CI 3.27-3.70). JNS: Spine (191/775, 24.64%), Spine (103/775, 13.29%), and Neurosurgery (56/775, 7.23%) had the greatest number of published articles. The US represented the highest number of published articles (616/775, 79.48%). CONCLUSIONS: The publication rate of the Spine Summit is among the highest compared to other spine meetings. Many of the abstracts initially presented at the meeting are further published in high-IF journals and had a high citation count. Therefore, the Spine Summit maintains its high standards of scientific papers, which reflects the high quality of the research performed in the spine surgery field in North America.

Adolescent idiopathic scoliosis: evaluating perioperative back pain through a simultaneous morphological and biomechanical approach.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) has been associated with diminished postural stability and a greater prevalence of back pain. Currently, the literature is lacking information on the effect of spinal fusion on both postural stability and its association with back pain. Our objectives were to evaluate the postsurgical effect of spinal morphological changes on static standing balance and assess the influence of these alterations on reported pain throughout the perioperative period. METHODS: Twenty consecutive AIS patients schedule to undergo spinal fusion surgery were recruited and followed prospectively at the Shriners Hospitals for Children-Canada. Data was collected at the preoperative, 6 weeks and 6 months postoperative visits. Spinal morphology data was collected through 3D reconstructed simultaneous standing biplanar radiographs using the SterEOS software. Postural balance was assessed through Moticon© sensor insoles and analyzed through their software. The data was simultaneously collected as part of the Global Biomechanical and morphological Assessment. Pain was evaluated through self-reported questionnaires. RESULTS: Morphological curve parameters were significantly reduced after surgery. Balance parameters did not change significantly throughout the perioperative period with the exception of the Center of Pressure of the left foot medial/lateral transient shift (P = 0.017) at 6 weeks. Of note, preoperative balance parameters were associated with the degree of right thoracic Cobb angles (P = 0.029 R = 0.528). Pain scores significantly improved 6 weeks and 6 months after the surgery. Pain intensity diminished in the thoracic and lumbar spine but worsen in the neck region at the 6 weeks and 6 months postoperative time points (P = 0.044). Greater residual Cobb angle difference between Mid thoracic and Thoracolumbar/Lumbar curves was associated with greater pain severity at 6 weeks postop (P < 0.005). In addition, greater residual thoracic deformity was associated with significant pain severity 6 months after surgery (P < 0.05). CONCLUSIONS: Improved spinal morphology of postsurgical AIS patients has no significant impact on their static standing balance. Suggesting that other factors apart from the spinal morphology may contribute to AIS patients' balance during stance. Although balance did not influence pain severity, spinal morphology and its correction appear to have influenced the intensity and location of back pain.

Predicting Acute Postoperative Pain Trajectories and Long-Term Outcomes of Adolescents after Spinal Fusion Surgery.

Objectives: Acute pain trajectories are associated with long-term outcomes such as persistent pain and functional disability in adults. However, there are limited data on acute postoperative pain trajectories in the pediatric population. The aims of this study were to investigate acute postoperative pain trajectories, their predictors, and their impact on long- term outcomes in adolescents with idiopathic scoliosis. Methods: We evaluated the preoperative pain intensity, use of analgesics, psychosocial measures and physical functioning of adolescents scheduled to undergo spinal fusion, and their average 6-hour self-reported pain intensity scores for their entire hospital stay. Six months after surgery, baseline variables were reassessed. We used growth mixture modeling to conduct acute postoperative pain trajectory analysis and to identify predictors of pain trajectories. Generalized linear models were conducted to determine whether acute pain trajectories predict long-term outcomes. Results: One hundred and six patients were included in the best-fitted acute pain trajectory model that included four classes that differed in initial pain intensity and rates of change over time. Preoperative pain catastrophizer status and use of analgesics significantly predicted pain trajectory membership. Furthermore, at the 6-month follow-up, patients experiencing moderate-to-severe pain in the acute postoperative period were more likely to report higher levels of pain severity, use pain medication, and miss a greater number of school/work days due to back pain in the last three months. Discussion. Preoperative assessment and analyzing the progression of pain in the acute postoperative period can help identify those at risk of negative long-term outcomes after surgery.

The Tampa Scale of Kinesiophobia: Structural Validation among Adolescents with Idiopathic Scoliosis Undergoing Spinal Fusion Surgery.

AIMS: Spinal fusion surgery is one of the most invasive orthopedic surgeries. Pain while moving or a fear of experiencing pain after surgery may delay return to function and cause prolonged disability. The purpose of the study was to examine the psychometric properties of the Tampa Scale of Kinesiophobia (TSK) in pediatric patients undergoing scoliosis surgery. METHODS: Fifty-five adolescents (10-18 years old) scheduled for spinal fusion surgery were enrolled. Participants completed the TSK questionnaire before surgery and six weeks after surgery. Reliability, exploratory and confirmatory factor analyses were performed on the two-factors TSK including activity avoidance (TSK-AA) and somatic focus (TSK-SF). RESULTS: Before and after surgery, all TSK-AA items conformed into the same factor component and revealed good internal reliability with Cronbach's alpha of .76 and .70 respectively. TSK-SF items were separated into different factor components and revealed poor reliability (.11 and .56). The TSK-AA also produced an adequate fit to the data, as reflected with several fit indices at both timepoints, respectively: χ2/df = 1.19 and 1.22; CFI=.96 and .94; and RMSEA=.06 and .06. CONCLUSIONS: The TSK-AA demonstrated good psychometric properties in patients undergoing scoliosis surgery, which provides empirical evidence for pediatrics. Its validation in distinct populations and settings is recommended prior to its use.

Screw-Related Complications After Instrumentation of the Osteoporotic Spine: A Systematic Literature Review With Meta-Analysis.

STUDY DESIGN: Systematic literature review with meta-analysis. OBJECTIVE: Osteoporosis is common in elderly patients, who frequently suffer from spinal fractures or degenerative diseases and often require surgical treatment with spinal instrumentation. Diminished bone quality impairs primary screw purchase, which may lead to loosening and its sequelae, in the worst case, revision surgery. Information about the incidence of spinal instrumentation-related complications in osteoporotic patients is currently limited to individual reports. We conducted a systematic literature review with the aim of quantifying the incidence of screw loosening in osteoporotic spines. METHODS: Publications on spinal instrumentation of osteoporotic patients reporting screw-related complications were identified in 3 databases. Data on screw loosening and other local complications was collected. Pooled risks of experiencing such complications were estimated with random effects models. Risk of bias in the individual studies was assessed with an adapted McHarm Scale. RESULTS: From 1831 initial matches, 32 were eligible and 19 reported screw loosening rates. Studies were heterogeneous concerning procedures performed and risk of bias. Screw loosening incidences were variable with a pooled risk of 22.5% (95% CI 10.8%-36.6%, 95% prediction interval [PI] 0%-81.2%) in reports on nonaugmented screws and 2.2% (95% CI 0.0%-7.2%, 95% PI 0%-25.1%) in reports on augmented screws. CONCLUSIONS: The findings of this meta-analysis suggest that screw loosening incidences may be considerably higher in osteoporotic spines than with normal bone mineral density. Screw augmentation may reduce loosening rates; however, this requires confirmation through clinical studies. Standardized reporting of prespecified complications should be enforced by publishers.

The Effects of Breast Reduction on Back Pain and Spine Measurements: A Systematic Review.

The aim of this review article was to synthesize the literature on reduction mammaplasty and its effects on the spine. The particular focus was to find these few radiological studies and those investigating changes in spinal angles, posture, center of gravity, and back pain reduction. METHODS: We performed a thorough review of the literature, searching the Medline database for all relevant published data studying reduction mammaplasty and the spine. The search yielded 107 articles of which 11 articles met our specific inclusion criteria. The primary outcome measures of the studies and their respective results were tabulated, contrasted, and compared. RESULTS: The 11 cohort studies included in this review cover the period from 2005 to 2015 and focus on breast hypertrophy and spine. According to these 11 quantitative studies, breast hypertrophy causes objective, quantitative, measurable disturbances to women living with this condition. Reduction mammaplasty produces an unmistakable improvement in signs, symptoms, and quantifiable measures. Although the majority of included articles in this review described postoperative improvement in spinal angles, there remain discrepancies of results between them. CONCLUSIONS: The studies included in this review did offer a promising glimpse into the complex interaction between breast hypertrophy and the spine. However, future research initiatives can improve upon what these investigators have begun with more refined, objective, radiological evidence. More specifically, we aim to clarify some of the basic hypotheses in our center with the use of EOS.

Assessing publication rate of abstracts presented in spine conferences as a quality benchmark: the example of the Canadian Spine Society Annual Meetings.

INTRODUCTION: Publication rate can indirectly assess the quality of research presented in scientific meetings. Considering presentations at orthopedic surgery and neurosurgery meetings, 10.5-66% of abstracts are published in scientific journals. Publication rate of abstracts presented at CSS Meetings is unknown. The objective of this study was to evaluate the publication rate of abstracts presented at the Canadian Spine Society(CSS) Annual Meetings from 2005to2014. METHODS: In October2018, a systematic PubMed search was performed using title and authors of all abstracts presented at CSS Meetings from 2005 to 2014. The following information was retrieved from the articles and abstracts: year, type of presentation, publication in PubMed, time from presentation to final publication, journal and its impact factor(IF). RESULTS: A total of 621 abstracts were presented at CSS meetings from 2005 to 2014. Publication rate in PubMed was 54.8%(N=340/621). Oral presentations were more likely to be published than poster presentations(63.8%vs44.0%; OR=1.45; CI95%=1.20-1.75; P<0.0001). The mean time from presentation to publication was 1.76 years(±1.93). The 340 identified articles were published in 87 different journals. Most common journals were Spine(N=75; 22.1%), The Spine Journal(N=40;11.8%), and Journal of Neurosurgery:Spine(N=28;8.2%). IF ranged from 0.18 to 47.66(mean=3.73±4.68). IF of articles presented orally were higher than those presented as poster(P=0.038). CONCLUSIONS: The CSS scientific meeting maintain along the years a steady high quality research presentations as manifested by its significant publication rate(54.8%) in medical journals with mean IF of 3.73. In comparison with other spine scientific meetings, publication rates of abstracts presented at CSS meeting is amongst the highest.

Acute postoperative opioid consumption trajectories and long-term outcomes in pediatric patients after spine surgery.

Background: The days following surgery are a critical period where the use of opioids predicts long-term outcomes in adults. It is currently unknown as to whether opioid consumption throughout the acute postoperative period is associated with long-term outcomes in pediatric patients. The aims of this study were to characterize opioid consumption trajectories in the acute postoperative period, identify predictors of trajectory membership and determine associations between opioid consumption trajectories and long-term patient outcomes. Materials and methods: Medication use, pain and mental health status were assessed at baseline in adolescents with idiopathic scoliosis who were scheduled for spinal fusion surgery. Cumulative 6-hr opioid consumption was recorded for up to 5 days after spinal surgery. At 6 months after surgery, medication use, pain and functional activity were evaluated. Growth mixture modeling was used to identify opioid trajectories. Results: One hundred and six patients were included in the study. Mean cumulative 6-hr opioid consumption in the acute postoperative period was 13.23±5.20 mg/kg. The model with the best fit contained 5 acute postoperative trajectories and a quadratic term (AIC =6703.26, BIC =6767.19). Two types of patient behaviors were identified: high opioid consumers (trajectories 4 and 5) and low opioid consumers (trajectories 1, 2 and 3). Intraoperative intrathecal morphine dose was a predictor of trajectory membership (p=0.0498). Opioid consumption during the acute postoperative period was not significantly associated with pain, functional activity or pain medication use at 6 months after surgery. Conclusion: In pediatric patients, intraoperative intrathecal morphine dose predicts opioid consumption in the acute postoperative period. Importantly, opioid consumption during this period does not affect long-term outcomes in pediatric patients after a spine surgery.

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.

Perioperative Pain Assessment in a 14-Year-Old Boy with Lumbar Disc Herniation.

This case report illustrates the value of a comprehensive perioperative pain assessment composed of quantitative sensory testing and self-reported measures that highlight the impact of pain experienced by a 14-year-old boy suffering from chronic low back pain and sciatica. Before surgery, the pain assessment revealed inefficient endogenous inhibitory pain control with presence of temporal summation of pain. The severe pain was constant and lasted for 18 months. The patient was in a high-anxiety state, and reported significant functional disability and poor sleep quality. Six months after surgery, the patient was pain free. Quantitative sensory testing showed an improvement in his inhibitory pain control with the absence of temporal summation of pain. The patient was no longer anxious, was back to normal functional abilities, and reported good sleep quality. By including neurophysiology and other pain measures, the clinical application of a comprehensive pain assessment can provide objective measurements of treatment efficacy.

Anatomical and technical factors associated with superior facet joint violation in lumbar fusion.

OBJECTIVE The aim of this study was to evaluate the anatomical and surgical risk factors for screw-related facet joint violation at the superior level in lumbar fusion. METHODS The authors conducted a retrospective review of a consecutive series of posterior lumbar instrumented fusions performed by a single surgeon. Inclusion criteria were primary lumbar fusion of 1 or 2 levels for degenerative disorders. The following variables were analyzed as possible risk factors: surgical technique (percutaneous vs open screw placement), depth of surgical field, degree of anterior slippage of the superior level, pedicle and facet angle, and facet degeneration of the superior level. Postoperative CT scans were evaluated by 2 independent reviewers. Axial, sagittal, and coronal views were reviewed. Pedicle screws were graded as intra-articular if they clearly interposed between the superior and inferior facet joints of the superior level. Multivariate logistic regression analyses were conducted to assess the factors associated with this complication. RESULTS One hundred thirty-one patients were included. Interobserver reliability for facet joint violation assessment was high (κ = 0.789). The incidence of superior facet joint violation was 12.59% per top-level screw (33 of 262 proximal screws). The rate of facet violation was 28.0% in the percutaneous technique group (14 of 50 patients) and 12.3% in the open surgery group (10 of 81 patients) (OR 2.26, 95% CI 1.09-4.21; p = 0.024). In multivariate logistic regression analysis, independent predictors of facet violation were percutaneous screw placement (adjusted OR 3.31, 95% CI 1.42-7.73; p = 0.006), right-side pedicle screw (adjusted OR 3.14, 95% CI 1.29-7.63; p = 0.011), and facet angle > 45° (adjusted OR 10.95, 95% CI 4.64-25.84; p < 0.0001). CONCLUSIONS The incidence of facet joint violation was higher in percutaneous minimally invasive than in open technique for posterior lumbar spine surgery. Also, coronal orientation of the facet joint is a significant risk factor independent of the surgical technique.

Facet joint degeneration in adolescent idiopathic scoliosis.

Adolescent idiopathic scoliosis (AIS) is a poorly understood deformity of the thoracolumbar spine which affects the intervertebral discs (IVDs) and the articular facet joints. The knowledge concerning facet joints in this context is very limited, although facet joint degeneration is a known contributor of back pain. In this study, a comprehensive investigation was performed to characterize the facet joint chondrocytes and extracellular matrix within the scoliotic spine. Surgically removed articular facet joint tissues were collected from patients undergoing spinal corrective surgery for AIS deformities, while non-scoliotic articular facet joint tissues were obtained from cadaveric organ donors. Alterations in cartilage tissue structure were evaluated histologically with safranin-O fast green and a modified OARSI grading scale. Pro-inflammatory cytokines, matrix-degrading proteases, and fragmented matrix molecules associated with cartilage degradation were analyzed by immunohistochemistry and western blotting. Safranin-O fast green staining revealed that young scoliotic facet joints show clear signs of degeneration with substantial proteoglycan loss, similar to osteoarthritis (OA). The proteoglycan levels were significantly lower than in healthy asymptomatic non-scoliotic control individuals. In comparison to controls, scoliotic articular facets showed increased cell density, increased expression of the proliferation marker Ki-67, and higher expression of MMP-3, MMP-13, and IL-1ß. Expression and fragmentation of the small leucine-rich proteins (SLRPs) chondroadherin, decorin, biglycan, lumican, and fibromodulin were analyzed with western blot. Chondroadherin and decorin were fragmented in cartilage from patients with a curve greater than 70°, whereas biglycan and fibromodulin did not show curve-related fragmentation. AIS facet joint cartilage shows hallmarks of OA including proteoglycan loss, overexpression of pro-inflammatory mediators, increased synthesis of matrix-degrading proteases and fragmentation of SLRPs. As with patients with age-related OA, the premature joint degeneration seen in scoliotic patients is likely to contribute to the pain perceived in some individuals.

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.