Validation and Estimation of Obesity-Induced Intervertebral Disc Degeneration through Subject-Specific Finite Element Modelling of Functional Spinal Units.

(1) Background: Intervertebral disc degeneration has been linked to obesity; its potential mechanical effects on the intervertebral disc remain unknown. This study aimed to develop and validate a patient-specific model of L3-L4 vertebrae and then use the model to estimate the impact of increasing body weight on disc degeneration. (2) Methods: A three-dimensional model of the functional spinal unit of L3-L4 vertebrae and its components were developed and validated. Validation was achieved by comparing the range of motions (RoM) and intradiscal pressures with the previous literature. Subsequently, the validated model was loaded according to the body mass index and estimated stress, deformation, and RoM to assess disc degeneration. (3) Results: During validation, L3-L4 RoM and intradiscal pressures: flexion 5.17° and 1.04 MPa, extension 1.54° and 0.22 MPa, lateral bending 3.36° and 0.54 MPa, axial rotation 1.14° and 0.52 MPa, respectively. When investigating the impact of weight on disc degeneration, escalating from normal weight to obesity reveals an increased RoM, by 3.44% during flexion, 22.7% during extension, 29.71% during lateral bending, and 33.2% during axial rotation, respectively. Also, stress and disc deformation elevated with increasing weight across all RoM. (4) Conclusions: The predicted mechanical responses of the developed model closely matched the validation dataset. The validated model predicts disc degeneration under increased weight and could lay the foundation for future recommendations aimed at identifying predictors of lower back pain due to disc degeneration.

The association between inflammatory biomarkers and low back disorder: a systematic review and meta-analysis.

INTRODUCTION: Low back disorder (LBD) is a major cause of disability worldwide. Inflammation results in proliferation of cytokines or consequent degradation products (collectively known as inflammatory biomarkers) that activate pain pathways which can result in non-specific LBD. This systematic review and meta-analysis aim to evaluate the relationship between inflammatory biomarkers and clinical outcomes in patients with LBD. METHODS: The PRISMA guideline was followed for the systematic reivew. Three online databases were searched. Four RCTs and sixteen observational studies with 1142 LBD patients were analysed. The primary outcomes were back and leg pain scores, back-specific disability scores and expression of inflammatory biomarkers. Standardized mean difference (SMD) and their 95% confidence intervals (CI) were evaluated. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to summarize the strength of evidence. RESULTS: Four RCTs and sixteen observational studies were included in the analysis of 1142 patients with LBD. There was a statistically significant reduction in back pain score and IL-1 beta and increase in the expression of CTX-1 and IL-10 levels post treatment. There was a significant relationship between increase in the expression of MCP- and reduction in the expression of hsCRP with increase in back pain. Significant relationship was also observed between increase in the expression of MCP-1 and reduction in the expression of IL-6 with increase in leg pain. Increase in the expression of IL-8 and reduction in the expression of hsCRP was also associated with increased disability score. CONCLUSION: Inflammatory biomarkers play a significant role in the pathogenesis of LBD. CTX-1, IL-10 and IL-1 beta may be responsible for the decrease in back pain scores post treatment. There is a relationship between MCP-1, IL-6, IL-8 and hsCRP with clinical and functional assessments for LBD. Further studies will improve understanding of the pathogenesis of LBD and aid in targeted management strategies.

Imaging predictors of progression of lumbar spondylolysis to spondylolisthesis: a systematic review.

BACKGROUND CONTEXT: Isthmic spondylolisthesis (IS) is defined as the anterior translation of one lumbar vertebra relative to the next caudal segment as a result of a unilateral or bilateral fracture of the pars interarticularis. These fractures are interchangeably known as "pars defects" or "spondylolysis." Many risk factors have been proposed to explain the progression of a spondylolytic defect to IS, however, none are validated. PURPOSE: This systematic review provides an overview of various radiological and imaging parameters that can help predict the risk of progression of a spondylolytic defect into IS. STUDY DESIGN: Systematic review. METHODS: Medline, Embase and Cochrane online database were searched. The various correlations between imaging features with observed spondylolisthesis prevalence or severity or spondylolysis rates of spondylolisthesis were evaluated to provide a list of imaging risk factors to predict IS. Significance of the correlations in the original article was recorded to enable comparison of the collected evidence of separate image features. RESULTS: All searches combined generated a total of 431 results of which 26 articles were included into this study. Of the 22 potential risk factors identified, 5 were found to be statistically insignificant, 8 were found to be significant and 9 had mixed results. The following features were found to be significant risk factors in at least on study: disc degeneration, transverse process width, pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, lumbar index, thoracic kyphosis, facet joint angle above the level of defect, facet joint degeneration, facet tropism, multifidus size, lateral erector spinae size, mesenteric fat thickness, subcutaneous fat thickness and soft tissue calcification. CONCLUSION: Our research suggests that only disc degeneration had moderately strong evidence with consistent significant associations with development of IS in patients with spondylolysis. Transverse process width, pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, lumbar index, thoracic kyphosis, facet joint angle above the level of defect, facet joint degeneration, facet tropism, multifidus size, lateral erector spinae size, mesenteric fat thickness, subcutaneous fat thickness and soft tissue calcification had some evidence. All other radiological factors had weak evidence. The results of this study can be used to improve early clinical decision making for patients with spondylolysis.

In subjects with chronic low back pain, does neuropathia exclusively correlated to neuronal compression? A correlation study of PainDETECT questionnaire and corresponding MRI and X-ray findings.

INTRODUCTION: Understanding the complex nature of low back pain (LBP) is crucial for effective management. The PainDETECT questionnaire is a tool that distinguishes between neuropathic (NeP), nociceptive (NoP), and ambiguous pain. This study aimed to investigate the relationship between pain classification and lumbar intervertebral degenerative parameters obtained from imaging. METHODS: A cohort study was conducted involving 279 patients, aged 18 years and above, who completed PainDETECT questionnaires and underwent lumbar MRI and/or X-ray scans. RESULTS: The study included 102 patients with NoP, 78 with ambiguous pain, and 99 with NeP. The NeP group had lower mean age (58.21 vs. 53.63, p < 0.05) and higher mean numerical rating scale score (7.9 vs. 5.9, p < 0.001) compared to the NoP group. A negative correlation was found between PainDETECT scores and pelvic incidence (τ = - 0.177, p = 0.043). The NeP group exhibited significantly higher severity of foraminal stenosis (U = 18.962, p = 0.002), spinal stenosis (U = 14.481, p = 0.005), and Pfirrmann grade (U = 14.221, p = 0.028) compared to the NoP group. A higher proportion of NeP patients had intervertebral disk bulge (96% vs. 78% vs. 78%, p = 0.002) and high-intensity zones (51% vs. 41% vs. 19%, p < 0.001) compared to those with NoP and ambiguous pain. CONCLUSION: NeP, as determined by the PainDETECT questionnaire, is associated with more severe neural compression, increased presence of discogenic disease and inflammatory disk severity, and decreased pelvic incidence. This pioneering study establishes a connection between pathological findings and pain categorization, providing clinicians with valuable guidance for formulating tailored management plans and reducing the need for unnecessary pharmacotherapy, imaging, and non-targeted surgical interventions.

Reconsidering high intensity zones: its role in intervertebral disk degeneration and low back pain.

PURPOSE: High intensity zones (HIZ) in the lumbar intervertebral disk (IVD) can be associated with degenerative changes which may ultimately manifest as low back pain (LBP). However, the relationship between the prevalence of HIZ and lumbar degenerative parameters is still unclear. The purpose of this study was to determine the prevalence of HIZ in the lumbar spine, analyze the independent relationship between HIZ and lumbar degenerative parameters measured on MRI and X-ray and determine the association between HIZ and the presence of LBP. METHODS: A retrospective review of MRI data, X-ray data, and radiology reports for 136 consecutively recruited patients, above 18-years-age and with both lumbar MRI and X-ray scans was conducted. 57 patients with HIZ were identified. Patients without HIZ (n = 79) made up the control group. RESULTS: HIZ was prevalent in 41.9% of patients and in 11.0% of all lumbar IVDs. The odds of developing HIZ were 6.4 (Exp(B) 6.4, 95%CI [3.157-12.988]) and 3.0 (Exp(B) 3.0, 95%CI [1.603, 5.674]) times higher in IVDs with disk bulge/protrusion and nucleus degeneration, respectively. Odds of HIZ was also increased in disks with larger IVD angle (Exp(B) 1.1, 95%CI [1.034, 1.169]). The odds of patients presenting to imaging with LBP was 3.0 (OR 3.0, 95%CI [1.478-6.338]) times higher in the HIZ compared to the control group. CONCLUSIONS: HIZ was prevalent in 41.9% of participants that were recruited in this study. Nucleus degeneration, disk bulge/protrusion and increased IVD angle were found to be independently associated with HIZ and since there is an increased likelihood of LBP, we posit that HIZ is likely a symptomatic and clinically meaningful diagnostic tool in the assessment of LBP.

Nociceptive pain assessed by the PainDETECT questionnaire may predict response to opioid treatment for chronic low back pain.

Introduction: The pharmacological management of chronic low back pain (LBP) is complex. The World Health Organisation recommends a laddered approach to pain medication usage. The PainDETECT questionnaire distinguishes between neuropathic pain (NeP), nociceptive pain (NoP), and ambiguous pain. By elucidating the difference in medication efficacy between these groups, clinicians can provide a tailored treatment plan to manage patient's pain. This study aimed to investigate the relationship between pharmacological treatments, pain categorizations, and medication efficacy as reported by patients. Methods: A secondary retrospective analysis of a prospectively collected database was conducted involving 318 consecutively recruited patients, aged 18 years and above, who completed PainDETECT, medication history and patient reported medication efficacy questionnaires. Medication history was categorized into four lines of treatment: first line (paracetamol ± non-prescribed anti-inflammatories), second line (prescribed anti-inflammatories), third line (anticonvulsants/neuromodulators) and fourth line (opioids). Medication efficacy was measured using a three-point Likert scale: effective (+2), somewhat effective (+1), no effect (0). Findings: The study included 120, 50, 54 and 94 patients on first line, second line, third line and fourth line treatment, respectively. The NeP group had higher mean numerical rating scale (NRS) compared to NoP group in all four lines of treatment (8.10 ± 1.59 vs. 5.47± 2.27, p < 0.001, 8.64± 1.43 vs. 5.52± 1.86, p < 0.001, 8.00± 1.07 vs. 6.37± 2.39, p < 0.01, and 8.05± 1.73 vs. 7.2± 1.29, p < 0.05). When confounding for severity of LBP as measured by NRS, the distribution of medication efficacy significantly differed amongst the NeP, ambiguous and NoP groups in patients undergoing fourth line pharmacological treatment (r2 = 8.623, p < 0.05). The NoP group exhibited significantly higher medication efficacy compared to the NeP group (U = 14.038, p < 0.05). There was no significant difference in medication efficacy across the pain classifications for first, second- and third-line treatment. Interpretation: Opioids was the only line of treatment more effective in targeting NoP, as determined by the PainDETECT questionnaire, compared to NeP. This pioneering study illustrates the complex nature of pharmacological management for chronic LBP. It underscores the importance of tailoring pharmacological treatment plans to fit individual pain profiles and expectations instead of adopting a blanket approach to pain management.

How often do we alter constitutional limb alignment, joint line obliquity, and Coronal Plane Alignment of the Knee (CPAK) phenotype when performing mechanically aligned TKA?

Aims: While mechanical alignment (MA) is the traditional technique in total knee arthroplasty (TKA), its potential for altering constitutional alignment remains poorly understood. This study aimed to quantify unintentional changes to constitutional coronal alignment and joint line obliquity (JLO) resulting from MA. Methods: A retrospective cohort study was undertaken of 700 primary MA TKAs (643 patients) performed between 2014 and 2017. Lateral distal femoral and medial proximal tibial angles were measured pre- and postoperatively to calculate the arithmetic hip-knee-ankle angle (aHKA), JLO, and Coronal Plane Alignment of the Knee (CPAK) phenotypes. The primary outcome was the magnitude and direction of aHKA, JLO, and CPAK alterations. Results: The mean aHKA and JLO increased by 0.1° (SD 3.4°) and 5.8° (SD 3.5°), respectively, from pre- to postoperatively. The most common phenotypes shifted from 76.3% CPAK Types I, II, or III (apex distal JLO) preoperatively to 85.0% IV, V, or VI (apex horizontal JLO) postoperatively. The proportion of knees with apex proximal JLO increased from 0.7% preoperatively to 11.1% postoperatively. Among all MA TKAs, 60.0% (420 knees) were changed from their constitutional alignments into CPAK Type V, while 40.0% (280 knees) either remained in constitutional Type V (5.0%, 35 knees) or were unintentionally aligned into other CPAK types (35.0%; 245 knees). Conclusion: Fixed MA targets in TKA lead to substantial changes from constitutional alignment, primarily a significant increase in JLO. These findings enhance our understanding of alignment alterations resulting from both unintended changes to knee phenotypes and surgical resection imprecision.

A confirmatory factor analysis of an electronic format painDETECT questionnaire for patients with low back pain.

BACKGROUND: The substantial burden of low back pain on patients and healthcare systems is exacerbated by unclear pathology and ineffective diagnostic methods, hindering effective management. The painDETECT questionnaire (PD-Q) has been used to facilitate the evaluation and categorization of low back pain. While preliminary validation and translations of the paper-based format of PD-Q into languages such as Spanish and Dutch have been accomplished, the underlying factor model inherent to the electronic format of the PD-Q remains to be established. OBJECTIVE: The objective of this study was to utilise confirmatory factor analysis (CFA) to investigate the factor structure of an electronic format PD-Q among patients with neuropathic low back pain. METHODS: This cross-sectional study was conducted at a Spinal Clinic in Sydney between November 2020 and October 2022. Eligible participants were adults over 18 with low back pain and no history of lumbar surgery or systemic co-morbidities. Participants completed the electronic format of the PD-Q, and CFA was employed to assess the validity of the suggested two-factor, nine-item structure. Recommended cut-offs for goodness-of-fit indices were used to evaluate the model fit. RESULTS: Of the 236 patients that visited the clinic during the data collection period, 142 (71, 50% female, mean age 51.26 ± 15.28 years) participated in the study. Median pain severity was 9/10 over 4 weeks. CFA indicated strong model fit, with goodness-of-fit and comparative fit indices over 0.9, and overall internal consistency was 0.77. Construct validity analysis demonstrated the PD-Q's effectiveness in distinguishing neuropathic, mixed, and nociceptive LBP, aiding neuropathic pain evaluation in low back pain patients. CONCLUSION: This study confirms the reliability and two-factor structure of the electronic PD-Q for neuropathic pain assessment in low back pain patients. To enhance comprehension of the clinical applicability of the electronic format PD-Q, future research should conduct clinimetric evaluations.

Clinical effectiveness of reduction and fusion versus in situ fusion in the management of degenerative lumbar spondylolisthesis: a systematic review and meta-analysis.

PURPOSE: To compare the clinical effectiveness of reduction and fusion with in situ fusion in the management of patients with degenerative lumbar spondylolisthesis (DLS). METHODS: The systematic review was conducted following the PRISMA guidelines. Relevant studies were identified from PubMed, Embase, Scopus, Cochrane Library, ClinicalTrials.gov, and Google Scholar. The inclusion criteria were: (1) comparative studies of reduction and fusion versus in situ fusion for DLS patients, (2) outcomes reported as VAS/NRS, ODI, JOA score, operating time, blood loss, complication rate, fusion rate, or reoperation rate, (3) randomized controlled trials and observational studies published in English from the inception of the databases to January 2023. The exclusion criteria included: (1) reviews, case series, case reports, letters, and conference reports, (2) in vitro biomechanical studies and computational modeling studies, (3) no report on study outcomes. The risk of bias 2 (RoB2) tool and the Newcastle-Ottawa scale was conducted to assess the risk of bias of RCTs and observational studies, respectively. RESULTS: Five studies with a total of 704 patients were included (375 reduction and fusion, 329 in situ fusion). Operating time was significantly longer in the reduction and fusion group compared to in situ fusion group (weighted mean difference 7.20; 95% confidence interval 0.19, 14.21; P = 0.04). No additional significant intergroup differences were noted in terms of other outcomes analyzed. CONCLUSION: While the reduction and fusion group demonstrated a statistically longer operating time compared to the in situ fusion group, the clinical significance of this difference was minimal. The findings suggest no substantial superiority of lumbar fusion with reduction over without reduction for the management of DLS.

Early outcomes of oblique lateral interbody fusion with posterior fixation versus posterior interbody fusion with fixation for treating adult degenerative scoliosis.

OBJECTIVE: To compare the surgical trauma and outcomes between oblique lateral interbody fusion (OLIF) and posterior fixation and posterior lumbar interbody fusion (PLIF) with fixation for adult degenerative scoliosis (ADS). METHODS: We included ADS patients who underwent OLIF with fixation or PLIF with fixation treatment from June 2020 to December 2022. The preoperative and postoperative spinal pelvic parameters were measured using X-rays. Clinical symptoms were measured using the Oswestry Disability Index and a visual analog scale. We recorded operation time, intraoperative blood loss, blood transfusion, albumin infusion, surgical fixation segment, surgical osteotomy segment, time, and drainage volume. RESULTS: Forty patients with ADS were included: 20 with OLIF with posterior fixation and 20 with PLIF matched for age, sex, pelvic incidence, and Cobb angle with the OLIF group. There were no significant differences in age, gender, BMI, preoperative spinal parameters, or preoperative clinical symptoms between the groups (p > 0.05). There were no statistical differences in postoperative spinal parameters or clinical symptoms (p > 0.05). Patients in the OLIF group had less intraoperative blood loss (p < 0.01) and fewer intraoperative blood transfusions (p < 0.001) than the posterior surgery group. The number of fixed segments was fewer (p < 0.01), and there were fewer total osteotomy segments (p < 0.001). CONCLUSION: OLIF with posterior fixation surgery can achieve the same corrective effect and efficacy as a posterior internal fusion with fixation surgery for treating ADS. OLIF with posterior fixation surgery causes less trauma and reduces the number of fixation segments.

Intrinsic variables associated with low back pain and lumbar spine injury in fast bowlers in cricket: a systematic review.

BACKGROUND: Lumbar spine injuries in fast bowlers account for the greatest missed playing time in cricket. A range of extrinsic and intrinsic variables are hypothesised to be associated with low back pain and lumbar spine injury in fast bowlers, and an improved understanding of intrinsic variables is necessary as these may alter load tolerance and injury risk associated with fast bowling. This review critically evaluated studies reporting intrinsic variables associated with low back pain and lumbar spine injury in fast bowlers and identified areas for future investigation. METHODS: OVID Medline, EMBASE, SPORTDiscus, CINAHL, Web of Science and SCOPUS databases were last searched on 3 June 2022 to identify studies investigating intrinsic variables associated with low back pain and lumbar spine injury in cricket fast bowlers. Terms relevant to cricket fast bowling, and intrinsic variables associated with lumbar spine injury and low back pain in fast bowlers were searched. 1,503 abstracts were screened, and 118 full-text articles were appraised to determine whether they met inclusion criteria. Two authors independently screened search results and assessed risk of bias using a modified version of the Quality in Prognostic Studies tool. RESULTS: Twenty-five studies met the inclusion criteria. Overall, no included studies demonstrated a low risk of bias, two studies were identified as moderate risk, and twenty-three studies were identified as high risk. Conflicting results were reported amongst studies investigating associations of fast bowling kinematics and kinetics, trunk and lumbar anatomical features, anthropometric traits, age, and neuromuscular characteristics with low back pain and lumbar spine injury. CONCLUSION: Inconsistencies in results may be related to differences in study design, injury definitions, participant characteristics, measurement parameters, and statistical analyses. Low back pain and lumbar spine injury occurrence in fast bowlers remain high, and this may be due to an absence of low bias studies that have informed recommendations for their prevention. Future research should employ clearly defined injury outcomes, analyse continuous datasets, utilise models that better represent lumbar kinematics and kinetics during fast bowling, and better quantify previous injury, lumbar anatomical features and lumbar maturation. TRIAL REGISTRATION: Open Science Framework https://doi.org/10.17605/OSF.IO/ERKZ2 .

Partial atlantooccipital assimilation causing atlantoaxial instability and early myelopathy in an adult treated with occipitocervical fusion: A case report.

INTRODUCTION & IMPORTANCE: Atlanto-occipital assimilation is a rare congenital abnormality which can cause atlantoaxial instability. Basilar invagination and instability can lead to cord compression and myelopathy in young individuals. CASE REPORT & DISCUSSION: A 37-year-old male presented with gradually worsening axial neck pain for four years duration His deep tendon reflexes are exaggerated in all four limbs but there is no weakness or imbalance. Following radiological evaluation, he was diagnosed to have partial atlantooccipital assimilation causing atlantoaxial instability, basilar invagination and early myelopathy. He was treated with occipital-cervical fusion after the closed reduction of the atlantoaxial joint. CONCLUSION: Atlanto-axial assimilation can lead to atlantoaxial instability and subsequently myelopathy. Dynamic radiographs and computed tomography are helpful in the diagnosis. Reducible atlantoaxial instability can be managed with closed reduction and occipitocervical fusion.

Deep Learning Model to Classify and Monitor Idiopathic Scoliosis in Adolescents Using a Single Smartphone Photograph.

Importance: Adolescent idiopathic scoliosis (AIS) is the most common pediatric spinal disorder. Routine physical examinations by trained personnel are critical to diagnose severity and monitor curve progression in AIS. In the presence of concerning malformation, radiographs are necessary for diagnosis or follow-up, guiding further management, such as bracing correction for moderate malformation and spine surgery for severe malformation. If left unattended, progressive deterioration occurs in two-thirds of patients, leading to significant health concerns for growing children. Objective: To assess the ability of an open platform application (app) using a validated deep learning model to classify AIS severity and curve type, as well as identify progression. Design, Setting, and Participants: This diagnostic study was performed with data from radiographs and smartphone photographs of the backs of adolescent patients at spine clinics. The ScolioNets deep learning model was developed and validated in a prospective training cohort, then incorporated and tested in the AlignProCARE open platform app in 2022. Ground truths (GTs) included severity, curve type, and progression as manually annotated by 2 experienced spine specialists based on the radiographic examinations of the participants' spines. The GTs and app results were blindly compared with another 2 spine surgeons' assessments of unclothed back appearance. Data were analyzed from October 2022 to February 2023. Exposure: Acquisitions of unclothed back photographs using a mobile app. Main Outcomes and Measures: Outcomes of interest were classification of AIS severity and progression. Quantitative statistical analyses were performed to assess the performance of the deep learning model in classifying the deformity as well as in distinguishing progression during 6-month follow-up. Results: The training data set consisted of 1780 patients (1295 [72.8%] female; mean [SD] age, 14.3 [3.3] years), and the prospective testing data sets consisted of 378 patients (279 [73.8%] female; mean [SD] age, 14.3 [3.8] years) and 376 follow-ups (294 [78.2%] female; mean [SD] age, 15.6 [2.9] years). The model recommended follow-up with an area under receiver operating characteristic curve (AUC) of 0.839 (95% CI, 0.789-0.882) and considering surgery with an AUC of 0.902 (95% CI, 0.859-0.936), while showing good ability to distinguish among thoracic (AUC, 0.777 [95% CI, 0.745-0.808]), thoracolumbar or lumbar (AUC, 0.760 [95% CI, 0.727-0.791]), or mixed (AUC, 0.860 [95% CI, 0.834-0.887]) curve types. For follow-ups, the model distinguished participants with or without curve progression with an AUC of 0.757 (95% CI, 0.630-0.858). Compared with both surgeons, the model could recognize severities and curve types with a higher sensitivity (eg, sensitivity for recommending follow-up: model, 84.88% [95% CI, 75.54%-91.70%]; senior surgeon, 44.19%; junior surgeon, 62.79%) and negative predictive values (NPVs; eg, NPV for recommending follow-up: model, 89.22% [95% CI, 84.25%-93.70%]; senior surgeon, 71.76%; junior surgeon, 79.35%). For distinguishing curve progression, the sensitivity and NPV were comparable with the senior surgeons (sensitivity, 63.33% [95% CI, 43.86%-80.87%] vs 77.42%; NPV, 68.57% [95% CI, 56.78%-78.37%] vs 72.00%). The junior surgeon reported an inability to identify curve types and progression by observing the unclothed back alone. Conclusions: This diagnostic study of adolescent patients screened for AIS found that the deep learning app had the potential for out-of-hospital accessible and radiation-free management of children with scoliosis, with comparable performance as spine surgeons experienced in AIS management.

Characteristics of baseline frequency data in spinal RCTs do not suggest widespread non-random allocation.

BACKGROUND: Recent signs of fraudulent behaviour in spine RCTs have queried the integrity of trials in the field. RCTs are particularly important due to the weight they are accorded in guiding treatment decisions, and thus, ensuring RCTs' reliability is crucial. This study investigates the presence of non-random baseline frequency data in purported RCTs published in spine journals. METHODS: A PubMed search was performed to obtain all RCTs published in four spine journals (Spine, The Spine Journal, the Journal of Neurosurgery Spine, and European Spine Journal) between Jan-2016 and Dec-2020. Baseline frequency data were extracted, and variable-wise p values were calculated using the Pearson Chi-squared test. These p values were combined for each study into study-wise p values using the Stouffer method. Studies with p values below 0.01 and 0.05 and those above 0.95 and 0.99 were reviewed. Results were compared to Carlisle's 2017 survey of anaesthesia and critical care medicine RCTs. RESULTS: One hundred sixty-seven of the 228 studies identified were included. Study-wise p values were largely consistent with expected genuine randomized experiments. Slightly more study-wise p values above 0.99 were observed than expected, but a number of these had good explanations to account for that excess. The distribution of observed study-wise p values was more closely matched to the expected distribution than those in a similar survey of the anaesthesia and critical care medicine literature. CONCLUSION: The data surveyed do not show evidence of systemic fraudulent behaviour. Spine RCTs in major spine journals were found to be consistent with genuine random allocation and experimentally derived data.

The association between low virulence organisms in different locations and intervertebral disc structural failure: A meta-analysis and systematic review.

Many factors may trigger intervertebral disc (IVD) structural failure (intervertebral disc degeneration (IDD) and endplate changes), including inflammation, infection, dysbiosis, and the downstream effects of chemical factors. Of these, microbial diversity in the IVD and elsewhere in the body has been considered as one of the potential reasons for disc structural failure. The exact relationships between microbial colonization and IVD structural failure are not well understood. This meta-analysis aimed to investigate the impact of microbial colonization and its location (such as skin, IVD, muscle, soft tissues, and blood) on IVD structural failure and corresponding low back pain (LBP) if any. We searched four online databases for potential studies. The potential relationships between microbial colonization in different sample sources (such as skin, IVD, muscle, soft tissues, and blood) and IDD and endplate change were considered as primary outcomes. Odds ratio (OR) and 95% confidence intervals (CI) for direct comparisons were reported. Grading of Recommendations Assessment, Development and Evaluation (GRADE) scale was used to assess the quality of evidence. Twenty-five cohort studies met the selection criteria. Overall pooled prevalence of microbial colonization in 2419 patients with LBP was 33.2% (23.6%-43.6%). The pooled prevalence of microbial colonization in 2901 samples was 29.6% (21.0%-38.9%). Compared with the patients without endplate change, the patients with endplate changes had higher rates of microbial colonization of disc (OR = 2.83; 95% CI = 1.93-4.14; I 2 = 37.6%; p = 0.108). The primary pathogen was Cutibacterium acnes which was present in 22.2% of cases (95% CI = 13.3%-32.5%; I 2 = 96.6%; p = 0.000). This meta-analysis and systematic review found low-quality grade evidence for an association between microbial colonization of disc with endplate changes. The primary pathogen was C. acnes. Due to lack of enough high-quality studies and methodological limitations of this review, further studies are required to improve our understanding of the potential relationships and mechanisms of microbiota, dysbiosis, IVD colonization and IVD structural failure.

Phase 1 evaluation of an elastomeric nucleus pulposus device as an option to augment disc at microdiscectomy: Experimental results from biomechanical and biocompatibility testing and first in human.

Objective: Whilst microdiscectomy is an excellent reliever of pain for recalcitrant lumbar disc herniation (LDH), it has a high failure rate over time due to the ensuing reduction in mechanical stabilization and support of the spine. One option is to clear the disc and replace it with a nonhygroscopic elastomer. Here, we present the evaluation of biomechanical and biological behavior of a novel elastomeric nucleus device (Kunovus disc device [KDD]), consisting of a silicone jacket and a two-part in situ curing silicone polymer filler. Materials and Methods: ISO 10993 and American Society for Testing and Materials (ASTM) standards were used to evaluate the biocompatibility and mechanics of KDD. Sensitization, intracutaneous reactivity, acute systemic toxicity, genotoxicity, muscle implantation study, direct contact matrix toxicity assay, and cell growth inhibition assay were performed. Fatigue test, static compression creep testing, expulsion testing, swell testing, shock testing, and aged fatigue testing were conducted to characterize the mechanical and wear behavior of the device. Cadaveric studies to develop a surgical manual and evaluate feasibility were conducted. Finally, a first-in-human implantation was conducted to complete the proof of principle. Results: The KDD demonstrated exceptional biocompatibility and biodurability. Mechanical tests showed no Barium-containing particles in fatigue test, no fracture of nucleus in static compression creep testing, no extrusion and swelling, and no material failure in shock and aged fatigue testing. Cadaver training sessions showed that KDD was deemed implantable during microdiscectomy procedures in a minimally invasive manner. Following IRB approval, the first implantation in a human showed no intraoperative vascular and neurological complications and demonstrated feasibility. This successfully completed Phase 1 development of the device. Conclusion: The elastomeric nucleus device may mimic native disc behavior in mechanical tests, offering an effective way for treating LDH by way of Phase 2 and subsequent clinical trials or postmarket surveillance in the future.

Smoking and tetramer tryptase accelerate intervertebral disc degeneration by inducing METTL14-mediated DIXDC1 m6 modification.

Although cigarette smoking (CS) and low back pain (LBP) are common worldwide, their correlations and the mechanisms of action remain unclear. We have shown that excessive activation of mast cells (MCs) and their proteases play key roles in CS-associated diseases, like asthma, chronic obstructive pulmonary disease (COPD), blood coagulation, and lung cancer. Previous studies have also shown that MCs and their proteases induce degenerative musculoskeletal disease. By using a custom-designed smoke-exposure mouse system, we demonstrated that CS results in intervertebral disc (IVD) degeneration and release of MC-restricted tetramer tryptases (TTs) in the IVDs. TTs were found to regulate the expression of methyltransferase 14 (METTL14) at the epigenetic level by inducing N6-methyladenosine (m6A) deposition in the 3' untranslated region (UTR) of the transcript that encodes dishevelled-axin (DIX) domain-containing 1 (DIXDC1). That reaction increases the mRNA stability and expression of Dixdc1. DIXDC1 functionally interacts with disrupted in schizophrenia 1 (DISC1) to accelerate the degeneration and senescence of nucleus pulposus (NP) cells by activating a canonical Wnt pathway. Our study demonstrates the association between CS, MC-derived TTs, and LBP. These findings raise the possibility that METTL14-medicated DIXDC1 m6A modification could serve as a potential therapeutic target to block the development of degeneration of the NP in LBP patients.

Intervertebral disc-on-a-chip: a precision engineered toolbox for low back pain studies.

Current in vitro intervertebral disc (IVD) models do not fully recapitulate the complex mechanobiology of native tissue, and so far there is no strategy to effectively evaluate IVD regeneration. The development of a modular microfluidic on-chip model is expected to enhance the physiological relevance of experimental data leading to successful clinical outcomes.

Global Coronal Malalignment in Degenerative Lumbar Scoliosis and Priority-Matching Correction Technique to Prevent Postoperative Coronal Decompensation.

STUDY DESIGN: A prospective case-control study. OBJECTIVE: To analyze global coronal malalignment (GCM) in degenerative lumbar scoliosis (DLS) and to prospectively investigate the performance of priority-matching correction technique on preventing postoperative coronal imbalance. METHODS: A total of 444 DLS inpatients and outpatients were recruited. GCMs were classified into 2 types: Type 1, GCM with thoracolumbar (TL/L) curve as the main contribution on coronal imbalance; Type 2, GCM with lumbosacral (LS) curve as the main contribution on coronal imbalance. Patients receiving priority-matching correction were assigned to Group P-M and receiving traditional correction were assigned to Group T form August 2020. The fundamental principle of priority-matching technique was to first correct the key curve contributing to coronal imbalance rather than the curve with greater magnitude. RESULTS: Type 1 GCM accounted for 45% and Type 2 GCM accounted for 55% of patients. Type 2 GCM was detected to have greater LS Cobb angle and L4 tilt. At 1-year follow-up, 29.8% of patients with Type 2 GCM, whereas 11.7% of patients with Type 1 GCM were observed to have postoperative coronal decompensation. Patients with postoperative imbalance were revealed to have greater preoperative LS Cobb angle and L4 tilt and smaller correction extent of LS curve and L4 tilt. 6.25% of patients developed postoperative coronal imbalance in Group P-M, whereas 40.5% developed in Group T. CONCLUSION: Highlighting priority and aggressive correction of the key curve to coronal imbalance, priority-matching technique was proved to be able to limit the development of postoperative coronal decompensation.