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.

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.

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.

Age-based exclusion is common and multifactorial in spinal RCTs: a systematic review and quantitative analysis.

Most diseases of the spine disproportionately impact older persons, with the modal (i.e., commonest) patient a female in their 8th decade of life. We examined the corpus of spinal RCTs to determine how many included "average" spine patients. We searched PubMed for randomized clinical trials published in the top 7 spine journals over a period of 5 years from 2016 to 2020 and extracted nominal upper age cut-offs and the distribution of ages actually recruited. We identified 186 trials of 26,238 patients. We found that only 4.8% of trials could be applied to an "average" 75-year-old patient. This age-based exclusion was not dependent on funding source. Age-based exclusion was exacerbated by explicit upper age cut-offs, however, the age-based exclusion went beyond explicit age cut-offs. Only few trials were applicable to older patients even amongst trials with no age cut-off specified. Age-based exclusion from clinical trials starts at late middle age. The mismatch between spinal patient's age seen in clinical practice and spinal patient's age in trials was so severe that over the 5 years (2016-2020) almost no RCT evidence was produced applicable to the "average" aged-patient across the body of literature available. In conclusion, age-based exclusion is ubiquitous, multifactorial, and happens on a supratrial level. Eliminating age-based exclusion involves more than an arbitrary lifting of explicitly stated upper age cut-offs. Instead, recommendations include increasing input from geriatricians and ethics committees, establishing updated or new models of cares, and creating new protocols to facilitate further research.

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.

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.

Clinicians' perceptions around discectomy surgery for lumbar disc herniation: a survey of orthopaedic and neuro-surgeons in Australia and New Zealand.

INTRODUCTION: Understanding practice-based differences in treatment of lumbar disc herniations (LDHs) is vital for reducing unwarranted variation in the delivery of spine surgical health care. Identifying factors that influence surgeons' decision-making will offer useful insights for developing the most cost-effective and safest surgical strategy as well as developing surgeon education materials for common lumbar pathologies. This study was to capture any variation in techniques used by surgeons in Australia and New Zealand (ANZ) region, and perceived complications of different surgical procedures for primary and recurrent LDH (rLDH). MATERIALS AND METHODS: Web-based survey study was emailed to orthopaedic and neurosurgeons who routinely performed spinal surgery in ANZ from Decmber 20, 2018 to February 20, 2020. The response data were analyzed to assess for differences based on geography, practice setting, speciality, practice experience, practice length, and operative volume. RESULTS: Invitations were sent to 150 surgeons; 96 (64%) responded. Most surgeons reported microdiscectomy as their surgical technique of choice for primary LDH (73%) and the first rLDH (72%). For the second rLDH, the preferred choice for most surgeons was fusion surgery (82%). A surgeon's practice setting (academic/private/hybrid) was a statistically significant factor in what surgical procedure was chosen for the first rLDH (P = 0.014). When stratifying based on surgeon experience, there were statisfically significant differences based on the annual volume of spine surgeries performed (perceived reherniation rates following primary discectomy, P = 0.013; perceived reherniation rates following revision surgeries, P = 0.017; perceived intraoperative complications rates following revision surgeries, P = 0.016) and based on the annual volume of lumbar discectomies performed (perceived reherniation rates following revision surgeries, P = 0.022; perceived intraoperative complications rates following revision surgeries, P = 0.036; perceived durotomy rates following primary discectomy, P = 0.023). CONCLUSIONS: Surgeons' annual practice volume and practice setting have significant influences in the selection of surgical procedures and the perception of surgical complications when treating LDHs.

Gut-disc axis: A cause of intervertebral disc degeneration and low back pain?

PURPOSE: Low back pain (LBP), a widely prevalent and costly disease around the world, is mainly caused by intervertebral disc (IVD) degeneration (IDD). Although numerous factors may trigger this degenerative process, microbiome dysbiosis has recently been implicated as one of the likely causes. However, the exact relationship between the microbiome and IDD is not well understood. This review summarizes the potential mechanisms and discusses microbiome dysbiosis's possible influence on IDD and LBP. METHODS: Prospective literature review. RESULTS: Alterations in microbiome composition and host responses to the microbiota causing pathological bone development and involution, led to the concept of gut-bone marrow axis and gut-bone axis. Moreover, the concept of the gut-disc axis was also proposed to explain the microbiome's role in IDD and LBP. According to the existing evidence, the microbiome could be an important factor for inducing and aggravating IDD through changing or regulating the outside and inside microenvironment of the IVD. Three potential mechanisms by which the gut microbiota can induce IVD and cause LBP are: (1) translocation of the bacteria across the gut epithelial barrier and into the IVD, (2) regulation of the mucosal and systemic immune system, and (3) regulation of nutrient absorption and metabolites formation at the gut epithelium and its diffusion into the IVD. Furthermore, to investigate whether IVD is initiated by pathogenic bacteria and establish the correlation between the presence of certain microbial groups with the disease in question, microbiome diversity analysis based on16S rRNA data can be used to characterise stool/blood microbiota from IVD patients. CONCLUSION: Future studies on microbiome, fungi and viruses in IDD is necessary to revolutionize our thinking about their possible role in the development of IVD diseases. Furthermore, we believe that inflammation inhibition and interruption of amplification of cascade reaction in IVD by targeting the gut and IVD microbiome is worthwhile for the treatment of IDD and LBP. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.

Interventions for promoting evidence-based guideline-consistent surgery in low back pain: a systematic review and meta-analysis of randomised controlled trials.

PURPOSE: Examine the effectiveness of interventions to approach guideline-adherent surgical referrals for low back pain assessed via systematic review and meta-analysis. METHODS: Five databases (10 September 2021), Google Scholar, reference lists of relevant systematic reviews were searched and forward and backward citation tracking of included studies were implemented. Randomised controlled/clinical trials in adults with low back pain of interventions to optimise surgery rates or referrals to surgery or secondary referral were included. Bias was assessed using the Cochrane ROB2 tool and evidence certainty via Grading of Recommendations Assessment, Development and Evaluation (GRADE). A random effects meta-analysis with a Paule Mandel estimator plus Hartung-Knapp-Sidik-Jonkman method was used to calculate the odds ratio and 95% confidence interval, respectively. RESULTS: Of 886 records, 6 studies were included (N = 258,329) participants; cluster sizes ranged from 4 to 54. Five studies were rated as low risk of bias and one as having some concerns. Two studies reporting spine surgery referral or rates could only be pooled via combination of p values and gave evidence for a reduction (p = 0.021, Fisher's method, risk of bias: low). This did not persist with sensitivity analysis (p = 0.053). For secondary referral, meta-analysis revealed a non-significant odds ratio of 1.07 (95% CI [0.55, 2.06], I2 = 73.0%, n = 4 studies, Grading of Recommendations Assessment, Development and Evaluation [GRADE] evidence certainty: very low). CONCLUSION: Few RCTs exist for interventions to improve guideline-adherent spine surgery rates or referral. Clinician education in isolation may not be effective. Future RCTs should consider organisational and/or policy level interventions. PROSPERO REGISTRATION: CRD42020215137.

The association between pain scores and disc height change following discectomy surgery in lumbar disc herniation patients: a systematic review and meta-analysis.

PURPOSE: To evaluate the impact of discectomy on disc height (DH) in lumbar disc herniation (LDH) patients following discectomy surgery and address the association of DH change with pain score change. METHODS: We searched three online databases for randomized controlled trials (RCTs) and observational studies. In LDH patients, eligible for discectomy surgery, the changes in pre- and post-operative back and/or leg pain score and DH and/or disc height index (DHI) were considered as primary outcomes. Standardize mean difference (SMD) and their 95% confidence intervals (CI) were evaluated. The GRADE approach was used to summarize the strength of evidence. RESULTS: Two RCTs and sixteen observational studies were included in the analysis of 893 LDH patients undergoing discectomy surgery. The mean overall follow-up was 211 weeks. There was a statistically significant reduction in DH (14.4% reduction: SMD = -0.74 (95% CI = -0.86 to -0.61)) and DHI (11.5% reduction: SMD = -0.81 (95% CI = -0.97 to -0.65)) following discectomy surgery. There was a significant relationship between the reduction in DH and decrease in back pain score (r = 0.68, (95% CI = 0.07-1.30), p = 0.034) after discectomy surgery. No significant relationship between DHI change and decrease in clinical pain scores (back and leg pain) could be established. CONCLUSION: Discectomy surgery produces significant and quantifiable reductions in DH and DHI. Additionally, the reduction in DH is responsible for the decrease in back pain scores post discectomy, but further studies will improve understanding and aid preoperative counselling.

Fat infiltration in the multifidus muscle is related to inflammatory cytokine expression in the muscle and epidural adipose tissue in individuals undergoing surgery for intervertebral disc herniation.

PURPOSE: Recent animal studies have discovered dysregulation of local inflammatory activity as a novel mechanism to explain fat and connective tissue accumulation in the multifidus muscle in association with intervertebral disc (IVD) degeneration/injury. This study aimed to test whether similar mechanisms are active in humans by investigation of whether expression of inflammatory genes in the multifidus muscle differed between individuals with low and high levels of intra-muscular fat in the muscle. The secondary aims were to compare inflammatory gene expression in the intra-muscular, subcutaneous and epidural fat between groups. METHODS: Muscle and fat were procured from 24 individuals undergoing spine surgery for IVD herniation. Gene expression was quantified using qPCR assays. Participants were allocated to high- and low-fat infiltration groups based on clinical assessment of multifidus fat using Kjaer grading of MRI. RESULTS: TNF expression in the multifidus muscle was greater in participants with high rather than low levels of fat infiltration. This group also had greater expression of leptin, but lower arginase-1 (marker of anti-inflammatory M2 macrophages) in intra-muscular and subcutaneous adipose tissue, and greater expression of TNF, adiponectin and nitric oxide synthase 2 (marker of pro-inflammatory M1 macrophages) in epidural fat. CONCLUSION: The results support the hypothesis that IVD degeneration is associated with dysregulation of the inflammatory state of the local multifidus muscle, which provides initial evidence for translation of some, but not all, observations from recent animal studies to humans. Discovery of inflammatory dysregulation in epidural adipose tissue has potential for broad impact on tissue health and LBP symptoms.

Surgeon-defined assessment is a poor predictor of knee balance in total knee arthroplasty: a prospective, multicenter study.

BACKGROUND: The accuracy of surgeon-defined assessment (SDA) of soft tissue balance in total knee arthroplasty (TKA) is poorly understood despite balance being considered a significant determinant of surgical success. The study's hypothesis was that intra-operative SDA is a poor predictor of coronal balance in TKA. METHODS: A prospective, multicenter study assessing accuracy of SDA of balance was conducted in 250 patients (285 TKAs). Eight surgeons and thirteen trainees participated, and all were blinded to sensor measurements. The primary outcome was test accuracy of SDA measured at 10°, 45° and 90° compared to sensor measures as the gold standard test. Cohen's kappa coefficient was calculated to determine chance-corrected agreement. Secondary outcomes include the relationship of SDA to level of surgical experience, analysis of between-surgeon differences, and the influence of patient and operative factors on SDA accuracy. RESULTS: Average accuracy of SDA was 58.3%, 61.2% and 66.5% at 10°, 45° and 90° respectively. Cohen's kappa coefficient was 0.18 at all angles and rated as "slight agreement". SDA sensitivities to correctly identify a balanced knee (76.2% at 10°; 82.6% at 45°; 83.2% at 90°) were approximately twice specificities to correctly identify an unbalanced knee (42.6% at 10°; 34.1% at 45°; 41.4% at 90°). Surgical experience (surgeon versus trainee) had no effect on capacity to determine balance. Considerable between-surgeon variability was found (33-65% at 10°, 41-73% at 45°, 55-89% at 90°). CONCLUSION: SDA was a poor predictor of balance, particularly when assessing the unbalanced TKA. Surgeon experience had no effect on test accuracy and considerable between-surgeon variability was recorded. These findings question the accuracy of SDA in TKA. TRIAL REGISTRATION NUMBER: ACTRN# 12618000817246.

Does the Use of Intraoperative Pressure Sensors for Knee Balancing in Total Knee Arthroplasty Improve Clinical Outcomes? A Comparative Study With a Minimum Two-Year Follow-Up.

BACKGROUND: It is undetermined whether using sensors for knee balancing in total knee arthroplasty (TKA) improves patient outcomes. The purpose of this study was to compare clinical outcomes of sensor balance (SB) with manual balance (MB) TKA with a minimum two-year follow-up. METHODS: A consecutive series of 207 MB TKAs was compared with 222 SB TKAs between April 2014 and April 2017. A single surgeon performed all surgeries, using the same prosthesis. The primary end point was the aggregated mean change in four subscales of the Knee injury and Osteoarthritis Outcome Score (KOOS4) between preoperative and two-year time points. Secondary outcomes included mean differences between groups in all five KOOS subscales, proportions of knee balancing procedures, and rates of reoperations including revisions and manipulations for stiffness. RESULTS: The mean changes in the KOOS4 aggregated means for MB TKA (42.4; standard deviation, 29.1) and SB TKA (41.5; standard deviation, 25.0) were not significantly different (mean difference, 0.9; 95% confidence interval: -2.6 to 4.4, P = .62). There were significantly more balancing procedures in the SB group (55.9% versus 16.9%; P < .01). There were no significant differences in the number of reoperations (1.4% SB versus 1.4% MB; P = .71) or manipulations for stiffness (3.7% SB versus 4.4% MB; P = .69). CONCLUSION: The use of sensors in TKA to achieve knee balance did not result in improved clinical outcomes, despite significantly increasing the number of surgical interventions required to achieve a balanced knee. Sensors did not alter the rates of revision surgery or requirements for manipulation. It remains to be determined whether precise soft-tissue balancing improves prosthetic survivorship and joint biomechanics.

Complication rates of different discectomy techniques for symptomatic lumbar disc herniation: a systematic review and meta-analysis.

PURPOSE: This meta-analysis aims to compare the complication rates of discectomy/microdiscectomy (OD/MD), microendoscopic discectomy (MED), percutaneous endoscopic lumbar discectomy (PELD), percutaneous laser disc decompression (PLDD), and tubular discectomy for symptomatic lumbar disc herniation (LDH) using general classification and modified Clavien-Dindo classification (MCDC) schemes. METHODS: We searched three online databases for randomized controlled trials (RCTs) and cohort studies. Overall complication rates and complication rates per the above-mentioned classification schemes were considered as primary outcomes. Risk ratio (RR) and their 95% confidence intervals (CI) were evaluated. RESULTS: Seventeen RCTs and 20 cohort studies met the eligibility criteria. RCTs reporting OD/MD, MED, PELD, PLDD, and tubular discectomies had overall complication rates of 16.8% and 16.1%, 21.2%, 5.8%, 8.4%, and 25.8%, respectively. Compared with the OD/MD, there was moderate-quality evidence suggesting that PELD had a lower risk of overall complications (RR = 0.52, 95% CI 0.29-0.91) and high-quality evidence suggesting a lower risk of Type I complications per MCDC (RR = 0.37, 95% CI 0.16-0.81). Compared with the OD/MD data from cohort studies, there was low-quality evidence suggesting a higher risk of Type III complications per MCDC (RR = 10.83, 95% CI 1.29-91.18) for MED, higher risk of reherniations (RR = 1.67,95% CI 1.05-2.64) and reoperations (RR = 1.75, 95% CI 1.20-2.55) for PELD, lower risk of overall complication rates (RR = 0.42, 95% CI 0.25-0.70), post-operative complication rates (RR = 0.42, 95% CI 0.25-0.70), Type III complications per MCDC (RR = 0.39, 95% CI 0.22-0.69), reherniations (RR = 0.56, 95% CI 0.33-0.97) and reoperations (RR = 0.39, 95% CI 0.22-0.69) for PLDD. CONCLUSIONS: Compared with the OD/MD, results of this meta-analysis suggest that PELD has a lower risk of overall complications and a lower risk of complications necessitating conservative treatment. These slides can be retrieved under Electronic Supplementary Material.

A novel tool to provide predictable alignment data irrespective of source and image quality acquired on mobile phones: what engineers can offer clinicians.

PURPOSE: Existing automated spine alignment is based on original X-rays that are not applicable for teleradiology for spinal deformities patients. We aim to provide a novel automated vertebral segmentation method enabling accurate sagittal alignment detection, with no restrictions imposed by image quality or pathology type. METHODS: A total of 428 optical images of original sagittal X-rays taken by smartphones or screenshots for consecutive patients attending our spine clinic were prospectively collected. Of these, 300 were randomly selected and their vertebrae were labelled with Labelme. The ground truth was specialists measured sagittal alignment parameters. Pre-trained Mask R-CNN was fine-tuned and trained to predict the vertebra level(s) on the remaining 128 testing cases. The sagittal alignment parameters including the thoracic kyphosis (TK), lumbar lordosis (LL) and sacral slope (SS) were auto-detected, based on the segmented vertebra. Dice similarity coefficient (DSC) and mean intersection over union (mIoU) were calculated to evaluate the accuracy of the predicted vertebra. The detected sagittal alignments were then quantitatively compared with the ground truth. RESULTS: The DSC was 84.6 ± 3.8% and mIoU was 72.1 ± 4.8% indicating accurate vertebra prediction. The sagittal alignments detected were all strongly correlated with the ground truth (p < 0.001). Standard errors of the estimated parameters had a small difference from the specialists' results (3.5° for TK and SS; 3.4° for LL). CONCLUSION: This is the first study using fine-tuned Mask R-CNN to predict vertebral locations on optical images of X-rays accurately and automatically. We provide a novel alignment detection method that has a significant application on teleradiology aiding out-of-hospital consultations. These slides can be retrieved under Electronic Supplementary Material.

Morphological characteristics of the kangaroo lumbar intervertebral discs and comparison with other animal models used in spine research.

PURPOSE: Animal models are frequently used to elucidate pathomechanism and pathophysiology of various disorders of the human intervertebral disc (IVD) and also to develop therapeutic approaches. Here we report morphological characteristics of the kangaroo lumbar IVDs and compare them with other animal models used in spine research. METHODS: Twenty-five fresh-frozen cadaveric lumbar spines (T12-S1) derived from kangaroo carcases (Macropus giganteus) of undetermined age were first scanned in a C-Arm X-ray machine. A photograph of the axial section of the disc including a calibrated metric scale was also acquired. The digital radiographs and photographs were processed in ImageJ to determine the axial and sagittal plane dimensions for the whole disc (WD) and the nucleus pulposus (NP) and the mid-sagittal disc height for all the lumbar levels. RESULTS: Our results suggest that the L6-S1 IVD in kangaroos is distinctly large compared with the upper lumbar IVDs. Based on previously published data, human lumbar IVDs are the largest of all the animal IVDs used in spine research, with camelid cervical IVDs being the closest relative in absolute dimensions (llamas: 78% in disc height, 40% in WD volume, and 38% in NP volume). Kangaroo L6-S1 IVD was approximately 51% in height, 20% in WD volume, and 20% in NP volume of the human lumbar IVD. CONCLUSIONS: We conclude that morphological similarities exist between a kangaroo and human lumbar IVD, especially with the lima bean shape in the axial plane, wedge shape in the sagittal plane, convexity at the cephalad endplates, and percentage volume occupied by the NP in the IVD. These slides can be retrieved under Electronic Supplementary Material.

Assessment of degenerative cervical stenosis on T2-weighted MR imaging: sensitivity to change and reliability of mid-sagittal and axial plane metrics.

STUDY DESIGN: A retrospective cross-sectional study. OBJECTIVE: To assess the sensitivity to change and reliability of various mid-sagittal and axial plane metrics in the assessment of patients with single-level degenerative cervical stenosis on T2-weighted MR imaging. SETTING: A diagnostic MR imaging facility in Sydney (Australia). METHODS: We retrospectively reviewed T2-weighted MR images of 85 consecutive patients (48 M and 37 F) with single-level degenerative cervical stenosis. Canal compromise and cord compression were evaluated using three mid-sagittal plane metrics (M1, M2, and M3) and two axial plane metrics (M4 and M5), at the level of stenosis and nonstenotic cephalad and caudal levels (controls). Sensitivity to change (SC) for each metric was evaluated as the percentage deviation of the measured value from the estimated normal value based on cephalad and caudal controls. Reliability for each metric was evaluated using intraclass correlation coefficients. RESULTS: Degenerative cervical stenosis showed a bimodal distribution peaking at C5-6 (n = 32) and C3-4 (n = 29) levels. The changes in the canal and cord geometry along the rostrocaudal axis were inconsistent. Across all individual subjects (reflecting a range of stenosis severity), M3 (-32.87% ± 10.60%) was more sensitive to change compared with M1 (16.64% ± 16.48%) and M2 (-23.95% ± 11.12%). Similarly, M4 (-24.62% ± 12.17%) was more sensitive to change compared with M5 (-6.71% ± 11.08%). The level of reliability was "moderate" to "excellent" for mid-sagittal plane measurements, and "poor" to "excellent" for axial plane measurements. CONCLUSION: Changes in canal dimensions in the mid-sagittal plane and cord shape in the axial plane are sensitive indicators of degenerative cervical stenosis on T2-weighted MR images.

Advanced Strategies for the Regeneration of Lumbar Disc Annulus Fibrosus.

Damage to the annulus fibrosus (AF), the outer region of the intervertebral disc (IVD), results in an undesirable condition that may accelerate IVD degeneration causing low back pain. Despite intense research interest, attempts to regenerate the IVD have failed so far and no effective strategy has translated into a successful clinical outcome. Of particular significance, the failure of strategies to repair the AF has been a major drawback in the regeneration of IVD and nucleus replacement. It is unlikely to secure regenerative mediators (cells, genes, and biomolecules) and artificial nucleus materials after injection with an unsealed AF, as IVD is exposed to significant load and large deformation during daily activities. The AF defects strongly change the mechanical properties of the IVD and activate catabolic routes that are responsible for accelerating IVD degeneration. Therefore, there is a strong need to develop effective therapeutic strategies to prevent or reconstruct AF damage to support operational IVD regenerative strategies and nucleus replacement. By the way of this review, repair and regenerative strategies for AF reconstruction, their current status, challenges ahead, and future outlooks were discussed.

Regenerative Response of Degenerate Human Nucleus Pulposus Cells to GDF6 Stimulation.

Growth differentiation factor (GDF) family members have been implicated in the development and maintenance of healthy nucleus pulposus (NP) tissue, making them promising therapeutic candidates for treatment of intervertebral disc (IVD) degeneration and associated back pain. GDF6 has been shown to promote discogenic differentiation of mesenchymal stem cells, but its effect on NP cells remains largely unknown. Our aim was to investigate GDF6 signalling in adult human NP cells derived from degenerate tissue and determine the signal transduction pathways critical for GDF6-mediated phenotypic changes and tissue homeostatic mechanisms. This study demonstrates maintained expression of GDF6 receptors in human NP and annulus fibrosus (AF) cells across a range of degeneration grades at gene and protein level. We observed an anabolic response in NP cells treated with recombinant GDF6 (increased expression of matrix and NP-phenotypic markers; increased glycosaminoglycan production; no change in catabolic enzyme expression), and identified the signalling pathways involved in these responses (SMAD1/5/8 and ERK1/2 phosphorylation, validated by blocking studies). These findings suggest that GDF6 promotes a healthy disc tissue phenotype in degenerate NP cells through SMAD-dependent and -independent (ERK1/2) mechanisms, which is important for development of GDF6 therapeutic strategies for treatment of degenerate discs.