In Vitro Characterization of a Tissue Renin-Angiotensin System in Human Nucleus Pulposus Cells.

Low back pain is a clinically highly relevant musculoskeletal burden and is associated with inflammatory as well as degenerative processes of the intervertebral disc. However, the pathophysiology and cellular pathways contributing to this devastating condition are still poorly understood. Based on previous evidence, we hypothesize that tissue renin-angiotensin system (tRAS) components, including the SARS-CoV-2 entry receptor angiotensin-converting enzyme 2 (ACE2), are present in human nucleus pulposus (NP) cells and associated with inflammatory and degenerative processes. Experiments were performed with NP cells from four human donors. The existence of angiotensin II, angiotensin II type 1 receptor (AGTR1), AGTR2, MAS-receptor (MasR), and ACE2 in human NP cells was validated with immunofluorescent staining and gene expression analysis. Hereafter, the cell viability was assessed after adding agonists and antagonists of the target receptors as well as angiotensin II in different concentrations for up to 48 h of exposure. A TNF-α-induced inflammatory in vitro model was employed to assess the impact of angiotensin II addition and the stimulation or inhibition of the tRAS receptors on inflammation, tissue remodeling, expression of tRAS markers, and the release of nitric oxide (NO) into the medium. Furthermore, protein levels of IL-6, IL-8, IL-10, and intracellular as well as secreted angiotensin II were assessed after exposing the cells to the substances, and inducible nitric oxide synthase (iNOS) levels were evaluated by utilizing Western blot. The existence of tRAS receptors and angiotensin II were validated in human NP cells. The addition of angiotensin II only showed a mild impact on gene expression markers. However, there was a significant increase in NO secreted by the cells. The gene expression ratios of pro-inflammatory/anti-inflammatory cytokines IL-6/IL-10, IL-8/IL-10, and TNF-α/IL-10 were positively correlated with the AGTR1/AGTR2 and AGTR1/MAS1 ratios, respectively. The stimulation of the AGTR2 MAS-receptor and the inhibition of the AGTR1 receptor revealed beneficial effects on the gene expression of inflammatory and tissue remodeling markers. This finding was also present at the protein level. The current data showed that tRAS components are expressed in human NP cells and are associated with inflammatory and degenerative processes. Further characterization of the associated pathways is warranted. The findings indicate that tRAS modulation might be a novel therapeutic approach to intervertebral disc disease

Freehand Technique for Pedicle Screw Placement during Surgery for Adolescent Idiopathic Scoliosis Is Associated with Less Ionizing Radiation Compared to Intraoperative Navigation

Purpose: We aim to compare radiation exposure and implant-related complications of the freehand (FH) technique versus intraoperative image-guided navigation (IN) for pedicle screw placement in adolescent idiopathic scoliosis (AIS) and estimate associated lifetime attributable cancer risks. Methods: A retrospective analysis of prospectively collected data from 40 consecutive AIS patients treated with pedicle screw instrumentation using the FH technique was performed. The dose area product (DAP) and effective dose (ED) were calculated. Screw-related complications were analysed, and the age- and gender-specific lifetime attributable cancer risks were estimated. The results were compared to previously published data on IN used during surgery for AIS. Results: There were no implant-related complications in our cohort. Implant density was 86.6%. The mean Cobb angle of the main curve was 75.2° (SD ± 17.7) preoperatively and 27.7° (SD ± 10.8) postoperatively. The mean ED of our cohort and published data for the FH technique was significantly lower compared to published data on the IN technique (p p < 0.001), ranging from 0.0071 to 0.124% and from 0.0144 to 0.253% for male and female patients, respectively. Conclusion: The routine use of intraoperative navigation in AIS surgery does not necessarily reduce implant-related complications but may increase radiation exposure to the patient

Quality of life after surgery for neuromuscular scoliosis

Surgery in patients with neuromuscular scoliosis is associated with a higher rate of complications. It is still controversially discussed whether the patients truly benefit from deformity correction. The purpose of this study is to investigate if the quality of life has been improved and if the patients and their caregivers are satisfied with the results of surgery. This is a retrospective clinical outcome study of 46 patients with neuromuscular scoliosis which were treated with primary stable posterior pedicle screw instrumentation and correction. To achieve fusion only autologous bone was used. Follow up was minimum 2 years and maximum 5 years with an average of 36 months. The patients and/or their caregivers received a questionnaire based on the PEDI (pediatric disability inventory) and the GMFS (gross motor function score). The patients (and their caregivers) were also asked if the quality of life has improved after surgery. Only 32 of 46 patients answered the questionnaire. The answers showed a high approval-rate regarding the patients satisfaction with the surgery and the improvement of quality of life. The questionnaire could be answered from 1 (I do not agree) to 4 (I completely agree). The average agreement to the following statements was: i) the quality of life has improved: 3.35; ii) I am satisfied with surgery: 3.95; iii) the operation has fulfilled my expectations: 3.76. The average age at surgery was 12.7 years. The mean pre-operative cobb-angle of the main curve was 83.1° with a correction post-operatively to a mean of 36.9° and 42.6° at final follow-up. That is an average correction of 56.9%. Although spinal fusion in neuromuscular scoliosis is associated with a higher rate of complications our results show that the patients and their caregivers are satisfied with the operation and the quality of life has improved after surgery

Revision surgery for incomplete resection or recurrence of cervical spine chordoma: a consecutive case series of 24 patients

Purpose!#!Chordomas are rare tumors with an annual incidence of approximately one per million. Chordomas rarely metastasize but show a high local recurrence rate. Therefore, these patients present a major clinical challenge, and there is a paucity of the literature regarding the outcome after revision surgery of cervical spine chordomas. Available studies suggest a significantly worse outcome in revision scenarios. The purpose of this study is to analyze the survival rate, and complications of patients that underwent revision surgery for local recurrence or incomplete resection of chordoma at the craniocervical junction or at the cervical spine.!##!Methods!#!24 consecutive patients that underwent revision surgery for cervical spine chordoma remnants or recurrence at a single center were reviewed retrospectively. We analyzed patient-specific surgical treatment strategies, complications, and outcome. Kaplan-Meier estimator was used to analyze five-year overall survival.!##!Results!#!Gross total resection was achieved in 17 cases. Seven patients developed dehiscence of the pharyngeal wall, being the most common long-term complication. No instability was observed. Postoperatively, four patients received proton beam radiotherapy and 12 patients had combined photon and proton beam radiotherapy. The five-year overall survival rate was 72.6%.!##!Conclusion!#!With thorough preoperative planning, appropriate surgical techniques, and the addition of adjuvant radiotherapy, results similar to those in primary surgery can be achieved

Novel AI-Based Algorithm for the Automated Computation of Coronal Parameters in Adolescent Idiopathic Scoliosis Patients

Study design: Retrospective, mono-centric cohort research study. Objectives: The purpose of this study is to validate a novel artificial intelligence (AI)-based algorithm against human-generated ground truth for radiographic parameters of adolescent idiopathic scoliosis (AIS). Methods: An AI-algorithm was developed that is capable of detecting anatomical structures of interest (clavicles, cervical, thoracic, lumbar spine and sacrum) and calculate essential radiographic parameters in AP spine X-rays fully automatically. The evaluated parameters included T1-tilt, clavicle angle (CA), coronal balance (CB), lumbar modifier, and Cobb angles in the proximal thoracic (C-PT), thoracic, and thoracolumbar regions. Measurements from 2 experienced physicians on 100 preoperative AP full spine X-rays of AIS patients were used as ground truth and to evaluate inter-rater and intra-rater reliability. The agreement between human raters and AI was compared by means of single measure Intra-class Correlation Coefficients (ICC; absolute agreement; .75 rated as excellent), mean error and additional statistical metrics. Results: The comparison between human raters resulted in excellent ICC values for intra- (range: .97-1) and inter-rater (.85-.99) reliability. The algorithm was able to determine all parameters in 100% of images with excellent ICC values (.78-.98). Consistently with the human raters, ICC values were typically smallest for C-PT (eg, rater 1A vs AI: .78, mean error: 4.7°) and largest for CB (.96, -.5 mm) as well as CA (.98, .2°). Conclusions: The AI-algorithm shows excellent reliability and agreement with human raters for coronal parameters in preoperative full spine images. The reliability and speed offered by the AI-algorithm could contribute to the efficient analysis of large datasets (eg, registry studies) and measurements in clinical practice

Artificial Intelligence-Driven Prediction Modeling and Decision Making in Spine Surgery Using Hybrid Machine Learning Models

Healthcare systems worldwide generate vast amounts of data from many different sources. Although of high complexity for a human being, it is essential to determine the patterns and minor variations in the genomic, radiological, laboratory, or clinical data that reliably differentiate phenotypes or allow high predictive accuracy in health-related tasks. Convolutional neural networks (CNN) are increasingly applied to image data for various tasks. Its use for non-imaging data becomes feasible through different modern machine learning techniques, converting non-imaging data into images before inputting them into the CNN model. Considering also that healthcare providers do not solely use one data modality for their decisions, this approach opens the door for multi-input/mixed data models which use a combination of patient information, such as genomic, radiological, and clinical data, to train a hybrid deep learning model. Thus, this reflects the main characteristic of artificial intelligence: simulating natural human behavior. The present review focuses on key advances in machine and deep learning, allowing for multi-perspective pattern recognition across the entire information set of patients in spine surgery. This is the first review of artificial intelligence focusing on hybrid models for deep learning applications in spine surgery, to the best of our knowledge. This is especially interesting as future tools are unlikely to use solely one data modality. The techniques discussed could become important in establishing a new approach to decision-making in spine surgery based on three fundamental pillars: (1) patient-specific, (2) artificial intelligence-driven, (3) integrating multimodal data. The findings reveal promising research that already took place to develop multi-input mixed-data hybrid decision-supporting models. Their implementation in spine surgery may hence be only a matter of time

Impact of different surgical and non-surgical interventions on health-related quality of life after thoracolumbar burst fractures without neurological deficit: protocol for a comprehensive systematic review with network meta-analysis

Introduction There is no international consensus on how to treat thoracolumbar burst fractures (TLBFs) without neurological deficits. The planned systematic review with network meta-analyses (NMA) aims to compare the effects on treatment outcomes, focusing on midterm health-related quality of life (HRQoL).Methods and analysis We will conduct a comprehensive and systematic literature search, identifying studies comparing two or more treatment modalities. We will search MEDLINE, EMBASE, Google Scholar, Scopus and Web of Science from January 2000 until July 2023 for publications. We will include (randomised and non-randomised) controlled clinical trials assessing surgical and non-surgical treatment methods for adults with TLBF. Screening of references, data extraction and risk of bias (RoB) assessment will be done independently by two reviewers. We will extract relevant studies, participants and intervention characteristics. The RoB will be assessed using the revised Cochrane RoB V.2.0 tool for randomised trials and the Newcastle-Ottawa Scale for controlled trials. The OR for dichotomous data and standardised mean differences for continuous data will be presented with their respective 95% CIs. We will conduct a random-effects NMA to assess the treatments and determine the superiority of the therapeutic approaches. Our primary outcomes will be midterm (6 months to 2 years after injury) overall HRQoL and pain. Secondary outcomes will include radiological or clinical findings. We will present network graphs, forest plots and relative rankings on plotted rankograms corresponding to the treatment rank probabilities. The ranking results will be represented by the area under the cumulative ranking curve. Analyses will be performed in Stata V.16.1 and R. The quality of the evidence will be evaluated according to the Grading of Recommendations, Assessment, Development and Evaluations framework.Ethics and dissemination Ethical approval is not required. The research will be published in a peer-reviewed journal

Hybrid instrumentation in lumbar spinal fusion : a biomechanical evaluation of three different Instrumentation techniques

Study Design Ex vivo human cadaveric study. Objective The development or progression of adjacent segment disease (ASD) after spine stabilization and fusion is a major problem in spine surgery. Apart from optimal balancing of the sagittal profile, dynamic instrumentation is often suggested to prevent or impede ASD. Hybrid instrumentation is used to gain stabilization while allowing motion to avoid hypermobility in the adjacent segment. In this biomechanical study, the effects of two different hybrid instrumentations on human cadaver spines were evaluated and compared with a rigid instrumentation. Methods Eighteen human cadaver spines (T11-L5) were subdivided into three groups: rigid, dynamic, and hook comprising six spines each. Clinical parameters and initial mechanical characteristics were consistent among groups. All specimens received rigid fixation from L3-L5 followed by application of a free bending load of extension and flexion. The range of motion (ROM) for every segment was evaluated. For the rigid group, further rigid fixation from L1-L5 was applied. A dynamic Elaspine system (Spinelab AG, Winterthur, Switzerland) was applied from L1 to L3 for the dynamic group, and the hook group was instrumented with additional laminar hooks at L1-L3. ROM was then evaluated again. Results There was no significant difference in ROM among the three instrumentation techniques. Conclusion Based on this data, the intended advantage of a hybrid or dynamic instrumentation might not be achieve