Conditioned Medium of Intervertebral Disc Cells Inhibits Osteo-Genesis on Autologous Bone-Marrow-Derived Mesenchymal Stromal Cells and Osteoblasts.

Low back pain (LBP) is associated with the degeneration of human intervertebral discs (IVDs). Despite progress in the treatment of LBP through spinal fusion, some cases still end in non-fusion after the removal of the affected IVD tissue. In this study, we investigated the hypothesis that the remaining IVD cells secrete BMP inhibitors that are sufficient to inhibit osteogenesis in autologous osteoblasts (OBs) and bone marrow mesenchymal stem cells (MSCs). A conditioned medium (CM) from primary human IVD cells in 3D alginate culture was co-cultured with seven donor-matched OB and MSCs. After ten days, osteogenesis was quantified at the transcript level using qPCR to measure the expression of bone-related genes and BMP antagonists, and at the protein level by alkaline phosphatase (ALP) activity. Additionally, cells were evaluated histologically using alizarin red (ALZR) staining on Day 21. For judging ALP activity and osteogenesis, the Noggin expression in samples was investigated to uncover the potential causes. The results after culture with the CM showed significantly decreased ALP activity and the inhibition of the calcium deposit formation in alizarin red staining. Interestingly, no significant changes were found among most bone-related genes and BMP antagonists in OBs and MSCs. Noteworthy, Noggin was relatively expressed higher in human IVD cells than in autologous OBs or MSCs (relative to autologous OB, the average fold change was in 6.9, 10.0, and 6.3 in AFC, CEPC, and NPC, respectively; and relative to autologous MSC, the average fold change was 2.3, 3.4, and 3.2, in AFC, CEPC, and NPC, respectively). The upregulation of Noggin in residual human IVDs could potentially inhibit the osteogenesis of autologous OB and MSC, thus inhibiting the postoperative spinal fusion after discectomy surgery.

Validation of the AO Spine CROST (Clinician Reported Outcome Spine Trauma) in the clinical setting.

PURPOSE: To evaluate feasibility, internal consistency, inter-rater reliability, and prospective validity of AO Spine CROST (Clinician Reported Outcome Spine Trauma) in the clinical setting. METHODS: Patients were included from four trauma centers. Two surgeons with substantial amount of experience in spine trauma care were included from each center. Two separate questionnaires were administered at baseline, 6-months and 1-year: one to surgeons (mainly CROST) and another to patients (AO Spine PROST-Patient Reported Outcome Spine Trauma). Descriptive statistics were used to analyze patient characteristics and feasibility, Cronbach's α for internal consistency. Inter-rater reliability through exact agreement, Kappa statistics and Intraclass Correlation Coefficient (ICC). Prospective analysis, and relationships between CROST and PROST were explored through descriptive statistics and Spearman correlations. RESULTS: In total, 92 patients were included. CROST showed excellent feasibility results. Internal consistency (α = 0.58-0.70) and reliability (ICC = 0.52 and 0.55) were moderate. Mean total scores between surgeons only differed 0.2-0.9 with exact agreement 48.9-57.6%. Exact agreement per CROST item showed good results (73.9-98.9%). Kappa statistics revealed moderate agreement for most CROST items. In the prospective analysis a trend was only seen when no concerns at all were expressed by the surgeon (CROST = 0), and moderate to strong positive Spearman correlations were found between CROST at baseline and the scores at follow-up (rs = 0.41-0.64). Comparing the CROST with PROST showed no specific association, nor any Spearman correlations (rs = -0.33-0.07). CONCLUSIONS: The AO Spine CROST showed moderate validity in a true clinical setting including patients from the daily clinical practice.

The bone morphogenetic protein 2 analogue L51P enhances spinal fusion in combination with BMP2 in an in vivo rat tail model.

Bone morphogenic protein 2 (BMP2) is known to induce osteogenesis and is applied clinically to enhance spinal fusion despite adverse effects. BMP2 needs to be used in high doses to be effective due to the presence of BMP2 inhibitors. L51P is a BMP2 analogue that acts by inhibition of BMP2 inhibitors. Here, we hypothesized that mixtures of BMP2 and L51P could achieve better spinal fusion outcomes regarding ossification. To test whether mixtures of both cytokines are sufficient to improve ossification, 45 elderly Wistar rats (of which 21 were males) were assigned to seven experimental groups, all which received spinal fusion surgery, including discectomy at the caudal 4-5 level using an external fixator and a porous ß-tricalcium phosphate (ßTCP) carrier. These ßTCP carriers were coated with varying concentrations of BMP2 and L51P. X-rays were taken immediately after surgery and again six and twelve weeks post-operatively. Histological sections and µCT were analyzed after twelve weeks. Spinal fusion was assessed using X-ray, µCT and histology according to the Bridwell scale by voxel-based quantification and a semi-quantitative histological score, respectively. The results were congruent across modalities and revealed high ossification for high-dose BMP2 (10 µg), while PBS induced no ossification. Low-dose BMP2 (1 µg) or 10 µg L51P alone did not induce relevant bone formation. However, all combinations of low-dose BMP2 with L51P (1 µg + 1/5/10 µg) were able to induce similar ossificationas high-dose BMP2. These results are of high clinical relevance, as they indicate L51P is sufficient to increase the efficacy of BMP2 and thus lower the required dose for spinal fusion. STATEMENT OF SIGNIFICANCE: Spinal fusion surgery is frequently applied to treat spinal pathologies. Bone Morphogenic Protein-2 (BMP2) has been approved by the U .S. Food and Drug Administration (FDA-) and by the "Conformité Européenne" (CE)-label. However, its application is expensive and high concentrations cause side-effects. This research targets the improvement of the efficacy of BMP2 in spinal fusion surgery.

Supplementary value and diagnostic performance of computed tomography scout view in the detection of thoracolumbar spine injuries.

PURPOSE: Assessing the diagnostic performance and supplementary value of whole-body computed tomography scout view (SV) images in the detection of thoracolumbar spine injuries in early resuscitation phase and identifying frequent image quality confounders. METHODS: In this retrospective database analysis at a tertiary emergency center, three blinded senior experts independently assessed SV to detect thoracolumbar spine injuries. The findings were categorized according to the AO Spine classification system. Confounders impacting SV image quality were identified. The suspected injury level and severity, along with the confidence level, were indicated. Diagnostic performance was estimated using the caret package in R programming language. RESULTS: We assessed images of 199 patients, encompassing 1592 vertebrae (T10-L5), and identified 56 spinal injuries (3.5%). Among the 199 cases, 39 (19.6%) exhibited at least one injury in the thoracolumbar spine, with 12 (6.0%) of them displaying multiple spinal injuries. The pooled sensitivity, specificity, and accuracy were 47%, 99%, and 97%, respectively. All experts correctly identified the most severe injury of AO type C. The most common image confounders were medical equipment (44.6%), hand position (37.6%), and bowel gas (37.5%). CONCLUSION: SV examination holds potential as a valuable supplementary tool for thoracolumbar spinal injury detection when CT reconstructions are not yet available. Our data show high specificity and accuracy but moderate sensitivity. While not sufficient for standalone screening, reviewing SV images expedites spinal screening in mass casualty incidents. Addressing modifiable factors like medical equipment or hand positioning can enhance SV image quality and assessment.

Cervical spine trauma - Evaluating the diagnostic power of CT, MRI, X-Ray and LODOX.

BACKGROUND: Traumatic cervical spine (c-spine) injuries account for 10% of all spinal injuries. The c-spine is prone to injury by blunt acceleration/deceleration traumas. The Canadian C-Spine rule and NEXUS criteria guide clinical decision-making but lack consensus on imaging modality when necessary. This study aims to evaluate the sensitivity and specificity of CT, MRI, X-Ray, and, for the first time, LODOX-Statscan in identifying c-spine injuries in patients with blunt trauma and neck pain. METHODS: We conducted a retrospective monocenter cohort study using patient data from the emergency department at Inselspital, Bern, Switzerland's largest level one trauma center. We identified patients presenting with trauma and neck pain during the recruitment period from 01.01.2012 to 31.12.2017. We included all patients that required a radiographic c-spine evaluation according to the NEXUS criteria. Certified spine surgeons reviewed each case, analyzed patient demographics, injury classification, trauma mechanism, and emergency management. The retrospective full case review was established as gold standard to decide whether the c-spine was injured. Sensitivity and specificity were calculated for CT, MRI, LODOX, and X-Ray imaging methods. RESULTS: We identified 4996 patients, of which 2321 met the inclusion criteria. 91.3% (n = 2120) patients received a CT scan, 8.9% (n = 206) a MRI, 9.3% (n = 215) an X-ray, and 21.5% (n = 498) a LODOX scan. By retrospective case review, 186 participants were classified as injured. The sensitivity of CT was 88.6% (specificity 99%), and 89.8% (specificity 99.2%) with orthopedic surgeon consultation. MRI had a sensitivity of 88.5% (specificity of 96.9%); highlighting 14 cases correctly diagnosed as injured by MRI and misdiagnosed by CT. Projection radiography (36.4% sensitivity, 95.1% specificity) and LODOX (5.3% sensitivity, 100% specificity) were unsuitable for ruling out spinal injury. CONCLUSION: While CT offers high sensitivity for detecting traumatic c-spine injury, MRI holds clinical significance in revealing injuries not recognized by CT in symptomatic patients. LODOX and projection radiography are insufficient for accurately ruling out c-spine injury. For patients with neurological symptoms, we recommend extended MRI use when CT scans are negative.

Anterior thoracolumbar column reconstruction with the vertebral body stent-safety and efficacy.

PURPOSE: The aim of this study was to assess safety and efficacy of vertebral body stenting (VBS) by analyzing (1) radiographic outcome, (2) clinical outcome, and (3) perioperative complications in patients with vertebral compression fractures treated with VBS at minimum 6-month follow-up. METHODS: In this retrospective cohort study, 78 patients (61 ± 14 [21-90] years; 67% female) who have received a vertebral body stent due to a traumatic, osteoporotic or metastatic thoracolumbar compression fracture at our hospital between 2012 and 2020 were included. Median follow-up was 0.9 years with a minimum follow-up of 6 months. Radiographic and clinical outcome was analyzed directly, 6 weeks, 12 weeks, 6 months postoperatively, and at last follow-up. RESULTS: Anterior vertebral body height of all patients improved significantly by mean 6.2 ± 4.8 mm directly postoperatively (p < 0.0001) and remained at 4.3 ± 5.1 mm at last follow-up compared to preoperatively (p < 0.0001). The fracture kyphosis angle of all patients improved significantly by mean 5.8 ± 6.9 degrees directly postoperatively (p < 0.0001) and remained at mean 4.9 ± 6.9 degrees at last follow-up compared to preoperatively (p < 0.0001). The segmental kyphosis angle of all patients improved significantly by mean 7.1 ± 7.6 degrees directly postoperatively (p < 0.0001) and remained at mean 2.8 ± 7.8 degrees at last follow-up compared to preoperatively (p = 0.03). Back pain was ameliorated from a preoperative median Numeric Rating Scale value of 6.5 to 3.0 directly postoperatively and further bettered to 1.0 six months postoperatively (p = 0.0001). Revision surgery was required in one patient after 0.4 years. CONCLUSION: Vertebral body stenting is a safe and effective treatment option for osteoporotic, traumatic and metastatic compression fractures.

Radiofrequency Neurotomy Does Not Cause Fatty Degeneration of the Lumbar Paraspinal Musculature in Patients with Chronic Lumbar Pain-A Retrospective 3D-Computer-Assisted MRI Analysis Using iSix Software.

OBJECTIVE: The present study aimed (1) to analyze the relative paraspinal autochthonous intramuscular fat volume before and after radiofrequency neurotomy (RFN) and (2) to compare it to the contralateral non-treated side. DESIGN: Retrospective cohort study. SETTING: Inselspital, University Hospital Bern, University of Bern. SUBJECTS: Twenty patients (59.60 ± 8.49 years; 55% female) with chronic low back pain, treated with RFN (L2/3-L5/S1) due to symptomatic facet joint syndrome (FCS) between 2008 and 2017 were included. METHODS: All patients received a magnetic resonance imaging (MRI) of the lumbar spine before and at a minimum of 6 months after RFN. The absolute (cm3) and relative (%) paraspinal muscle and fat volume was analyzed three-dimensionally on standard T2-MRI sequences using a newly developed software (iSix, Osiris plugin). Both sides were examined and allocated as treated or non-treated side. RESULTS: A total of 31 treated and 9 non-treated sides (Level L2/3-L5/S1) were examined. There were no differences in the relative paraspinal intramuscular fat volume before and at a median of 1.4 [0.9 - 2.6] years after RFN (P = .726). We found no differences in the relative fat volume between the treated and non-treated side before (P = .481) and after (P = .578) RFN. CONCLUSIONS: Our study shows that there are no differences in the paraspinal muscle/fat distribution after RFN. RFN of the medial branches for FCS does not seem to cause fatty degeneration of the lumbar paraspinal muscles as a sign of iatrogenic muscle denervation.

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.

Gender authorship trends in spine research publications - Research across different countries from 1976 to 2020.

•Gender trends in authorship showed an increase in female authors from 1976 to 2020.•In 2020, Europe had the highest and Asia the lowest proportion of female authors.•The Netherlands had the highest proportion of women and Japan the lowest.

Venous injection of a triphasic calcium-based implant in a sheep model of pulmonary embolism demonstrates minimal acute systemic effects.

PURPOSE: Implant leakage is the most common complication of vertebral augmentation. Alternative injectable materials must demonstrate intravascular safety comparable to or better than polymethyl methacrylate (PMMA). This study assessed the systemic effects of a triphasic calcium-based implant or PMMA injected directly into the femoral vein in a large animal model designed to mimic severe intravascular implant leakage. METHODS: Six skeletally mature female sheep were randomly assigned (n = 3) to either the PMMA or the triphasic implant (AGN1, composition: calcium sulfate, ß-tricalcium phosphate, brushite) treatment group. Femoral veins of each sheep were directly injected with 0.5 mL of implant material to mimic leakage volumes reported during PMMA vertebroplasty. To compare acute systemic effects of the materials, cardiovascular parameters, laboratory coagulation markers, and calcium and sulfate serum levels were monitored for 60 min after implant injection. Thrombotic and embolic events were evaluated by radiologic imaging, necropsy, and histopathology. RESULTS: Heart rate, systemic arterial blood pressure, arterial oxygenation, arterial carbon dioxide content, and coagulation markers remained within physiological range after either AGN1 or PMMA injection. No blood flow interruption in the larger pulmonary vessels was observed in either group. Lung histopathology revealed that the severity of thrombotic changes after AGN1 injection was minimal to slight, while changes after PMMA injection were minimal to massive. CONCLUSION: Acute systemic effects of intravascular AGN1 appeared to be comparable to or less than that of intravascular PMMA. Furthermore, in this preliminary study, the severity and incidence of pulmonary histological changes were lower for AGN1 compared to PMMA.

Comparison and optimization of sheep in vivo intervertebral disc injury model.

Background: The current standard of care for intervertebral disc (IVD) herniation, surgical discectomy, does not repair annulus fibrosus (AF) defects, which is partly due to the lack of effective methods to do so and is why new repair strategies are widely investigated and tested preclinically. There is a need to develop a standardized IVD injury model in large animals to enable comparison and interpretation across preclinical study results. The purpose of this study was to compare in vivo IVD injury models in sheep to determine which annulus fibrosus (AF) defect type combined with partial nucleus pulposus (NP) removal would better mimic degenerative human spinal pathologies. Methods: Six skeletally mature sheep were randomly assigned to one of the two observation periods (1 and 3 months) and underwent creation of 3 different AF defect types (slit, cruciate, and box-cut AF defects) in conjunction with 0.1 g NP removal in three lumbar levels using a lateral retroperitoneal surgical approach. The spine was monitored by clinical CT scans pre- and postoperatively, at 2 weeks and euthanasia, and by magnetic resonance imaging (MRI) and histology after euthanasia to determine the severity of degeneration (disc height loss, Pfirrmann grading, semiquantitative histopathology grading). Results: All AF defects led to significant degenerative changes detectable on CT and MR images, produced bulging of disc tissue without disc herniation and led to degenerative and inflammatory histopathological changes. However, AF defects were not equal in terms of disc height loss at 3 months postoperatively; the cruciate and box-cut AF defects showed significantly decreased disc height compared to their preoperative height, with the box-cut defect creating the greatest disc height loss, while the slit AF defect showed restoration of normal preoperative disc height. Conclusions: The tested IVD injury models do not all generate comparable disc degeneration but can be considered suitable IVD injury models to investigate new treatments. Results of the current study clearly indicate that slit AF defect should be avoided if disc height is used as one of the main outcomes; additional confirmatory studies may be warranted to generalize this finding.

Asia Now Surpasses Europe in Spine Research Productivity: An Analysis From 1976-2020.

STUDY DESIGN: Bibliometric review. OBJECTIVE: This study aims to understand the worldwide research productivity trends in spine-related research over the past five decades. SUMMARY OF BACKGROUND DATA: Research productivity in the field of spine surgery has increased tremendously over the past decades. However, knowledge regarding the detailed regional disparity is limited. METHODS: We evaluated original research articles published in four prestigious journals on spine research (European Spine Journal, Journal of Neurosurgery: Spine, Spine, and The Spine Journal) from 1976 to 2020. For 1 year of each decade, the origin of the first and the senior author was assigned to their region of origin. For the year 2020, a detailed analysis of countries and states of origin was performed, and the number of articles was normalized by registered MDs per country (per 10,000 population). RESULTS: We included a total of 4436 articles and 8776 authors for analysis. From 1976 to 2020, the percentage of publications originating from North America decreased (77%-38%). In contrast, Asian contributions drastically increased (3%-36%), whereas articles originating from Europe only slightly raised (20%-22%). In 2020, the United States was the most productive country worldwide (34% with most articles from New York (19%), followed by China (16%) and Japan (10%). After normalization to registered MDs (per 10,000 population), the United States proved to have the highest number of articles. Besides this, India now ranked fourth and Egypt eighth in terms of the most productive countries per MDs. CONCLUSION: North America contributed the largest share of all articles published in the last five decades. Asia, which ranks second in 2020, has overtaken Europe. Normalization to registered MDs can be a helpful tool to reflect a country's research productivity more accurately.Level of Evidence: 3.

Injuries in alpine summer sports - types, frequency and prevention: a systematic review.

INTRODUCTION: Summer alpine sports, including mountain biking, hiking and airborne pursuits, have experienced a recent surge in popularity. Accordingly, trauma associated with these activities has increased. There is a scarcity of literature exploring clinical aspects surrounding injuries. Specifically, no single article provides a general overview, as individual studies tend to focus on one particular sport. In the present study, we performed a systematic literature review to summarize existing knowledge and explore the potential for prevention and clinical decision making in this group. METHOD: Literature searches were performed using the PubMed and Scopus database for the most commonly ventured sports associated with injury: mountain biking, climbing, airborne sports, paragliding, and base jumping. From this search, studies were identified for qualitative and quantitative analyses. These searches were done according to PRISMA guidelines for systematic reviews. Studies were then analyzed regarding epidemiology of injuries, relevant anatomical considerations and prevention strategies were discussed. RESULTS: A broad spectrum of injury sites and mechanisms are seen in mountain biking, climbing or airborne sports. Mountain biking related injuries commonly involve the upper extremity, with fractures of the clavicle being the most common injury, followed by fractures of the hand and wrist. Scaphoid fractures remain of paramount importance in a differential diagnosis, given their often subtle clinical and radiological appearance. Paragliding, skydiving, and base jumping particularly affect transition areas of the spine, such as the thoracolumbar and the spinopelvic regions. Lower limb injuries were seen in equal frequency to spinal injuries. Regarding relative risk, mountain biking has the lowest risk for injuries, followed by climbing and airborne sports. Male alpinists are reported to be more susceptible to injuries than female alpinists. Generally, the literature surrounding hiking and water-related mountain sports is insufficient, and further work is required to elucidate injury mechanisms and effective preventative measures. A helmet seems to decrease the likelihood of face and head injuries in mountain sports and be a meaningful preventive measurement.

Epidemiologic analysis of 8000 acute vertebral fractures: evolution of treatment and complications at 10-year follow-up.

STUDY DESIGN: This is a retrospective cohort study. OBJECTIVES: This study aims to determine the proportional incidence, clinical characteristics, treatment patterns with complications and changes in treatment of vertebral fractures over 10 years at a Swiss university hospital. METHODS: A retrospective cohort study was performed. All patients with an acute vertebral fracture were included in this study. The extracted anonymized data from the medical records were manually assessed. Demographic data, exact location, etiology, type of treatment and complications related to the treatment were obtained. RESULTS: Of 330,225 treated patients, 4772 presented with at least one vertebral fracture. In total 8307 vertebral fractures were identified, leading to a proportional incidence of 25 vertebral fractures in 1000 patients. Fractures were equally distributed between genders. Male patients were significantly younger and more likely to sustain a traumatic fracture, while female patients more commonly presented with osteoporotic fractures. The thoracolumbar junction (Th11-L2) was the most frequent fracture site in all etiologies. More than two-thirds of vertebral fractures were treated surgically (68.6%). Out of 4622 performed surgeries, we found 290 complications (6.3%). The odds for surgical treatment in osteoporotic fractures were two times higher before 2010 compared to 2010 and after (odds ratio: 2.1, 95% CI 1.5-2.9, p < 0.001). CONCLUSION: Twenty-five out of 1000 patients presented with a vertebral fracture. More than 4000 patients with over 8307 vertebral body fractures were treated in 10 years. Over two-thirds of all fractures were treated surgically with 6.3% complications. There was a substantial decrease in surgeries for osteoporotic fractures after 2009.

Should Degenerated Intervertebral Discs of Patients with Modic Type 1 Changes Be Treated with Mesenchymal Stem Cells?

Low back pain (LBP) has been among the leading causes of disability for the past 30 years. This highlights the need for improvement in LBP management. Many clinical trials focus on developing treatments against degenerative disc disease (DDD). The multifactorial etiology of DDD and associated risk factors lead to a heterogeneous patient population. It comes as no surprise that the outcomes of clinical trials on intradiscal mesenchymal stem cell (MSC) injections for patients with DDD are inconsistent. Intradiscal MSC injections have demonstrated substantial pain relief and significant disability-related improvements, yet they have failed to regenerate the intervertebral disc (IVD). Increasing evidence suggests that the positive outcomes in clinical trials might be attributed to the immunomodulatory potential of MSCs rather than to their regenerative properties. Therefore, patient stratification for inflammatory DDD phenotypes may (i) better serve the mechanisms of action of MSCs and (ii) increase the treatment effect. Modic type 1 changes-pathologic inflammatory, fibrotic changes in the vertebral bone marrow-are frequently observed adjacent to degenerated IVDs in chronic LBP patients and represent a clinically distinct subpopulation of patients with DDD. This review discusses whether degenerated IVDs of patients with Modic type 1 changes should be treated with an intradiscal MSC injection.

Intraoperative color-coded duplex ultrasound for safe surgical reduction of displaced hangman fractures in patients with atypical course of the vertebral artery: A case report of two patients.

An atypical course of the vertebral artery can be medically relevant in displaced Hangman fractures, especially if the artery course runs within the fracture gap of the C2 isthmus. During surgical reduction, the artery can be occluded inside the fracture, potentially leading to ischemic conditions of the brain. The aim of this study was to report two cases according to the CARE (case reporting) guidelines, in which intraoperative color-coded duplex-ultrasound was performed to secure safe surgical reduction of hangman fractures in two patients with an atypical course of the vertebral artery. Two patients with displaced hangman fractures (Effendi-Levine type II) were diagnosed with an atypical course of the vertebral artery running inside the fracture gap. This endangered safe surgical management with the risk of iatrogenic occlusion or injury during reduction through entrapment of the vessel inside the fracture gap. Therefore, an intraoperative color-coded duplex-ultrasound of the vertebral artery was conducted before and after reduction of the fracture, as well as at the end of the surgery. The surgical treatment in both cases included posterior unilateral spondylodesis, followed by anterior cervical discectomy and fusion (ACDF). In both patients, a safe reduction of the fracture was performed. Neither occlusion nor dissection of the vertebral artery occurred. The duplex ultrasound before and after reduction, and at the end of the procedure showed normal blood flow and morphology of both vertebral arteries. At follow-up examinations, the patients showed a favorable clinical outcome, radiographic signs of fusion, and no irregularity of the vertebral arteries. This case report serves as proof-of-concept, demonstrating the feasibility of this regimen to minimize the risk of entrapment or occlusion of the vertebral artery in the surgical management of displaced Hangman fractures with atypical course of the vertebral artery running inside the fracture gap.

Establishment of a Novel Method for Spinal Discectomy Surgery in Elderly Rats in an In Vivo Spinal Fusion Model.

The rat model is a common model for intervertebral disc (IVD) and spinal research. However, complications remain challenging. Standard Operating Procedures (SOPs) are validated methods to minimize complications and improve safety and quality of studies. However, a SOP for rat spinal fusion surgery has been missing until now. Therefore, the aim of the study was to develop a SOP for spinal tail disc surgery in elderly Wistar rats (419.04 ± 54.84 g). An initial preoperative, intraoperative, and postoperative surgical setup, including specific anaesthesia and pain management protocols, was developed. Anaesthesia was induced by subcutaneous injection of a pre-mixture of fentanyl, midazolam, and medetomidin with the addition of 0.5% isoflurane in oxygen and caudal epidural analgesia. The surgery itself consisted of the fixation of a customized external ring fixator with ⌀ 0.8 mm Kirschner wires at the proximal rat tail and a discectomy and replacement with bone morphogenetic protein coated beta-tricalcium-phosphate carrier. The postoperative setup included heating, analgesia with buprenorphine, and meloxicam, as well as special supplementary food. Anaesthesia, surgery, and pain management were sufficient. In the presented optimized SOP, no animals developed any complications. A SOP for spinal surgery in elderly rats in an in vivo spinal fusion model was developed successfully. This novel protocol can improve transparency, reproducibility, and external validity in experimental rat spinal surgery experiments.

In Vitro Evaluation of a Nanoparticle-Based mRNA Delivery System for Cells in the Joint.

Biodegradable and bioresponsive polymer-based nanoparticles (NPs) can be used for oligonucleotide delivery, making them a promising candidate for mRNA-based therapeutics. In this study, we evaluated and optimized the efficiency of a cationic, hyperbranched poly(amidoamine)s-based nanoparticle system to deliver tdTomato mRNA to primary human bone marrow stromal cells (hBMSC), human synovial derived stem cells (hSDSC), bovine chondrocytes (bCH), and rat tendon derived stem/progenitor cells (rTDSPC). Transfection efficiencies varied among the cell types tested (bCH 28.4% ± 22.87, rTDSPC 18.13% ± 12.07, hBMSC 18.23% ± 14.80, hSDSC 26.63% ± 8.81) and while an increase of NPs with a constant amount of mRNA generally improved the transfection efficiency, an increase of the mRNA loading ratio (2:50, 4:50, or 6:50 w/w mRNA:NPs) had no impact. However, metabolic activity of bCHs and rTDSPCs was significantly reduced when using higher amounts of NPs, indicating a dose-dependent cytotoxic response. Finally, we demonstrate the feasibility of transfecting extracellular matrix-rich 3D cell culture constructs using the nanoparticle system, making it a promising transfection strategy for musculoskeletal tissues that exhibit a complex, dense extracellular matrix.