Heterotopic ossification, osteolysis and implant failure following cervical total disc replacement with the M6-C™ artificial disc.

INTRODUCTION: A recent study reported a 34% mid-term revision rate after M6-C™ cervical total disc replacement (CTDR) for wear-related osteolysis. Here, we aim to investigate the prevalence, risk factors, and radiographic characteristics of periprosthetic bony changes and implant failure of the M6-C™ artificial disc. METHODS: We retrospectively analysed radiographic (conventional X-ray, CT scan) and clinical outcomes (EQ-5D-5L, Neck Disability Index (NDI), and Visual Analog Scale (VAS) for neck and arm pain) data collected during routine follow-up of patients who underwent CTDR with the M6-C™ between 2011 and 2015. RESULTS: In total, 85 patients underwent CTDR with the M6-C™. Follow-up data were available for 43 patients (54% female, mean age 44 years) with 50 implants and a mean follow-up of 8.1 years (6.5-11 years). Implant failure with the presence of severe osteolysis was identified in 5 (12%) patients who were all male (p = 0.016) and implanted at the C5/6 level (p = 0.11). All failed implants required revision surgery. The overall prevalence of osteolysis was 44% (22/50 implants) and 34% (17/50 implants) for significant heterotopic ossification. Patients with high-grade osteolysis showed higher VAS arm pain (p = 0.05) and lower EQ-5D-VAS health VAS (p = 0.03). CONCLUSION: We report a lower reoperation rate for failed M6-C™ implants than previously published, but confirmed that osteolysis and heterotopic ossification are common following CTDR with the M6-C™ and may be asymptomatic. Therefore, we strongly recommend ongoing clinical and radiographic monitoring after CTDR with the M6-C™, particularly for male patients implanted at the C5/6 level.

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.

Medialized Dome and Anatomic Onlay Patella Designs in the Modern Posterior Stabilized Rotating Platform Total Knee Arthroplasty Demonstrate No Clinical or Radiological Differences at One Year.

BACKGROUND: A successful outcome after total knee arthroplasty (TKA) includes the restoration of patellofemoral function. Modern patella component designs in TKA include a medialized dome and more recently, an anatomic design. There is a paucity of literature comparing these 2 implants. METHODS: This prospective nonrandomized study examined 544 consecutive TKAs with patella resurfacing using a posterior-stabilized, rotating platform knee prothesis performed by a single surgeon. A medialized dome patella design was used in the first 323 cases and an anatomic design in the subsequent 221 cases. Patients were assessed preoperatively, at 4 weeks and 1-year post-TKA for Oxford Knee Score (OKS) (total, pain, and kneeling components) and range of movement (ROM). Radiolucent lines (RLLs), patellar tilts and displacements, as well as reoperations were assessed at 1-year post-TKA. RESULTS: At 1-year post-TKA, both groups demonstrated similar improvements in ROM, OKS, pain, and kneeling scores, and had a similar incidence of fixed-flexion deformity (all P > .05). Radiographically, there was no clinically significant difference in the incidence of RLLs, patellar tilts, and displacements. The prevalence of reoperations (1.8 versus 3.2%, P = .526) was similar between the designs with no patella-related complications. CONCLUSION: Both medialized dome and anatomic patella designs result in improved ROM and OKS with no patella-related complications. However, our study showed no differences between the designs at 1 year.

Celecoxib alleviates nociceptor sensitization mediated by interleukin-1beta-primed annulus fibrosus cells.

PURPOSE: This study aims to analyze the effect of pro-inflammatory cytokine-stimulated human annulus fibrosus cells (hAFCs) on the sensitization of dorsal root ganglion (DRG) cells. We further hypothesized that celecoxib (cxb) could inhibit hAFCs-induced DRG sensitization. METHODS: hAFCs from spinal trauma patients were stimulated with TNF-α or IL-1ß. Cxb was added on day 2. On day 4, the expression of pro-inflammatory and neurotrophic genes was evaluated using RT-qPCR. Levels of prostaglandin E2 (PGE-2), IL-8, and IL-6 were measured in the conditioned medium (CM) using ELISA. hAFCs CM was then applied to stimulate the DRG cell line (ND7/23) for 6 days. Then, calcium imaging (Fluo4) was performed to evaluate DRG cell sensitization. Both spontaneous and bradykinin-stimulated (0.5 µM) calcium responses were analyzed. The effects on primary bovine DRG cell culture were performed in parallel to the DRG cell line model. RESULTS: IL-1ß stimulation significantly enhanced the release of PGE-2 in hAFCs CM, while this increase was completely suppressed by 10 µM cxb. hAFCs revealed elevated IL-6 and IL-8 release following TNF-α and IL-1ß treatment, though cxb did not alter this. The effect of hAFCs CM on DRG cell sensitization was influenced by adding cxb to hAFCs; both the DRG cell line and primary bovine DRG nociceptors showed a lower sensitivity to bradykinin stimulation. CONCLUSION: Cxb can inhibit PGE-2 production in hAFCs in an IL-1ß-induced pro-inflammatory in vitro environment. The cxb applied to the hAFCs also reduces the sensitization of DRG nociceptors that are stimulated by the hAFCs CM.

3D analysis of fatty infiltration of the paravertebral lumbar muscles using T2 images-a new approach.

PURPOSE: Factors influencing paraspinal muscle degeneration are still not well understood. Fatty infiltration is known to be one main feature of the degeneration cascade. The aim of this cross-sectional study was to illustrate the 3D cluster of paraspinal lumbar muscle degeneration on T2-weighted MRI images using our newly developed software application 'iSix'. METHODS: Mono- (Mm. rotatores), multi- (Mm. multifidus) and pluri-segmental (M. erector spinae) lumbar muscles groups were segmented on T2-weighted MR sequences using a novel computer-assisted technique for quantitative muscle/fat discrimination. The degree of fatty infiltration of the three predefined muscle groups was compared on a 3-dimensional basis, with regard to segment involvement and age. General linear models were utilized for statistical comparison. RESULTS: N = 120 segments (age: 52.7; range 16-87 years) could be included. The overall relative fatty infiltration of the mono-segmental muscles was higher (21.1 14.5%) compared to the multi-segmental (16.0 8.8% p = 0.049) and pluri-segmental muscles (8.5 8.0%; p = 0.03). Mono-segmental muscles on the levels L4/5 (22.9 ± 10.2 [CI 17.6-28.2] %) and L5/S1 (27.01 ± 15.1 [CI 21.4-32.7] %) showed a significant higher amount of fat compared to the levels L2/3 (8.2 ± 6.8 [CI 2.2-14.2] %; L4/5 vs. L2/3, p = 0.03; L5/S1 vs. L2/3, p = 0.02) and L3/4 (13.2 ± 5.4 [CI 8.6-17.7]%; L4/5 vs. L3/4, p = 0.02; L5/S1 vs. L3/4, p < 0.01). Multivariate linear regression analyses revealed age and Pfirrmann grade as independent factors for fatty muscle degeneration. CONCLUSIONS: 3D analysis of fatty infiltration is an innovative tool to study lumbar muscle degeneration. Mono-segmental muscles are more severely affected by degeneration compared to multi-/pluri-segmental muscles, especially at the L4/5 and L5/S1 level. Age and disc degeneration independently correlate with muscle degeneration.

"How to measure the outcome in the surgical treatment of vertebral compression fractures? A systematic literature review of highly cited level-I studies".

BACKGROUND: The economic burden of vertebral compression fractures (VCF) caused by osteoporosis was estimated at 37 billion euros in the European Union in 2010. In addition, the incidence is expected to increase by 25% in 2025. The recommendations for the therapy of VCFs (conservative treatment versus cement augmentation procedures) are controversial, what could be partly explained by the lack of standardized outcomes for measuring the success of both treatments. Consensus on outcome parameters may improve the relevance of a study and for further comparisons in meta-analyses. The aim of this study was to analyze outcome measures from frequently cited randomized controlled trials (RCTs) about VCF treatments in order to provide guidance for future studies. MATERIAL AND METHODS: We carried out a systematic search of all implemented databases from 1973 to 2019 using the Web of Science database. The terms "spine" and "random" were used for the search. We included: Level I RCTs, conservative treatment or cement augmentation of osteoporotic vertebral fractures, cited ≥50 times. The outcome parameters of each study were extracted and sorted according to the frequency of use. RESULTS: Nine studies met the inclusion criteria. In total, 23 different outcome parameters were used in the nine analyzed studies. Overall, the five most frequently used outcome parameters (≥ 4 times used) were the visual analogue scale (VAS) for pain (n = 9), European Quality of Life-5 Dimensions (EQ-5D; n = 4) and Roland-Morris Disability Questionnaire (RMDQ, n = 4). CONCLUSION: With our study, we demonstrated that a large inconsistency exists between outcome measures in highly cited Level I studies of VCF treatment. Pain (VAS), followed by HrQoL (EQ-5D) and disability and function (RMDQ), opioid use, and radiological outcome (kyphotic angle, VBH, and new VCFs) were the most commonly used outcome parameters.

Anterior-posterior view by full-body digital X-ray to rule out severe spinal injuries in Polytraumatized patients.

BACKGROUND: Spinal injuries are present in 16-31% of polytraumatized patients. Rapid identification of spinal injuries requiring immobilization or operative treatment is essential. The Lodox-Statscan (LS) has evolved into a promising time-saving diagnostic tool to diagnose life-threatening injuries with an anterior-posterior (AP)-full-body digital X-ray. METHODS: We aimed to analyze the diagnostic accuracy and the interrater reliability of AP-LS to detect spinal injuries in polytraumatized patients. Therefore, within 3 years, AP-LS of polytraumatized patients (ISS ≥ 16) were retrospectively analyzed by three independent observers. The sensitivity and specificity of correct diagnosis with AP-LS compared to CT scan were calculated. The diagnostic accuracy was evaluated by using the area under the ROC (receiver operating characteristic curve) for sensitivity and specificity. Interrater reliability between the three observers was calculated using Fleiss' Kappa. The sensitivity of AP-LS was further analyzed by the severity of spinal injuries. RESULTS: The study group included 320 patients (48.5 years ±19.5, 89 women). On CT scan, 207 patients presented with a spinal injury (65%, total of 332 injuries). AP-LS had a low sensitivity of 9% (31 of 332, range 0-24%) and high specificity of 99% (range 98-100%). The sensitivity was highest for thoracic spinal injuries (14%). The interrater reliability was slight (κ = 0.02; 95% CI: 0.00, 0.03). Potentially unstable spinal injuries were more likely to be detected than stable injuries (sensitivity 18 and 6%, respectively). CONCLUSION: This study demonstrated high specificity with low sensitivity of AP-LS in detecting spinal injuries compared to CT scan. In polytraumatized patients, AP-LS, implemented in the Advanced Trauma Life Support-algorithm, is a helpful tool to diagnose life-threatening injuries. However, if spinal injuries are suspected, performing a full-body CT scan is necessary for correct diagnosis.

Spheroid-Like Cultures for Expanding Angiopoietin Receptor-1 (aka. Tie2) Positive Cells from the Human Intervertebral Disc.

Lower back pain is a leading cause of disability worldwide. The recovery of nucleus pulposus (NP) progenitor cells (NPPCs) from the intervertebral disc (IVD) holds high promise for future cell therapy. NPPCs are positive for the angiopoietin-1 receptor (Tie2) and possess stemness capacity. However, the limited Tie2+ NPC yield has been a challenge for their use in cell-based therapy for regenerative medicine. In this study, we attempted to expand NPPCs from the whole NP cell population by spheroid-formation assay. Flow cytometry was used to quantify the percentage of NPPCs with Tie2-antibody in human primary NP cells (NPCs). Cell proliferation was assessed using the population doublings level (PDL) measurement. Synthesis and presence of extracellular matrix (ECM) from NPC spheroids were confirmed by quantitative Polymerase Chain Reaction (qPCR), immunostaining, and microscopy. Compared with monolayer, the spheroid-formation assay enriched the percentage of Tie2+ in NPCs' population from ~10% to ~36%. Moreover, the spheroid-formation assay also inhibited the proliferation of the Tie2- NPCs with nearly no PDL. After one additional passage (P) using the spheroid-formation assay, NPC spheroids presented a Tie2+ percentage even further by ~10% in the NPC population. Our study concludes that the use of a spheroid culture system could be successfully applied to the culture and expansion of tissue-specific progenitors.

Direct anterior decompression of L4 and L5 nerve root in sacral fractures using the pararectus approach: a technical note.

PURPOSE: To describe a new surgical technique for neurolysis and decompression of L4 and L5 nerve root entrapment after vertical sacral fractures via the pararectus approach for acetabular fractures, and to present four case examples. PATIENTS AND METHODS: We retrospectively evaluated four patients suffering radiculopathy from entrapment of the L4 or L5 nerve root in vertical sacral fractures between January and December 2016. The mean follow-up period after surgery was 18 (range 7-27) months. All patients underwent direct decompression and neurolysis of the L4 and L5 nerve roots via the single-incision, intrapelvic, extraperitoneal pararectus approach. RESULTS: In all patients, the L4 and L5 nerve root was successfully visualized and decompressed, proving feasibility of the pararectus approach for this indication. No patient presented with a neural tear. Complete neurologic recovery was present in one patient at last follow-up; two patients had incomplete recovery of their radiculopathy; and one patient had no improvement after nerve root decompression. CONCLUSIONS: The pararectus approach allows for sufficient visualisation and direct decompression and neurolysis of the L4 and L5 nerve root entrapped in vertical sacral fractures. Although neurologic recovery was not achieved in all patients in this small case series, the approach may be a suitable alternative to posterior approaches and other anterior approaches such as the lateral window of the ilioinguinal approach.

IL-1ß promotes transendothelial migration of PBMCs by upregulation of the FN/α5ß1 signalling pathway in immortalised human brain microvascular endothelial cells.

Neuroinflammation is often associated with pathological changes in the function of the blood-brain barrier (BBB) caused by disassembly of tight and adherens junctions that under physiological conditions are important for the maintenance of the BBB integrity. Consequently, in inflammation the BBB becomes dysfunctional, facilitating leukocyte traversal of the barrier and accumulation of immune cells within the brain. The extracellular matrix (ECM) also contributes to BBB integrity but the significance of the main ECM receptors, the ß1 integrins also expressed on endothelial cells, is less well understood. To evaluate whether ß1 integrin function is affected during inflammation and impacts barrier function, we used a transformed human brain microvascular endothelial cell (THBMEC)-based Interleukin 1ß (IL-1ß)-induced inflammatory in vitro BBB model. We demonstrate that IL-1ß increases cell-matrix adhesion and induces a redistribution of active ß1 integrins to the basal surface. In particular, binding of α5ß1 integrin to its ligand fibronectin is enhanced and α5ß1 integrin-dependent signalling is upregulated. Additionally, localisation of the tight junction protein claudin-5 is altered. Blockade of the α5ß1 integrin reduces the IL-1ß-induced transendothelial migration of peripheral blood mononuclear cells (PBMCs). These data imply that IL-1ß-induced inflammation not only destabilizes tight junctions but also increases α5ß1 integrin-dependent cell-matrix adhesion to fibronectin.

Fibrin-Hyaluronic Acid Hydrogel (RegenoGel) with Fibroblast Growth Factor-18 for In Vitro 3D Culture of Human and Bovine Nucleus Pulposus Cells.

We investigated the effects of a fibrin-hyaluronic acid hydrogel (FBG-HA) and fibroblast growth factor 18 (FGF-18) for nucleus pulposus (NP) regeneration. Healthy bovine (n = 4) and human degenerated NP cells (n = 4) were cultured for 14 days in FBG-HA hydrogel with FGF-18 (∆51-mutant or wild-type) in the culture medium. Gene expression, DNA content, and glycosaminoglycan (GAG) synthesis were evaluated on day 7 and 14. Additionally, histology was performed. Human NP cells cultured in FBG-HA hydrogel showed an increase in collagen type II (COL2) and carbonic anhydrase XII (CA12) gene expression after 14 or 7 days of culture, respectively. GAG release into the conditioned medium increased over 14 days. Healthy bovine NP cells showed increased gene expression of ACAN from day 7 to day 14. Wild type FGF-18 up-regulated CA12 gene expression of human NP cells. Histology revealed an increase of proteoglycan deposition upon FGF-18 stimulation in bovine but not in human NP cells. The FBG-HA hydrogel had a positive modulatory effect on human degenerated NP cells. Under the tested conditions, no significant effect of FGF-18 was observed on cell proliferation or GAG synthesis in human NP cells.

Improved postoperative kneeling ability in posterior stabilized total knee arthroplasty with medialized dome-patella resurfacing: A retrospective comparative outcome analysis.

OBJECTIVES: This investigation aimed to evaluate if the modifications to prosthesis designs improve patients' clinical and functional outcomes after total knee arthroplasty (TKA), with a special focus on pain and kneeling ability. METHODS: Retrospective and comparative analysis of consecutive patients who were treated with posterior stabilized TKA using two different prostheses designs (single surgeon, single vendor). Group 1 received a traditional design TKA (PFC Sigma; DePuy, Inc., Warsaw, IN) with conventional dome-patella resurfacing, and group 2 received a modern design implant (Attune; DePuy, Inc., Warsaw, IN) with medialized dome-patella resurfacing. Functional outcome (range of motion: ROM) and the Oxford Knee Score (OKS) were collected preoperatively, at 4-6 weeks and 12 months following surgery. RESULTS: Ninety-nine participants were included. Of these, 30 received traditional-design implants and 69 received modern-design knee implants. The comparison between the two implants showed a statistically significant increase in total OKS and kneeling ability in the modern design cohort at 1-year follow-up compared to the traditional design cohort (p â€‹< â€‹0.01). In the modern design group, 53% (N â€‹= â€‹37) could kneel easily or with little difficulty, compared to 30% (N â€‹= â€‹9) in the traditional design group. No statistically significant differences in ROM or the OKS pain component were seen. CONCLUSION: The incorporation of a medialized dome-patella in modern knee implant design may offer advantages over traditional designs, as seen in improved total OKS and kneeling ability at one-year follow-up. Further research with larger cohorts is needed to confirm these findings and explore the broader impact of implant design changes on patient outcomes. LEVEL OF EVIDENCE: Clinical Study, Level III.

Audio-biofeedback versus the scale method for improving partial weight-bearing adherence in healthy older adults: a randomised trial.

PURPOSE: To investigate how audio-biofeedback during the instruction of partial weight-bearing affected adherence, compared to traditional methods, in older adults; and to investigate the influence of individual characteristics. METHODS: The primary outcome measure of this randomised controlled trial was the amount of load, measured as the ground reaction force, on the partial weight-bearing leg. The secondary outcome was the influence of individual characteristics on the amount of load. Included were healthy volunteers 60 years of age or older without gait impairment. Participants were randomly allocated to one of two groups; blinding was not possible. Partial weight-bearing of 20 kg was trained using crutches with audio-biofeedback (intervention group) or a bathroom scale (control group). The degree of weight-bearing was measured during six activities with sensor insoles. A mean load between 15 and 25 kg was defined as adherent. RESULTS: There was no statistically significant difference in weight-bearing between the groups for all activities measured. For the sit-stand-sit activity, weight-bearing was within the adherence range of 15-25 kg (audio-biofeedback: 21.7 ± 16.6 kg; scale: 22.6 ± 13 kg). For standing, loading was below the lower threshold (10 ± 7 vs. 10 ± 10 kg). Weight-bearing was above the upper threshold for both groups for: walking (26 ± 11 vs. 34 ± 16), step-up (29 ± 18 vs. 34 ± 20 kg) and step-down (28 ± 15 vs. 35 ± 19 kg). Lower level of cognitive function, older age, and higher body mass index were correlated with overloading. CONCLUSION: Audio-biofeedback delivered no statistically significant benefit over the scale method. Lower cognitive function, older age and higher body mass index were associated with overloading. TRIAL REGISTRATION: Not applicable due not being a clinical trial and due to the cross-sectional design (one measurement point, no health intervention, no change in health of a person).

Return to sports/activity level after 360° thoracolumbar fusion after burst fractures in young patients.

Introduction: Traumatic thoracolumbar burst fractures are the most common spinal injuries and the proper treatment is controversial. In central Europe in particular, these fractures are often treated with minimally invasive anterior-posterior reduction and fusion, whereas a conservative approach is preferred in the USA. Independent of the treatment strategy, no data exists regarding the outcome related to return to activity level/sport. Research question: The aim of this study was to evaluate the return to sports and activity levels after 360° fusion in patients with thoracolumbar burst fractures without neurological deficits. Methods: Between January 2013 and December 2022, 46 patients aged 18 to 40 years underwent partial or complete vertebral body replacement in the thoracolumbar region due to traumatic burst fractures without neurologic deficit as an isolated injury. Patients were contacted retrospectively by phone calls to assess their activities using a modified version of the Tegner activity scale at different time points: Before trauma, 3, 6, and 12 months post-surgery. Results: After applying exclusion criteria, data collection was complete for 28 patients. The median modified Tegner activity scale was 5.4 before sustaining the fracture, declined to 2.9 at three months post-trauma, improved to 4.2 at six months, and reached 5.0 at 12 months. The majority (83%) of patients achieved their pre-accident activity level within 12 months. No significant differences were observed between patients with partial or complete corpectomy. Conclusion: This is the first study assessing return to sports/physical activity based on the modified Tegner scale in young patients undergoing 360° fusion for spinal burst fractures. The majority of patients (83%) return to the pre-injury activity level within 12 months after surgery.

Exposure of the Lumbosacral Plexus by Using the Pararectus Approach: A Technical Note.

BACKGROUND: Surgical exploration of the lumbosacral plexus is challenging. Previously described approaches reach from invasive open techniques with osteotomy of the ilium to laparoscopic techniques. OBJECTIVE: To describe a novel surgical technique to explore lumbosacral plexopathies such as benign nerve tumors or iatrogenic lesions of the lumbosacral plexus in 4 case examples. METHODS: We retrospectively evaluated 4 patients suffering from pathologies or injuries of the lumbosacral plexus between 2017 and 2019. The mean follow-up period after surgery was 23.5 (range 11-52) months. All patients underwent neurolysis of the lumbosacral plexus using the single incision, intrapelvic, extraperitoneal pararectus approach. RESULTS: In all patients, the pathology of the lumbosacral plexus was successfully visualized, proving feasibility of the extraperitoneal pararectus approach for this indication. There were no major complications, and all patients recovered well. CONCLUSION: The pararectus approach allows excellent visualization of the lumbar plexus and intrapelvic lesions of the femoral and sciatic nerves.

Reliability and Validity of the German Version of the AO Spine Patient Reported Outcome Spine Trauma Questionnaire.

STUDY DESIGN: A single-center validation study. OBJECTIVE: To translate and cross-culturally adapt the AO Spine PROST (Patient Reported Outcome Spine Trauma) into German, and to test its psychometric properties among German-speaking Swiss spine trauma patients. METHODS: Patients were recruited from a level-1 Swiss trauma center. Next to the AO Spine PROST, the EQ-5D-3L questionnaire was used for concurrent validity. Questionnaires were filled out at two-time points for test-retest reliability. Patient characteristics were analyzed using descriptive statistics. For content validity, floor, and ceiling effects, as well as any irrelevant and missing questions were analyzed. Construct validity of the AO Spine PROST questionnaire to the EQ-5D-3L was tested using Spearman correlation tests. RESULTS: The AOSpine PROST was translated and adapted into German using established guidelines. We included 179 patients. The floor effect for all items was well within the optimal range (below 15%), while the ceiling effect of seven items was within the optimal range. None of the items displayed a problematic floor or ceiling effect. The overall test-retest reliability of the total PROST score was excellent, with an ICC of .83 (95% CI .69-.91). The Spearman correlation coefficient between the total PROST summary score and EQ-5D-3 L was ρ = .63. CONCLUSIONS: The German version of the AO Spine PROST questionnaire demonstrated very good validity and reliability results.

Assessing lower extremity loading during activities of daily living using continuous-scale physical functional performance 10 and wireless sensor insoles: a comparative study between younger and older adults.

PURPOSE: This study aims to investigate the lower extremity loading during activities of daily living (ADLs) using the Continuous Scale of Physical Functional Performance (CS-PFP 10) test and wireless sensor insoles in healthy volunteers. METHODS: In this study, 42 participants were recruited, consisting of 21 healthy older adults (mean age 69.6 ± 4.6 years) and 21 younger healthy adults (mean age 23.6 ± 1.8 years). The performance of the subjects during ADLs was assessed using the CS-PFP 10 test, which comprised 10 tasks. The lower extremity loading was measured using wireless sensor insoles (OpenGo, Moticon, Munich, Germany) during the CS-PFP 10 test, which enabled the measurement of ground reaction forces, including the mean and maximum total forces during the stance phase, expressed in units of body weight (BW). RESULTS: The total CS-PFP 10 score was significantly lower in older participants compared to the younger group (mean total score of 57.1 ± 9.0 compared to 78.2 ± 5.4, respectively). No significant differences in the mean total forces were found between older and young participants. The highest maximum total forces were observed during the tasks 'endurance walk' (young: 1.97 ± 0.34 BW, old: 1.70 ± 0.43 BW) and 'climbing stairs' (young: 1.65 ± 0.36 BW, old: 1.52 ± 0.28 BW). Only in the endurance walk, older participants showed a significantly higher maximum total force (p < 0.001). CONCLUSION: The use of wireless sensor insoles in a laboratory setting can effectively measure the load on the lower extremities during ADLs. These findings could offer valuable insights for developing tailored recommendations for patients with partial weight-bearing restrictions.

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.

Effect of glucose depletion and fructose administration during chondrogenic commitment in human bone marrow-derived stem cells.

BACKGROUND: Bone marrow mesenchymal stromal cells (BMSCs) are promising for therapeutic use in cartilage repair, because of their capacity to differentiate into chondrocytes. Often, in vitro differentiation protocols employ the use of high amount of glucose, which does not reflect cartilage physiology. For this reason, we investigated how different concentrations of glucose can affect the chondrogenic differentiation of BMSCs in cell culture pellets. Additionally, we investigated how fructose could influence the chondrogenic differentiation in vitro. METHODS: BMSC were isolated from six donors and cultured in DMEM containing glucose at either 25 mM (HG), 5.5 mM (LG) or 1 mM (LLG), and 1% non-essential amino acids, 1% ITS+, in the presence of 100 nM dexamethasone, 50 µg/ml ascorbic acid-2 phosphate and 10 ng/ml TGF-ß1. To investigate the effect of different metabolic substrates, other groups were exposed to additional 25 mM fructose. The media were replaced every second day until day 21 when all the pellets were harvested for further analyses. Biochemical analysis for glycosaminoglycans into pellets and released in medium was performed using the DMMB method. Expression of GLUT3 and GLUT5 was assayed by qPCR and validated using FACS analysis and immunofluorescence in monolayer cultures. Chondrogenic differentiation was further confirmed by qPCR analysis of COL2A1, COL1A1, COL10A1, ACAN, RUNX2, SOX9, SP7, MMP13, and PPARG, normalized on RPLP0. Type 2 collagen expression was subsequently validated by immunofluorescence analysis. RESULTS: We show for the first time the presence of fructose transporter GLUT5 in BMSC and its regulation during chondrogenic commitment. Additionally, decreasing glucose concentration during chondrogenesis dramatically decreased the yield of differentiation. However, the use of fructose alone or together with low glucose concentrations does not limit cell differentiation, but on the contrary it might help in maintaining a stable chondrogenic phenotype comparable with the standard culture conditions (high glucose). CONCLUSION: This study provides evidence that BMSC express GLUT5 and differentially regulate GLUT3 in the presence of glucose variation. This study gives a better comprehension of BMSCs sugar use during chondrogenesis.

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.