To develop an international guideline (AOGO) about use of osteobiologics in Anterior Cervical Discectomy and Fusion (ACDF) for treating degenerative spine conditions. The guideline development process was guided by AO Spine Knowledge Forum Degenerative (KF Degen) and followed the Guideline International Network McMaster Guideline Development Checklist. The process involved 73 participants with expertise in degenerative spine diseases and surgery from 22 countries. Fifteen systematic reviews were conducted addressing respective key topics and evidence were collected. The methodologist compiled the evidence into GRADE Evidence-to-Decision frameworks. Guideline panel members judged the outcomes and other criteria and made the final recommendations through consensus.Introduction
Method
In order to release the contracture band completely without damaging normal tissues (such as the sciatic nerve) in the surgical treatment of gluteal muscle contracture (GMC), we tried to display the relationship between normal tissue and contracture bands by magnetic resonance neurography (MRN) images, and to predesign a minimally invasive surgery based on the MRN images in advance. A total of 30 patients (60 hips) were included in this study. MRN scans of the pelvis were performed before surgery. The contracture band shape and external rotation angle (ERA) of the proximal femur were also analyzed. Then, the minimally invasive GMC releasing surgery was performed based on the images and measurements, and during the operation, incision lengths, surgery duration, intraoperative bleeding, and complications were recorded; the time of the first postoperative off-bed activity was also recorded. Furthermore, the patients’ clinical functions were evaluated by means of Hip Outcome Score (HOS) and Ye et al’s objective assessments, respectively.Aims
Methods
Studies and meta-analyses worldwide show an increased use of one-stage revisions for treating periprosthetic hip infections, often yielding comparable or better outcomes than two-stage revisions. However, it remains unclear if these successful results can be consistently achieved nationwide besides large centers. This observational cohort study used data from the German Arthroplasty Registry (EPRD) to compare the mortality and re-revision rates between one-stage (n=8183) and two-stage (n=657) first-time revision total hip arthroplasty (RTHA). Kaplan-Meier estimates were applied to evaluate the re-revision rate and cumulative mortality for RTHA. There was a significant difference in mortality between one-stage and two-stage RTHA (p=0.02). One-year post-surgery, the mortality rate was 9.4% for one-stage revisions and 5.5% for two-stage revisions. At the five-year follow-up, the mortality rate for one-stage revisions was 25.5%, compared to 20.0% for two-stage revisions. No significant differences (p=0.30) were found in re-revision rates between one-stage and two-stage revisions after one year (one-stage 16.5% vs. two-stage 13.5%) or five years (one-stage 21.6% vs. two-stage 20.8%). For multiple revisions, the mortality differences were even larger (p<0.001), with a one-year mortality rate of 12.8% for one-stage RTHA and 5.7% for two-stage RTHA. Despite the excellent results of one-stage RTHA in the literature from individual large centers, it shows a significantly higher mortality rate with equal re-revision rate compared to two-stage revision in the nationwide care besides large centers. Significant differences can already be seen within the first year, indicating an increased perioperative mortality for one-stage revision, which might be explained by longer surgery duration, blood-loss and patient selection or maybe a lack of experience concerning proper surgical debridement for one-stage revision. This illustrates the need to establish centers for joint-revision surgery that provide interdisciplinary care and high case numbers to improve perioperative outcomes.
Implant fracture of modular revision stems is a major complication after total hip arthroplasty revision (rTHA). Studies looking at specific modular designs report fracture rates of 0.3% to 0.66% whereas fractures of monobloc designs are only reported anecdotally. It is unclear whether the overall re-revision rate of modular designs is higher and if, whether stem fractures or other revision reasons are responsible for this elevation. All revisions within 5 years after implantation of a revision stems (n0=13,900; n5=2506) were analysed using Cox regression with design (modular: n=17, monobloc: n=27), BMI, Sex and Elixhauser Score as independent variables. One stage and two stage revisions were analysed separately (1-stage: modular n= 7,102; monobloc n= 4,542; 2-stage: 1,551 / 704). The revision volume of the hospitals was also considered (low: <20 revisions, medium: 21–50 revisions, high: >50 revisions). For the 1-stage revisions, the re-revision risk after 4 years was 14,3% [13.2%, 15.5%] for monobloc and 17.4% [16.40%, 18.40%] for modular stems (p< 0.001). Stem fracture was the reason for re-revision in 2.4% of the modular (fracture rate 0.42%) and 0.6% of the monobloc revisions. The difference in re-revision rates between the designs was mainly due to differences in dislocation and stem loosening. For the 2-stage revisions, the revision risks for either design were similar (21.7% [18,5%, 25.4%] vs. 23.0% [20.8%, 25.4%]; p=0.05). Patient characteristics influenced the comparison between the two designs in the 1-stage group but very little in the 2-stage group. Modular revision stem fractures only contribute very minor to re-revision risk. In 2-stage revisions, no difference in overall re-revision rates between designs was observed. This might indicate that the differences observed for 1-stage procedures are due to differences between the patient cohorts, not reflected by the parameters available or surgeon choice.
To explore the efficacy of extracorporeal shockwave therapy (ESWT) in the treatment of osteochondral defect (OCD), and its effects on the levels of transforming growth factor (TGF)-β, bone morphogenetic protein (BMP)-2, -3, -4, -5, and -7 in terms of cartilage and bone regeneration. The OCD lesion was created on the trochlear groove of left articular cartilage of femur per rat (40 rats in total). The experimental groups were Sham, OCD, and ESWT (0.25 mJ/mm2, 800 impulses, 4 Hz). The animals were euthanized at 2, 4, 8, and 12 weeks post-treatment, and histopathological analysis, micro-CT scanning, and immunohistochemical staining were performed for the specimens.Aims
Methods
This study compares the re-revision rate and mortality following septic and aseptic revision hip arthroplasty (rTHA) in registry data, and compares the outcomes to previously reported data. This is an observational cohort study using data from the German Arthroplasty Registry (EPRD). A total of 17,842 rTHAs were included, and the rates and cumulative incidence of hip re-revision and mortality following septic and aseptic rTHA were analyzed with seven-year follow-up. The Kaplan-Meier estimates were used to determine the re-revision rate and cumulative probability of mortality following rTHA.Aims
Methods
Lumbar spinal stenosis (LSS) is a common skeletal system disease that has been partly attributed to genetic variation. However, the correlation between genetic variation and pathological changes in LSS is insufficient, and it is difficult to provide a reference for the early diagnosis and treatment of the disease. We conducted a transcriptome-wide association study (TWAS) of spinal canal stenosis by integrating genome-wide association study summary statistics (including 661 cases and 178,065 controls) derived from Biobank Japan, and pre-computed gene expression weights of skeletal muscle and whole blood implemented in FUSION software. To verify the TWAS results, the candidate genes were furthered compared with messenger RNA (mRNA) expression profiles of LSS to screen for common genes. Finally, Metascape software was used to perform enrichment analysis of the candidate genes and common genes.Aims
Methods
We investigated factors associated with postoperative lipiduria and hypoxemia in patients undergoing surgery for orthopedic fractures. We enrolled patients who presented to our emergency department due to traumatic fractures between 2016 and 2017. We collected urine samples within 24 hours after the patients had undergone surgery to determine the presence of lipiduria. Hypoxemia was defined as an SpO2 <95% determined with a pulse oximeter during the hospitalization. Patients’ anthropometric data, medical history, and laboratory test results were collected from the electronic medical record. Logistic regression analyses were used to determine the associations of clinical factors with postoperative lipiduria and hypoxemia with multivariate adjustment. A total of 144 patients were analyzed (mean age 51.3 ± 22.9 years, male 50.7%). Diabetes (odd ratio 3.684, 95% CI 1.256-10.810, p=0.018) and operation time (odd ratio 1.005, 95% CI 1.000-1.009, p=0.029) were independently associated with postoperative lipiduria, while age (odd ratio 1.034, 95% CI 1.003-1.066, p=0.029), body mass index (odd ratio 1.100, 95% CI 1.007-1.203, p=0.035), and operation time (odd ratio 1.005, 95% CI 1.000-1.010, p=0.033) were independently associated with postoperative hypoxemia. We identified several factors independently associated with postoperative lipiduria and hypoxemia in patients with fracture undergoing surgical intervention. Operation time was associated with both postoperative lipiduria and hypoxemia, and we recommend that patients with prolonged operation for fractures should be carefully monitored for clinical signs related to fat embolism syndrome.
This study aimed to investigate the role and mechanism of meniscal cell lysate (MCL) in fibroblast-like synoviocytes (FLSs) and osteoarthritis (OA). Meniscus and synovial tissue were collected from 14 patients with and without OA. MCL and FLS proteins were extracted and analyzed by liquid chromatography‒mass spectrometry (LC‒MS). The roles of MCL and adenine nucleotide translocase 3 (ANT3) in FLSs were examined by enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunofluorescence, and transmission electron microscopy. Histological analysis was performed to determine ANT3 expression levels in a male mouse model.Aims
Methods
Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive. Predicted whole-blood and skeletal muscle gene expression and genome-wide association study (GWAS) data from a DCS database were integrated, and functional summary-based imputation (FUSION) software was used on the integrated data. A transcriptome-wide association study (TWAS) was conducted using FUSION software to assess the association between predicted gene expression and DCS risk. The TWAS-identified genes were verified via comparison with differentially expressed genes (DEGs) in DCS RNA expression profiles in the Gene Expression Omnibus (GEO) (Accession Number: GSE153761). The Functional Mapping and Annotation (FUMA) tool for genome-wide association studies and Meta tools were used for gene functional enrichment and annotation analysis.Aims
Methods
To verify whether secretory leucocyte protease inhibitor (SLPI) can promote early tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction. In vitro: the mobility of the rat bone mesenchymal stem cells (BMSCs) treated with SLPI was evaluated by scratch assay. Then the expression levels of osteogenic differentiation-related genes were analyzed by real-time quantitative PCR (qPCR) to determine the osteogenic effect of SLPI on BMSCs. In vivo: a rat model of ACL reconstruction was used to verify the effect of SLPI on tendon-to-bone healing. All the animals of the SLPI group and the negative control (NC) group were euthanized for histological evaluation, micro-CT scanning, and biomechanical testing.Aims
Methods
Osteochondral (OC) defects of the knee are associated with pain and significant limitation of activity. Studies have demonstrated the therapeutic efficacy of mesenchymal stem cell (MSC) therapies in treating osteochondral defects. There is increasing evidence that the efficacy of MSC therapies may be a result of the paracrine secretion, particularly exosomes. Here, we examine the effects of MSC exosomes in combination with Hyaluronic Acid (HA) as an injectable therapy on functional osteochondral regeneration in a rabbit osteochondral defect model. Exosomes were purified from human MSC conditioned medium by size fractionation. A circular osteochondral defect of 4.5 mm diameter and 2.5 mm depth was surgically created in the trochlear grooves of 16 rabbit knees. Thereafter, eight knees received three weekly injections of 200 µg of exosomes in one ml of 3% HA, and the remaining eight knees received three weekly injections of one ml of 3% HA only. The rabbits were sacrificed at six weeks. Analyses were performed by macroscopic and histological assessments, and functional competence was analysed via Young Modulus calculation at five different points (central, superior, inferior, medial and lateral) of the repaired osteochondral defect site. MSC exosomes displayed a modal size of 100 nm and expressed exosome markers (CD81, TSG101 and ALIX). When compared to HA alone, MSC exosomes in combination with HA showed significantly better repair histologically and biomechanically. The Young Modulus was higher in 4 out of the 5 points. In the central region, the Young Modulus of MSC exosome and HA combination therapy was significantly higher: 5.42 MPa [SD=1.19, 95% CI: 3.93–6.90] when compared to HA alone: 2.87 MPa [SD=2.10, 95% CI: 0.26–5.49], p < 0 .05. The overall mean peripheral region was also significantly higher in the MSC exosome and HA combination therapy group: 5.87 MPa [SD=1.19, 95% CI: 4.40–7.35] when compared to HA alone: 2.70 MPa [SD=1.62, 95% CI: 0.79–4.71], p < 0 .05. The inferior region showed a significantly higher Young Modulus in the combination therapy: 7.34 MPa [SD=2.14, 95% CI: 4.68–10] compared to HA alone: 2.92 MPa [SD=0.98, 95% CI: 0.21–5.63], p < 0.05. The superior region showed a significantly higher Young Modulus in the combination therapy: 7.31 MPa [SD=3.29, 95% CI: 3.22–11.39] compared to HA alone: 3.59 MPa [SD=2.55, 95% CI: 0.42–6.76], p < 0.05. The lateral region showed a significantly higher Young Modulus in the combination therapy: 8.05 MPa [SD=2.06, 95% CI: 5.49–10.61] compared to HA alone: 3.56 MPa [SD=2.01, 95% CI: 1.06–6.06], p < 0.05. The medial region showed a higher Young Modulus in the combination therapy: 6.68 MPa [SD=1.48, 95% CI: 4.85–8.51] compared to HA alone: 3.45 MPa [SD=3.01, 95% CI: −0.29–7.19], but was not statistically significant. No adverse tissue reaction was observed in all the immunocompetent animals treated with MSC exosomes. Three weekly injections of MSC exosomes in combination with HA therapy results in a more functional osteochondral regeneration as compared to HA alone.
The zonal organization of articular cartilage is crucial in providing the tissue with mechanical properties to withstand compression and shearing force. Current treatments available for articular cartilage injury are not able to restore the hierarchically organized architecture of the tissue. Implantation of zonal chondrocyte as a multilayer tissue construct could overcome the limitation of current treatments. However, it is impeded by the lack of efficient zonal chondrocyte isolation protocol and dedifferentiation of chondrocytes during expansion on tissue culture plate (TCP). This study aims to develop a protocol to produce an adequate number of high-quality zonal chondrocytes for clinical application via size-based zonal chondrocyte separation using inertial spiral microchannel device and expansion under dynamic microcarrier culture. Full thickness (FT) chondrocytes isolated from porcine femoral condyle cartilage were subjected to two serial of size-based sorting into three subpopulations of different cell sizes, namely small (S1), medium (S2), and large (S3) chondrocytes. Zonal phenotype of the three subpopulations was characterised. To verify the benefit of stratified zonal chondrocyte implantation in the articular cartilage regeneration, a bilayer hydrogel construct composed of S1 chondrocytes overlaying a mixture of S2 and S3 (S2S3) chondrocytes was delivered to the rat osteochondral defect model. For chondrocyte expansion, two dynamic microcarrier cultures, sort-before-expansion and sort-after-expansion, which involved expansion after or before zonal cells sorting, were studied to identify the best sort-expansion strategy. Size-sorted zonal chondrocytes showed zone-specific characteristics in qRT-PCR with a high level of PRG4 expression in S1 and high level of aggrecan, Type II and IX collagen expression in S2 and S3. Cartilage reformation capability of sorted zonal chondrocytes in three-dimensional fibrin hydrogel showed a similar trend in qRT-PCR, histology, extracellular matrix protein quantification and mechanical compression test, indicating the zonal characteristics of S1, S2 and S3 as superficial (SZ), middle (MZ) and deep (DZ) zone chondrocytes, respectively. Implantation of bilayered zonal chondrocytes resulted in better cartilage tissue regeneration in a rat osteochondral defect model than FT control group, with predominantly Type II hyaline cartilage tissue and significantly lower Type I collagen. Dynamic microcarrier expansion of sorted zonal chondrocytes was able to retain the zonal cell size difference that correlate to zonal phenotype, while maintaining the rounded chondrocyte morphology and F-actin distribution similar to that in mature articular cartilage. With the better retention of zonal cell size and zonal phenotype relation on microcarrier, zonal cells separation was achievable in the sort-after-expansion strategy with cells expanded on microcarrier, in comparison to cells expanded on TCP. Inertial spiral microchannel device provides a label-free and high throughput method to separate zonal chondrocytes based on cell size. Stratified implantation of zonal chondrocytes has the potential to improve articular cartilage regeneration. Dynamic microcarrier culture allows for size-based zonal chondrocyte separation to be performed on expanded chondrocytes, thus overcoming the challenge of limited tissue availability from the patients. Our novel zonal chondrocyte isolation and expansion protocol provide a translatable strategy for stratified zonal chondrocyte implantation that could improve articular cartilage regeneration of critical size defects.
Adult articular cartilage mechanical functionality is dependent on the unique zonal organization of its tissue. Current mesenchymal stem cell (MSC)-based treatment has resulted in sub-optimal cartilage repair, with inferior quality of cartilage generated from MSCs in terms of the biochemical content, zonal architecture and mechanical strength when compared to normal cartilage. The phenotype of cartilage derived from MSCs has been reported to be influenced by the microenvironmental biophysical cues, such as the surface topography and substrate stiffness. In this study, the effect of nano-topographic surfaces to direct MSC chondrogenic differentiation to chondrocytes of different phenotypes was investigated, and the application of these pre-differentiated cells for cartilage repair was explored. Specific nano-topographic patterns on the polymeric substrate were generated by nano-thermal imprinting on the PCL, PGA and PLA surfaces respectively. Human bone marrow MSCs seeded on these surfaces were subjected to chondrogenic differentiation and the phenotypic outcome of the differentiated cells was analyzed by real time PCR, matrix quantification and immunohistological staining. The influence of substrate stiffness of the nano-topographic patterns on MSC chondrogenesis was further evaluated. The ability of these pre-differentiated MSCs on different nano-topographic surfaces to form zonal cartilage was verified in in vitro 3D hydrogel culture. These pre-differentiated cells were then implanted as bilayered hydrogel constructs composed of superficial zone-like chondro-progenitors overlaying the middle/deep zone-like chondro-progenitors, was compared to undifferentiated MSCs and non-specifically pre-differentiated MSCs in a osteochondral defect rabbit model. Nano-topographical patterns triggered MSC morphology and cytoskeletal structure changes, and cellular aggregation resulting in specific chondrogenic differentiation outcomes. MSC chondrogenesis on nano-pillar topography facilitated robust hyaline-like cartilage formation, while MSCs on nano-grill topography were induced to form fibro/superficial zone cartilage-like tissue. These phenotypic outcomes were further diversified and controlled by manipulation of the material stiffness. Hyaline cartilage with middle/deep zone cartilage characteristics was derived on softer nano-pillar surfaces, and superficial zone-like cartilage resulted on softer nano-grill surfaces. MSCs on stiffer nano-pillar and stiffer nano-grill resulted in mixed fibro/hyaline/hypertrophic cartilage and non-cartilage tissue, respectively. Further, the nano-topography pre-differentiated cells possessed phenotypic memory, forming phenotypically distinct cartilage in subsequent 3D hydrogel culture. Lastly, implantation of the bilayered hydrogel construct of superficial zone-like chondro-progenitors and middle/deep zone-like chondro-progenitors resulted in regeneration of phenotypically better cartilage tissue with higher mechanical function. Our results demonstrate the potential of nano-topographic cues, coupled with substrate stiffness, in guiding the differentiation of MSCs to chondrocytes of a specific phenotype. Implantation of these chondrocytes in a bilayered hydrogel construct yielded cartilage with more normal architecture and mechanical function. Our approach provides a potential translatable strategy for improved articular cartilage regeneration using MSCs.
Clinical observations suggest mid-flexion instability may occur more commonly with rotating platform (RP) total knee arthroplasty (TKA), including increased revision rates and patient-reported instability and pain. We propose that increased gap laxity leads to liftoff of the lateral femoral condyle with decreased conformity between the femoral component and polyethylene (PE) insert surface leading to PE subluxation or dislocation. The objectives of this study were to define “at risk” loading conditions that predispose patients to PE insert subluxation or spinout, and to quantify the margin of error for flexion/extension gap laxity in preventing these adverse events under physiologic loading conditions. Biomechanical testing was performed on six fresh frozen cadaveric knees implanted with a posterior stabilized RP TKA using a gap balancing technique. Rotational displacement and torque were measured over time, while stiffness, yield torque, max torque and displacement were calculated using a post-processing, custom MatLab code. Revision with varying size femoral components (size 3–6) and PE insert thicknesses (10–15mm), by downsizing one step, were used to create a spectrum of flexion/extension gap mismatch. Each configuration was subjected to three loaded testing conditions (0°, 30° and 60° flexion) in balanced and eccentric varus loading, known to represent daily clinical function and “at risk” circumstances.Introduction
Methods
Cervical spondylosis is often accompanied by dizziness. It has
recently been shown that the ingrowth of Ruffini corpuscles into
diseased cervical discs may be related to cervicogenic dizziness.
In order to evaluate whether cervicogenic dizziness stems from the
diseased cervical disc, we performed a prospective cohort study
to assess the effectiveness of anterior cervical discectomy and
fusion on the relief of dizziness. Of 145 patients with cervical spondylosis and dizziness, 116
underwent anterior cervical decompression and fusion and 29 underwent
conservative treatment. All were followed up for one year. The primary
outcomes were measures of the intensity and frequency of dizziness.
Secondary outcomes were changes in the modified Japanese Orthopaedic
Association (mJOA) score and a visual analogue scale score for neck
pain.Aims
Patients and Methods