Synovial fluid monocyte-to-lymphocyte ratio in knee osteoarthritis patients predicts patient response to conservative treatment: a retrospective cohort study.

BACKGROUND: Biomarkers that predict the treatment response in patients with knee osteoarthritis are scarce. This study aimed to investigate the potential role of synovial fluid cell counts and their ratios as biomarkers of primary knee osteoarthritis. METHODS: This retrospective study investigated 96 consecutive knee osteoarthritis patients with knee effusion who underwent joint fluid aspiration analysis and received concomitant intra-articular corticosteroid injections and blood tests. The monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) were calculated. After 6 months of treatment, patients were divided into two groups: the responder group showing symptom resolution, defined by a visual analog scale (VAS) score of ≤ 3, without additional treatment, and the non-responder group showing residual symptoms, defined by a VAS score of > 3 and requiring further intervention, such as additional medication, repeated injections, or surgical treatment. Unpaired t-tests and univariate and multivariate logistic regression analyses were conducted between the two groups to predict treatment response after conservative treatment. The predictive value was calculated using the area under the receiver operating characteristic curve, and the optimal cutoff value was determined. RESULTS: Synovial fluid MLR was significantly higher in the non-responder group compared to the responder group (1.86 ± 1.64 vs. 1.11 ± 1.37, respectively; p = 0.02). After accounting for confounding variables, odds ratio of non-responder due to increased MLR were 1.63 (95% confidence interval: 1.11-2.39). The optimal MLR cutoff value for predicting patient response to conservative treatment was 0.941. CONCLUSIONS: MLR may be a potential biomarker for predicting the response to conservative treatment in patients with primary knee osteoarthritis.

Exosomes Secreted During Myogenic Differentiation of Human Fetal Cartilage-Derived Progenitor Cells Promote Skeletal Muscle Regeneration through miR-145-5p.

BACKGROUND: Currently, there is no apparent treatment for sarcopenia, which is characterized by diminished myoblast function. We aimed to manufacture exosomes that retain the myogenic differentiation capacity of human fetal cartilage-derived progenitor cells (hFCPCs) and investigate their muscle regenerative efficacy in myoblasts and a sarcopenia rat model. METHODS: The muscle regeneration potential of exosomes (F-Exo) secreted during myogenic differentiation of hFCPCs was compared to human bone marrow mesenchymal stem cells-derived (hBMSCs) exosomes (B-Exo) in myoblasts and sarcopenia rat model. The effect of F-Exo was analyzed through known microRNAs (miRNAs) analysis. The mechanism of action of F-Exo was confirmed by measuring the expression of proteins involved in the Wnt signaling pathway. RESULTS: F-Exo and B-Exo showed similar exosome characteristics. However, F-Exo induced the expression of muscle markers (MyoD, MyoG, and MyHC) and myotube formation in myoblasts more effectively than B-Exo. Moreover, F-Exo induced greater increases in muscle fiber cross-sectional area and muscle mass compared to B-Exo in a sarcopenia rat. The miR-145-5p, relevant to muscle regeneration, was found in high concentrations in the F-Exo, and RNase pretreatment reduced the efficacy of exosomes. The effects of F-Exo on the expression of myogenic markers in myoblasts were paralleled by the miR-145-5p mimics, while the inhibitor partially negated this effect. F-Exo was involved in the Wnt signaling pathway by enhancing the expression of Wnt5a and ß-catenin. CONCLUSION: F-Exo improved muscle regeneration by activating the Wnt signaling pathway via abundant miR-145-5p, mimicking the remarkable myogenic differentiation potential of hFCPCs.

Controlled posterior condylar milling technique for unicompartmental knee arthroplasty minimises tibia resection during gap balancing: Short-term clinical results.

PURPOSE: The purpose of this study was to demonstrate the clinical utility of controlled posterior condylar milling (CPCM) in gap balancing while minimally resecting the tibia during fixed-bearing unicompartmental knee arthroplasty (UKA). METHODS: This study is a retrospective cohort study. Patients who underwent medial UKA for isolated medial compartment osteoarthritis with a minimum follow-up of 2 years were included. The patients were divided into two groups: the conventional group (n = 56) and the CPCM group (n = 66). In the CPCM group, the proximal tibia was resected at the level of the distal end of the subchondral bone. If the flexion gap was tighter than extension, the posterior condyle was additionally milled to adjust gap tightness. Standing knee X-ray and scanogram were used to evaluate alignment and tibia resection amount. Range of motion (ROM) and Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) scores were used to evaluate clinical outcomes. RESULTS: The CPCM group showed significantly smaller tibia resection (3.6 ± 1.9 mm) compared to the conventional group (5.2 ± 2.7 mm) (p < 0.001). Postoperative ROM (133.0 ± 8.3°, 135.2 ± 7.2°, n.s.) and WOMAC (19.3 ± 13.6, 23.6 ± 17.7, n.s.) were not significantly different between the two groups. Postoperative periprosthetic fractures occurred in two patients in conventional group, while the CPCM group had no periprosthetic fractures. CONCLUSION: The CPCM technique may be a simple and useful intraoperative technique that can achieve minimal tibia resection and promising clinical outcomes while easily adjusting gap tightness between flexion and extension during medial fixed-bearing UKA. LEVEL OF EVIDENCE: Level III.

Fixed-Bearing Unicompartmental Knee Arthroplasty in Tibia Vara Knees Results in Joint Surface Malalignment and Varus Joint Line Obliquity, but Does Not Affect Functional Outcomes at Greater Than 5 Years Follow-Up.

BACKGROUND: This study aimed to investigate the clinical outcomes of fixed-bearing medial unicompartmental knee arthroplasty (UKA) for tibia vara knees and the associated changes in joint space malalignment (JSM) and joint line obliquity (JLO). METHODS: We retrospectively analyzed a consecutive group of 100 patients who underwent fixed-bearing medial UKA with a preoperative medial proximal tibia angle (MPTA) ≥86° (n = 50) and MPTA <86° (n = 50) and who had a minimum 5-year follow-up. Radiological parameters, including the hip-knee-ankle angle, MPTA, and the postoperative JSM and JLO, were measured. Functional evaluation was performed using the range of motion, visual analog scale, Knee Society Knee Score, Knee Society Function Score, and Western Ontario and McMaster Universities Osteoarthritis Index score. RESULTS: The MPTA <86° group showed significantly higher postoperative JLO (91.8 versus 90.4°, respectively; P = .002) and JSM (6.1 versus 4.2°, respectively; P = .026) compared to the MPTA ≥86° group. Functional outcomes, including range of motion, visual analog scale, Knee Society Knee Score, Knee Society Function Score, and Western Ontario and McMaster Universities Osteoarthritis Index scores, were not significantly different between the 2 groups. CONCLUSIONS: Fixed-bearing medial UKA is a safe and effective surgical option for patients who have tibia vara knees, as an increase in JLO and JSM postoperatively does not have a clinically relevant impact, even after a minimum 5-year follow-up.

Recombinant Human Parathyroid Hormone Biocomposite Promotes Bone-to-Tendon Interface Healing by Enhancing Tenogenesis, Chondrogenesis, and Osteogenesis in a Rabbit Model of Chronic Rotator Cuff Tears.

PURPOSE: To investigate the effect of recombinant human parathyroid hormone (rhPTH) biocomposite on bone-to-tendon interface (BTI) healing for surgical repair of a chronic rotator cuff tear (RCT) model of rabbit, focusing on genetic, histologic, biomechanical and micro-computed tomography (CT) evaluations. METHODS: Sixty-four rabbits were equally assigned to the 4 groups: saline injection (group A), nanofiber sheet alone (group B), rhPTH-soaked nanofiber sheet (nanofiber sheet was soaked with rhPTH, group C), and rhPTH biocomposite (rhPTH permeated the nanofiber sheet by coaxial electrospinning, group D). The release kinetics of rhPTH (groups C and D) was examined for 6 weeks in vitro. Nanofiber scaffolds were implanted on the surface of the repair site 6 weeks after the induction of chronic RCT. Genetic and histologic analyses were conducted 4 weeks after surgery. Furthermore, genetic, histologic, biomechanical, micro-CT, and serologic analyses were performed 12 weeks after surgery. RESULTS: In vivo, group D showed the highest collagen type I alpha 1 (COL1A1), collagen type III alpha 1 (COL3A1), and bone morphogenetic protein 2 (BMP-2) messenger RNA (mRNA) expression levels (all P < .001) 4 weeks after surgery; however, there were no differences between groups at 12 weeks postsurgery. After 12 weeks postsurgery, group D showed better collagen fiber continuity and orientation, denser collagen fibers, more mature bone-to-tendon junction, and greater fibrocartilage layer formation compared with the other groups (all P < .05). Furthermore, group D showed the highest load-to-failure rate (28.9 ± 2.0 N/kg for group A, 30.1 ± 3.3 N/kg for group B, 39.7 ± 2.7 N/kg for group C, and 48.2 ± 4.5 N/kg for group D, P < .001) and micro-CT outcomes, including bone and tissue mineral density, and bone volume/total volume rate (all P < .001) at 12 weeks postsurgery. CONCLUSIONS: In comparison to rhPTH-soaked nanofiber sheet and the other control groups, rhPTH biocomposite effectively accelerated BTI healing by enhancing the mRNA expression levels of COL1A1, COL3A1, and BMP-2 at an early stage and achieving tenogenesis, chondrogenesis, and osteogenesis at 12 weeks after surgical repair of a chronic RCT model of rabbit. CLINICAL RELEVANCE: The present study might be a transitional study to demonstrate the efficacy of rhPTH biocomposites on BTI healing for surgical repair of chronic RCTs as an adaptable polymer biomaterial in humans.

Synovium-Derived Mesenchymal Stem Cell-Based Scaffold-Free Fibrocartilage Engineering for Bone-Tendon Interface Healing in an Anterior Cruciate Ligament Reconstruction Model.

BACKGROUND: Current tendon and ligament reconstruction surgeries rely on scar tissue healing which differs from native bone-to-tendon interface (BTI) tissue. We aimed to engineer Synovium-derived mesenchymal stem cells (Sy-MSCs) based scaffold-free fibrocartilage constructs and investigate in vivo bone-tendon interface (BTI) healing efficacy in a rat anterior cruciate ligament (ACL) reconstruction model. METHODS: Sy-MSCs were isolated from knee joint of rats. Scaffold-free sy-MSC constructs were fabricated and cultured in differentiation media including  TGF-ß-only, CTGF-only, and TGF-ß + CTGF. Collagenase treatment on tendon grafts was optimized to improve cell-to-graft integration. The effects of fibrocartilage differentiation and collagenase treatment on BTI integration was assessed by conducting histological staining, cell adhesion assay, and tensile testing. Finally, histological and biomechanical analyses were used to evaluate in vivo efficacy of fibrocartilage construct in a rat ACL reconstruction model. RESULTS: Fibrocartilage-like features were observed with in the scaffold-free sy-MSC constructs when applying TGF-ß and CTGF concurrently. Fifteen minutes collagenase treatment increased cellular attachment 1.9-fold compared to the Control group without affecting tensile strength. The failure stress was highest in the Col + D + group (22.494 ± 13.74 Kpa) compared to other groups at integration analysis in vitro. The ACL Recon + FC group exhibited a significant 88% increase in estimated stiffness (p = 0.0102) compared to the ACL Recon group at the 4-week postoperative period. CONCLUSION: Scaffold-free, fibrocartilage engineering together with tendon collagenase treatment enhanced fibrocartilaginous BTI healing in ACL reconstruction.

Selective Extracellular Matrix Guided Mesenchymal Stem Cell Self-Aggregate Engineering for Replication of Meniscal Zonal Tissue Gradient in a Porcine Meniscectomy Model.

Degenerative meniscus tears (DMTs) are prevalent findings in osteoarthritic knees, yet current treatment is mostly limited to arthroscopic partial meniscectomy rather than regeneration, which further exacerbates arthritic changes. Translational research regarding meniscus regeneration is hindered by the complex, composite nature of the meniscus which exhibit a gradient from inner cartilage-like tissue to outer fibrous tissue, as well as engineering hurdles often requiring growth factors and cross-linking agents. Here, a meniscus zonal tissue gradient is proposed using zone-specific decellularized meniscus extracellular matrix (DMECM) and autologous synovial mesenchymal stem cells (SMSC) via self-aggregation without the use of growth factors or cross-linking agents. Combination with zone-specific DMECM during self-aggregation of MSCs forms zone-specific meniscus tissue that reflects the respective DMECM harvest site. The implantation of these constructs leads to the regeneration of meniscus tissue resembling the native meniscus, demonstrating inner cartilaginous and outer fibrous characteristics as well as recovery of native meniscal microarchitecture in a porcine partial meniscectomy model at 6 months. In all, the findings offer a potential regenerative therapy for DMTs that may improve current partial meniscectomy-based patient care.

Fibrocartilage extracellular matrix augmented demineralized bone matrix graft repairs tendon-to-bone interface in a rabbit tendon reconstruction model.

Current tendon/ligament reconstructions integrate via scar tissue rather than proper bone-tendon interface regeneration, which affects graft longevity, changes in bone tunnel size, and functional outcomes. The purpose of this study was to develop a functional demineralized bone matrix (DBM) + fibrocartilage extracellular matrix (FCECM) composite scaffold, characterize its physicochemical properties, and evaluate its efficacy in repairing tendon-bone interface in a rabbit tendon reconstruction model. Solubilized FCECM was loaded and crosslinked on to DBM scaffolds via gamma-irradiation to create DBM + FCECM scaffolds. The resulting scaffold showed interconnected pores coated with FCECM and protein cargo similar to FCECM. The addition of FCECM modified the physicochemical properties of the DBM scaffold, including microstructure, biochemical composition, mechanical strength, thermodynamic properties, and degradation period. The DBM + FCECM scaffold was biocompatible for mesenchymal stem cells (MSCs) and resulted in elevation of fibrochondrogenic gene markers compared to DBM scaffolds in vitro. In vivo implantation of DBM + FCECM scaffold resulted in neofibrocartilage formation, better pullout strength, and less bone tunnel widening compared to DBM only group in a rabbit tendon reconstruction model. In conclusion, the FCECM augmented DBM scaffold repairs the tendon-bone interface with osseous-fibrocartilage tissue, which may be utilized to improve current tendon reconstruction surgeries.

Lateral Retinacular Release During Medial Unicompartmental Knee Arthroplasty in the Presence of Patello-Femoral Joint Arthritis Relieves Patello-Femoral Joint Pressure and Improves Associated Symptoms.

BACKGROUND: This study evaluated the effects of concomitant lateral patellar retinacular release (LPRR) during medial unicompartmental knee arthroplasty (UKA). METHODS: We retrospectively analyzed 100 patients who had patello-femoral joint (PFJ) arthritis who underwent medial UKA with (n = 50) and without (n = 50) LPRR who had ≥2 years follow-up. Radiological parameters associated with lateral retinacular tightness, including patellar tilt angle (PTA), lateral patello-femoral angle (LPFA), and congruence angle, were measured. Functional evaluation was performed using the Knee Society Pain Score, Knee Society Function Score (KSFS), Kujala Score, and the Western Ontario McMaster Universities Osteoarthritis Index score. Intraoperative patello-femoral pressure evaluation was performed on 10 knees to evaluate the pressure changes before and after LPRR. Mann-Whitney U-tests were used for statistical analyses. RESULTS: Demographic data did not differ between the LPRR(+) and LPRR(-) groups. A decrease in PTA and an increase in LPFA were observed in the LPRR(+) group compared to those in the LPRR(-) group (PTA; -0.54 versus -1.74, P = .002, LPFA; 0.51 versus 2.01, P = .010). The LPRR(+) group showed significantly better KSFS and Kujala scores than the LPRR(-) group (KSFS: 90 versus 80, P = .017; Kujala score: 86 versus 79, P = .009). Intraoperative patello-femoral pressure analysis showed a 22.6% reduction in the PFJ contact pressure and an 18.7% reduction in PFJ peak pressure after LPRR. (P = .0015, P < .0001, respectively) CONCLUSION: A LPRR during UKA may be a simple and useful adjunct procedure to relieve PFJ symptoms with concomitant PFJOA.

Effects of glycosaminoglycan content in extracellular matrix of donor cartilage on the functional properties of osteochondral allografts evaluated by micro-CT non-destructive analysis.

Osteochondral allograft (OCA) is an important surgical procedure used to repair extensive articular cartilage damage. It is known that chondrocyte viability is crucial for maintaining the biochemical and biomechanical properties of OCA, which is directly related to the clinical success of the operation and is the only standard for preoperative evaluation of OCA. However, there is a lack of systematic research on the effect of the content of cellular matrix in OCA cartilage tissue on the efficacy of transplantation. Therefore, we evaluated the effect of different GAG contents on the success of OCA transplantation in a rabbit animal model. Each rabbit OCA was treated with chondroitinase to regulate glycosaminoglycan (GAG) content in the tissue. Due to the different action times of chondroitinase, they were divided into 4 experimental groups (including control group, 2h, 4h, and 8h groups). The treated OCAs of each group were used for transplantation. In this study, transplant surgery effects were assessed using micro-computed tomography (µCT) and histological analysis. Our results showed that tissue integration at the graft site was poorer in the 4h and 8h groups compared to the control group at 4 and 12 weeks in vivo, as were the compressive modulus, GAG content, and cell density reduced. In conclusion, we evaluated the biochemical composition of OCAs before and after surgery using µCT analysis and demonstrated that the GAG content of the graft decreased, it also decreased during implantation; this resulted in decreased chondrocyte viability after transplantation and ultimately affected the functional success of OCAs.

Circumferential Rim Augmentation Suture Around the Perimeniscal Capsule Decreases Meniscal Extrusion and Progression of Osteoarthritis in Rabbit Meniscus Root Tear Model.

BACKGROUND: We recently analyzed the joint capsule adjacent to the medial meniscus and found that the perimeniscal joint capsule has collagen fiber orientation similar to that of circumferential meniscal fibers, potentially playing a role in preventing extrusion. PURPOSE: To analyze the meniscal extrusion prevention potential of the circumferential rim augmentation suture around the perimeniscal capsule in a rabbit root tear model and analyze the biomechanical function in a porcine cadaveric knee. STUDY DESIGN: Controlled laboratory study. METHODS: Rabbit medial meniscus root tear models were divided into 3 experimental groups: root tear, root tear and suture repair, and root tear and circumferential rim augmentation suture. As for the circumferential rim augmentation suture procedure, a suture was placed to circumscribe the outer rim of the medial meniscus and passed through bone tunnels located at the tibial insertion of each root. After 4 and 8 weeks, meniscal extrusion was analyzed by micro-computed tomography, gross morphology, and histologic analysis of the medial femoral cartilage. For biomechanical analysis, porcine knees were divided into groups similar to rabbit experiments. Tibiofemoral contact parameters were assessed using a pressure mapping sensor system after applying a load of 200 N on the knee joint. RESULTS: The root tear and circumferential rim augmentation suture group showed less meniscal extrusion, less gap within the tear site, and less cartilage degeneration compared with other groups after 4 and 8 weeks of surgery in the rabbit root tear model. Biomechanical analysis showed the root tear and circumferential rim augmentation suture group had larger contact area and lower peak contact pressure compared with root tear and root tear and suture repair groups. CONCLUSION: The circumferential rim augmentation suture reduced the degree of meniscal extrusion while restoring meniscal function, potentially preventing progression of arthritis in a rabbit root tear model and porcine knee biomechanical analysis. CLINICAL RELEVANCE: The circumferential rim augmentation suture may be a novel augmentation option during root tear treatment.

LncRNA GAS5 Interacts with MicroRNA-10b to Inhibit Cell Proliferation and Migration and Induces Apoptosis in Colorectal Cancer.

OBJECTIVE: The purpose of this study was to study the effects of the GAS5/microRNA-10b (miR-10b) axis on proliferation, migration, and apoptosis of colorectal cancer (CRC). METHODS: The expression levels of GAS5 and miR-10b in CRC tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Wound healing experiment was used to detect the effects of GAS5 and miR-10b on the migration of CRC cells. The luciferase reporter gene experiment was used to verify miRNA targets. Immunohistochemical assay was used to detect the expression of proteins related to metastasis and apoptosis in tumor tissues. RESULTS: The expression of GAS5 was downregulated in CRC tissues and cell lines. The overexpression of GAS5 can inhibit cell proliferation and progression, induce apoptosis in vitro, and inhibit the growth of CRC tumor in vivo. In contrast, the expression of miR-10b, a downstream target of GAS5, was increased in CRC tissues and cells. Suppression of the miR-10b gene can inhibit proliferation and metastasis and cause apoptosis of CRC cells. In addition, luciferase reports show that GAS5 inhibits the progression of CRC cells by binding to miR-10b. Rescue experiments showed that overexpressed miR-10b could reverse GAS5-mediated antitumor effect on CRC cells in vivo and in vitro. CONCLUSIONS: LncRNA GAS5 interacts with miR-10b to inhibit cell proliferation and migration and induces apoptosis in colorectal cancer. GAS5 and miR-10b could become potential therapeutic targets for CRC.

Quantification of Lumbar Spinal Canal Stenosis by Quantitative Fat-Suppressed Contrast-Enhanced Magnetic Resonance Imaging.

Fat-suppressed T1-weighted magnetic resonance images (MRIs) enhanced with gadolinium can evaluate the internal vertebral venous plexus and cauda equina. This study compared such findings with clinical situations and discusses whether these are helpful for symptomatic grading and selection at the surgical level in patients with lumbar central stenosis. A total of 263 patients (337 levels < 75 mm2 of dural cross sectional area (DCSA)) were included. The enhancement patterns of dorsal epidural vein (DVCE), periradicular vein (PVCE) and intraradicular vein (IRCE) were assessed qualitatively. The quantification of IRCE was acquired by the ratio (%) (enhancement parameters: MS/P1, MS/P2, WR/P1, WR/P2) of signal intensities between the cauda equina (MS-IRCE: maximal spot rootlet, WR-IRCE: whole rootlets) and psoas muscle (P1, P2). Receiver-operator characteristic curves were plotted to obtain imaginary cutoff values for the prediction of symptomatic appearance or operation decision. All levels were classified into seven groups on the basis of pain distribution and the presence of IRCE. PVCE was significantly related to high incidences of symptoms, unilaterality and operation. DVCE and IRCE were connected with high incidences of symptoms, bilaterality and operation. IRCE was also related to high visual analogue scale (VAS), small DCSA and high enhancement parameters. The order of the group was concordant with the degree of enhancement parameters (p = 0.000). Cutoff values of enhancement parameters for prediction were as follows: symptoms (147/123/140/121), bilaterality (165/139/157/137) and operation (164/139/159/138). Enhancement patterns and parameters could help in stratification, grading and decision-making at the surgical level.

Biomechanical investigation of extragraft bone formation influences on the operated motion segment after anterior cervical spinal discectomy and fusion.

Although the clinical importance of extragraft bone formation (ExGBF) and bridging (ExGBB) has been reported, few studies have investigated the biomechanical influences of ExGBF on the motion segment. In this study, ExGBF was simulated at the C5-C6 motion segment after anterior cervical discectomy and fusion using a developed finite element model and a sequential bone-remodelling algorithm in flexion and extension. The computer simulation results showed that extragraft bone was primarily formed in the extension motion and grew to form ExGBB. A stepwise decrease in the intersegmental rotation angle, maximum von Mises stress and strain energy density on the trabecular bone with ExGBF were predicted in extension. When ExGBB was formed in the trabecular bone region, the intersegmental rotation angle slightly decreased with additional bone formation. However, the stress and strain energy density on the trabecular bone region decreased until ExGBB reached the peripheral cortical margin. The results offer a rationale supporting the hypothesis that mechanical stimuli influence ExGBF. ExGBF was helpful in increasing the stability of the motion segment and decreasing the fracture risk of trabecular bones, even in cases in which ExGBB was not formed. ExGBB can be classified as either soft or hard bridging based on a biomechanical point of view.

Epidemiology of C5 Palsy after Cervical Spine Surgery: A 21-Center Study.

OBJECTIVE: C5 palsy is a severe complication after cervical spine surgery, the pathophysiology of which remains unclear. This multicenter study investigated the incidence of C5 palsy following cervical spine surgery in Korea. METHODS: We conducted a retrospective multicenter study involving 21 centers from the Korean Cervical Spine Study Group. The inclusion criteria were cervical spine surgery patients between 2012 and 2016, excluding cases of neck surgery. In patients with C5 palsy, the operative methods, disease category, onset time of C5 palsy, recovery time, C5 manual muscle testing (MMT) grade, and post-C5 palsy management were analyzed. RESULTS: We collected 15,097 cervical spine surgery cases from 21 centers. C5 palsy occurred in 88 cases (0.58%). C5 palsy was more common in male patients (p=0.019) and after posterior approach procedures (p<0.001). C5 palsy usually occurred within 3 days after surgery (77 of 88, 87.5%) and most C5 palsy patients recovered within 6 months (51 of 88, 57.95%). Thirty C5 palsy patients (34.09%) had motor weakness, with an MMT grade≤2. Only four C5 palsy patients (4.5%) did not recover during follow-up. Posterior cervical foraminotomy was performed in 7 cases (7.95%), and steroids were used in 56 cases (63.63%). Twenty-six cases (29.55%) underwent close observation only. CONCLUSION: The overall incidence of C5 palsy was relatively low (0.58%). C5 palsy was more common after posterior cervical surgery and in male patients. C5 palsy usually developed within 3 days after surgery, and more than half of patients with C5 palsy recovered within 6 months.

Epidemiology of Iatrogenic Vertebral Artery Injury in Cervical Spine Surgery: 21 Multicenter Studies.

BACKGROUND: The overall incidence of iatrogenic vertebral artery injury (IVAI) in cervical spine surgeries (CSSs) is reported to be 0.07%-1.4%. Although IVAI occurred during C1-2 fusion, there is no accurate information regarding the surgery-specific risk of IVAI. This study aimed to stratify incidence of IVAI by surgical method and evaluate the correlation between IVAI and its sequelae. METHODS: This retrospective, multicenter study involved clinical and radiologic evaluations for IVAI. All CSSs performed between 2012 and 2016 were included; neck mass excision and pain intervention were excluded. Patient characteristics, diagnosis, surgical technique, complications, and presence of IVAI were collected. In IVAI cases, technique details, characteristics, and sequelae were investigated. RESULTS: This study included 14,722 patients with 15,582 CSSs in 21 centers. IVAIs were identified in 13 (0.08%) patients. Surgery-specific incidence of IVAI was 1.35% in cases involving C1-2 posterior fixation and 0.20% in cases involving C3-6 posterior fixation. Common injury mechanisms were screw-in (31%) and high-speed drilling (23%). Screw-related IVAI occurred in 9 (69%) patients, and IVAI of the C1 lateral mass and C2 pedicle screws occurred in 4 and 3 patients, respectively. Of 13 cases of IVAI, 3 (23%) involved cerebellar or stem infarction; the infarction had no substantial correlation with injury grade or dominancy. CONCLUSIONS: Overall incidence of IVAI in CSSs was 0.08%. C1-2 posterior fixation had the highest incidence of IVAI (1.35%). Although clinical results of IVAI can be highly variable, controlling risk factors of IVAI is important.

Effect of a 12-Week Aerobic Exercise Training on Serum Fetuin-A and Adipocytokine Levels in Type 2 Diabetes.

OBJECTIVE: We aimed to evaluate the effect of 12-week aerobic exercise training on fetuin-A levels in type 2 diabetes mellitus and examine the relationships between fetuin-A and adipocytokine levels and cardiovascular risk factors. METHODS: The study included 32 patients with type 2 diabetes mellitus who were assigned to an exercise or a control group. The exercise group underwent 12 weeks of exercise (consisting of a 5-min warm-up, 60-min aerobic bicycle training performed at 70% of the maximal heart rate, a cool-down period, 5 times/week). Adiponectin, resistin, and fetuin-A serum levels were measured using enzyme-linked immunosorbent assay. Leptin serum levels were measured by a radioimmunoassay. RESULTS: Exercise for 12 weeks significantly reduced serum fetuin-A (643.1±109.4 to 448.7±92.5 µg/mL, P<0.05), leptin (11.9±7.2 to 8.6±5.7 ng/dL, P<0.05), and resistin (3.2±1.5 to 2.2±1.4 ng/mL, P<0.05) levels, but increased adiponectin (6.9±1.9 to 8.1±1.7 µg/mL, P<0.05) levels. In the exercise group, Δfetuin-A positively correlated with differences in weight (r=0.654, P=0.046), body mass index (r=0.725, P=0.002), waist circumference (r=0.898, P=0.013), and adiponectin levels (r=0.662, P=0.035). CONCLUSIONS: Aerobic exercise significantly decreased serum fetuin-A levels in type 2 diabetes mellitus, which can be attributed to weight loss and related to increased adiponectin levels.

mTOR inhibition sensitizes ONC201-induced anti-colorectal cancer cell activity.

We here tested the anti-colorectal cancer (CRC) activity by a first-in-class small molecule TRAIL inducer ONC201. The potential effect of mTOR on ONC201's actions was also examined. ONC201 induced moderate cytotoxicity against CRC cell lines (HT-29, HCT-116 and DLD-1) and primary human CRC cells. Significantly, AZD-8055, a mTOR kinase inhibitor, sensitized ONC201-induced cytotoxicity in CRC cells. Meanwhile, ONC201-induced TRAIL/death receptor-5 (DR-5) expression, caspase-8 activation and CRC cell apoptosis were also potentiated with AZD-8055 co-treatment. Reversely, TRAIL sequestering antibody RIK-2 or the caspase-8 specific inhibitor z-IETD-fmk attenuated AZD-8055 plus ONC201-induced CRC cell death. Further, mTOR kinase-dead mutation (Asp-2338-Ala) or shRNA knockdown significantly sensitized ONC201's activity in CRC cells, leading to profound cell death and apoptosis. On the other hand, expression of a constitutively-active S6K1 (T389E) attenuated ONC201-induced CRC cell apoptosis. For the mechanism study, we showed that ONC201 blocked Akt, but only slightly inhibited mTOR in CRC cells. Co-treatment with AZD-8055 also concurrently blocked mTOR activation. These results suggest that mTOR could be a primary resistance factor of ONC201 in CRC cells.

Effect of mechanical loading on heterotopic ossification in cervical total disc replacement: a three-dimensional finite element analysis.

The development of heterotopic ossification (HO) is considered one of the major complications following cervical total disc replacement (TDR). Even though previous studies have identified clinical and biomechanical conditions that may stimulate HO, the mechanism of HO formation has not been fully elucidated. The objective of this study is to investigate whether mechanical loading is a biomechanical condition that plays a substantial role to decide the HO formation. A finite element model of TDR on the C5-C6 was developed, and HO formation was predicted by simulating a bone adaptation process under various physiological mechanical loadings. The distributions of strain energy on vertebrae were assessed after HO formation. For the compressive force, most of the HO formation occurred on the vertebral endplates uncovered by the implant footplate which was similar to the Type 1 HO. For the anteriorly directed shear force, the HO was predominantly formed in the anterior parts of both the upper and lower vertebrae as the Type 2 HO. For both the flexion and extension moments, the HO shapes were similar to those for the shear force. The total strain energy was reduced after HO formation for all loading conditions. Two distinct types of HO were predicted based on mechanically induced bone adaptation processes, and our findings were consistent with those of previous clinical studies. HO formation might have a role in compensating for the non-uniform strain energy distribution which is one of the mechanical parameters related to the bone remodeling after cervical TDR.

PGC-1α may associated with the anti-obesity effect of taurine on rats induced by arcuate nucleus lesion.

OBJECTIVE: To observe the effect of taurine treatment in rats with monosodium glutamate (MSG)-induced obesity. METHODS: Rats with MSG-induced obesity were administered taurine for five weeks. The Lee's index, food intake, blood pressure, body temperature, body mass index (BMI), fat weight, and triglyceride (TG), low density lipoprotein (LDL), and high density lipoprotein (HDL) levels were compared. The PGC-1α expression levels in white and brown adipose were measured using reverse transcription polymerase chain reaction and western blotting, and pathological changes in the arcuate nucleus and liver were examined. RESULTS: Compared with the model group, BMI, TG, and LDL in the high and low taurine dose groups were significantly lower, while HDL was higher. Body temperature in the taurine treatment groups was higher, and blood pressure was lower. The weight of brown fat in the taurine treatment groups was significantly higher than in the model group, while the white fat weight was significantly lower. Compared with the control group, the PGC-1α levels in white and brown adipose were higher in the taurine treatment groups and more significantly up-regulated in brown adipose. DISCUSSION: This study suggests that taurine prevents obesity in MSG-treated rats and may be closely associated with energy metabolism.