Integration of statistical shape modeling and alternating interpolation-based model tracking technique for measuring knee kinematics in vivo using clinical interleaved bi-plane fluoroscopy.

Background: A 2D fluoroscopy/3D model-based registration with statistical shape modeling (SSM)-reconstructed subject-specific bone models will help reduce radiation exposure for 3D kinematic measurements of the knee using clinical alternating bi-plane fluoroscopy systems. The current study aimed to develop such an approach and evaluate in vivo its accuracy and identify the effects of the accuracy of SSM models on the kinematic measurements. Methods: An alternating interpolation-based model tracking (AIMT) approach with SSM-reconstructed subject-specific bone models was used for measuring 3D knee kinematics from dynamic alternating bi-plane fluoroscopy images. A two-phase optimization scheme was used to reconstruct subject-specific knee models from a CT-based SSM database of 60 knees using one, two, or three pairs of fluoroscopy images. Using the CT-reconstructed model as a benchmark, the performance of the AIMT with SSM-reconstructed models in measuring bone and joint kinematics during dynamic activity was evaluated in terms of mean target registration errors (mmTRE) for registered bone poses and the mean absolute differences (MAD) for each motion component of the joint poses. Results: The mmTRE of the femur and tibia for one image pair were significantly greater than those for two and three image pairs without significant differences between two and three image pairs. The MAD was 1.16 to 1.22° for rotations and 1.18 to 1.22 mm for translations using one image pair. The corresponding values for two and three image pairs were 0.75 to 0.89° and 0.75 to 0.79 mm; and 0.57 to 0.79° and 0.6 to 0.69 mm, respectively. The MAD values for one image pair were significantly greater than those for two and three image pairs without significant differences between two and three image pairs. Conclusions: An AIMT approach with SSM-reconstructed models was developed, enabling the registration of interleaved fluoroscopy images and SSM-reconstructed models from more than one asynchronous fluoroscopy image pair. This new approach had sub-millimeter and sub-degree measurement accuracy when using more than one image pair, comparable to the accuracy of CT-based methods. This approach will be helpful for future kinematic measurements of the knee with reduced radiation exposure using 3D fluoroscopy with clinically alternating bi-plane fluoroscopy systems.

Collagen-binding peptides for the enhanced imaging, lubrication and regeneration of osteoarthritic articular cartilage.

Treatments for osteoarthritis would benefit from the enhanced visualization of injured articular cartilage and from the targeted delivery of disease-modifying drugs to it. Here, by using ex vivo human osteoarthritic cartilage and live rats and minipigs with induced osteoarthritis, we report the application of collagen-binding peptides, identified via phage display, that are home to osteoarthritic cartilage and that can be detected via magnetic resonance imaging when conjugated with a superparamagnetic iron oxide. Compared with the use of peptides with a scrambled sequence, hyaluronic acid conjugated with the collagen-binding peptides displayed enhanced retention in osteoarthritic cartilage and better lubricated human osteoarthritic tissue ex vivo. Mesenchymal stromal cells encapsulated in the modified hyaluronic acid and injected intra-articularly in rats showed enhanced homing to osteoarthritic tissue and improved its regeneration. Molecular docking revealed WXPXW as the consensus motif that binds to the α1 chain of collagen type XII. Peptides that specifically bind to osteoarthritic tissue may aid the diagnosis and treatment of osteoarthritic joints.

Cre/LoxP Genetic Recombination Sustains Cartilage Anabolic Factor Expression in Hyaluronan Encapsulated MSCs Alleviates Intervertebral Disc Degeneration.

(1) Background: Inexplicable low back and neck pain frequently results from spinal disc degeneration with an imbalanced intervertebral disc (IVD) cell homeostasis. We hypothesize that introducing MSC expressing a sustained cartilage-anabolic factor in the IVD may stimulate the mucoid materials secreted from the IVD cells, promote the MSC's chondrogenesis and maintain the hydration content providing mechanical strength to decelerate the disc degeneration progression; (2) Methods: This study expressed a cartilage-anabolic factor runx1 by a baculoviral vector (BV) transduced MSCs through a Cre/LoxP gene editing and recombination system for sustained recombinant runx1 transcription factor production. The Cre/LoxP BV modified MSCs were encapsulated by hyaluronan hydrogel, due to its' vital composition in ECM of a healthy disc and transplanted to a punctured coccygeal disc in rats through micro-injection, followed by X-ray radiography and histological analysis at the 4- and 12-weeks post-transplantation; (3) Results: Data reveals the Cre/LoxP BV system-mediated long-termed runx1 gene expression, possessing good biosafety characteristics in the in vitro cell transduction and in vivo MSCs transplantation, and maintained superior hydration content in the disc than that of mock transduced MSCs; (4) Conclusions: This proof-of-concept study fulfills the need of implanting therapeutic cells accompanied with microinjection in the disc, such as a discography and paves a road to manufacture composite hyaluronan, such as peptide modified hyaluronan as an MSC carrier for IVD regeneration in the future study.

Makoplasty medial unicondylar knee replacement: Correction or postoperative angle matters?

INTRODUCTION: Various considerations prevail around optimal postoperative varus deformity, correction angle and physiological constitutional varus deformity. The goal of our present study was to understand correlation between these parameters and their influence over Western Ontario McMaster University Osteoarthritis Index scale (WOMAC). MATERIALS AND METHODS: Consecutive robotic-arm-assisted medial onlay fixed bearing unicompartmental knee arthroplasty (UKA) in 143 knees studied. WOMAC score was recorded preoperatively and at specific intervals after surgery for consecutive 2 years. RESULTS: Mean preoperative and postoperative varus deformities were 10.2° and 4.8°, respectively, and mean correction angle was 5.4°. The preoperative varus and correction angles were found well correlated (r = 0.815). The amount of improvement in the WOMAC total score was not influenced by the postoperative varus angle. CONCLUSION: The correction angle has a stronger correlation with preoperative varus deformity, and postoperative varus deformity does not imply favourable clinical outcomes.

Three-Dimensional Subject-Specific Knee Shape Reconstruction with Asynchronous Fluoroscopy Images Using Statistical Shape Modeling.

Background and objectives: Statistical shape modeling (SSM) based on computerized tomography (CT) datasets has enabled reasonably accurate reconstructions of subject-specific 3D bone morphology from one or two synchronous radiographs for clinical applications. Increasing the number of radiographic images may increase the reconstruction accuracy, but errors related to the temporal and spatial asynchronization of clinical alternating bi-plane fluoroscopy may also increase. The current study aimed to develop a new approach for subject-specific 3D knee shape reconstruction from multiple asynchronous fluoroscopy images from 2, 4, and 6 X-ray detector views using a CT-based SSM model; and to determine the optimum number of planar images for best accuracy via computer simulations and in vivo experiments. Methods: A CT-based SSM model of the knee was established from 60 training models in a healthy young Chinese male population. A new two-phase optimization approach for 3D subject-specific model reconstruction from multiple asynchronous clinical fluoroscopy images using the SSM was developed, and its performance was evaluated via computer simulation and in vivo experiments using one, two and three image pairs from an alternating bi-plane fluoroscope. Results: The computer simulation showed that subject-specific 3D shape reconstruction using three image pairs had the best accuracy with RMSE of 0.52 ± 0.09 and 0.63 ± 0.085 mm for the femur and tibia, respectively. The corresponding values for the in vivo study were 0.64 ± 0.084 and 0.69 ± 0.069 mm, respectively, which was significantly better than those using one image pair (0.81 ± 0.126 and 0.83 ± 0.108 mm). No significant differences existed between using two and three image pairs. Conclusion: A new two-phase optimization approach was developed for SSM-based 3D subject-specific knee model reconstructions using more than one asynchronous fluoroscopy image pair from widely available alternating bi-plane fluoroscopy systems in clinical settings. A CT-based SSM model of the knee was also developed for a healthy young Chinese male population. The new approach was found to have high mode reconstruction accuracy, and those for both two and three image pairs were much better than for a single image pair. Thus, two image pairs may be used when considering computational costs and radiation dosage. The new approach will be useful for generating patient-specific knee models for clinical applications using multiple asynchronous images from alternating bi-plane fluoroscopy widely available in clinical settings. The current SSM model will serve as a basis for further inclusion of training models with a wider range of sizes and morphological features for broader applications.

Accuracy of robot-assisted versus conventional freehand pedicle screw placement in spine surgery: a systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis investigated differences in accuracy, operation time, and radiation exposure time between robot-assisted and freehand techniques for pedicle screw insertion. Two investigators independently searched for articles on randomized controlled trials (RCTs) published from 2012 to 2019. The final meta-analysis included seven RCTs. We compared the accuracy of pedicle screw placement, operation time, and radiation exposure time between robot-assisted and conventional freehand groups. Seven RCTs included 540 patients and placement of 2,476 pedicle screws, of which 1,220 were inserted using the robot-assisted technique and 1,256 were inserted using the conventional freehand technique. The pedicle screw positions were classified using the Gertzbein and Robbins classification (grade A-E). The combined results of Grade A [odds ratio (OR) =1.68; 95% confidence intervals (CI): 0.82-3.44; P=0.16), Grade A+B (OR =1.70; 95% CI: 0.47-6.13; P=0.42), and Grade C+D+E (OR =0.59; 95% CI: 0.16-2.12; P=0.42) for the accuracy rate revealed no significant difference between the two groups. Subgroup analysis results revealed that the TiRobot-assisted technique presented a significantly improved pedicle screw insertion accuracy rate compared with that of the conventional freehand technique, based on Grade A, Grade A+B, and Grade C+D+E classifications. The SpineAssist-assisted technique presented an inferior pedicle screw insertion accuracy rate compared with that of the conventional freehand technique, based on Grade A, Grade A+B, and Grade C+D+E classifications. No difference between the Renaissance-assisted and conventional freehand techniques was noted for pedicle screw insertion accuracy rates, based on both Grade A (OR =1.58; 95% CI: 0.85-2.96; P=0.15), Grade A+B (OR =2.20; 95% CI: 0.39-12.43; P=0.37), and Grade C+D+E (OR =0.45; 95% CI: 0.08-2.56; P=0.37) classifications. Regarding operation time, robot-assisted surgery had significantly longer operation time than conventional freehand surgery. The robot-assisted group had significantly shorter radiation exposure time. Regarding the pedicle screw insertion accuracy rate, the TiRobot-assisted technique was superior, the SpineAssist-assisted technique was inferior, and Renaissance was similar to the conventional freehand technique.

Epidemiology of fatal/non-fatal suicide among patients with chronic osteomyelitis (COM): a nationwide population-based study.

OBJECTIVE: Chronic osteomyelitis (COM) can induce systemic inflammation, and systemic inflammation may be associated with suicide tendency. However, no studies have investigated the correlation between COM and suicide tendency. METHODS: The aim of this population-based study was to determine the epidemiology of fatal/non-fatal suicide among COM patients. Subjects with at least two outpatient visits or one course of inpatient care diagnosed with COM were recruited into a COM cohort. The control/COM subject ratio was approximately 4:1 matched by age, sex, major depression coding and index year (COM patients). Subjects with suicide attempts before COM diagnosis and subjects aged <20 years were excluded. RESULTS: COM patients had 1.93 (95% confidence interval [CI]: 1.11-3.36) times the risk of fatal/non-fatal suicide as control subjects. Considering death as the competing event of fatal/non-fatal suicide, COM patients had 1.76 (95% CI: 1.03-3.01) times the risk of fatal/non-fatal suicide (competing risk regression model). The effect of COM on fatal/non-fatal suicide was more prominent among diabetic patients. COM severity also correlated with the risk of fatal/non-fatal suicide. CONCLUSIONS: More attention must be paid to suicide tendency among COM patients.

Corrigendum to "The Epidemiology of Hip Fracture among Subjects with Pyogenic Liver Abscess (PLA): A Nationwide Population-Based Study".

[This corrects the article DOI: 10.1155/2020/5901962.].

A combination of bimalleolar fracture and fracture on talar body and neck: A rare case report.

RATIONALE: Talar fracture accompanied with malleolar fracture is rare, and its management is complex. Ankle soft tissue is much thinner than other parts of the human body, and the shape of the ankle makes wounds difficult to close immediately after surgery, which may result in poor skin condition if the wound tension is too high. However, joint congruity and osteonecrosis are the main concerns of talar fracture. PATIENT CONCERNS: A 57-year-old man presented at the emergency department following a motorcycle accident. DIAGNOSES: Physical examination revealed swelling and tenderness of the left ankle and midfoot. The patient had comminuted talar fracture and was indicated for dual-screw fixation or even plate with screw fixation. INTERVENTIONS: We performed single screw fixation after assessing the soft tissue condition and employed a technique of using continuous longitudinal force to bring together fracture fragments (ankle ligamentotaxis) during surgery. Open reduction with a mini-hook plate and tension band wire was used for bimalleolar fracture repair using the combined anteromedial and anterolateral approach with extension of the incision. Kirschner wire for temporary fixation was performed using ligamentotaxis, and a 2.4 headless screw was inserted from the posteromedial to the anterolateral direction. OUTCOMES: The patient was discharged with a standard short leg splint and was instructed not to bear weight on the affected ankle for 2 months. The patient walked well without discomfort, and the Hawkins sign was clearly visible. Single screw fixation preserves the integrity of the talus bone as minimal space is used for this operative technique. Single screw fixation preserves more bony stock when most of the internal fixator is located within the bone. Additionally, surgery time is shorter than multiple implantations even when performing the same procedure; as a result, there was less ankle soft tissue swelling. LESSONS: This case provides evidence of using the single screw fixation technique for addressing both malleolar and talar fractures, and that talar fracture management can be less aggressive with limited weight bearing and initial limited range of motion given the presence of malleolar fracture. The alignment and stability of bony fragments also benefit from ankle ligamentotaxis.

The Epidemiology of Hip Fracture among Subjects with Pyogenic Liver Abscess (PLA): A Nationwide Population-Based Study.

Pyogenic liver abscess (PLA) is a potentially fatal disease that can stimulate prominent systemic inflammation. Osteoporotic hip fracture is a major complication of systemic inflammation. This study tried to determine the epidemiology of hip fractures among PLA patients. All subjects admitted due to PLA during 1999∼2010 were assessed, excluding the subjects with a history of high energy trauma, malignancy, and previous hip fracture. We matched the control subjects to PLA patients according to age, gender, and the coding of osteoporosis by 1 : 4 ratio. The PLA patients had a 1.17-fold risk of hip fracture than the controls (aHR = 1.17, 95% CI = 1.07-1.29) after adjusting for gender, age, and comorbidities. Considering death as the competing event of suicide, the PLA patients had 1.10-fold suicide risk (aHR = 1.10, 95% CI: 1.00-1.21) than the control subjects under the competing risks regression model. The cumulative incidence of hip fracture was higher in the PLA cohort (log-rank test, p < 0.001). When compared to the controls, the fracture risk was 18.4-fold (aHR = 18.4, 95% CI = 13.0-26.1) for the PLA patients admitted 2-3 times per year and 46.0-fold (aHR = 46.0, 95% CI = 31.2-67.8) for the PLA patients admitted ≧4 times per year. The impact of PLA is more prominent among the subjects aged <45 years (aHR = 2.81, 95% CI = 1.42-5.56). Preventive measures for hip fracture might be warranted for PLA patients.

3D Real-Time Image-Guided Navigation Spine Corpectomy with Ultrasonic Bone Cutter: Technical Note.

BACKGROUND: Surgical interventions for congenital scoliosis are challenging for spine surgeons. The coordination of 3-dimensional (3D), real-time, image-guided navigation with an ultrasonic bone cutter allows surgeons to localize the affected area of the spine accurately and remove the lesion without damaging soft tissue structures. The goal of this technical paper is to report a previously undescribed method of hemivertebrectomy that combines 3D, real-time, image-guided navigation and an ultrasonic bone cutter. We highlight the feasibility and safety of this method in spinal surgery. METHODS: Three patients with congenital scoliosis were treated with this technique. We present three illustrative cases comprising hemivertebrectomies for congenital scoliosis. Intraoperative photos demonstrating the technique are also provided. RESULTS: All surgeries were completed without complications. The hemivertebrae were completely removed, and marked correction of congenital scoliosis was noted. CONCLUSIONS: We believe that the combination of 3D, real-time image navigation and an ultrasonic bone cutter improves hemivertebrectomy by increasing accuracy and avoiding dura laceration, major organ damage, or potential vessel damage.

The Accuracy of 3D Printing Assistance in the Spinal Deformity Surgery.

BACKGROUND: The pedicle screw is one of the main tools used in spinal deformity correction surgery. Robotic and navigated surgeries are usually used, and they provide superior accuracy in pedicle screw placement than free-hand and fluoroscopy-guided techniques. However, their high cost and space limitation are problematic. We provide a new solution using 3D printing technology to facilitate spinal deformity surgery. METHODS: A workflow was developed to assist spinal deformity surgery using 3D printing technology. The trajectory and profile of pedicle screws were determined on the image system by the surgical team. The engineering team designed drill templates based on the bony surface anatomy and the trajectory of pedicle screws. Their effectiveness and safety were evaluated during a preoperative simulation surgery. The surgery consisted in making a pilot hole through the drill template on a computed tomography- (CT-) based, full-scale 3D spine model for every planned segment. Somatosensory evoke potential (SSEP) and motor evoke potential (MEP) were used for intraoperative neurophysiological monitoring. Postoperative CT was obtained 6 months after the correction surgery to confirm the screw accuracy. RESULTS: From July 2015 to November 2016, we performed 10 spinal deformity surgeries with 3D printing technology assistance. In total, 173 pedicle screws were implanted using drill templates. No notable change in SSEP and MEP or neurologic deficit was noted. Based on postoperative CT scans, the acceptable rate was 97.1% (168/173). We recorded twelve pedicle screws with medial breach, six with lateral breach, and five with inferior breach. Medial breach (12/23) was the main type of penetration. Lateral breach occurred mostly in the concave side (5/6). Most penetrations occurred above the T8 level (69.6%, 16/23). CONCLUSION: 3D printing technology provides an effective alternative for spinal deformity surgery when expensive medical equipment, such as intraoperative navigation and robotic systems, is unavailable.

TGF-ß1 enhances FOXO3 expression in human synovial fibroblasts by inhibiting miR-92a through AMPK and p38 pathways.

Osteoarthritis (OA) is an age-related disease marked by synovial inflammation and cartilage destruction arising from synovitis, joint swelling and pain. OA therapy that targets the synovium is a promising strategy for mitigating the symptoms and disease progression. Altered activity of the transforming growth factor-ß1 isoform (TGF-ß1) during aging underlies OA progression. Notably, aberrant forkhead box class O 3 (FOXO3) activity is implicated in the pathogenesis of various age-related diseases, including OA. This study explored the interaction and cross-talk of TGF-ß1 and FOXO3 in human osteoarthritis synovial fibroblasts (OASFs). TGF-ß1 stimulated FOXO3 synthesis in OASFs, which was mitigated by blocking adenosine monophosphate-activated protein kinase (AMPK) and p38 activity. TGF-ß1 also inhibited the expression of miR-92a, which suppresses FOXO3 transcription. The suppression of miR-92a was effectively reversed with the blockade of the AMPK and p38 pathways. Our study showed that TGF-ß1 promotes anti-inflammatory FOXO3 expression by stimulating the phosphorylation of AMPK and p38 and suppressing the downstream expression of miR-92a. These results may help to clarify OA pathogenesis and lead to better targeted treatment.

New Strategy for Minimally Invasive Endoscopic Surgery to Treat Infectious Spondylodiscitis in the Thoracolumbar Spine.

BACKGROUND: Eradicating infection, protecting neurologic function, and maintaining structural alignment are the 3 objectives of treatment for infectious spondylodiscitis. For some patients, surgery may be necessary to achieve these goals; however, open surgeries are associated with high morbidity and mortality in elderly patients and those with multiple comorbidities. Endoscopic surgery provides a minimally invasive surgical option for obtaining a culture sample to aid identification of pathogens, while also providing a route for adequate decompression and drainage. The clinical results of this study were analyzed. OBJECTIVES: To evaluate the efficacy and safety of spinal endoscopic surgery, the basic characteristics of patients analyzed and their inflammatory markers, pain levels, and local kyphotic angles were recorded before surgery and at regular intervals after surgery. The patients' cultured pathogens and previous antibiotic treatments were also recorded and analyzed. STUDY DESIGN: Retrospective observational study (institutional review board: CMUH 105-REC2-101). SETTING: Inpatient surgery center. METHODS: From October 2006 to March 2017, of 508 patients who received spinal endoscopic surgery, 60 with infectious spondylodiscitis were treated using this new strategy. All 60 patients underwent plain film radiography and enhanced magnetic resonance imaging of the affected region to obtain evidence of infectious spondylodiscitis. The role of a computed tomography-guided biopsy and some indications for open surgery were replaced with endoscopic surgery. RESULTS: All the patients reported rapid pain relief after endoscopic surgery and antibiotic treatment. No significant changes in sagittal alignment were observed in final follow-up radiography images. Causative pathogens were identified in 34 patients (culture rate: 77.27%) without previous antibiotic treatment. The patients' erythrocyte sedimentation rates and C-reactive protein levels had decreased significantly 3 months after endoscopic surgery. Two patients (3.3%) experienced infection relapse following initial endoscopic surgery; both of them were efficiently resolved through a second round of endoscopic surgery. No surgery-related complications were observed and no open spinal surgery was required during the follow-up period. LIMITATIONS: This was a retrospective study; bias was unavoidable because of the single-center nature of the study design. CONCLUSIONS: Regarding the culture rate, recurrence rate, kyphotic change, and surgery-related complications, this new strategy for endoscopic surgery is safe and effective for treating infectious spondylodiscitis in the thoracic or lumbar spine and may be considered a new trend in treating diseases of this type. KEY WORDS: Spine, endoscopic, discectomy, spondylodiscitis, minimally invasive surgery.

A preliminary study of the novel antibiotic-loaded cement computer-aided design-articulating spacer for the treatment of periprosthetic knee infection.

BACKGROUND: In comparison to static spacers, articulating spacers have been shown to result in a similar infection eradication rate in two-stage revision of periprosthetic knee infections. However, the optimal construct for articulating spacers has not been identified yet. The aim of this study was to present a preliminary result of treatment for periprosthetic knee infection using a novel computer-aided design (CAD)-articulating spacer. METHODS: We retrospectively reviewed 32 consecutive cases of chronic periprosthetic knee infection occurring from January 2015 to December 2015. In these cases, we used an antibiotic-loaded, optimized CAD-articulating spacer based on the retrieved knee prosthesis. Evaluation included infection eradication rate, the Hospital of Special Surgery (HSS) knee score, range of motion (ROM), and spacer-related mechanical complications. All cases were regularly followed-up for 2 years minimum. RESULTS: Twenty-eight of 32 patients (87.5%) had infection eradication; 18 patients (56.3%) received reimplantation successfully. The mean interval between spacer insertion and reimplantation was 8.8 months (range 4.0-12.5 months). The mean HSS knee score and ROM significantly increased during each interval (p < 0.0001 for both). The mean HSS knee scores were 31.2 (range 20-48) at initial visit, 65.4 (range 60-78.8) at 1 month after spacer insertion, and 84.2 (range 78-90) at 3 months after reimplantation (p < 0.0001). The mean ROM were 72.0° (range 15-100°), 85.6° (range 35-110°), and 102.0° (range 80-122°), respectively (p = 0.002). Two (6.3%) spacer-related mechanical complications occurred. CONCLUSIONS: The CAD-articulating spacer in two-staged revision of periprosthetic knee infection significantly controlled infection, improved clinical outcomes, increased ROM, and decreased mechanical complications in the preliminary study. Further larger clinical studies are needed to confirm the findings presented here.

Association of Traditional Chinese Medicine Therapy with Risk of Total Hip Replacement in Patients with Nontraumatic Osteonecrosis of the Femoral Head: A Population-Based Cohort Study.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) contributes to 45% of total hip replacements (THRs) annually in Taiwan. Nontraumatic ONFH (NONFH) is multifactorial; no effective Western medicine is available to delay the disease process. This population-based cohort study investigated the association of traditional Chinese medicine (TCM) therapy with risk of THR in patients with NONFH. METHODS: This retrospective study was conducted using claims data from all insured residents covered by the National Health Insurance from 2000 to 2010. We enrolled 1,680 newly diagnosed ONFH patients who had not undergone THR, before or within 6 months after diagnosis of ONFH; these patients did not exhibit hip fracture or dislocation before the endpoint. In total, 595 propensity score-matched pairs were selected from among 1,028 TCM users and 652 non-TCM users. The association between TCM use and risk of THR was analyzed using a Cox proportional hazard model. Kaplan-Meier and log rank tests were performed to plot the cumulative incidence of THR. RESULTS: The mean follow-up periods were 5.00 years and 3.57 years for TCM and non-TCM cohorts, respectively. Compared to the non-TCM cohort, the TCM cohort had fewer patients undergoing THR surgery (25.4% vs. 18.2%, adjusted hazard ratio: 0.60, p<0.0001). The risk of reduction was noted in the group aged 30-59 years (adjusted hazard ratio: 0.56, p<0.0001), but there was no association with gender nor socioeconomic status. There was a significantly lower cumulative incidence of THR in TCM users (p<0.0001). Shu-Jing-Huo-Xue-Tang and Yan Hu Suo were the most frequently prescribed formula and single herb, respectively. CONCLUSIONS: NONFH patients using TCM had a lower risk of THR; the risk of reduction was noted in the group aged 30-59 years but was not associated with gender nor socioeconomic status. TCM might be useful in conservative treatment for NONFH.

Osteochondral Tissue Regeneration Using a Tyramine-Modified Bilayered PLGA Scaffold Combined with Articular Chondrocytes in a Porcine Model.

Repairing damaged articular cartilage is challenging due to the limited regenerative capacity of hyaline cartilage. In this study, we fabricated a bilayered poly (lactic-co-glycolic acid) (PLGA) scaffold with small (200⁻300 µm) and large (200⁻500 µm) pores by salt leaching to stimulate chondrocyte differentiation, cartilage formation, and endochondral ossification. The scaffold surface was treated with tyramine to promote scaffold integration into native tissue. Porcine chondrocytes retained a round shape during differentiation when grown on the small pore size scaffold, and had a fibroblast-like morphology during transdifferentiation in the large pore size scaffold after five days of culture. Tyramine-treated scaffolds with mixed pore sizes seeded with chondrocytes were pressed into three-mm porcine osteochondral defects; tyramine treatment enhanced the adhesion of the small pore size scaffold to osteochondral tissue and increased glycosaminoglycan and collagen type II (Col II) contents, while reducing collagen type X (Col X) production in the cartilage layer. Col X content was higher for scaffolds with a large pore size, which was accompanied by the enhanced generation of subchondral bone. Thus, chondrocytes seeded in tyramine-treated bilayered scaffolds with small and large pores in the upper and lower parts, respectively, can promote osteochondral regeneration and integration for articular cartilage repair.

Continuous Passive Motion Promotes and Maintains Chondrogenesis in Autologous Endothelial Progenitor Cell-Loaded Porous PLGA Scaffolds during Osteochondral Defect Repair in a Rabbit Model.

Continuous passive motion (CPM) is widely used after total knee replacement. In this study, we investigated the effect of CPM combined with cell-based construct-transplantation in osteochondral tissue engineering. We created osteochondral defects (3 mm in diameter and 3 mm in depth) in the medial femoral condyle of 36 knees and randomized them into three groups: ED (empty defect), EPC/PLGA (endothelial progenitor cells (EPCs) seeded in the poly lactic-co-glycolic acid (PLGA) scaffold), or EPC/PLGA/CPM (EPC/PLGA scaffold complemented with CPM starting one day after transplantation). We investigated the effects of CPM and the EPC/PLGA constructs on tissue restoration in weight-bearing sites by histological observation and micro-computed tomography (micro-CT) evaluation 4 and 12 weeks after implantation. After CPM, the EPC/PLGA construct exhibited early osteochondral regeneration and prevention of subchondral bone overgrowth and cartilage degeneration. CPM did not alter the microenvironment created by the construct; it up-regulated the expression of the extracellular matrix components (glycosaminoglycan and collagen), down-regulated bone formation, and induced the biosynthesis of lubricin, which appeared in the EPC/PLGA/CPM group after 12 weeks. CPM can provide promoting signals during osteochondral tissue engineering and achieve a synergistic effect when combined with EPC/PLGA transplantation, so it should be considered a non-invasive treatment to be adopted in clinical practices.

The Incidence and Risk Factors of Hip Fracture after Liver Transplantation (LT): A Nationwide Population-Based Study.

BACKGROUND: Osteoporosis and fragility fracture are the major complications after liver transplantation (LT). The aim of the study was to determine the incidence and risk factors of hip fracture after LT. METHODS: We conducted a retrospective population-based cohort study, enrolling the patients receiving LT between January 1999 and December 2010. Control subjects were randomly matched to every recipient by age and sex by 1 : 10 ratios. RESULTS: During the follow-up period, 17 recipients (0.77%) and 70 (0.32%) control subjects suffered from hip fractures. The incident rates (per 10000 person-years) were 21.49 for recipients and 7.52 for controls (adjusted hazard ratio = 2.71; 95% confidence interval = 1.21-6.05). The cumulative incidence of hip fracture was significantly higher among the recipients (p < 0.0001). Among the recipients, the subjects aged >65 years at transplantation and with pretransplant steroid use are more susceptible to posttransplant hip fracture. Immunosuppressive agents did not significantly affect the risk of hip fracture among recipients. CONCLUSIONS: Liver transplantation is a risk factor for hip fractures. Aged >65 years at transplantation and pretransplant steroid use are risk factors for posttransplant hip fractures among the recipients.

Pro-Inflammatory Stimuli Influence Expression of Intercellular Adhesion Molecule 1 in Human Anulus Fibrosus Cells through FAK/ERK/GSK3 and PKCδ Signaling Pathways.

OBJECTIVE: Intervertebral disc (IVD) degeneration and disc herniation are major causes of lower back pain, which involve the presence of inflammatory mediators and tissue invasion by immune cells. Intercellular adhesion molecule 1 (ICAM1, also termed CD54) is an adhesion molecule that mediates cell-cell interactions, particularly between immune cells and target tissue. The aim of this study was to examine the intracellular signaling pathways involved in inflammatory stimuli-induced ICAM1 expression in human anulus fibrosus (AF) cells. METHODS: Quantitative reverse transcription-polymerase chain reaction (qPCR), western blotting, and flow cytometry were performed to dissect the roles of different signaling pathways in inflammatory stimuli-mediated ICAM1 expression. RESULTS: Using qPCR and western blot analyses, a significant increase in ICAM1 expression was observed in AF cells after stimulation of lipopolysaccharide (LPS) plus interferon-gamma (IFNγ) in a time-dependent manner. Flow cytometry revealed ICAM1 upregulation on the surface of AF cells. Importantly, LPS plus IFNγ treatment also significantly promoted Chemokine ligand (CCL)2 expression, but not CCL3. The enhanced ICAM1 expression was abolished after incubation with antibody against CCL2. In AF cells, treatment with LPS plus IFNγ activated the FAK/ERK/GSK3 signaling pathways, promoted a time-dependent increase in PKCδ phosphorylation, and promoted PKCδ translocation to the nucleus. Treatment with the pharmacological PKCδ inhibitor; rottlerin, effectively blocked the enhanced productions of ICAM1 and CCL2. CONCLUSIONS: Inflammatory stimuli in AF cells are part of a specific pathophysiology in IVD degeneration and disc herniation that modulates CCL2/ICAM1 activation through the FAK/ERK/GSK3 and PKCδ signaling pathways in AF cells.