Interim Use of Antibiotic-Loaded Cement Spacer for Patients with Infected Cervical Fusion.

OBJECTIVE: The management of postoperative deep infection after anterior cervical discectomy and fusion (ACDF) remains challenging for spine surgeons. Our institution uses handmade antibiotic-loaded cement spacers to treat these complex cases. This study aimed to determine the efficacy and feasibility of this treatment. METHODS: This study included 4 patients with deep cervical spine infections after ACDF who underwent our treatment between March 2012 and January 2022. Patients' laboratory data, visual analog scale scores, comorbidities, complications, and neurological status were recorded. Their clinical conditions were also evaluated based on the Neck Disability Index, Japanese Orthopaedic Association score, and Odom criteria. RESULTS: Infection eradication was achieved in all patients after treatment. The average preoperative visual analog scale score was 7.5 (range: 7-8); this decreased to 1.25 (range: 1-2) at 1 year postoperatively. None of the patients experienced severe complications, such as neurological deterioration or bone graft dislodgement. The Neck Disability Index improved from a preoperative value of 54% (range: 48-60%) to 6% (range: 4-8%) at 1 year postoperatively. The Japanese Orthopaedic Association score improved from a preoperative score of 10.25 (range: 10-11)-14.75 (range: 14-16) at 1 year postoperatively. All patients achieved excellent outcomes based on Odom criteria at 1 year postoperatively. CONCLUSIONS: Good clinical outcomes were achieved in this study. Although 2-stage surgery is required, this technique could be an alternative for patients with postoperative deep infection after ACDF.

Surgical reconstructions for adult brachial plexus injuries. Part II: Treatments for total arm type.

Brachial plexus injuries (BPI) contribute not only to physical dysfunction but also to socioeconomic aspects and psychological disability. Patients with total arm-type BPI will lose not only the shoulder and elbow function but also the hand function, making reconstruction particularly challenging. Reconstructive procedures commonly include nerve repair, grafting, neurotization (nerve transfer), tendon transfer and free functional muscle transfer (FFMT). Although it is difficult to achieve prehensile hand function, most of patients with total arm-type BPI can be treated with satisfied outcomes. In addition to surgical techniques, comprehensive rehabilitation is another important factor for successful outcomes, and efficient communication can help to boost patient morale and eliminate uncertainty.

First 100 total hip arthroplasties performed by a young surgeon using the direct anterior approach: learning curve and complications.

INTRODUCTION: Most of the reported discussions about the learning curve for the direct anterior approach (DAA) in total hip arthroplasty (THA) have been by experienced surgeons. The study's aim was to describe the learning curve, short-term outcomes, complications, and adaptations to the DAA used in the first 100 THA cases experienced by a young surgeon who had received DAA training for trauma surgeries. MATERIALS AND METHODS: This retrospective study summarizes the first 100 consecutive cases experienced by a young surgeon who performed the unilateral DAA for THA between 2019 and 2021. Cumulative sum (CUSUM) analysis was performed to evaluate the learning curve on the basis of operative time and overall complications. The demographics data, short-term outcomes, and complications of the first 50 and second 50 cases were compared. RESULTS: The CUSUM curve declined after 49 and 55 cases, measured by operative time and overall complications, respectively. The median operative time (104 vs. 80 min) and intraoperative fluoroscopic time (38 vs. 12 s) increased significantly in the first 50 cases compared with the times in the second 50 cases. Complications tended to occur in the first 50 cases (12% vs. 6%), and the overall rate was 9%. Major complications all occurred in the first 50 cases, with a rate of 4%. Only one case, which involved a complicated periprosthetic fracture around the stem that extended to the tip, required the intervention of a senior surgeon. CONCLUSIONS: Even after receiving training on the DAA for trauma surgeries, the young surgeon experienced a steep learning curve and more complications in the first 50 cases. The DAA for THA is a technically demanding procedure and may require guidance from an experienced surgeon to manage unexpected complications.

Isoliquiritigenin inhibits apoptosis and ameliorates oxidative stress in rheumatoid arthritis chondrocytes through the Nrf2/HO-1-mediated pathway.

Rheumatoid arthritis (RA) is a chronic inflammatory condition known for its irreversible destructive impact on the joints. Chondrocytes play a pivotal role in the production and maintenance of the cartilage matrix. However, the presence of inflammatory cytokines can hinder chondrocyte proliferation and promote apoptosis. Isoliquiritigenin (ISL), a flavonoid, potentially exerts protective effects against various inflammatory diseases. However, its specific role in regulating the nuclear factor E2-associated factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in chondrocytes in RA remains unclear. To investigate this, this study used human chondrocytes and Sprague-Dawley rats to construct in vitro and in vivo RA models, respectively. The study findings reveal that cytokines markedly induced oxidative stress, the activation of matrix metalloproteinases, and apoptosis both in vitro and in vivo. Notably, ISL treatment significantly mitigated these effects. Moreover, Nrf2 or HO-1 inhibitors reversed the protective effects of ISL, attenuated the expression of Nrf2/HO-1 and peroxisome proliferator-activated receptor gamma-coactivator-1α, and promoted chondrocyte apoptosis. This finding indicates that ISL primarily targets the Nrf2/HO-1 pathway in RA chondrocytes. Moreover, ISL treatment led to improved behavior scores, reduced paw thickness, and mitigated joint damage as well as ameliorated oxidative stress in skeletal muscles in an RA rat model. In conclusion, this study highlights the pivotal role of the Nrf2/HO-1 pathway in the protective effects of ISL and demonstrates the potential of ISL as a treatment option for RA.

Cyclic Stability of Locking Plate Augmented with Intramedullary Polymethyl Methacrylate (PMMA) Strut Fixation for Osteoporotic Humeral Fractures: A Biomechanical Study.

The locking plate may provide improved fixation in osteoporotic bone; however, it has been reported to fail due to varus collapse or screw perforation of the articular surface, especially in osteoporotic bone with medial cortex comminution. Using bone graft as an intramedullary strut together with plate fixation may result in a stronger construct. However, the drawbacks of bone grafts include limited supply, high cost, and infection risk. PMMA (so-called bone cement) has been widely used for implant fixation due to its good mechanical properties, fabricability, and biocompatibility. The risk of donor-site infection and the drawbacks of allografting may be overcome by considering PMMA struts as alternatives to fibular grafts for humeral intramedullary grafting surgeries. However, the potential effects of intramedullary PMMA strut on the dynamic behaviour of osteoporotic humerus fractures remain unclear. This study aimed to investigate the influence of an intramedullary PMMA strut on the stability of unstable proximal humeral fractures in an osteoporotic synthetic model. Two fixation techniques, a locking plate alone (non-strut group) and the same fixation augmented with an intramedullary PMMA strut (with-strut group), were cyclically tested in 20 artificial humeral models. Axially cyclic testing was performed to 450 N for 10,000 cycles, intercyclic motion, cumulated fragment migration, and residual deformation of the constructs were determined at periodic cyclic intervals, and the groups were compared. Results showed that adding an intramedullary PMMA strut could decrease 1.6 times intercyclic motion, 2 times cumulated fracture gap migration, and 1.8 times residual deformation from non-strut fixation. During cycling, neither screw pull-out, cut-through, nor implant failure was observed in the strut-augmented group. We concluded that the plate-strut mechanism could enhance the cyclic stability of the fixation and minimize the residual displacement of the fragment in treating osteoporotic proximal humeral unstable fractures. The PMMA strut has the potential to substitute donor bone and serve as an intramedullary support when used in combination with locking plate fixation. The intramedullary support with bone cement can be considered a solution in the treatment of osteoporotic proximal humeral fractures, especially when there is medial comminution.

Long-Term Use of Immunosuppressive Agents Increased the Risk of Fractures in Patients with Autoimmune Diseases: An 18-Year Population-Based Cohort Study.

The risk of fractures is higher in patients with autoimmune diseases, but it is not clear whether the use of immunosuppressive agents can further increase this risk. To investigate this issue, a retrospective study was conducted using data from Taiwan's National Health Insurance Research Database. Patients diagnosed with autoimmune diseases between 2000 and 2014, including psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, and systemic lupus erythematosus, were included in the study. A control group of patients without autoimmune diseases was selected from the same database during the same period. Patients with autoimmune diseases were divided into two sub-cohorts based on their use of immunosuppressive agents. This study found the risk of fractures was 1.14 times higher in patients with autoimmune diseases than in those without. Moreover, we found that patients in the immunosuppressant sub-cohort had a higher risk of fractures compared to those in the non-immunosuppressant sub-cohort. The adjusted sub-distribution hazard ratio for shoulder fractures was 1.27 (95% CI = 1.01-1.58), for spine fractures was 1.43 (95% CI = 1.26-1.62), for wrist fractures was 0.95 (95% CI = 0.75-1.22), and for hip fractures was 1.67 (95% CI = 1.38-2.03). In conclusion, the long-term use of immunosuppressive agents in patients with autoimmune diseases may increase the risk of fractures.

Comorbidity of cardiorespiratory and locomotor dysfunction following cervical spinal cord injury in the rat.

Cervical spinal cord injury interrupts supraspinal pathways innervating thoracic sympathetic preganglionic neurons and results in cardiovascular dysfunction. Both respiratory and locomotor functions were also impaired due to damages of motoneuron pools controlling respiratory and forelimb muscles, respectively. However, no study has investigated autonomic and somatic motor functions in the same animal model. The present study aimed to establish a cervical spinal cord injury model to evaluate cardiorespiratory response and locomotor activity in unanesthetized rats. Cardiovascular response and respiratory behavior following laminectomy or cervical spinal contusion were measured using noninvasive blood pressure analyzer and plethysmography systems, respectively. Locomotor activity was evaluated by an open-field test and a locomotor rating scale. The results demonstrated that mean arterial blood pressure and heart rate were significantly reduced in contused rats compared with uninjured rats at the acute injured stage. Tidal volume was also significantly reduced during the acute and subchronic stages. Moreover, locomotor function was severely impaired, evidenced by decreasing moving ability and locomotor rating scores from the acute to chronic injured stages. Retrograde neurotracer results revealed that cervical spinal cord injury caused a reduction in number of phrenic and triceps motoneurons. Immunofluorescence staining revealed a significant attenuation of serotonergic, noradrenergic, glutamatergic, and GABAergic fibers innervating the thoracic sympathetic preganglionic neurons in chronically contused rats. These results revealed the pathological mechanism underlying the comorbidity of cardiorespiratory and locomotor dysfunction following cervical spinal cord injury. We proposed that this animal model can be used to evaluate the therapeutic efficacy of potential strategies to improve different physiological functions.NEW & NOTEWORTHY The present study establishes a preclinical rodent model to comprehensively investigate physiological functions under unanesthetized condition following cervical spinal cord contusion. The results demonstrated that cervical spinal cord contusion is associated with impairments in cardiovascular, respiratory, and locomotor function. Respiratory and forelimb motoneurons and neurochemical innervations of sympathetic preganglionic neurons were damaged following injury. This animal model can be used to evaluate the therapeutic efficacy of potential strategies to improve different physiological functions.

Influence of Simulated State of Disc Degeneration and Axial Stiffness of Coupler in a Hybrid Performance Stabilisation System on the Biomechanics of a Spine Segment Model.

Spinal fusion surgery leads to the restriction of mobility in the vertebral segments postoperatively, thereby causing stress to rise at the adjacent levels, resulting in early degeneration and a high risk of adjacent vertebral fractures. Thus, to address this issue, non-fusion surgery applies some pedicle screw-based dynamic stabilisation systems to provide stability and micromotion, thereby reducing stress in the fusion segments. Among these systems, the hybrid performance stabilisation system (HPSS) combines a rigid rod, transfer screw, and coupler design to offer a semi-rigid fixation method that preserves some mobility near the fusion site and reduces the adjacent segment compensatory effects. However, further research and confirmation are needed regarding the biomechanical effects of the dynamic coupler stiffness of the HPSS on the intrinsic degenerated adjacent segment. Therefore, this study utilised the finite element method to investigate the impact of the coupler stiffness of the HPSS on the mobility of the lumbar vertebral segments and the stress distribution in the intervertebral discs under flexion, extension, and lateral bending, as well as the clinical applicability of the HPSS on the discs with intrinsic moderate and severe degeneration at the adjacent level. The analytical results indicated that, regardless of the degree of disc degeneration, the use of a dynamic coupler stiffness of 57 N/mm in the HPSS may reduce the stress concentrations at the adjacent levels. However, for severely degenerated discs, the postoperative stress on the adjacent segments with the HPSS was still higher compared with that of the discs with moderate degeneration. We conclude that, when the discs had moderate degeneration, increasing the coupler stiffness led to a decrease in disc mobility. In the case of severe disc degeneration, the effect on disc mobility by coupler stiffness was less pronounced. Increasing the coupler stiffness ked to higher stress on intervertebral discs with moderate degeneration, while its effect on stress was less pronounced for discs with severe degeneration. It is recommended that patients with severe degeneration who undergo spinal dynamic stabilisation should remain mindful of the risk of accelerated adjacent segment degeneration.

Prespinal Versus Conventional Hemicontralateral C7 Nerve Transfer in the Treatment of Total Brachial Plexus Roots Avulsion Injuries: A Retrospective Study With a Minimum Follow-Up Period of 4 Years.

PURPOSE: Contralateral C7 (CC7)-to-median nerve transfer has been commonly used to restore hand function in brachial plexus injury. To shorten the nerve graft, the prespinal route was described and achieved direct coaptation when combined with humeral shortening osteotomy. The limb was positioned at 0° shoulder abduction and neutral head position. Given our concern about donor-site morbidity when harvesting the whole CC7 nerve and tension across the neurorrhaphy site after mobilization, we aimed to describe our modified prespinal route and compare its outcomes and complications with the conventional hemi-CC7 transfer. METHODS: From 2004 to 2014, 39 patients with preganglionic total brachial plexus root avulsion injuries, with a minimum of 4 years of follow-up, were included. Overall, 20 and 19 patients underwent the conventional hemi-CC7-to-median nerve and hemi-CC7-to-lower trunk (LT) transfer through the modified prespinal route, respectively. The modified prespinal route was combined with bilateral clavicle shortening osteotomy to achieve direct coaptation to the LT at 45° shoulder abduction. RESULTS: The modified prespinal route showed the median period to achieve ≥M3 hand grip assessed in clinical follow-up was shorter (26.5 months vs 45.5 months), and a higher proportion of patients achieved ≥M3 hand grip recovery (63% vs 30%). One patient experienced symptomatic phrenic nerve injury; however, the hemidiaphragm fully recovered after 6 months. The long-term donor-site complication rate was 2.6%, including one sensory abnormality, and no permanent donor-site weakness after hemi-CC7 harvesting was observed. CONCLUSIONS: The modified prespinal route combined with clavicle osteotomy allowed direct coaptation to the LT and did not require head immobilization. It may allow a higher proportion of patients to achieve ≥M3 hand grip more quickly than conventional hemi-CC7 transfer. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Cisplatin triggers oxidative stress, apoptosis and pro-inflammatory responses by inhibiting the SIRT1-mediated Nrf2 pathway in chondrocytes.

Although the height of the proliferating layer that was suppressed in the growth plate has been recognized as an adverse effect of cisplatin in pediatric cancer survivors, the detailed pathological mechanism has not been elucidated. Sirtuin-1 (SIRT1) has been reported as an essential modulator of cartilage homeostasis, but its role in cisplatin-induced damage of chondrocytes remains unclear. In this study, we examined how cisplatin affected the expression of SIRT1 and cell viability. Next, we showed downregulation of SIRT1 after cisplatin treatment resulted in suppression of Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), leading to inhibition of Nrf2 nuclear translocation and subsequently decreased Heme oxygenase-1(HO-1) and NAD(P)H Quinone Dehydrogenase 1(NQO-1) expression. Blockage of the SIRT1/ PGC-1α axis not only increased oxidative stress with lower antioxidant SOD and GSH, but also contributed to mitochondrial dysfunction evidenced by the collapse of membrane potential and repression of mitochondrial DNA copy number and ATP. We also found that Cisplatin up-regulated the p38 phosphorylation, pro-inflammatory events and matrix metalloproteinases (MMPs) in chondrocytes through the SIRT1-modulated antioxidant manner. Collectively, our findings suggest that preservation of SIRT1 in chondrocytes may be a potential target to ameliorate growth plate dysfunction for cisplatin-receiving pediatric cancer survivors.

Dumontier group 2 radiocarpal fracture-dislocation: The results of open reduction and fixation without volar ligament repair.

INTRODUCTION: The radiocarpal fracture-dislocations are a spectrum of severe injury involving both the bony and ligamentous structures that stabilise the wrist joint. The aim of this study was to analyse the outcome of open reduction and fixation without volar ligament repair for Dumontier group 2 radiocarpal fracture-dislocation and to evaluate the incidence and clinical relevance of ulnar translation and advanced osteoarthritis. PATIENTS AND METHODS: We retrospectively reviewed 22 patients with Dumontier group 2 radiocarpal fracture-dislocation treated in our institute. Clinical and radiological outcomes were recorded. Postoperative visual analogue scale (VAS) score for pain, Disabilities of the Arm, Shoulder and Hand Outcome Measure (DASH), and Mayo modified wrist scores (MMWS) were collected. Furthermore, extension‒flexion and supination‒pronation arcs were collected by reviewing chart, either. We divided the patients into two groups according to the presence or absence of advanced osteoarthritis, and presented the differences in the pain, disability, wrist performance, and range of motion between the two groups. We performed the same comparison between the patients with and those without the ulnar translation of the carpus. RESULTS: There were sixteen men and six women with a median age of 23 years (range, 20‒48 years). The median follow-up period was 33 months (range, 12-149 months). The median VAS, DASH and MMWS were 0 (range 0-2), 9.1 (range, 0-65.9) and 80 (range, 45-90), respectively. The median flexion‒extension and pronation‒supination arcs were 142.5° (range, 20°â€’170°) and 147.5° (range, 70°â€’175°), respectively. Ulnar translation was recognised in four patients and the development of advanced osteoarthritis was noted in 13 patients during the follow-up period. However, neither was highly correlated with functional outcomes. CONCLUSION: The current study postulated that ulnar translation might occur following treatment for Dumontier group 2 lesions, whereas injury was predominantly caused by rotational force. Therefore, radiocarpal instability should be recognized during the operation. However, the clinical relevance of ulnar translation and wrist osteoarthritis needs to be assessed in further comparison studies.

Use of Silicone Tubes as Antiadhesion Devices in a Modified Two-Stage Flexor Tendon Reconstruction in Zone II: A Retrospective Study.

PURPOSE: This study aimed to assess the outcome of a modified two-stage flexor tendon reconstruction using silicone tubes as antiadhesion devices while performing simultaneous tendon grafting. METHODS: From April 2008 to October 2019, 16 patients (21 fingers) with zone II flexor tendon injuries, who sustained failed tendon repair or neglected tendon laceration, were treated by a modified two-stage flexor tendon reconstruction. The first stage of treatment comprised flexor tendon reconstruction with interposition of silicone tubes to minimize fibrosis and adhesion around the tendon graft; the second stage of treatment comprised silicone tube removal under local anesthesia. RESULTS: The patient median age was 38 (range, 22-65) years. After a median follow-up period of 14 (range, 12-84) months, the median total active motion (TAM) of fingers was 220° (range, 150-250°). Excellent and good TAM ratings were identified in 71.4%, 76.2%, and 76.2% according to the Strickland, modified Strickland, and American Society for Surgery of the Hand (ASSH) evaluation systems, respectively. At follow-up, complications included superficial infections in two fingers of one patient whose silicone tube was removed 4 weeks postoperatively. The most common complication was a flexion deformity of the proximal interphalangeal joint (four fingers) and/or distal interphalangeal joint (nine fingers). The rate of failed reconstruction was higher in patients with preoperative stiffness and infection. CONCLUSIONS: Silicone tubes are suitable antiadhesion devices, and the modified two-stage flexor tendon reconstruction technique is an alternative procedure with a shorter rehabilitation period for complicated flexor tendon injury, compared with current popular reconstructions. Preoperative stiffness and postoperative infection may compromise the final clinical outcome. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Using an Internal Joint Stabilizer Through a Single Posterior Approach for Elderly Patients With Terrible Triad Injury.

Introduction: Treating a terrible triad injury of the elbow remains a challenge for orthopedic surgeons, especially in elderly patients due to the poor quality of the surrounding soft tissue and bony structures. In the present study, we propose a treatment protocol using an internal joint stabilizer through a single posterior approach and analyze the clinical results. Materials and Methods: We retrospectively reviewed 15 elderly patients with terrible triad injuries of the elbow who underwent our treatment protocol from January 2015 to December 2020. The surgery involved a posterior approach, identification of the ulnar nerve, bone and ligament reconstruction, and the application of the internal joint stabilizer. A rehabilitation program was initiated immediately after the operation. Surgery-related complications, elbow range of motion (ROM), and functional outcomes were evaluated. Results: The mean follow-up period was 21.7 months (range, 16-36 months). ROM at the final follow-up was 130° in extension to flexion and 164° in pronation to supination. The mean Mayo Elbow Performance Score was 94 at the final follow-up. Major complications included breaking of the internal joint stabilizer in 2 patients, transient numbness over the ulnar nerve territory in one, and local infection due to irritation of the internal joint stabilizer in one. Conclusions: Although the current study involved only a small number of patients and the protocol comprised two stages of operation, we believe that such a technique may be a valuable alternative for the treatment of these difficult cases. Level of Clinical Evidence: 4.

Percutaneous Sacroplasty for Symptomatic Sacral Pedicle Screw Loosening.

Background: This study aimed to evaluate the efficacy of fluoroscopy-guided percutaneous sacroplasty in patients with sacral pedicle screws loosening after instrumented spinal fusion. Methods: We retrospectively reviewed the medical records of 18 patients who underwent percutaneous sacroplasty to treat sacral pedicle screws loosening from January 2016 to December 2019. Imaging studies, visual analog scale (VAS), length of hospital stay, and complications were recorded. The clinical outcomes based on the Oswestry disability index (ODI) and the modified Brodsky's criteria (MBC) were also evaluated to determine the efficacy of percutaneous sacroplasty. Results: All patients had undergone at least 1 year of follow-up in our institute (range, 12-24 months). The average VAS score was 5.6 (range, 4-7) before surgery and decreased to 1.7 (range, 1-3) at the final visit. All patients were discharged on the next day after surgery. No patients experienced complications, such as cement leakage, deep infection, or neurologic deterioration. All patients achieved good or excellent outcomes based on the MBC. The ODI scores improved from 51.8 preoperatively to 25.6 postoperatively. Conclusion: Percutaneous sacroplasty was an effective treatment approach for relieving the patient's symptoms caused by sacral pedicle screws loosening and could be a valuable treatment alternative to extensive revision surgery. Level of clinical evidence: IV.

Single Posterior Approach for Circumferential Debridement and Anterior Reconstruction Using Fibular Allograft in Patients With Skipped Multifocal Pyogenic Spondylodiscitis.

OBJECTIVE: Skipped multifocal pyogenic spondylodiscitis is a rare presentation of spinal infection. In our institution, we used the single posterior approach for circumferential debridement and anterior reconstruction with fibular allograft for treatment. This study aimed to ascertain the viability and reliability of this technique for these difficult cases. METHODS: Nine patients with skipped pyogenic spondylodiscitis who received our treatment method from January 2012 to December 2019 were enrolled in this study. Visual analog scale scores, causative agents, laboratory data, comorbidities, and complications were recorded. The patients' clinical conditions were evaluated based on modified Brodsky's criteria, visual analogue scale, and Oswestry Disability Index. RESULTS: All the patients achieved infection eradication without repeat surgical treatment. The average visual analog scale score was 8.4 (range, 8-9) before operation, which decreased to 1.9 (range, 1-3) 1 year after the surgery. No patient experienced severe complications such as neurologic deterioration or fixation failure. All patients achieved a good or excellent outcome based on modified Brodsky's criteria. The Oswestry Disability Index improved from 80.4 (range, 70-86) preoperatively to 25.1 (range, 20-32) 1 year after the surgery. CONCLUSIONS: In our case series, good clinical outcomes and high successful rates could be achieved through the single-stage posterior-only approach. This could be considered an alternative method to manage patients with skipped pyogenic spondylodiscitis.

Therapeutic effect of induced pluripotent stem cell -derived extracellular vesicles in an in vitro and in vivo osteoarthritis model.

Background/Objective: Osteoarthritis (OA) is a multifactorial joint disease associated with the deterioration of chondrocytes and inflammation. Treatment of OA is only aimed at reducing pain and improving joint function. Recently, extracellular vesicles (EVs) secreted from stem cells have emerged as a cell regenerative tool in several degenerative diseases, including OA. We hypothesised that induced pluripotent stem cell (iPSC)-derived EVs would be beneficial for regenerating chondrocytes and OA therapy. Therefore, we aimed to investigate iPSC-EVs' effects on chondrocyte behaviour in an interleukin 1 beta (IL-1ß)-induced in vitro OA model and anterior cruciate ligament transection (ACLT)-induced in vivo OA model of rabbit articular cartilage. Methods: The iPSC-EVs were isolated by sequential ultracentrifugation from a 48-h-incubated conditional medium of iPSC. The isolated iPSC-EVs were characterised by transmission electron microscopy, western blot analyses, and dynamic light scatter. The effects of iPSC-EVs on the viability of human primary chondrocytes and cell senescence were analysed. Premature senescence of cells was induced by long-term incubation with low doses of hydrogen peroxide. To investigate the therapeutic effect of iPSC-EVs on OA chondrocytes in vitro, IL-1ß was used to induce chondrocyte damage. Inflammatory macrophages were activated from THP-1 monocytes to observe the impact of iPSC-EV on macrophage polarisation. The phenotypes of the macrophages exposed to iPSC-EVs were evaluated by ELISA and western blot analyses. The primary chondrocytes were co-cultured with different phenotypes of macrophages to observe the expression of collagen II and catabolic enzymes in chondrocytes. iPSC-EVs were injected intraarticularly into the rabbit with an ACLT-induced OA model. The progression of lesions was assessed through macroscopic and histopathological studies. Results: We showed that iPSC-EVs significantly stimulated the proliferation of primary human chondrocytes and suppressed cell senescence by regulating the expression of p21 and collagen II. iPSC-EVs reduced matrix degradation enzymes and IL-6 expression and attenuated IL-1ß-mediated cell death of chondrocytes. Furthermore, iPSC-EVs modulated macrophage polarisation, resulting in the rescue of damaged chondrocytes in an inflammatory microenvironment. In the rabbit ACLT model, the OA-like lesions, including inflammation, subchondral bone protrusion, and articular cartilage destruction, were ameliorated by iPSC-EV. A histopathological study consistently revealed that iPSC-EVs attenuated ACLT-mediated alteration of MMP13 and ADAMTS5 and collagen II expression. Conclusion: iPSC-EVs protected chondrocytes by enhancing cell proliferation, suppressing premature senescence, and maintaining homeostasis of collagen II synthesis and matrix degradation enzymes such as matrix metalloproteinases (MMPs) and ADAMTS5. iPSC-EVs also reduced cell death in IL-1ß-mediated chondrocyte cell damage. In the rabbit ACLT-induced OA model, iPSC-EV injection reduced cartilage destruction, as indicated by the upregulation of collagen II and down-regulation of MMP13 and ADAMTS5. Overall, our results suggest that iPSC-EVs possess therapeutic potential and may be used as an OA treatment option. The translational potential of this article: This study highlights the potential of iPSC-EVs as a therapeutic option for chondrocyte regeneration and OA treatment.

Using External Joint Stabilizer - Elbow (EJS-E) for treating elbow instability-biomechanical assessment and clinical outcomes.

BACKGROUND: This study aimed to evaluate the outcome of using an External Joint Stabilizer - Elbow (EJS-E) for persistent elbow instability based on biomechanical experiments and analysis of clinical results. METHODS: An EJS-E was used in 17 elbow instability patients. The median follow-up was 26 months (range, 12-42 months). We evaluated the flexion-extension and pronation-supination movement arcs, visual analog scale (VAS) score, Mayo Elbow Performance Score (MEPS), Broberg and Morrey classification system, and occurrence of complications in these patients. Moreover, construct stiffness and maximum strength tests were performed to evaluate the strength of the fixation techniques. RESULTS: The final median range of the extension-to-flexion and pronation-to-supination arc of the elbow was 135° (range, 110°-150°) and 165° (range, 125°-180°), respectively. The VAS pain scores were > 3 in two patients. The median MEPS was 90 (range, 80-100 points). Five patients showed signs of grade I post-traumatic osteoarthritis according to the Broberg and Morrey radiographic classification system, while grade II changes were observed in three patients. Complications included axis pin loosening with pin-tract infection in two patients, transient ulnar nerve symptoms in two patients, heterotopic ossification in two patients, and suture anchors infection in one patient. Based on the biomechanical testing results, the EJS-E exhibited higher stiffness and resisting force in varus loading. It was 0.5 (N/mm) stiffer and 1.8 (N·m) stronger than the internal joint stabilizer (IJS) by difference of medians (p < 0.05). CONCLUSIONS: Biomechanical and clinical outcomes show that EJS-E via the posterior approach can restore mobility and stability in all patients, thus serving as a valuable alternative option for the treatment of persistent instability of the elbow.

Incidence and risk factors of vertebral body collapse after posterior instrumented spinal fusion in elderly patients: An observational study.

This study investigates the incidence and risk factors of new vertebral body collapse (VC) after posterior instrumented spinal fusion in patients older than 70 years. This retrospective study analyzed the data of elderly patients who underwent posterior instrumented spinal fusion in the thoracolumbar spine between January 2013 and December 2017. The 2 subsamples comprised of patients who had experienced vertebral compression fracture (VCF) before the index spinal surgery (group 1, n = 324) and those who had not (group 2, n = 1040). We recorded and analyzed their baseline characteristics, their underlying comorbidities, and the details of their current instrumented spinal fusion. The incidences of new VC and screw loosening were recorded. In groups 1 and 2, the incidences of new VC were 31.8% and 22.7%, respectively, and those of new VC with screw loosening were 25.6% and 33%, respectively. The risk factor was upper screw level at the thoracolumbar junction (hazard ratio [HR] = 2.181, 95% confidence interval [CI]: 1.135-4.190) with previous VCF. The risk factors were age ≥ 80 years (HR = 1.782, 95% CI: 1.132-2.805), instrumented levels > 4 (HR = 1.774, 95% CI: 1.292-2.437), and peptic ulcer (HR = 20.219, 95% CI: 2.262-180.731) without previous VCF. Clinicians should closely monitor new VC after posterior instrumented spinal fusion in elderly patients with previous VCF with upper screw level at the thoracolumbar junction and in patients without previous VCF aged ≥ 80 years, with instrumented levels > 4 and peptic ulcer.