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.

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.

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.

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.

Clinical prognosis of surgical resection versus transarterial chemoembolization for single large hepatocellular carcinoma (≥5 cm): A propensity score matching analysis.

Favorable prognostic factors and therapeutic strategies are important for patients with single large hepatocellular carcinoma (HCC). This retrospective study aimed to investigate the prognostic factors in patients with single large (≥5 cm) HCC with Child-Pugh (CP) class A patients and to recommend therapeutic strategies. Overall, 298 HCC patients with single and large (≥5 cm) tumors with CP class A, but without distant metastasis and macrovascular invasion were included, and their clinicopathological data, overall survival (OS), and progression-free survival (PFS) were recorded. OS and PFS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed. The 298 HCC patients were 79.2% male and median age of 64 years. For the initial treatment, surgical resection (SR) and transarterial chemoembolization (TACE) was 50.8% and 49.2%, respectively. The OS and PFS were significantly higher in patients receiving SR than those receiving TACE before and after PSM. Furthermore, in multivariate analysis, cirrhosis (Hazard ratio [HR]: 2.04; 95% confidence interval [CI]: 1.35-3.03, p < 0.001, CP class A5/6 [HR: 4.01; 95% CI: 2.43-6.66, p < 0.001], and initial treatment [SR vs. TACE HR = 3.23; 95% CI: 2.13-5.01, p < 0.001]) remained significantly associated with mortality. Moreover, in multivariate analysis, CP class A5/6 (HR: 3.23; 95% CI: 1.89-5.88, p < 0.001), and initial treatment (Resection vs. TACE; HR = 4.17; 95% CI: 1.64-8.33, p = 0.039) remained significantly associated with recurrence. In conclusion, SR was associated with significantly higher OS and PFS rates than TACE before and after PSM for single large HCC patients.

Comparison of intra-articular injection of ArtiAid®-Mini with Ostenil®-Mini for trapeziometacarpal osteoarthritis: A double-blind, prospective, randomized, non-inferiority trial.

OBJECTIVES: This study aims to compare the effectiveness and safety of intra-articular hyaluronic acid (HA) injections of ArtiAid®-Mini (AAM) and Ostenil®-Mini (OM) for the treatment of trapeziometacarpal joint osteoarthritis. PATIENTS AND METHODS: Between February 2018 and April 2020, this 24-week, double-blind, prospective, randomized, non-inferiority trial included a total of 17 patients (8 males, 9 females; mean age: 60.3±9.5 years; range, 42 to 76 years) who were treated with either intra-articular AAM (n=8) or OM (n=9). The primary outcome was pain according to a change in Visual Analog Scale (VAS) at 12 weeks after the last injection. The secondary outcomes included the change of VAS at Weeks 2, 4, and 24 after the injection, satisfaction, range of motion (ROM) of trapeziometacarpal joint, pinch strength, grip strength, and adverse events at Weeks 2, 4, 12, and 24 after the injection. RESULTS: Eight patients with AAM and eight patients with OM completed the follow-up. No significant differences in primary and secondary outcomes were observed between the two groups at baseline and each time point (p>0.05). The intra-group differences were significant in each time point. CONCLUSION: The intra-articular injection of either AAM or OM is effective and safe for patients with trapeziometacarpal osteoarthritis up to 24 weeks.

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.

NPRL2 down-regulation facilitates the growth of hepatocellular carcinoma via the mTOR pathway and autophagy suppression.

Hepatocellular carcinoma (HCC) is a highly invasive malignancy. Recently, GATOR1 (Gap Activity TOward Rags 1) complexes have been shown to play an important role in regulating tumor growth. NPRL2 is a critical component of the GATOR1 complex. Therefore, this study used NPRL2 knockdown to investigate how GATORC1 regulates the prognosis and development of HCC via the mammalian target of rapamycin (mTOR) and autophagy signaling pathways. We established HepG2 cells with NPRL2 knockdown using small interfering RNA (siRNA) and short hairpin RNA (shRNA) systems. The siRNA-mediated and shRNA-mediated NPRL2 down-regulation significantly reduced the expression of NPRL2 and two other GATPOR1 complex components, NPRL3 and DEPDC5, in HepG2 cells; furthermore, the efficient down-regulation of NPRL2 protein expression by both the shRNA and siRNA systems enhanced the proliferation, migration, and colony formation in vitro. Additionally, the NPRL2 down-regulation significantly increased HCC growth in the subcutaneous and orthotopic xenograft mouse models. The NPRL2 down-regulation increased the Rag GTPases and mTOR activation and inhibited autophagy in vitro and in vivo. Moreover, the NPRL2 level in the tumors was significantly associated with mortality, recurrence, the serum alpha fetoprotein level, the tumor size, the American Joint Committee on Cancer stage, and the Barcelona Clinic Liver Cancer stage. Low NPRL2, NPRL3, DEPDC5, and LC3, and high p62 and mTOR protein expression in the tumors was significantly associated with disease-free survival and overall survival in 300 patients with HCC after surgical resection. Conclusion: The efficient down-regulation of NPRL2 significantly increased HCC proliferation, migration, and colony formation in vitro, and increased HCC growth in vivo. Low NPRL2 protein expression in the tumors was closely correlated with poorer clinical outcomes in patients with HCC. These results provide a mechanistic understanding of HCC and aid the development of treatments for HCC.

External Locking Plate Fixation for Femoral Subtrochanteric Fractures.

Introduction: Internal fixation is the treatment of choice for subtrochanteric fractures in most conditions. However, it may be an unsuitable procedure for patients with poor health status, osteomyelitis, and surrounding soft tissue compromise. This study aimed to ascertain the viability and reliability of using external locking plate fixation for these difficult cases. Methods: Eleven patients with femoral subtrochanteric fractures who received external locking plate fixation in our institute from January 2014 to December 2019 were enrolled in our study. The bone union time, wound complication, alignment, and necessity for narcotic agents were evaluated. Results: The average length of follow-up was 17.5 months (range, 14-26 months). The mean time for bone union was 17.7 weeks (range, 15-21 weeks). The indications included poor health condition, soft tissue compromise, and post-operative osteomyelitis. Pin tract infection was noted in two patients who were treated successfully with oral antibiotics administration and removal of the involved screws. Osseous union with varus deformity <10° was achieved in all patients except one. Three patients required an orally administered pain killer at the final visit. The average Harris Hip Score at one year post-operatively was 66.6 (range, 49-80). Conclusions: Although the current study only involved 11 patients, we believe that our method may serve as a valuable alternative for the treatment of a femoral subtrochanteric fracture in selected cases. Level of Evidence: Level IV, retrospective case series.

Effects of percutaneous vertebroplasty on respiratory parameters in patients with osteoporotic vertebral compression fractures.

Background: Vertebral compression fractures (VCFs) often occur in patients with osteoporosis. These fractures can also lead to postural changes. Several studies have shown that patients with vertebral compression fractures have a restrictive pattern in their pulmonary function. Percutaneous vertebroplasty (PVP) is the standard treatment for vertebral compression fractures, with the benefits of pain relief and enhancement of vertebral stability for partially collapsed vertebral bodies. However, the effects of PVP on short-term recovery of respiratory performance have not been investigated. Therefore, this study aimed to investigate the changes in pulmonary function, respiratory muscle strength, maximal voluntary ventilation (MVV), and chest mobility in patients with vertebral compression fractures after PVP.Methods: This research was approved by the clinic committee of the E-DA Hospital Institutional Review Board (EMRP07109N) and registered in the Thai Clinical Trials Registry (TCTR20211029005). We recruited 32 VCF patients. Four-time points were measured: before and after PVP and 1 and 3 weeks after PVP. We measured pulmonary function and maximum voluntary ventilation (MVV) by using spirometry. Respiratory muscle strength was assessed by using a respiratory pressure meter. The chest expansion test was used to evaluate chest mobility. A visual analogue scale (VAS) was used to assess resting and aggravated back pain.Results: Chest expansion and back pain improved at each time point after PVP. MVV showed significant progress at both 1 and 3 weeks after discharge. Forced expiratory volume in 1 second (FEV1) and maximal inspiratory muscle strength significantly improved 1 week after discharge.Conclusion: Taking all the data together, PVP not only can resolve severe back pain but can also provide excellent improvements in MVV and chest mobility in patients with vertebral compression fractures.

Does an Internal Joint Stabilizer and Standardized Protocol Prevent Recurrent Instability in Complex Persistent Elbow Instability?

BACKGROUND: The treatment of complex persistent elbow instability after trauma is challenging. Previous studies on treatments have reported varied surgical techniques, which makes it difficult to establish a therapeutic algorithm. Furthermore, the surgical procedures may not sufficiently restore elbow stability, even with an additional device, and a noted high rate of arthritis progression.While a recently developed internal joint stabilizer effectively treats elbow instability, its clinical application for complex persistent elbow instability is limited and the standardized protocol is not well described. Additionally, we want to know whether the arthritis progression will cause a negative impact on the functional outcomes of complex persistent elbow instability. QUESTIONS/PURPOSES: (1) Does treatment of complex persistent elbow instability with a hinged internal joint stabilizer and a standardized protocol prevent recurrent instability and other complications? (2) What are the pre- to postoperative improvements in pain, disability, elbow performance, and ROM? (3) Is the development of post-traumatic arthritis associated with worse pain, disability, elbow performance, and ROM? METHODS: Between September 2014 and October 2019, we treated 22 patients for persistent dislocation or subluxation after initial treatment of traumatic elbow fracture-dislocations. Of those, we considered patients who were at least 20 years of age, with an interval of 6 weeks or more between the injury (initial treatment) and the index reconstructive procedure, which had been performed at our institute, as potentially eligible. During that time, we used an internal joint stabilizer with a standardized protocol for posttraumatic complex persistent elbow instability. We performed total elbow replacements in patients older than 50 years who had advanced elbow arthritis. Based on that, 82% (18 of 22) of patients were eligible; 14% (3 of 22) were excluded because total elbow replacements was undertaken, and another 5% (1 of 22) were lost before the minimum study follow-up of 1 year (median 24 months [range 12 to 63]), leaving 64% (14 of 22) for analysis in this retrospective study. We treated 14 patients (14 elbows) with posttraumatic complex persistent elbow instability with an internal joint stabilizer and a standardized protocol that comprised debridement arthroplasty with ulnar neurolysis, restoration of bony and ligamentous (reattachment) structures, application of an internal joint stabilizer, and early rehabilitation. There were eight men and six women in this study, with a median (range) age of 44 years (21 to 68). The initial elbow fracture-dislocation injury pattern was a terrible triad injury in seven patients, a posterolateral rotatory injury in four patients, and a posterior Monteggia fracture in three patients. Preoperative and follow-up radiographs were reviewed for evidence of recurrent instability and arthritis. Complications such as wound infection, seroma, neurovascular injury, and hardware complications were ascertained through chart review. Preoperative and postoperative VAS score for pain, DASH, and Mayo Elbow Performance Scores (MEPS) were collected and compared. Furthermore, extension-flexion and supination-pronation arcs were collected by chart review. We divided the patients into two groups according to whether or not they developed posttraumatic arthritis. We then presented the differences between pain, disability, elbow performance, and ROM. The hinged internal joint stabilizer was removed using another open procedure under general anesthesia 6 to 8 weeks after surgery. RESULTS: There were no recurrent instability during and after device removal. Seven patients developed complications, including wound infection, seroma, neurovascular injury, hardware complications, and heterotopic ossification. Two patients had complications related to internal joint stabilizers and three had complications linked to radial head prostheses. Median (range) preoperative to postoperative changes included decreased pain (VAS 5 [2 to 9] to 0 [0 to 3], difference of medians -5; p < 0.001), decreased disability (DASH 41 [16 to 66] to 7 [0 to 46], difference of medians -34; p < 0.001), improved function (MEPS 60 [25 to 70] to 95 [65 to 100], difference of medians 35; p < 0.001), improved extension-flexion arc (40° [10° to 70°] to 113° [75° to 140°], difference of medians 73°; p < 0.001), and supination-pronation arc (78° [30° to 165°] to 148° [70° to 175°], difference of medians 70°; p < 0.001). Between patients with and without development of post-traumatic arthritis, there were no differences in postoperative pain (VAS 0 [0 to 3] to 0 [0 to 1], difference of medians 0; p = 0.17), disability (DASH 7 [0 to 46] to 7 [0 to 18], difference of medians 0; p = 0.40), function (MEPS 80 [65 to 100] to 95 [75 to 100], difference of medians 15; p = 0.79), extension-flexion arc (105° [75° to 140°] to 115° [80° to 125°], difference of medians 10°; p = 0.40), and supination-pronation arc (155° [125° to 175°] to 135° [70° to 160°], difference of medians -20°; p < 0.18). CONCLUSION: In this small, retrospective study, we found that an internal joint stabilizer with a standardized treatment protocol could maintain concentric reduction while allowing early functional motion, and that it could improve clinical outcomes for patients with complex persistent elbow instability. However, patients must be counseled that the complications related to the radial head prostheses may occur, and that the benefits of early motion must compensate for an additional removal procedure and the risk of seroma formation. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Arthroscopic resection of recurrent wrist ganglions - A retrospective study of 17 patients.

BACKGROUND: Arthroscopic resection has become a favorable alternative for wrist ganglions. However, for recurrent wrist ganglions, arthroscopic resection is relatively contraindicated. The purpose of this study was to evaluate the clinical outcomes of arthroscopic resection for recurrent wrist ganglions and to identify their safety and efficacy. METHODS: From June 2011 to February 2017, 17 patients with recurrent wrist ganglion were treated with arthroscopic resection. We evaluated the visual analog scale, modified Mayo wrist score, and Disabilities of Arm, Shoulder and Hand Outcome Measure preoperatively and at the final follow-up. Patients were questioned for pain reduction, pain during pushups, and any difficulty in returning to work. Recurrence and complications were also assessed at each follow-up visit. RESULTS: We enrolled 17 patients and median follow-up was 58 months. The reduction in pain was significant. Only 2 of the 17 patients had residual pain after arthroscopic resection. One female patient showed recurrences 3 years later. Although 2 cases of stiffness were noted after the operation, no significant complication was present 3 months postoperatively. Most patients had good recovery and could resume work; however, 2 patients reported fair recovery. CONCLUSION: The results of this study confirmed that arthroscopic excision could be an effective and safe treatment for recurrent ganglions; therefore, should not be contraindicated for treating recurrent wrist ganglions. Nevertheless, further prospective studies with larger patient numbers are needed to establish a stronger evidence for arthroscopic resection of recurrent wrist ganglions.

Galectin-3 facilitates inflammation and apoptosis in chondrocytes through upregulation of the TLR-4-mediated oxidative stress pathway in TC28a2 human chondrocyte cells.

Osteoarthritis (OA) is a common degenerative joint disease. The pathological changes of chondrocytes involve oxidative stress, the pro-inflammatory response, and pro-apoptotic events. Galectin-3 (Gal-3) is a 35 kDa protein with a special chimeric structure. Gal-3 participates in the progression of many diseases, such as cancer metastasis and heart failure. A previous study demonstrated that Gal-3 expression in human cartilage with OA is increased. However, the role of Gal-3 in chondrocyte dysfunction in joints is still unclear. In this study, we applied Gal-3 (5-20 µg/ml) to TC28a2 human chondrocyte cells for 24 h to induce chondrocyte dysfunction. We found that Gal-3 upregulated TLR-4 and MyD88 expression and NADPH oxidase, thereby increasing intracellular ROS in the chondrocytes. Gal-3 increased phosphorylated MEK1/2 and ERK levels, and promoted NF-κB activity. This activation of NF-κB was reduced by silencing TLR-4 and NOX-2. In addition, Gal-3 caused apoptosis of chondrocytes through the mitochondrial-dependent pathway via the TLR-4/NADPH oxidase/MAPK axis. Our study proves the pathogenic role of Gal-3 in Gal-3-induced chondrocyte dysfunction and injuries.

Ginsenoside Rg3 Attenuates TNF-α-Induced Damage in Chondrocytes through Regulating SIRT1-Mediated Anti-Apoptotic and Anti-Inflammatory Mechanisms.

The upregulation of tumor necrosis factor-alpha (TNF-α) is a common event in arthritis, and the subsequent signaling cascade that leads to tissue damage has become the research focus. To explore a potential therapeutic strategy to prevent cartilage degradation, we tested the effect of ginsenoside Rg3, a bioactive component of Panax ginseng, on TNF-α-stimulated chondrocytes.TC28a2 Human Chondrocytes were treated with TNF-α to induce damage of chondrocytes. SIRT1 and PGC-1a expression levels were investigated by Western blotting assay. Mitochondrial SIRT3 and acetylated Cyclophilin D (CypD) were investigated using mitochondrial isolation. The mitochondrial mass number and mitochondrial DNA copy were studied for mitochondrial biogenesis. MitoSOX and JC-1 were used for the investigation of mitochondrial ROS and membrane potential. Apoptotic markers, pro-inflammatory events were also tested to prove the protective effects of Rg3. We showed Rg3 reversed the TNF-α-inhibited SIRT1 expression. Moreover, the activation of the SIRT1/PGC-1α/SIRT3 pathway by Rg3 suppressed the TNF-α-induced acetylation of CypD, resulting in less mitochondrial dysfunction and accumulation of reactive oxygen species (ROS). Additionally, we demonstrated that the reduction of ROS ameliorated the TNF-α-elicited apoptosis. Furthermore, the Rg3-reverted SIRT1/PGC-1α/SIRT3 activation mediated the repression of p38 MAPK, which downregulated the NF-κB translocation in the TNF-α-treated cells. Our results revealed that administration of Rg3 diminished the production of interleukin 8 (IL-8) and matrix metallopeptidase 9 (MMP-9) in chondrocytes via SIRT1/PGC-1α/SIRT3/p38 MAPK/NF-κB signaling in response to TNF-α stimulation. Taken together, we showed that Rg3 may serve as an adjunct therapy for patients with arthritis.

Ipsilateral vascularised fibula with external locking plate for treatment of massive tibial bone defects.

INTRODUCTION: Management of massive tibial bone defects remains challenging for orthopaedic doctors. This study aimed to ascertain the viability and reliability of utilising an ipsilateral vascularised fibula with an external locking plate for the difficult situation. MATERIALS AND METHODS: Between January 2012 and December 2017, eight patients (7 men) with a mean age of 32.3 (19-54) years who presented with massive tibial bone defects were treated using the described technique. The mean length of the bone defect was 12.4 (8-20) cm. The patients were assessed for clinical and radiographic results, hypertrophy of the fibular graft with DeBoer and Wood's method, and SF-36 functional score. RESULTS: The mean follow-up period was 40.3 (26-60) months. The average time for union was 5.6 (3-8) months. At the final follow-up, all patients had fully united grafts and walked without restriction. The mean graft hypertrophy index was 98.2 %. The SF-36 score was > 75 % in five patients, and 50-75 % in three. Three patients had a leg length discrepancy of > 1.5 cm. Two patients with equinus foot were treated using tibiotalocalcaneal fusion. Three patients had pin-tract infections. Four screws were broken in two cases. CONCLUSION: Ipsilateral vascularised fibular transfer combined with an external locking plate as a definitive external fixator provides a simple and comfortable treatment, and appropriate mechanical loading and vascularisation of the graft site to achieve hypertrophy of the fibular graft. Hence, our technique can serve as a valuable alternative for the treatment of massive tibial bone defects.

A cost and efficacy analysis of performing arthroscopic excision of wrist ganglions under wide-awake anaesthesia versus general anaesthesia.

BACKGROUND: Arthroscopic excision has currently become popular for the treatment of wrist ganglions. The objective of this study was to evaluate the clinical outcomes and cost effectiveness of arthroscopic wrist ganglion excisions under Wide-Awake Local Anaesthesia No Tourniquet versus general anaesthesia. METHODS: We retrospectively reviewed patients who underwent arthroscopic ganglionectomy from April 2009 to October 2016 at our institute. They were separated into two groups according to anaesthesia techniques: general anaesthesia and Wide-Awake Local Anaesthesia No Tourniquet. We compared the clinical outcomes and cost-effectiveness of the two groups. RESULTS: Seventy-four patients were included. Both groups were matched with regard to the demographics and preoperative clinical assessments. We found no significant differences between groups in postoperative visual analog scale, modified Mayo wrist score, Disabilities of Arm, Shoulder and Hand score, recurrence, residual pain, or complications. Recurrence was found in five of 74 patients, one (4.3%) in the Wide-Awake Local Anaesthesia No Tourniquet group and four (7.8%) in the general anaesthesia group. One extensor tendon injury and four extensor tenosynovitis cases occurred in the general anaesthesia group. Regarding cost effectiveness, the mean operating time in the Wide-Awake Local Anaesthesia No Tourniquet and general anaesthesia groups were 88.7 ± 24.51 and 121.5 ± 25.75 min, respectively (p < 0.001). The average total costs of the Wide-Awake Local Anaesthesia No Tourniquet and general anaesthesia groups were €487.4 ± 89.15 and €878.7 ± 182.13, respectively (p < 0.001). CONCLUSIONS: For arthroscopic wrist ganglion resections, both anaesthesia techniques were effective and safe regarding recurrence rates, complications, and residual pain. The most important finding of this study was that arthroscopic ganglionectomy under Wide-Awake Local Anaesthesia No Tourniquet was superior to that under general anaesthesia for cost-effectiveness. LEVEL OF EVIDENCE: Level III, Retrospective comparative study.

Inhibition of CD44 induces apoptosis, inflammation, and matrix metalloproteinase expression in tendinopathy.

Apoptosis has emerged as a primary cause of tendinopathy. CD44 signaling pathways exert anti-apoptotic and -inflammatory effects on tumor cells, chondrocytes, and fibroblast-like synoviocytes. The aim of this study was to examine the association among CD44, apoptosis, and inflammation in tendinopathy. Expression of CD44 and apoptotic cell numbers in tendon tissue from patients with long head of biceps (LHB) tendinopathy were determined according to the histological grades of tendinopathy. Primary tenocytes from Achilles tendon of Sprague-Dawley rats 1 week after collagenase injection were cultured with an antagonizing antibody against CD44. Treatment responses were determined by evaluating cell viability and expression of tendon-related proliferation markers, inflammatory mediators, and apoptosis. The expression of CD44 and apoptosis were positively correlated with the severity of tendinopathy in the human LHB tendinopathy. Furthermore, CD44 expression and apoptotic cells were co-stained in tendinopathic tendon. Blocking the CD44 signaling pathways in rat primary tenocytes by OX-50 induced cell apoptosis and the elevated levels of cleaved caspase-3. Furthermore, they had decreased cell viability and expression of collagen type I, type III, tenomodulin, and phosphorylated AKT. In contrast, there were elevated levels of inflammatory mediators, including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, cyclooxygenase-2, and phosphorylated NF-κB, as well as matrix metalloproteinase (MMP) family members including MMP-1, -3, -9, and -13 in tenocytes upon OX-50 treatment. This study is the first to demonstrate the association of CD44 and apoptosis in tendinopathy. Our data imply that CD44 may play a role in tendinopathy via regulating apoptosis, inflammation, and extracellular matrix homeostasis.

PKR Promotes Oxidative Stress and Apoptosis of Human Articular Chondrocytes by Causing Mitochondrial Dysfunction through p38 MAPK Activation-PKR Activation Causes Apoptosis in Human Chondrocytes.

Osteoarthritis (OA) is one of the most common types of arthritis in the elderly people. It has been known that chondrocyte apoptosis occurs in OA cartilage; however, the detailed molecular mechanism remains unclear. In the current study, we aimed to elucidate the role of double-stranded RNA-dependent protein kinase R (PKR) in the TNF-α-caused apoptosis in chondrocytes. Human articular chondrocytes were digested from cartilages of OA subjects who accepted arthroplastic knee surgery. Our results showed that phosphorylation of p38 MAPK was increased after TNF-α stimulation or PKR activation using poly (I:C), and TNF-α-induced p38 MAPK upregulation was inhibited by PKR inhibition, suggesting phosphor-p38 MAPK was regulated by PKR. Moreover, we found that PKR participated in the p53-dependent destruction of AKT following activation of p38 MAPK. The inhibition of AKT led to the reduced expression of PGC-1α, which resulted in mitochondrial dysfunction and increased oxidative stress. We showed that the reduction of oxidative stress using antioxidant Mito TEMPO lowered the TNF-α-induced caspase-3 activation and TUNEL-positive apoptotic cells. The diminished apoptotic response was also observed after repression of PKR/p38 MAPK/p53/AKT/PGC-1α signaling. Taken together, we demonstrated that the aberrant mitochondrial biogenesis and increased oxidative stress in chondrocytes after TNF-α stimulation were mediated by PKR, which may contribute to the chondrocyte apoptosis and cartilage degeneration in OA.