Full recovery of elective orthopedic surgery in the age of COVID-19: an 8-month retrospective cohort study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to dramatic disruptions to orthopedic services. The purpose of this study is to quantify the reinstatement of elective orthopedic surgeries of our institution in Shanghai, China, and share our first-hand experiences of how this region is managing the post-outbreak period. METHODS: The number of patients receiving elective orthopedic surgeries was analyzed in the timeframe of 8 months since the start of the pandemic (from January 20 to September 16) and compared with the patients receiving the same treatment during the same period in 2019. And a detailed workflow for handling patients about to receive elective surgeries in the COVID-19 post-outbreak period was described. RESULTS: The number of the selective surgeries in the first 3 months only accounted for 31.72% of the same period in 2019 (p = 0.0031), and the ratio reached 97.47% when it came to the last 5 months (p > 0.9999). The selective surgeries even surpassed the pre-epidemic level in months 7 and 8. And the difference of the surgeries was not significant in the whole eight observed months between 2019 and 2020 (p = 0.1526). No health care providers or hospitalized patients in orthopedic departments in Shanghai have been infected nosocomially. CONCLUSIONS: Elective orthopedic surgeries have been fully recovered from the COVID-19 pandemic in our institution, and the new normalcy established during the post-outbreak period helped this region co-exist with the impact of the virus well. TRIAL REGISTRATION: Retrospectively registered, registration number: ChiCTR2000039711 , date of registration: November 6, 2020.

Midterm Outcomes After Open Arthrolysis for Posttraumatic Elbow Stiffness in Children and Adolescents.

BACKGROUND: Open arthrolysis is used for treating elbow stiffness in adults. This study evaluated the midterm outcomes after open arthrolysis in children and adolescents with posttraumatic elbow stiffness. METHODS: Data of 31 children and adolescents with posttraumatic elbow stiffness following open arthrolysis with or without hinged external fixation from 2010 to 2014 were retrospectively analyzed. Their mean age was 15 (range: 6 to 19) years. At baseline and the follow-up (>4 y), we evaluated the outcomes (range of motion and Mayo Elbow Performance Index) and postoperative complications (pain, ulnar nerve symptoms, infections, and instability) and analyzed the association between outcomes and clinical variables. RESULTS: The Mayo Elbow Performance Index improved from 67.9 (range: 35 to 95 points) to 93.7 points (range: 65 to 100 points; P<0.001). The elbow active flexion/extension arc increased significantly from 49 degrees (range: 0 to 120 degrees) to 108 degrees (range: 0 to 120 degrees; P<0.001), with a mean flexion of 123 degrees (range: 70 to 140 degrees; P<0.001) and mean extension of 15 degrees (range: 0 to 85 degrees; P<0.001) postoperatively. The increasing age at surgery was associated with improved elbow motions (P=0.004). Patients with increased preoperative serum alkaline phosphatase level demonstrated decreased arc of motion (P=0.015). Patients with extra-articular fractures had better outcomes than the other patients. At the final follow-up, 8 patients experienced recurrent contracture in the flexion arc with heterotopic ossification. Two patients had postoperative pain, 1 elbow instability, and 1 ulnar neuropathy. CONCLUSIONS: Most patients showed satisfactory functional outcomes after arthrolysis, indicating that open release with or without hinged external fixation is an effective and maintained technique for children and adolescents with posttraumatic elbow stiffness. The age at surgery, preoperative alkaline phosphatase level, and injury type should be considered to achieve good outcomes. LEVEL OF EVIDENCE: Therapeutic level III.

Management of elbow dysfunction associated with giant cell tumor of the distal humerus: achieving oncologic safety and good function by a combined reconstruction.

BACKGROUND: The purpose of our study was to evaluate the functional outcomes and oncologic results of elbow salvage surgery using arthrolysis combined with ligament repair and external fixation for reconstruction of the elbow after tumor excision and autografting. METHODS: We retrospectively reviewed 6 patients with elbow dysfunction associated with giant cell tumor of the distal humerus. All patients were treated with our combined protocol. We assessed the Musculoskeletal Tumor Society system score, range of motion, Mayo Elbow Performance Score, recurrence, and complications for each patient. RESULTS: The mean follow-up period was 48 months (range, 36-60 months). There were no cases of postoperative fracture, infection, elbow dislocation, elbow stiffness, or local recurrence. The average Musculoskeletal Tumor Society score was 28 of 30 points (93%; range, 87%-100%). The Mayo Elbow Performance Score improved from a mean of 61 points to 93 points, with mean flexion of 135° and mean extension of 3°. CONCLUSIONS: Local tumor resection, autografting, and elbow reconstruction by arthrolysis combined with ligament repair and external fixation can be performed with oncologic safety and provide satisfactory functional outcomes with low complication rates.

Management of elbow stiffness after postoperative treatment of terrible triad elbow injury: maintaining mobility and stability using a combined protocol.

PURPOSES: The purpose of this study was to evaluate the results of our protocol that include the restoration of mobility using open release combined with external fixation and stability using ligament repair, to determine the optimal timing of surgery, and to investigate whether resection and replacement of the radial head are associated with different outcomes. METHODS: Twenty-six patients with elbow stiffness after operation of terrible triad injury of the elbow were treated with our protocol. We assessed the optimal timing of the operation by comparing outcomes between the early treatment group and the delayed treatment group. The comparison was performed to investigate whether the results differed between resection and replacement of the radial head. Stability of the elbow, range of motion (ROM), Mayo Elbow Performance Score (MEPS), and complications were assessed for each patient. RESULTS: The mean interval from the initial surgery to the index procedure was 13 months, and the mean follow-up period was 29 months. The MEPS increased from a mean of 65 points to 94 points. Twenty-five of 26 patients achieved stability of the elbow, and all patients achieved functional ROM. There were no significant differences between the two subgroups with respect to ROM and stability of the elbow. CONCLUSION: Our protocol can restore mobility and stability. Resection and replacement of the radial head are both feasible using this protocol. Lastly, the timing of the surgery was not very rigorous, and the surgical delay may be insignificant. LEVEL OF EVIDENCE: Level IV; Case Series; Treatment Study.

Down-regulation of RPS9 Inhibits Osteosarcoma Cell Growth through Inactivation of MAPK Signaling Pathway.

Objectives: Osteosarcoma is the most common malignant bone tumor in adolescents; however, the mechanisms involved in the pathogenesis and progression of osteosarcoma remain to be elucidated. Researchers have provided valuable insights into the tumorigenesis of Ribosomal protein S9 (RPS9) in some cancers. The purpose of this study was to elucidate the expression, functions, and mechanisms of RPS9 in human osteosarcoma. Methods: The expression of RPS9 in osteosarcoma tissues and cell lines was evaluated by qRT-PCR and western blotting. Knockdown of RPS9 induced by RNA interference (RNAi) method in three osteosarcoma cell lines (MNNG/HOS, MG63, and U2OS) was employed to analyze the effects of RPS9 on cell proliferation and cell cycle distribution. The host signaling pathways affected by RPS9 were detected using the intracellular signaling antibody array kit PathScan®. Results: The expression of RPS9 was found to be up-regulated in human osteosarcoma tissues and cell lines. Its expression was positively correlated with Enneking stage and the tumor recurrence. Down-regulation of RPS9 inhibited osteosarcoma cell proliferation, colony-forming ability, and cell cycle G1 phase in vitro. In addition, our data demonstrated that knockdown of RPS9 repressed the protein levels of phospho-SAPK/JNK and phospho-p38. Conclusion: RPS9 is up-regulated and has a pro-tumor effect in osteosarcoma through the activation of MAPK signaling pathway and thus can be used as a potential target for gene therapy.

Downregulation of BZW2 inhibits osteosarcoma cell growth by inactivating the Akt/mTOR signaling pathway.

Osteosarcoma is the most common malignant bone tumor in adolescents. The function of basic leucine zipper and W2 domains 2 (BZW2) in tumor progression has been reported. However, the role and mechanisms of BZW2 in osteosarcoma remain to be determined. The aim of the present study was to reveal the expression and biological functions of BZW2 in osteosarcoma and to elucidate the proximal mechanisms underlying these functions. The expression of BZW2 in osteosarcoma tissues and cell lines was assessed by qRT-PCR, western blotting and immunohistochemistry. BZW2 overexpression was detected in osteosarcoma cell lines. Clinically, BZW2 expression was higher in osteosarcoma tissues than in corresponding non-tumor tissues and was associated with advanced Enneking stage and tumor recurrence. The knockdown of BZW2 using siRNA inhibited osteosarcoma cell proliferation, colony-forming ability, and the cell cycle at the G2/M phase in vitro. Host signaling pathways affected by BZW2 were detected using a PathScan Intracellular Signaling Antibody Array kit. These data demonstrated that the knockdown of BZW2 suppresses protein phosphorylation in the Akt/mTOR signaling pathway. These observations suggest that BZW2 is upregulated and has a pro-tumor effect in osteosarcoma via activation of the Akt/mTOR signaling pathway and thus is a potential target for gene therapy.

Lentivirus-mediated microRNA-124 gene-modified bone marrow mesenchymal stem cell transplantation promotes the repair of spinal cord injury in rats.

Our study aims to explore the effects of lentivirus-mediated microRNA-124 (miR-124) gene-modified bone marrow mesenchymal stem cell (BMSC) transplantation on the repair of spinal cord injury (SCI) in rats. BMSCs were isolated from the bone marrow of rats. The target gene miR-124 was identified using a luciferase-reporter gene assay. Seventy-two rats were selected for construction of the SCI model, and the rats were randomly divided into the blank group, sham group, SCI group, negative control (NC) group, overexpressed miR-124 group and si-PDXK group. The mRNA expression of miR-124 and the mRNA and protein expression of pyridoxal kinase (PDXK) were detected by quantitative real-time polymerase chain reaction and western blotting. The locomotor capacity of the rats was evaluated using the Basso, Beattie and Bresnahan (BBB) scale. Brdu, neuron-specific enolase (NSE), neurofilament (NF) and microtubule-associated protein 2 (MAP2) were detected using immunohistochemistry. The expression levels of thyrotropin-releasing hormone (TRH), prostacyclin (PGI2) and gangliosides (GM) were measured using an enzyme-linked immunosorbent assay. PDXK was identified as the target gene of miR-124. The overexpressed miR-124 group exhibited higher miR-124 expression than the SCI, NC and si-PDXK groups. Compared with the SCI and NC groups, the PDXK expression was downregulated in the overexpressed miR-124 and si-PDXK groups, and the BBB scores were significantly increased 7, 21 and 35 days after transplantation. The double-labeled positive cell densities (Brdu+NSE/NF/MAP2) and the expression levels of TRH, PGI2 and GM in the overexpressed miR-124 group were significantly higher than those in the NC and SCI groups. These results indicated that miR-124 targeted PDXK to accelerate the differentiation of BMSCs into neurocytes and promote SCI repair.

Minichromosome maintenance protein 2 and 3 promote osteosarcoma progression via DHX9 and predict poor patient prognosis.

A label free quantitative proteomic approach (SWATH™ experiment) was performed to identify tumor-associated nuclear proteins that are differentially expressed between osteosarcoma cells and osteoblast cells. By functional screening, minichromosome maintenance protein 2 (MCM2) and minichromosome maintenance protein 3 (MCM3) were found to be related to osteosarcoma cell growth. Here, we show that knockdown of MCM2 or MCM3 inhibits osteosarcoma growth in vitro and in vivo. In co-immunoprecipitation and co-localization experiments, MCM2 and MCM3 were found to interact with DExH-box helicase 9 (DHX9) in osteosarcoma cells. A rescue study showed that the decreased growth of osteosarcoma cells by MCM2 or MCM3 knockdown was reversed by DHX9 overexpression, indicating that MCM2 and MCM3 activity was DHX9-dependent. In addition, the depletion of DHX9 hindered osteosarcoma cell proliferation. Notably, MCM2 and MCM3 expression levels were positively correlated with the DHX9 expression level in tumor samples and were associated with a poor prognosis in patients with osteosarcoma. Taken together, these results suggest that the MCM2/MCM3-DHX9 axis has an important role in osteosarcoma progression.

CSE1L interaction with MSH6 promotes osteosarcoma progression and predicts poor patient survival.

To discover tumor-associated proteins in osteosarcoma, a quantitative proteomic analysis was performed to identify proteins that were differentially expressed between osteosarcoma and human osteoblastic cells. Through clinical screening and a functional evaluation, chromosome segregation 1-like (CSE1L) protein was found to be related to the growth of osteosarcoma cells. To date, little is known about the function and underlying mechanism of CSE1L in osteosarcoma. In the present study, we show that knockdown of CSE1L inhibits osteosarcoma growth in vitro and in vivo. By co-immunoprecipitation and RNA-seq analysis, CSE1L was found to interact with mutS homolog 6 (MSH6) and function as a positive regulator of MSH6 protein in osteosarcoma cells. A rescue study showed that decreased growth of osteosarcoma cells by CSE1L knockdown was reversed by MSH6 overexpression, indicating that the activity of CSE1L was an MSH6-dependent function. In addition, depletion of MSH6 hindered cellular proliferation in vitro and in vivo. Notably, CSE1L expression was correlated with MSH6 expression in tumor samples and was associated with poor prognosis in patients with osteosarcoma. Taken together, our results demonstrate that the CSE1L-MSH6 axis has an important role in osteosarcoma progression.

Serum Mast Cell Tryptase as a Marker of Posttraumatic Joint Contracture in a Rabbit Model.

OBJECTIVES: Mast cells have been identified as key mediators of posttraumatic joint contracture, and stabilizing medications (ketotifen) have been shown to decrease contracture severity. Serum mast cell tryptase (SMCT) levels are used clinically to monitor mast cell-mediated conditions. The goals of this study were to determine if SMCT levels are elevated in the setting of joint contracture, if they can be decreased in association with ketotifen therapy, and if they correlate with contracture severity. METHODS: This study used a previously developed rabbit model in which 39 animals were divided into 4 groups: operatively created joint contracture (ORC, n = 13), operatively created contracture treated with ketotifen at 2 doses (KF0.5, n = 9; KF1.0, n = 9), and healthy rabbits (NC, n = 8). Range of motion measures were performed at 8 weeks after the surgery. Serum samples were collected on postoperative days 1, 3, 5, 7, 21, 35, and 49. SMCT levels were measured using a rabbit-specific enzyme-linked immunosorbent assay. RESULTS: Levels of SMCT were highest in the operatively created joint contracture group and were significantly greater compared with both ketotifen groups (P < 0.001). Levels were highest at postoperative day 1 with a trend to decrease over time. A positive correlation between SMCT levels and contracture severity was observed in all operative groups (P < 0.05). CONCLUSIONS: Levels of SMCT are elevated in the setting of joint contracture, decreased in association with ketotifen therapy, and positively correlated with contracture severity. This is the first study to establish a relationship between SMCT and joint injury. Measurement of SMCT may be valuable in identifying those at risk of posttraumatic joint contracture.

CNOT1 cooperates with LMNA to aggravate osteosarcoma tumorigenesis through the Hedgehog signaling pathway.

While treatments for childhood osteosarcoma have improved, the overall survival for this common type of bone cancer has not changed for three decades, and thus, new targets for therapeutic development are needed. To identify tumor-related proteins in osteosarcoma, we used isobaric tags in a relative and absolute quantitation proteomic approach to analyze the differentially expressed proteins between osteosarcoma cells and human osteoblastic cells. Through clinical screening and functional evaluation, CCR4-NOT transcription complex subunit 1 (CNOT1) correlated with the growth of osteosarcoma cells. To date, the mechanisms and regulatory roles of CNOT1 in tumors, including osteosarcoma, remain largely elusive. Here, we present evidence that knockdown of CNOT1 inhibits the growth of osteosarcoma in vitro and in vivo. Mechanistically, we observed that CNOT1 interacted with LMNA (lamin A) and functioned as a positive regulator of this intermediate filament protein. The RNA-seq analysis revealed that CNOT1 depletion inhibited the Hedgehog signaling pathway in osteosarcoma cells. A rescue study showed that the decreased growth of osteosarcoma cells and inhibition of the Hedgehog signaling pathway by CNOT1 depletion were reversed by LMNA overexpression, indicating that the activity of CNOT1 was LMNA dependent. Notably, the CNOT1 expression was significantly associated with tumor recurrence, Enneking stage, and poor survival in patients with osteosarcoma. Examination of clinical samples confirmed that CNOT1 expression positively correlated with LMNA protein expression. Taken together, these results suggest that the CNOT1-LMNA-Hedgehog signaling pathway axis exerts an oncogenic role in osteosarcoma progression, which could be a potential target for gene therapy.

Application of distal radius-positioned hinged external fixator in complete open release for severe elbow stiffness.

BACKGROUND: Radical release for severe stiff elbows may lead to instability. Hinged external fixation is used to treat unstable elbows. We hypothesized that extensive open release combined with a distal radius-positioned hinged external fixator would have good performance and low complications rate in treating severe elbow stiffness. Thus, the efficacy and security of this technique were assessed in this study. METHODS: We retrospectively reviewed 38 post-traumatic elbows with severe stiffness that underwent arthrolysis between February 2011 and February 2014. All patients were assessed as having elbow instability after complete arthrolysis. Ligament repair was combined with implantation of a hinged external fixator (fixed to the humerus and distal radius) to maintain elbow stability. Flexion arc, forearm rotation, Mayo Elbow Performance Score, elbow stability, and radiographs were evaluated preoperatively and postoperatively, and complications were documented. RESULTS: Mean follow-up was 31 months. Significant improvement was noted in flexion-extension arc (from 27° to 126°), forearm rotation (from 148° to 153°), and mean Mayo Elbow Performance Score (from 68 points to 96 points). Mean pronation arc decreased from 66° preoperatively to 6° at 1.5 months of follow-up and showed a transient reduction during first 6 months postoperatively. Pin-related infection occurred in 2 patients, which was cured with conservative treatment. Two patients had moderate instability after removal of the fixator and regained stability at the 12-month follow-up. At the last follow-up, complications included ulnar nerve paralysis in 3, recurrence of heterotopic ossification in 1, and moderate pain in 1. CONCLUSIONS: Complete open release combined with a distal radius-positioned hinged external fixator is an effective treatment for severe stiff elbows. This technique had a low complication rate.

Reconstruction of medial collateral ligament defects with a flexor-pronator fascia patch in complete open release of stiff elbows.

BACKGROUND: Because medial elbow stability is essential for stiff elbow release, surgical techniques have been reported for reconstructing medial elbow stability. However, medial collateral ligament (MCL) defects, caused by inevitable detachment and resection performed for complete release, make the reconstruction more challenging. To our knowledge, no study has evaluated the outcomes after using a flexor-pronator fascia patch in medial elbow reconstruction for open release of stiff elbows. We hypothesized that this technique is effective for repairing MCL defects. METHODS: We retrospectively reviewed the records of 10 patients. The MCL defects were all reconstructed with a flexor-pronator fascia patch. An external fixator was used in all patients. One patient could not be contacted and was thus excluded from the study. Outcome measures included stability, range of motion, Mayo Elbow Performance Score, ulnar nerve symptoms, power grip, and radiographic findings. RESULTS: The mean follow-up period was 19.6 months; all elbows were stable by the last follow-up. One patient presented with moderate elbow instability and then regained stability 3 months after the external fixator was removed. The Mayo Elbow Performance Score improved from 58 points to 94 points, and the mean flexion arc improved from 40° to 133°. No radiographic manifestations of elbow dislocation or suture anchor looseness were observed. CONCLUSION: A flexor-pronator fascia patch provides sufficient stability for repairing MCL defects without restricting the range of motion gained during arthrolysis.

Effect on muscle strength of the upper extremities after open elbow arthrolysis.

BACKGROUND: Open elbow arthrolysis manipulates tendons and soft tissues surrounding the elbow and may lead to strength decline after the operation. We hypothesized that strength of elbow and wrist motions and handgrip could be compromised after the procedure and that the strength recovery pattern may differ between men and women and between the dominant and nondominant side. METHODS: This was a prospective cohort study. We monitored 32 patients with post-traumatic elbow stiffness who underwent open arthrolysis between June 2014 and December 2014. All patients underwent standardized postoperative physical therapy. Preoperative and postoperative isometric strength were measured by a handheld dynamometer. Mayo Elbow Performance Score (MEPS) and arc of motion (AOM) were also analyzed. RESULTS: Mean follow-up was 26.13 months. Significant improvement was noticed in mean AOM (from 46° to 127°) and MEPS (from 67.97 to 96.86). No significant decline was noted in isometric strength at the last follow-up day. The strength ratios between men and women showed no significant difference from postoperative day 7 to the last follow-up day. At all follow-up assessments, isometric strength showed no significant difference between the dominant and nondominant side. CONCLUSIONS: AOM and MEPS achieved significant enhancement after open elbow arthrolysis. The procedure did not lead to isometric strength decline. Postoperative gain of strength was proportional to the baseline strength level of each muscle group, and men had a more prominent gain of strength than women during the entire follow-up. Dominance had no effect on postoperative strength recovery.

Open arthrolysis for elbow stiffness increases carrying angle but has no impact on functional recovery.

BACKGROUND: With the exception of normal anatomic changes in the medial collateral ligament and radial head, other factors related to carrying angle changes have not been systematically studied. We reviewed patients who underwent open arthrolysis of the elbow, and evaluated if open arthrolysis could change carrying angle. We then identified factors associated with carrying angle changes. METHODS: Fifty patients with a minimum of 24 months of follow-up after open arthrolysis were evaluated retrospectively. Preoperative and postoperative carrying angles were compared. RESULTS: The carrying angles of 36 elbows in 36 patients were unchanged after surgery (Group A), while the carrying angles of 14 elbows in 14 patients increased postoperatively (Group B). In Group A, mean postoperative extension and flexion were 7° (range 0-24°) and 125° (range 10-135°) respectively, while mean postoperative pronation and supination were 60° (range 50-80°) and 65° (range 30-85°), respectively. In Group B, mean postoperative extension and flexion were 25° (range 0-40°) and 128° (range 60-138°), while mean postoperative pronation and supination were 65° (range 45-85°) and 60° (range 45-75°), respectively. No significant difference in range of motion and Mayo Elbow Performance Score was observed between the two groups. CONCLUSIONS: During open arthrolysis, humeral trochlea debridement and techniques for improving forearm rotation could increase carrying angle. However, this had no impact on elbow functional recovery.

Stability of the distal phalanx fracture - A biomechanical study on the importance of the nail and the influence of fixation by crossing Kirschner wires.

BACKGROUND: With respect to the stability of displaced distal-phalanx fracture, the relevance of nail loss and the biomechanical effects of fixation using crossed Kirschner wires have not been investigated. The present study aimed to determine whether the nail or the type of fixation contributes to stabilizing distal-phalanx fracture. METHODS: In 48 specimens (fingers), a model of the comminuted fracture of the distal phalanx (AO type A3) was created by resecting a 1-mm osseous segment from the distal phalanx. Specimens were assigned to one of four groups, depending on whether the fracture was accompanied with nail loss, and whether the fracture fixation employed a single Kirschner wire or a crossing of two Kirschner wires. Each specimen was subjected to either a bending or a torsion test. FINDINGS: Regardless of the fixation form, the mean peak bending and torsion forces were higher for the specimens with the nail intact. Furthermore, these forces were also higher in specimens which had received fixations based on the Kirschner wires, compared to those specimens which had received fixations based on a single Kirschner wire. The highest mean peak torque 1.39 (0.12) N·m was found for the specimens with no nail loss and fixation using two crossed Kirschner wires, while the lowest mean peak torsion 0.46 (0.02) N·m was found for specimens with nail loss and fixation using a single Kirschner wire. INTERPRETATION: Our results suggest that the nail can provide additional stability for comminuted fractures of the distal phalanx after fixation. Furthermore, when nail loss occurs, fixation using two crossed Kirschner wires can provide significantly more stability than fixation using single Kirschner wire.

Open arthrolysis with pie-crusting release of the triceps tendon for treating post-traumatic contracture of the elbow.

BACKGROUND: Extensive loss of elbow flexion compromises the performance of daily activities. We examined the clinical outcomes of patients with post-traumatic extension contracture of the elbow treated with open arthrolysis and pie-crusting release of the triceps tendon. METHODS: We retrospectively reviewed the records of 7 patients (5 men and 2 women; mean age, 35 years) who underwent open arthrolysis via a combined lateral and medial approach with pie-crusting release of the triceps tendon for the treatment of post-traumatic elbow stiffness. All the patients had heterotopic ossification that restricted elbow motion and underwent removal of the ossified tissue and capsular release. The triceps tendon was gradually stretched by making multiple stab incisions on the tendon by using a No. 11 surgical blade. The range of motion of the elbow was recorded both preoperatively and at the final postoperative follow-up. Elbow function was assessed with the Mayo Elbow Performance Score. RESULTS: The patients were followed up for a mean of 24 months. After treatment, significant improvement was noted in the total arc of motion (from 44° to 116°, P <.001), mean flexion (from 80° to 124°, P < .001), and mean extension (from 31° to 8°, P = .004). The mean Mayo Elbow Performance Score improved significantly from 59 points preoperatively to 92 points at the final evaluation. No major postoperative complications developed in any of the patients. CONCLUSION: Our findings indicate that open arthrolysis with pie-crusting release of the triceps tendon is an effective and safe treatment approach for post-traumatic extension contracture of the elbow.

Analgecine, the extracts of Vaccinia-inoculated rabbit skin, effectively alleviates the chronic low back pain with little side effect - A randomized multi-center double-blind placebo-controlled phase 3 clinical trial.

BACKGROUND: Chronic low back pain affects daily activities at home and workplaces and causes a huge economic burden. Current therapeutic options are very limited and the effects of available pharmacological agents are less than satisfactory. While NSAIDs might be effective for the short term and opioids might help with urgent pain relief and improving the life quality, their long-term use is associated with significant side effects and drug misuse or abuse. To seek alternative pharmacological agents for effective treatment, we examined the therapeutic potential of the extracts of Vaccinia variola-inoculated rabbit skin (Analgecine, abbreviated as AGC) in patients with chronic low back pain due to degenerative vertebral disorders. METHODS: In this randomized multi-center double-blind placebo-controlled phase 3 clinical trial (Chinese Clinical Trial Registry number 2009L01498), we enrolled patients (aged 26-70 years) with chronic low back pain for at least 3 months due to degenerative spinal (vertebral) disorders from 7 medical centers in China, and randomly allocated 459 participants to receive oral AGC or placebo for 28 days to study the efficacy and safety of AGC. Randomization was performed according to a centralized randomization schedule, which was blocked by study sites and generated by an unmasked statistician independent of study conduct and data analysis. Both participants and staff at each study site were masked to treatment assignment. The primary efficacy endpoint was the change of the mean pain intensity, based on an 11-point numerical rating scale, between the baseline and the last week of treatment, with the primary efficacy analysis of intention to treat. The ratio between exposed and unexposed groups was designed to be 3:1 in order to increase the likelihood of demonstrating the AGC effect upon repeated measures. RESULTS: 347 patients were assigned to receive AGC (4 units/tablet; 2 tablets twice a day) and 112 patients were to take placebo. Among them, 324 patients taking AGC and 112 receiving placebo completed the assessment. Patients receiving AGC reported significant pain relief at the end of week 2 and 3 compared to those taking placebo, with mean reduction of the pain scores as 1.7 vs. 0.9 at week 2 (p < 0.0001) and 2.8 vs. 1.2 at week 3 (p < 0.0001). A total of 47 AGC-treated patients reported 85 treatment emergent adverse events while 16 patients taking placebo reported 26 events, but no serious side effects were found to be related to AGC treatment. CONCLUSION: Analgecine (AGC, 8 units twice daily) effectively alleviates chronic low back pain due to degenerative vertebral disorders when compared to placebo and is well tolerated by tested individuals, and can be considered as a first-line treatment for chronic low pain due to degenerative vertebral diseases.

MiR-542-5p is a negative prognostic factor and promotes osteosarcoma tumorigenesis by targeting HUWE1.

Recent evidence has demonstrated that microRNAs (miRNAs) are involved in the proliferation and metastasis of osteosarcoma. Using miRNA microarray and functional screening methods to compare miRNA expression profiles in osteosarcoma cell lines treated with Trichostatin A (TSA), overexpression of miR-542-5p was determined to be involved in the proliferation of osteosarcoma. We used isobaric tags for relative and absolute quantitation (iTRAQ) and nanoscale liquid chromatography-mass spectrometry (NanoLC-MS/MS) to identify differentially expressed proteins in MNNG/HOS and U2OS osteosarcoma cell lines transfected with miR-542-5p; in both cell lines, seven proteins were downregulated, and nine were upregulated. HUWE1 was found to be a direct target of miR-542-5p in both osteosarcoma cell lines, and was negatively correlated with miR-542-5p levels in human osteosarcoma tissues. Moreover, the expression of miR-542-5p was upregulated in human osteosarcoma tissue compared with non-tumor adjacent tissue. Kaplan-Meier analysis revealed that overexpression of miR-542-5p predicted poor prognosis for osteosarcoma patients. Taken together, our results indicated that miR-542-5p plays a critical role in the proliferation of osteosarcoma and targets HUWE1.