IOX1 epigenetically enhanced photothermal therapy of 3D-printing silicene scaffolds against osteosarcoma with favorable bone regeneration.

Osteosarcoma (OS) is the third most common malignancy in adolescence. Currently, the treatments of OS confront great obstacles of tumor recurrence and critical bone defects after surgery, severely affecting the survival rates and living qualities of patients. Hence, it is urged to develop distinct biomaterials with both efficient tumor therapeutic and osteogenic functions. Although photothermal therapy (PTT) has aroused expanding interest, characterizing negligible invasiveness and high spatiotemporal adjustment, few studies discussed its drawbacks, such as thermal injury to adjacent normal tissue and exceeded laser power density, implying that focusing on sensitizing OS to PTT instead of simply elevating the laser power density may be a fresh way to enhance the PTT efficacy and attenuate the side/adverse effects. Herein, we successfully constructed 3D-printing silicene bioactive glass scaffolds with preferable PTT efficacy at the second near-infrared (NIR-II) biowindow and outstanding osteogenic biofunctions owing to the release of bioactive elements during degradation. Impressively, a histone demethylase inhibitor, IOX1, was introduced before PTT to sensitize OS to thermal therapy and minimize the side/adverse effects. This work offered a distinctive paradigm for optimizing the PTT efficacy of osteogenic scaffolds against OS with epigenetic modulation agents.

Tranexamic acid in patients with post-traumatic elbow stiffness: protocol for a randomised, double-blind, placebo-controlled trial investigating the effectiveness of tranexamic acid at reducing the recurrence of heterotopic ossification after open elbow arthrolysis.

INTRODUCTION: Exaggerated inflammatory response is one of the main mechanisms underlying heterotopic ossification (HO). It has been suggested that the antifibrinolytic drug tranexamic acid (TXA) can exert a significant anti-inflammatory effect during orthopaedic surgery. However, no prospective studies have yet investigated the effects of TXA on HO recurrence in patients following open elbow arthrolysis (OEA). METHODS AND ANALYSIS: Here, we present a protocol for a single-centre, randomised, double-blind, placebo-controlled trial to investigate the effectiveness of TXA on HO recurrence after OEA in a single hospital. A minimum sample size of 138 eligible and consenting participants randomised into treatment and control groups in a 1:1 manner will be included. Patients will receive 2 g of intravenous TXA (experimental group) or placebo (normal saline, control group) administered before skin incision. The primary outcome is HO recurrence rate within 12 months after surgery. The secondary outcomes are the serum immune-inflammatory cytokines including erythrocyte sedimentation rate, C reactive protein, interleukin (IL)-6, IL-1ß, IL-13 at the first and third day postoperatively, and elbow range of motion and functional score at 1.5, 6, 9 and 12 months after surgery. After completion of the trial, the results will be reported in accordance with the extensions of the Consolidated Standards of Reporting Trials Statement for trials. The results of this study should determine whether TXA can reduce the rates of HO occurrence after OEA. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Medical Ethics Committee of the Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (reference number 2022-123-(1)). The results of this study will be disseminated through presentations at academic conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2300068106.

Procyanidins and Their Therapeutic Potential against Oral Diseases.

Procyanidins, as a kind of dietary flavonoid, have excellent pharmacological properties, such as antioxidant, antibacterial, anti-inflammatory and anti-tumor properties, and so they can be used to treat various diseases, including Alzheimer's disease, diabetes, rheumatoid arthritis, tumors, and obesity. Given the low bioavailability of procyanidins, great efforts have been made in drug delivery systems to address their limited use. Nowadays, the heavy burden of oral diseases such as dental caries, periodontitis, endodontic infections, etc., and their consequences on the patients' quality of life indicate a strong need for developing effective therapies. Recent years, plenty of efforts are being made to develop more effective treatments. Therefore, this review summarized the latest researches on versatile effects and enhanced bioavailability of procyanidins resulting from innovative drug delivery systems, particularly focused on its potential against oral diseases.

Macrophage Polarization Modulated by NF-κB in Polylactide Membranes-Treated Peritendinous Adhesion.

Foreign body reactions (FBR) to implants seriously impair tissue-implant integration and postoperative adhesion. The macrophage, owing to its phenotypic plasticity, is a major regulator in the formation of the inflammatory microenvironment; NF-κB signaling also plays a vital role in the process. It is hypothesized that NF-κB phosphorylation exerts a proinflammatory regulator in FBR to polylactide membranes (PLA-M) and adhesion. First, in vitro and in vivo experiments show that PLA-M induces NF-κB phosphorylation in macrophages, leading to M1 polarization and release of inflammatory factors. The inflammatory microenvironment formed due to PLA-M accelerates myofibroblast differentiation and release of collagen III and MMP2, jointly resulting in peritendinous adhesion. Therefore, JSH-23 (a selective NF-κB inhibitor)-loaded PLA membrane (JSH-23/PLA-M) is fabricated by blend electrospinning to regulate the associated M1 polarization for peritendinous anti-adhesion. JSH-23/PLA-M specifically inhibits NF-κB phosphorylation in macrophages and exhibits anti-inflammatory and anti-adhesion properties. The findings demonstrate that NF-κB phosphorylation has a critical role in PLA-induced M1 polarization and aggravating FBR to PLA-M. Additionally, JSH-23/PLA-M precisely targets modulation of NF-κB phosphorylation in FBR to break the vicious cycle in peritendinous adhesion therapy.

Effect of collagen cross-linkers on dentin bond strength: A systematic review and network meta-analysis.

Objective: This study aimed to evaluate the role of collagen cross-linkers in the bonding performance of the resin-dentin interface through a systematic review and a network meta-analysis. Sources: The literature search was conducted in several databases like PubMed, EMBASE, Cochrane, Scopus and Web of Science from their inception till 30 April 2022. Study selection: The inclusion criteria consisted of in vitro studies evaluating the micro-tensile and micro-shear bond strengths of different cross-linkers acting on dentin. Bayesian network meta-analysis was conducted using RStudio. Data: Out of the 294 studies evaluated in the full-text analysis, 40 were included in the systematic review and meta-analysis. Most studies have used cross-linkers as primer (65.1%), followed by incorporating them into in adhesives and acid etching agents. The application methods of the adhesive system were classified as "etch-and-rinse (ER) adhesives" (77%) and "self-etching (SE) adhesives". Moreover, there were six types of cross-linkers in this presented review, of which the most numerous were polyphenols. Conclusion: Different application methods of cross-linkers, the long-term results showed that were only effective when used for longer durations, the immediate results were not statistically different. According to immediate and long-term results, etch-and-rinse (ER) adhesives showed a greater bonding performance than the control groups (p ≤ 0.05), whereas self-etching (SE) adhesives showed similar bond strength values (p ≥ 0.05). The result of network meta-analysis (NMA) showed that Dope like compound showed higher long-term bonding performance than other cross-linkers. Clinical significance: Long-term clinical studies may be needed to determine the effect of the cross-linkers on the bonding properties.

Intravenous tranexamic acid reduce postoperative drainage and pain after open elbow arthrolysis: a randomized controlled trial.

BACKGROUND: Open elbow arthrolysis (OEA), which has become an established treatment for post-traumatic elbow stiffness (PTES), requires complete release of contracture tissue and wide excision of ectopic bone, which results in extensive bleeding. The aim of the present study is to evaluate the efficacy of intravenous tranexamic acid (TXA) on postoperative drainage, calculated blood loss, and early clinical outcomes in patients undergoing OEA. METHODS: A double-blind, randomized, placebo-controlled trial including 96 patients undergoing OEA was undertaken. Patients received intravenously either 100 mL saline (placebo group, n = 48), or 100 mL saline plus 1 g TXA (TXA group, n = 48) before skin incision. The primary outcome was the drainage volume on postoperative days (PODs) 1-3. Secondary outcomes included the calculated blood loss, elbow pain score measured by visual analog scale (VAS), elbow function valued by Mayo Elbow Performance Score (MEPS), and rate of complications after OEA. RESULTS: Mean total postoperative drainage volume (TXA group: 182 mL vs. placebo group: 214 mL, P = .003) and mean calculated total blood loss (TXA group: 582 mL vs. placebo group: 657 mL, P = .004) were significantly lower in the TXA group. No transfusions were necessary in either group. Mean VAS pain scores in elbow motion showed marked differences between both groups on POD 1 (TXA: 5 vs. placebo: 6, P = .003) and POD 2 (TXA: 4 vs. placebo: 5, P = .023) but not in other postoperative time points. No differences were detected in complications, such as pin-related infection, hematoma, new or exacerbation of ulnar nerve symptoms, and recurrent heterotopic ossification. At the 6-month follow-up, no statistical differences were found between the 2 groups with respect to the elbow functions including range of motion, VAS score, and MEPS. CONCLUSION: Intravenous administration of TXA significantly decreased the postoperative drainage volume and the total estimated blood loss and alleviated the elbow pain with motion during early postoperative days in patients undergoing OEA.

Risk Factors for the Occurrence and Progression of Posttraumatic Elbow Stiffness: A Case-Control Study of 688 Cases.

Background: Elbow stiffness is a severe complication after trauma. Surgical or conservative treatments may be ineffective for restoring functional elbow motion. We aim to evaluate intrinsic and extrinsic factors for the occurrence and severity of elbow stiffness. Methods: This retrospective case-control study included mild/moderate stiffness, severe stiffness, and non-stiffness groups between January 2011 and December 2017 at a single orthopedic center. Multivariable logistic regression analysis and subgroup analysis were used to evaluate age, gender, body mass index, muscle strength, fracture type and site, injury mechanism, immobilization time, elbow dysfunction time, multiple surgeries, nerve symptoms, physical therapy, smoking and alcohol abuse, and dominant hand of stiff elbow as potential risk factors for the occurrence and severity of elbow stiffness. Results: There were 461 patients in the stiffness group and 227 patients in the non-stiffness group. The odds ratios (ORs) of the age, muscle strength, and injury mechanism were 0.960, 0.333, and 0.216 for the occurrence of elbow stiffness. In subgroup evaluation, increased cast immobilization time might be a risk factor for patients receiving conservative therapies (OR = 2.02; p = 0.014). In the evaluation on factors for progression of elbow stiffness, "multiple surgeries" might be a risk factor in surgical treatment by subgroup analysis (OR = 1.943; p = 0.026). Nevertheless, alcohol abuse might increase severity of elbow stiffness in conservatively treated patients (OR = 3.082; p = 0.025). Conclusion: Increased cast immobilization time in the conservative therapy might be a risk factor for stiffness occurrence. Multiple surgeries might be risk factors for stiffness progression. Alcohol abuse potentially increased stiffness severity after conservative treatment.

Severe traumatic valgus instability of the elbow: pathoanatomy and outcomes of primary operation.

BACKGROUND: The objective of the study was to depict the pathoanatomy of traumatic valgus instability of the elbow and to report clinical outcomes of primary operation. METHODS: Thirty-one patients presented with traumatic valgus instability of the elbow without dislocation. Thirty-one patients underwent surgical intervention of radial head fractures (28 open reduction and internal fixation and 3 radial head resection) and anatomical repair of the anterior bundle of medial collateral ligament (AMCL) with suture anchors. Twenty patients with disruption of the flexor-pronator tendon (FPT) and 14 patients with tears of the anterior capsule had primary repair of the FPT and anterior capsule simultaneously. Clinical outcomes were evaluated with the Mayo Elbow Performance Score (MEPS), modified hospital for special surgery assessment scale (HSS), and Disabilities of the Arm, Shoulder, and Hand (DASH) score. RESULTS: The median follow-up was 37.3 months (range, 15-53 months). Radial head fractures and complete avulsion of the medial collateral ligament (MCL) from its humeral footprint were confirmed in all patients intraoperatively. Intraoperative findings indicated disruption of the FPT in 20 patients and tears of the anterior capsule in 14 patients. Twenty-nine of 31 patients returned to previous activity and work levels within 6 months after surgery. The MEPS, modified HSS, and DASH score were 94 ± 4, 91 ± 5, and 8 ± 2 at the latest follow-up. CONCLUSIONS: Radial head fractures with avulsion of the MCL can lead to severe valgus instability of the elbow. Primary operation to repair these disrupted structures, especially repair of the AMCL, can effectively restore valgus stability.

Chronic Posttraumatic Dislocation of Radial Head With Ulnar Nerve Entrapment in a Child: A Case Report and Literature Review.

We present an unusual case of chronic posttraumatic anteromedial dislocation of radial head with direct ulnar nerve entrapment in a child. Ulnar nerve decompression, open reduction of the radial head, and annular ligament reconstruction using a palmaris longus tendon graft were performed, and a satisfactory functional outcome was achieved at the 15-month follow-up. Through a review of literature, we conclude that early diagnosis and management for radial head dislocation are recommended to avoid nerve symptoms. Besides, open reduction and annular ligament reconstruction with a palmaris longus tendon graft would be an alternative surgery during chronic phase.

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.

Release of celecoxib from a bi-layer biomimetic tendon sheath to prevent tissue adhesion.

Posttraumatic tendon adhesion limits the motion of the limbs greatly. Biomimetic tendon sheaths have been developed to promote tendon healing and gliding. However, after introduction of these biomaterials, the associated inflammatory responses can decrease the anti-adhesion effect. Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) that can decrease inflammation responses. We blended hyaluronic acid and poly(l-lactic acid)-polyethylene glycol (PELA) with microgel electrospinning technology to form an inner layer of a bi-layer biomimetic sheath using sequential electrospinning of an outer celecoxib-PELA layer. Electrospun bi-layer fibrous membranes were mechanically tested and characterized by morphology, surface wettability, and drug release. The tensile strength showed a decreased trend and water contact angles were 114.7 ± 3.9°, 103.6 ± 4.4°, 116.3 ± 5.1°, 122.8 ± 4.7°, and 126.5 ± 4.2° for the surface of PELA, hyaluronic acid-PELA, 2, 6, and 10% celecoxib-PELA electrospun fibrous membranes, respectively. In vitro drug release studies confirmed burst release and then sustained release from the fibrous membranes containing celecoxib for 20 days. In a chicken model of flexor digitorum profundus tendon surgery, the outer celecoxib/PELA layer offered advanced anti-adhesion roles compared to the outer PELA layer and the inner hyaluronic acid-loaded PELA layer still offered tendon healing and gliding. Thus, celecoxib-loaded anti-adhesive tendon sheaths can continuously offer bi-layer biomimetic tendon sheath effects with celecoxib release from the outer layer to prevent tendon adhesion.

The time point in surgical excision of heterotopic ossification of post-traumatic stiff elbow: recommendation for early excision followed by early exercise.

BACKGROUND: Post-traumatic heterotopic ossification (HO) around the elbow may severely impair joint function. Although surgical excision is effective at restoring range of motion (ROM), traditional surgical treatment is postponed for at least 1 year to prevent recurrence, which leads to secondary contracture of the elbow. Because the optimal timing of resection is controversial, our study was performed to compare recurrence and elbow function between early and late excision in our patients to determine whether the delay is necessary. METHODS: We retrospectively reviewed 164 patients during a 4-year period. In the control group (112 patients), HO was excised at an average of 23.0 months after initial injury (range, 9-204 months); in the early excision group (52 patients), resection was performed at an average of 6.1 months (range, 3-8 months). HO recurrence was assessed by the Hastings classification system. Final ROM and Mayo Elbow Performance Scores were also evaluated. RESULTS: Recurrent HO was observed in 30 of 112 patients (26.8%) in the control group and 15 of 52 (28.9%) in early excision group. No significant difference in HO recurrence was found between the 2 groups (P = .942). Moreover, there were no notable differences regarding ROM, Mayo Elbow Performance Scores, and complications postoperatively. CONCLUSIONS: Early excision associated with early exercise is effective for the treatment of HO aiming at a low recurrence rate and satisfactory function. The conventional surgical delay of more than 1 year may be shortened.

Arthrolysis and delayed internal fixation combined with hinged external fixation for elbow stiffness associated with malunion or nonunion of capitellum fracture.

BACKGROUND: This study assessed outcomes after treatment of patients with capitellum fracture diagnosed >4 weeks after the trauma (delayed) who presented with stiff elbow. METHODS: We reviewed 7 patients with stiff elbows after delayed diagnosis of capitellum fractures between February 2007 and February 2012. They were treated with arthrolysis by twin incisions, late open reduction and internal fixation, and a hinged external fixator. According to the Bryan-Morrey-McKee classification, 3 patients had type I capitellum fractures and 4 patients had type IV. RESULTS: Mean follow-up was 28 months (range, 24-38 months). The mean delay from the initial trauma was 3.7 months. The flexion arc improved from a preoperative mean of 24° to a postoperative mean of 122°. The Mayo Elbow Performance Score increased from a mean of 56 points to 93 points. Anatomic fracture union occurred in all cases, and there was no secondary displacement. CONCLUSIONS: Arthrolysis, late internal fixation, and use of a hinged external fixator can solve problems associated with stiff elbow after delayed diagnosis of capitellum fracture. Combined use of these techniques may be a safe and effective treatment option.

Comparative study of radial head resection and prosthetic replacement in surgical release of stiff elbows.

PURPOSE: Elbow trauma can compromise the arc of elbow flexion and forearm rotation. This study aimed at comparing the outcomes of radial head resection and prosthetic replacement in the surgical release of post traumatic elbow stiffness and associated restriction in forearm rotation. METHODS: We retrospectively reviewed the data of patients who underwent open arthrolysis with radial head resection (n = 15; resection group) or radial head replacement (n = 19; replacement group). The pre- and postoperative measurements of the elbow range of motion (ROM) were recorded. Elbow function was evaluated by the Broberg and Morrey Evaluation System; the Mayo Elbow Performance Index (MEPI); and the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. RESULTS: Over a mean follow-up duration of 22 months, the improvement in the arc of flexion and extension was 79° (range, 45-125°) and 82° (range, 10-110°), while that in the ROM for forearm rotation was 96° (range, 40-150°) and 102° (range, 15-150°) in the resection and replacement groups, respectively. There were no significant intergroup differences in the elbow ROM measured at the last follow up. The Broberg and Morrey, MEPI, and Dash scores in the two groups were comparable. CONCLUSIONS: Both resection and prosthetic replacement of the radial head with open arthrolysis of post traumatic elbow stiffness were feasible in treating the associated restriction of forearm rotation. We recommend that if the elbow is stable after complete release, radial head resection is preferable to prosthetic replacement because it is technically less demanding.

Effect of cryotherapy after elbow arthrolysis: a prospective, single-blinded, randomized controlled study.

OBJECTIVE: To investigate the effect of cryotherapy after elbow arthrolysis on elbow pain, blood loss, analgesic consumption, range of motion, and long-term elbow function. DESIGN: Prospective, single-blinded, randomized controlled study. SETTING: University hospital. PARTICIPANTS: Patients (N=59; 27 women, 32 men) who received elbow arthrolysis. INTERVENTIONS: Patients were randomly assigned into a cryotherapy group (n=31, cryotherapy plus standard care) or a control group (n=28, standard care). MAIN OUTCOME MEASURES: Elbow pain at rest and in motion were measured using a visual analog scale (VAS) on postoperative day (POD) 1 to POD 7 and at 2 weeks and 3 months after surgery. Blood loss and analgesic consumption were recorded postoperatively. Elbow range of motion (ROM) was measured before surgery and on POD 1, POD 7, and 3 months after surgery. The Mayo Elbow Performance Score (MEPS) was evaluated preoperatively and 3 months postoperatively. RESULTS: VAS scores were significantly lower in the cryotherapy group during the first 7 PODs, both at rest and in motion (P<.05). There were no significant differences between the 2 groups in VAS scores at 2 weeks and 3 months after surgery. Less sufentanil was consumed by the cryotherapy group than the control group for pain relief (P<.01). No significant differences were found in blood loss, ROM, and MEPS between the 2 groups (P>.05). CONCLUSIONS: Cryotherapy is effective in relieving pain and reducing analgesic consumption for patients received elbow arthrolysis. The application of cryotherapy will not affect blood loss, ROM, or elbow function.

[Progress of treatment of cubital tunnel syndrome].

OBJECTIVE: To review the current progress of treatment of cubital tunnel syndrome (CTS). METHODS: Recent relevant literature on the treatment of CTS was extensively reviewed and summarized. RESULTS: CTS is one of the most common peripheral nerve compression diseases. The clinical presentations of CTS consist of numbness and tingling in the ring and small fingers of the hand, pain in the elbow and sensory change following long-time elbow bending. Severe symptoms such as weakness or atrophy of intrinsic muscles of the hand and claw hand deformity may occur. The etiology of CTS is ulnar nerve compression caused by morphological abnormalities and nerve paralysis after elbow trauma. CTS can be treated by nonsurgical methods and surgery. Surgical options include in situ decompression, ulnar nerve transposition, medial epicondylectomy, and endoscopic release. CONCLUSION: There are multiple options to treat CTS, but the indication and effectiveness of each treatment are still controversial. Further studies are required to form a generally accepted treatment system.

Intrawound application of vancomycin reduces wound infection after open release of post-traumatic stiff elbows: a retrospective comparative study.

BACKGROUND: With the improvements in wound healing through the use of intravenous prophylactic antibiotics and technical refinements, postoperative elbow infections have become less common but still occur in certain elective elbow surgeries. The objective of this study was to evaluate the safety and efficacy of prophylactic application of vancomycin into the operative site to reduce the incidence of infection after the open release of post-traumatic stiff elbows. METHODS: A retrospective review of 272 such patients during a 4-year period was performed. In the control group (93 patients), simple prophylaxis with standard intravenous antibiotics was performed; in the vancomycin group (179 patients), vancomycin powder was applied directly into the wound before closure along with standard intravenous prophylaxis. RESULTS: After a follow-up of at least 6 months, the control group was found to have 6 infections (6.45%; confidence interval: 2.40%-13.52%) compared with none (0%; confidence interval: 0-2%.04%) in the vancomycin group, which was a statistically significant difference (P = .0027). No adverse effects were documented from the direct use of the vancomycin powder. CONCLUSIONS: The local application of vancomycin powder may be a promising means of preventing postoperative elbow infections after elbow release in patients with post-traumatic elbow stiffness.