Intra-articular Ankle Fracture Research Articles

Potential Roles of Inflammation on Post-Traumatic Osteoarthritis of the Ankle.

Post-traumatic osteoarthritis of the ankle (PTOA) is frequently observed following a debilitating consequence of intra-articular ankle fractures. Numerous risk factors contribute to the pathogenesis of PTOA, including articular incongruity, joint malalignment, and concomitant soft tissue damage. Despite attempts to restore joint anatomy and manage soft tissues to avoid long-term complications after intra-articular ankle fractures, the incidence of PTOA remains markedly elevated. Inflammatory processes triggered by intra-articular ankle fractures have emerged as potential instigators that expedite the progression of PTOA. Injury to the articular cartilage and subchondral bone may lead to the release of inflammatory mediators, which can contribute to cartilage degradation and bone resorption. This study provides a narrative review on the current knowledge concerning the association between inflammation and the development of PTOA following intra-articular ankle fractures. We also discuss novel therapeutic agents that target inflammatory pathways to impede the progression of post-traumatic osteoarthritis after intra-articular ankle fractures. These medication and interventions were summarized within this review article.

Transient Exposure of Tissue-Engineered Cartilage Analogs to Synovial Fluid Hematoma After Ankle Fracture Promotes Chondrocyte Death and Alters Gene Expression Toward an Osteoarthritic Phenotype

Category: Basic Sciences/Biologics; Ankle Arthritis Introduction/Purpose: The first stage of fracture healing consists of hematoma formation with recruitment of proinflammatory cytokines and matrix metalloproteinases. Unfortunately, when there is an intra-articular fracture, these inflammatory mediators are not retained at the fracture site, but instead, bathe the healthy cartilage of the entire joint via the synovial fluid fracture hematoma (SFFH). These inflammatory cytokines and matrix metalloproteinases are known factors in the progression of osteoarthritis and rheumatoid arthritis. Despite the known inflammatory contents of the SFFH, little research has been done on the effects of the SFFH on healthy cartilage with regard to cell death and alteration in gene expression that could lead to post- traumatic osteoarthritis (PTOA). Methods: SFFH was collected from 12 patients with intraarticular ankle fracture at the time of surgery. Separately, human chondrocytes were three-dimensionally cultured to create scaffold -free cartilage tissue analogues (CTAs) to simulate articular cartilage. Experimental CTAs (n=12) were exposed to 100% SFFH for 3 days, washed, and transferred to complete media for 3 days. Control CTAs (n=12) were simultaneously cultured in complete medium. Subsequently, CTAs were harvested and underwent biochemical, histological, and gene expression analysis. Results: Exposure of CTAs to ankle SFFH 3 days significantly decreased chondrocyte viability by 34% (p = .027). Gene expression of both COL2A1 and SOX9 were significantly decreased after exposure to SFFH (p= .012 and p=.0013 respectively). COL1A1 expression trended upward in the SFFH exposure group while there was no difference in RUNX2 and MMP13 gene expression. Quantitative analysis of Picrosirius red staining demonstrated increased collagen I deposition with poor ultrastructural organization in SFFH exposed CTAs. Conclusion: Exposure of an organoid model of healthy cartilage tissue to SFFH after intraarticular ankle fracture resulted in decreased chondrocyte viability, decreased expression of genes regulating normal chondrocyte phenotype, and altered matrix ultrastructure indicating differentiation toward an osteoarthritis phenotype.

Exposure of Tissue-Engineered Cartilage Analogs to Synovial Fluid Hematoma After Ankle Fracture Is Associated With Chondrocyte Death and Altered Cartilage Maintenance Gene Expression.

The first stage of fracture healing consists of hematoma formation with recruitment of proinflammatory cytokines and matrix metalloproteinases. Unfortunately, when there is an intra-articular fracture, these inflammatory mediators are not retained at the fracture site, but instead, envelop the healthy cartilage of the entire joint via the synovial fluid fracture hematoma (SFFH). These inflammatory cytokines and matrix metalloproteinases are known factors in the progression of osteoarthritis and rheumatoid arthritis. Despite the known inflammatory contents of the SFFH, little research has been done on the effects of the SFFH on healthy cartilage with regard to cell death and alteration in gene expression that could lead to posttraumatic osteoarthritis (PTOA). SFFH was collected from 12 patients with intraarticular ankle fracture at the time of surgery. Separately, C20A4 immortalized human chondrocytes were 3-dimensionally cultured to create scaffold-free cartilage tissue analogs (CTAs) to simulate healthy cartilage. Experimental CTAs (n = 12) were exposed to 100% SFFH for 3 days, washed, and transferred to complete media for 3 days. Control CTAs (n = 12) were simultaneously cultured in complete medium without exposure to SFFH. Subsequently, CTAs were harvested and underwent biochemical, histological, and gene expression analysis. Exposure of CTAs to ankle SFFH for 3 days significantly decreased chondrocyte viability by 34% (P = .027). Gene expression of both COL2A1 and SOX9 were significantly decreased after exposure to SFFH (P = .012 and P = .0013 respectively), while there was no difference in COL1A1, RUNX2, and MMP13 gene expression. Quantitative analysis of Picrosirius red staining demonstrated increased collagen I deposition with poor ultrastructural organization in SFFH-exposed CTAs. Exposure of an organoid model of healthy cartilage tissue to SFFH after intraarticular ankle fracture resulted in decreased chondrocyte viability, decreased expression of genes regulating normal chondrocyte phenotype, and altered matrix ultrastructure indicating differentiation toward an osteoarthritis phenotype. The majority of ankle fracture open reduction and internal fixation does not occur immediately after fracture. In fact, typically these fractures are treated several days to weeks later in order to let the swelling subside. This means that the healthy innocent bystander cartilage not involved in the fracture is exposed to SFFH during this time. In this study, the SFFH caused decreased chondrocyte viability and specific altered gene expression that might have the potential to induce osteoarthritis. These data suggest that early intervention after intraarticular ankle fracture could possibly mitigate progression toward PTOA.

Хирургическая тактика при лечении пациентов с последствиями внутрисуставных повреждений дистального отдела костей голени (обзор литературы)

Background Management of patients with sequelae of intra-articular fractures of the distal tibia continues to be a substantial clinical challenge in orthopaedic trauma due to the high incidence, poor outcomes and high disability rate. The objective was to review Russian and international experience in repair of intra-articular ankle fractures and explore contemporary trends in treatment strategies. Material and methods The literature search was produced using medical electronic databases of eLibrary, PubMed, Medline, SpringerLink between 2000 and 2020 and keywords: cruzarthrosis, arthrodesis, total ankle arthroplasty, arthroscopy, distal tibia, ankle joint, joint replacement, intra-articular fractures of distal tibial. Results The article presents an insight into the problem of malunited and nonunited ankle fractures, ankle contractures and deformities, post-traumatic ankle arthritis. Major surgical techniques used to address sequelae of ankle fractures include correcting osteotomy, arthroscopy, distraction arthroplasty, arthrodesis, total ankle arthroplasty with the advantages and disadvantages with each of the practices. Discussion The surgical option would depend on the time of injury, condition of soft and bone tissue, malalignment and severity of ankle arthritis. Joint saving procedures of correcting osteotomy, arthroscopy or distraction arthroplasty can be applied at early stages of the disease, and arthrodesis or total ankle arthroplasty are secured for terminal stages of ankle arthritis. Benefits of total ankle arthroplasty include preservation and improvement of ankle mobility, a short inpatient period. Ankle fusion is associated with less complication rate and low costs. Conclusion There is an obvious need for a uniform treatment algorithm with specific indications and contraindications to each surgical option.

Intra-Articular Synovial Fluid With Hematoma After Ankle Fracture Promotes Cartilage Damage In Vitro Partially Attenuated by Anti-Inflammatory Agents.

Intra-articular ankle fracture (IAF) causes posttraumatic osteoarthritis (PTOA), but the exact mechanism is unknown. Proinflammatory mediators have been shown to be present in the synovial fluid fracture hematoma (SFFH) but have not been linked to cartilage damage. The purpose of this study was to determine if the SFFH causes cartilage damage and whether this damage can be attenuated by commercially available therapeutic agents. Synovial fluid was obtained from 54 IAFs and cultured with cartilage discs from the dome of fresh allograft human tali and randomly assigned to one of the following groups: (A) control-media only, (B) SFFH from days 0 to 2 after fracture, (C) SFFH from days 3 to 9, (D) SFFH from days 10 to 14, (E) group B + interleukin 1 receptor antagonist (IL-1Ra), and (F) group B + doxycycline. The cartilage discs underwent histological evaluation for cell survival and cartilage matrix components. The spent media were analyzed for inflammatory mediators. Cartilage discs cultured with SFFH in groups B, C, and D demonstrated significantly increased production of cytokines, metalloproteinases (MMPs), and extracellular matrix breakdown products. Safranin O staining was significantly decreased in group B. The negative effects on cartilage were partially attenuated with the addition of either IL-1RA or doxycycline. There was no difference in chondrocyte survival among the groups. Exposure of uninjured cartilage to IAF SFFH caused activation of cartilage damage pathways evident through cartilage disc secretion of inflammatory cytokines, MMPs, and cartilage matrix fragments. The addition of IL-1Ra or doxycycline to SFFH culture partially attenuated this response. IAFs create an adverse intra-articular environment consisting of significantly increased levels of inflammatory cytokines and MMPs able to damage cartilage throughout the joint. These data suggest that the acute addition of specific inflammatory inhibitors may decrease the levels of these proinflammatory mediators.

Association of acute inflammatory cytokines, fracture malreduction, and functional outcome 12 months after intra-articular ankle fracture\u2014a prospective cohort study of 46 patients with ankle fractures

BackgroundSeveral malreduction criteria have been proposed for ankle surgery, but the criteria of most importance for functional outcome remain undetermined. Furthermore, the acute inflammatory response in the ankle joint after fracture is hypothesized to result in osteoarthritis development, but no study has investigated the correlation between the levels of these inflammatory cytokines and post-surgical functional outcomes. We aimed to identify malreduction criteria and inflammatory cytokines associated with functional outcome after ankle surgery.MethodsDuring surgery, synovial fluid from the fractured and healthy contralateral ankles of 46 patients was collected for chemiluminescence analysis of 22 inflammatory cytokines and metabolic proteins. The quality of fracture reduction was based on 9 criteria on plain X-rays and 5 criteria on weight-bearing computed tomography (WBCT) scans. After 3 and 12 months, we recorded scores on American Orthopedic Foot and Ankle Society (AOFAS) scale, the Danish version of Foot Function Index (FFI-DK), EQ-5D-5L index score, the Kellgren-Lawrence score, and joint space narrowing.ResultsTibiofibular (TF) overlap (p = 0.02) and dime sign (p = 0.008) correlated with FFI-DK. Tibiotalar tilt correlated positively with joint space narrowing at 3 months (p = 0.01) and 12 months (p = 0.03). TF widening correlated with FFI-DK (p = 0.04), AOFAS (p = 0.02), and EQ-5D-5L (p = 0.02). No consistent correlations between synovial cytokine levels and functional outcomes were found at 12 months.ConclusionsMalreduction of TF overlap, TF widening, and tibiotalar tilt were the most important criteria for functional outcome after ankle surgery. Increased inflammatory cytokine levels after fracture did not affect functional outcome at 12 months.Trial registrationThis cohort study is registered the 10th of December 2018 at ClinicalTrials.gov (NCT03769909), was approved by the local committee on health ethics (The Regional Committees on Health Research Ethics for Southern Denmark: J.No. S-20170139), and was reported to the National Danish Data Protection Agency (17/28505).

Elevation of Inflammatory Cytokines and Proteins after Intra-Articular Ankle Fracture: A Cross-Sectional Study of 47 Ankle Fracture Patients.

Introduction Intra-articular fractures are the leading etiology for posttraumatic osteoarthritis (PTOA) in the ankle. Elevation of proinflammatory cytokines following intra-articular fracture may lead to synovial catabolism and cartilage degradation. We aimed to compare cytokine levels in injured and healthy ankle joints, examine the longer-term cytokine levels in fractured ankles, and investigate the association between cytokine levels in fractured ankles and plasma. Materials and Methods In this cross-sectional study, synovial fluid (SF) and plasma of forty-seven patients with acute intra-articular ankle fractures and eight patients undergoing implant removal were collected prior to surgery. We determined concentrations of sixteen inflammatory cytokines, two cartilage degradation proteins, and four metabolic proteins and compared the levels in acutely injured ankles with those of the healthy contralateral side or during metal removal. Cytokine levels in injured ankles were also compared to serum cytokine levels. Nonparametric Wilcoxon rank-sum and Spearman tests were used for statistical analysis, and a p value below 0.05 was considered significant. Results Compared to the healthy ankles, the synovial fluid in ankles with acute intra-articular fracture had elevated levels of several proinflammatory cytokines and proteases (IL-1β, IL-2, IL-6, IL-8, IL-12p70, TNF, IFNγ, MMP-1, MMP-3, and MMP-9) and anti-inflammatory cytokines (IL-1RA, IL-4, IL-10, and IL-13). The levels of cartilage degradation products (ACG, CTX-2) and metabolic mediators (TGF-β1 and TGF-β2) were also significantly higher. Synovial concentrations of ACG, IL-12-p70, IFNγ, IL-4, and bFGF correlated with serum levels. While most of the examined synovial cytokines were unchanged after implant removal, IL-4 and IL-6 levels were upregulated. Conclusions We show that an acute ankle fracture is followed by an inflammatory reaction and cartilage degeneration. These data contribute to the current understanding of the protein regulation behind the development of PTOA and is a further step towards supplementing the current surgical treatment. This cross-sectional study was “retrospectively registered” on the 31th October 2017 at ClinicalTrials.gov (NCT03769909). The registration was carried out after inclusion of the first patient and prior to finalization of patient recruitment and statistical analyses: https://clinicaltrials.gov/ct2/show/NCT03769909?term=NCT03769909&draw=2&rank=1.

The Intra-Articular Hematoma Immediately after Ankle Fracture Causes Cartilage Damage That is Partially Attenuated by Anti-Inflammatory Agents

Category:Ankle Arthritis; Basic Sciences/BiologicsIntroduction/Purpose:Post-traumatic osteoarthritis (PTOA) is a frequent cause of disability. The most common predisposing factor for ankle PTOA is intra-articular ankle fracture. It has been hypothesized that an early inflammatory response after intra- articular injury could lead to cartilage damage. Our group recently demonstrated significantly elevated inflammatory cytokines in the synovial fluid fracture hematoma (SFFH) immediately after intra-articular ankle fracture. The negative effect that this inflammatory environment has on cartilage is unknown but may be the reason for PTOA development. The purpose of this study was to determine if cartilage occurred when exposed to intra-articular SFFH and if anti-inflammatory agents could attenuate this damage.Methods:SFFH was obtained from 52 intra-articular ankle fractures at the time of surgery. Samples were divided into three groups based on time from fracture: acute (0-2 days), intermediate (3-9 days), late (>=10 days). A biopsy punch was used to create 5mm cartilage discs from the medial and lateral shoulders of fresh human talus cartilage. The cartilage discs were weighed and cultured in standard chondrocyte media (SCM) for 3 days. Next, the discs were randomly assigned to one of 4 groups (n=10 each) and cultured as follows for 6 days: A=control, SCM only; Group B=acute SFFH+SCM; Group C=intermediate SFFH+SCM; Group D=late SFFH+SCM. After 6 days of culture, the discs were rinsed and transferred to new wells and cultured for 3 more days in SCM only, to determine inflammatory cytokine and MMP release from the cartilage discs (cartilage damage). The post SFFH spent culture media was collected. The initial and post SFFH culture spent media were analyzed for inflammatory cytokines, MMPs, CTXII (cartilage breakdown marker), and sGAG. Safranin-O staining was then performed on the discs. The initial and post SFFH media from groups A, B, C, and D were compared to determine if there was a difference in damage caused by SFFH based on time from fracture. Based on the results, Group B (early) was felt to cause the most damage. Therefore, the following treatment groups were created and cultured exactly as before: Group E=same as Group B + IL-1Ra treatment; Group F=same as Group B + doxycycline treatment. Groups B, E, and F were compared to determine if the addition of IL-1Ra or doxycycline (known MMP inhibitor) attenuated the damage.Results:Early, intermediate, and late SFFH all caused some degree of cartilage damage in the form of significantly elevated inflammatory cytokine and MMP production from the cartilage discs (Figure 1). The early SFFH (Group B) was noted to cause significantly elevated production of IL-6, IL-8, CTXII, and decreased safranin-O staining. Therefore, it was chosen to compare with the therapeutic anti-inflammatory agents. The addition of IL-1Ra or doxycycline significantly reduced the production of IL-6, IL-8, CTXII, and MMPs 3, 9, and 10 (Figure 2).Conclusion:This is the first study to show that intra-articular hematoma immediately after ankle fracture causes cartilage damage that can be partially attenuated by current clinically available therapeutic agents. Additionally, further research should be performed regarding the safety and efficacy of anti-inflammatory agents to prevent ankle PTOA.

Cambios Degenerativos y Evaluación Funcional de Fracturas Intraarticulares de Tobillo en Pacientes Pediatricos

BackgroundAnkle fractures represent 12% of fractures in pediatric age. We hypothesized that patients with intra-articular ankle fractures will have an excellent functional result and will not present degenerative joint changes 6 months after surgery. The objective of the study is to carry out an analysis of the functional result, as well as the presence of early degenerative radiological changes in the follow-up of patients with intra-articular ankle fractures treated in our center. MethodsRetrospective cohort study, data were collected from patients with intra-articular ankle fractures between 2012 and 2016. They were classified and evaluated using AOFAS score and radiographs to classify according to Van Dijk. ResultsThe average age difference between triplanar and tillaux fractures is 17 months (p: 0.038). The mean AOFAS Score was 85.2%. 88.8% reported pain in relation to daily activities, despite having excellent or good functional results. There is no significant correlation between the AOFAS results in patients with transitional and non-transitional fractures. 43.4% had stage 0, 43.4% stage I, and 13% stage II Van Dijk. No case presented stage III. DiscussionBased on the findings of this study, and contrary to the hypothesized, most patients have a good functional result after the management of intra-articular ankle fractures and not excellent as previously thought. There is a group of patients who showed early degenerative changes demonstrable by radiography.

Time-Dependent Effects on Synovial Fluid Composition During the Acute Phase of Human Intra-articular Ankle Fracture.

The study objective was to examine the effect of time and fracture severity on the undiluted synovial fluid (SF) microenvironment during the acute phase following intra-articular fracture (IAF) of the human ankle. Ankle SF from 54 patients with an acute IAF was analyzed for concentrations of 10 cytokines, 5 matrix metalloproteinases, 2 products of cartilage catabolism, and combined products of heme metabolism. All analytes were correlated with time from fracture and further analyzed for an effect of 3 time subgroups (0-2 days, 3-9 days, and ≥10 days) corresponding to timepoints for clinical ankle fracture interventions. The effect of fracture severity was determined by grouping SF according to the number of radiographic intra-articular fracture lines. Fifteen of 18 analytes were significantly correlated with time. Temporal grouping of SF revealed an initial (0-2 days) spike of pro-inflammatory (IL-12p70, IL-1β, IL-6) and anti-inflammatory (IL-10 and IL-4) cytokines, matrix metalloproteinases (MMP) MMP-9, and sGAG, followed immediately (3-9 days) by products of heme metabolism and an unchallenged surge in mediators and products of cartilage catabolism (MMP-1, MMP-2, MMP-3, MMP-10, and CTX-II). After 10 days, there was a decrease in pro- and anti-inflammatory cytokines but a persistence of mediators of ECM catabolism. There was no clear relationship between the number of fracture lines and SF levels of analytes. This study demonstrated acute temporal fluctuations following ankle IAF resulting in an overall catabolic environment by 10 days post-fracture and supports consideration of an early evacuation of the joint space to reduce the intra-articular inflammatory burden. Clinical Relavence: This study contributes to the understanding of the intra-articular events that potentially contribute to the development of posttraumatic osteoarthritis acutely following IAF in the ankle.

2017 J. Leonard Goldner Award Winner

Category: Ankle,Ankle Arthritis,Basic Sciences/Biologics,Trauma Introduction/Purpose: Intra-articular ankle fracture (IAF) is known to cause post-traumatic osteoarthritis (PTOA) of the ankle. While the exact etiology remains elusive, the sequelae of intra-articular inflammation has been suggested and our previous work demonstrated a highly pro-inflammatory environment at the time of IAF fixation. ORIF of an IAF can occur 10-14days, or later, after fracture, subjecting the cartilage to this pro-inflammatory environment during this time. Therefore, there is ample time to intervene with an anti-inflammatory agent, yet the exact synovial fluid (SF) composition is unknown. This study examined the effect of time and fracture severity on the SF microenvironment during the acute phase following IAF. Knowledge of the intra- articular metabolic derangement after IAF will help to understand the pathology of PTOA and to develop therapeutic interventions. Methods: Ankle SF was collected from 54 patients with an IAF at the time of surgery for initial external fixation or definitive ORIF and analyzed for concentrations of 10 cytokines, 5 matrix metalloprotienases, 2 products of cartilage catabolism, and combined products of heme metabolism. All analytes were correlated with time from fracture and further analyzed for an effect of 3 clinically relevant time subgroups that correspond to potential clinical intervention time points for ankle fracture management: 0-2 days (initial ER presentation), 3-9 days (clinic presentation), and =10 days (definitive fixation). The effect of fracture severity was determined by grouping SF according to the number of radiographic intra-articular fracture lines. Results: Correlation analysis revealed a significant relationship with time from fracture for 15 of 18 analytes (Figure 1). Temporal grouping of SF revealed an initial (0-2 days) spike of pro-inflammatory (IL-12p70, IL-1?, IL-6) and anti-inflammatory (IL-10 and IL-4) cytokines, MMP-9, and sGAG, followed immediately (3-9 days) by exposure of the joint space to heme breakdown products and an accompanying surge in mediators and products of cartilage catabolism (MMP-1, MMP-2, MMP-3, MMP-10 and CTX-II). After 10 days there was a decrease in pro- and anti-inflammatory cytokines, but a persistence of mediators of cartilage matrix catabolism. While fracture severity had a significant effect on SF levels of MMP-2, MMP-9, and CTXII, there was no clear relationship between the number of fracture lines and SF levels of analytes. Conclusion: This study provides novel insights into temporal inflammatory fluctuations following acute IAF of the ankle and supports consideration of an early evacuation of the jointspace to reduce the intra-articular inflammatory burden and exposure of the cartilage and synovium to these detrimental factors. Moreover, this study identifies the temporal composition of SF products that are known to cause osteoarthritis. Therefore, this information can be used to develop novel therapeutics that can tailored to the time of presentation after intra-articular ankle fracture.

Does Hardware Removal Improve Function Following Ankle Open Reduction and Internal Fixation?

Category: Ankle, Trauma Introduction/Purpose: Orthopaedic hardware removal (HWR) is one of the most common orthopaedic procedures performed, with rates reported between 5% and 16%. Despite the high rates of HWR, there is still no consensus or guideline for removal after osseous healing without infection. Outcome studies for HWR are scarce, particularly in the lower extremity. The purpose of this study is to evaluate the effect of removal of symptomatic ankle hardware using the Short Musculoskeletal Function Assessment (SMFA) dysfunction index as the primary outcome. We hypothesize that HWR after ankle fracture will result in improved functional outcomes. Methods: Utilizing a prospectively collected ankle fracture registry, all patients that underwent HWR between 2013 and 2016 were retrospectively reviewed. Inclusion criteria were skeletal maturity, closed intra-articular ankle fracture, symptomatic ankle hardware and completion of the SMFA questionnaire prior to and 5-months after hardware removal. Exclusion criteria were development of a nonunion, infection or complex regional pain syndrome from initial surgery. The primary outcome was change in SMFA score from baseline. Paired t-test was used to compare baseline and follow-up SMFA scores. A multiple linear regression model evaluated the effects of age, sex, body mass index (BMI), smoking status, number of comorbidities, and Lauge-Hansen fracture classification on outcomes. Results: The study included 43 patients (31 females, 12 males), mean age 49.9 (range, 19 to 83). Mean time from initial surgery to HWR was 37±46 months (range, 2.2 to 209). Follow-up SMFA questionnaires were completed 5.7±0.5 months (range, 5.1 to 7.4) after HWR. The fractures were classified as 23 (53%) supination-external rotation, 6 (14%) pronation-external rotation, 2 (4.7%) pronation-abduction and 1 (2.3%) supination-adduction. Eleven fractures (26%) were classified as pilons. The SMFA dysfunction index improved significantly from baseline to follow-up (3.71±7.4, p=0.002). Significant improvement was seen in the secondary outcomes of SMFA bother index (4.40±8.9, p=0.003) and SMFA daily activities domain (4.12±9.1, p=0.006). Regression analysis revealed a significant improvement in the bother index correlating with female gender (p=0.01) and decreasing number of comorbidities (p=0.03). Conclusion: Our study demonstrates that patients with ankle fractures have a significant improvement in function following the removal of symptomatic ankle hardware. Patients also showed a significant improvement in the bother index and daily activities domain of the SMFA. Further investigation into the specific indications for HWR and the impact of injury and fracture pattern on outcomes is warranted.

Osteotomy for malunion of intra-articular ankle fracture assisted by 3D printing relay template

Objective To explore the effectiveness of our self-designed 3D printing relay template in the treatment of malunion of irregular intra-articular ankle fractures. Methods From October 2013 to October 2015, our self-designed 3D printing relay template was used in 14 patients with severe malunion of intra-articular ankle fracture to assist their intra-articular osteotomy. They were 10 males and 4 females, with an average age of 40.5 years (from 34 to 59 years). Thin slice CT scan was preformed preoperatively for all the ankles involved. The computer fictitious tibial and fibular models for location and osteotomy navigation templates were acquired from the data of CT scan after processing, design and reconstruction by software. After the navigation templates which fit the size of solid ankle were printed by a 3D printer, they were ster-ilized and reserved. The guide plates were used in turn during operation. The irregular malunited bone blocks in the posterior malleolus were completely resected along the osteotomy template. After fracture reduction, the bone blocks were stabilized with internal fixation. Fracture union time was recorded. Scores of visual analogue scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) and the short form-36 (SF-36), ankle ROM and complications were also recorded at the final follow-ups. Results The 14 patients obtained an average follow-up of 28.6 months (from 14 to 35 months). Bony union was achieved after an average of 3.7 months (from 3 to 6 months). At the final follow-ups, on average, VAS score (2.2±0.8), AOFAS ankle and hindfoot score (81.1±6.8), SF-36 score (82.5±5.2), dorsal extension (27.5°±2.5°), and plantar flexion (24.2°±6.3°) were significantly improved compared with the preoperative values (6.3±1.8, 43.1±12.0, 37.6±9.9, 14.1°±3.8° and 14.4°±3.9°, respectively) (P< 0.05). No implant failure, soft tissue complications or post-traumatic arthritis occurred during the follow-up. Conclusion Since our self-designed 3D printing relay templates for osteotomy can accurately position the fracture lines of the distal tibia via limited incision and invasion, they help a lot in precise osteotomy and anatomical reduction of malunited intra-articular ankle fracture, preventing incidence of traumatic arthritis. Key words: Ankle joint; Fractures, bone; Surgery, computer-assisted; 3D printing

Inflammatory Microenvironment Persists After Bone Healing in Intra-articular Ankle Fractures.

Post-traumatic osteoarthritis (PTOA) is responsible for the majority of cases of ankle arthritis. While acute and end-stage intra-articular inflammation has previously been described, the state of the joint between fracture healing and end-stage PTOA remains undefined. This study characterized synovial fluid (SF) composition of ankles after bone healing of an intra-articular fracture to identify factors that may contribute to the development of PTOA. Of an original 21 patients whose SF was characterized acutely following intra-articular ankle fractures, 7 returned for planned hardware (syndesmotic screw) removal after bone healing (approximately 6 months) and consented to a second bilateral SF collection. SF concentrations of 15 cytokines and matrix metalloproteinases (MMPs) and 2 markers each of cartilage catabolism (CTXII and glycosaminoglycan) and hemarthrosis (biliverdin and bilirubin) were compared for previously fractured and contralateral, uninjured ankles from the same patient. Analysis was also performed to determine the effect of the number of fracture lines and involvement of soft tissue on SF composition. Interleukin (IL)-6, IL-8, MMP-1, MMP-2, and MMP-3 were significantly elevated in the SF from healed ankles compared to matched contralateral uninjured ankles at approximately 6 months after fracture. There were no differences in markers of cartilage catabolism or hemarthrosis. Only IL-1α was affected by the number of fracture lines while differences were not detected for other analytes or with respect to the involvment of soft tissue. Sustained intra-articular inflammation, even after complete bone healing, was suggested by elevations of pro-inflammatory cytokines (IL-6 and IL-8). In addition, elevated concentrations of MMPs were also noted and were consistent with a persistent inflammatory environment. This study suggests new evidence of persistent intra-articular inflammation after intra-articular ankle fracture healing and suggests potential mediators for PTOA development. This work may be relevant to the clinical diagnosis and treatment of post-traumatic osteoarthritis.

Lipid profile of human synovial fluid following intra-articular ankle fracture.

This study characterizes the metabolic profile of synovial fluid after intra-articular ankle fracture with an emphasis on changes in the lipid profile. Bilateral ankle synovial fluid from 19 patients with unilateral intra-articular ankle fracture was submitted for metabolic profiling. Contralateral ankle synovial fluid from each patient served as a matched control. Seven patients participated in a second bilateral synovial fluid collection after 6 months. Random forest classification, matched pairs t-tests (α < 0.01), repeated measures ANOVA with post-test contrasts (α < 0.01), correlation to cytokines and matrix metalloproteinases, and fracture and injury classification analyses yielded key lipid biomarkers in synovial fluid following intra-articular fracture. Free fatty acids, sphingomyelins, and lysolipids demonstrated significant elevation in fractured ankles at baseline. Fatty acids and sphingomyelins showed a significant decrease 6 months post-surgery. Random forest analysis showed predominantly fatty acids differentiating between groups. Significant correlations included fatty acids, sphingomyelins, and lysolipids with inflammatory cytokines and matrix metalloproteinases. Fracture classification showed increased fatty acids, lysolipids, and inositol metabolites as fracture severity increased. Fatty acid and sn-1 lysolipid elevation could be detrimental to the joint, as these strongly correlated with matrix metalloproteinases and TNF-α. This elevation also suggests involvement of phospholipase A2 , a potential target for therapeutic intervention. Together with elevated 2-hydroxyl fatty acids, these findings suggest elevated sn-1 lysolipids, sphingomyelins, and subsequent lipid metabolites in synovial fluid as biomarkers of ankle injury. Reversal of this signature after 6 months suggests temporary involvement of these metabolites in disease progression, although they may activate signaling pathways which drive progression to osteoarthritis. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:657-666, 2017.

Inflammatory Cytokines and Matrix Metalloproteinases in the Synovial Fluid After Intra-articular Ankle Fracture.

Posttraumatic osteoarthritis (PTOA) can occur after intra-articular fracture despite anatomic fracture reduction. It has been hypothesized that an early inflammatory response after intra-articular injury could lead to irreversible cartilage damage that progresses to PTOA. Therefore, in addition to meticulous fracture reduction, it would be ideal to prevent this initial inflammatory response but little is known about the composition of the synovial environment after intra-articular fracture. The purpose of this work was to characterize the inflammatory cytokine and matrix metalloproteinase (MMP) composition in the synovial fluid (SF) of patients with acute intra-articular ankle fractures. Twenty-one patients with an intra-articular ankle fracture were included in this study. All patients had a contralateral ankle joint that was pain free, had no radiographic evidence of arthritis, and no history of trauma. The uninjured ankle served as a matched control. SF was obtained from bilateral ankles at the time of surgery which occurred at a mean of 17 days post-fracture (range 8-40). The SF was analyzed for granulocyte macrophage colony-stimulating factor (GM-CSF), interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, MMP-1, MMP-2, MMP-3, MMP-9, MMP-10, CTXII, sGAG, and bilirubin/biliverdin (markers of hemearthrosis) using either multiplex assay or ELISA using commercially available kits. Mean concentrations of each factor were compared between SF from fractured and control ankles, and correlation analysis was done to determine potential relationships between levels of cytokines and time from fracture and age at fracture. Twelve of 18 measured factors including GM-CSF, IL-10, IL-1β, IL-6, IL-8, TNF-α, MMP-1, MMP-2, MMP-3, MMP-9, MMP-10, and bilirubin/biliverdin were found to be significantly higher in the fractured ankles. Mean concentrations of ECM degradation markers (sGAG and CTXII) were not found to be significatnly different between groups. These data indicate that after intra-articular ankle fracture the SF exhibits a largely pro-inflammatory and extra-cellular matrix degrading environment similar to that described in idiopathic osteoarthritis. IL-6, IL-8, MMP-1, MMP-2, MMP-3, MMP-9, and MMP-10 were significantly elevated and may play a role in the development of PTOA. In addition to anatomic fracture reduction, these data lend credence to reducing acute intra-articular inflammation through the development of antagonists to these pro-inflammatory and degrading mediators. Likewise, intra-articular lavage might reduce this inflammatory burden.

Standard perioperative imaging modalities are unreliable in assessing articular congruity of ankle fractures.

To determine the sensitivity, specificity, and interobserver and intraobserver reliabilities of intraoperative fluoroscopy and postoperative plain radiographs (XR) in the assessment of articular congruency after open reduction and internal fixation (ORIF) of ankle fractures involving the tibial plafond. Retrospective cohort. Academic level 1 trauma center. One hundred five patients treated surgically for rotational ankle fractures. ORIF. Sensitivity, specificity, and interobserver and intraobserver reliabilities of fluoroscopy and plain radiographs when compared with computed tomography imaging. The sensitivities of fluoroscopy and XR were 21% and 36%, respectively. Specificities were 95% (fluoroscopy) and 89% (XR). Fluoroscopy interobserver reliability was κ = 0.15, and mean intraobserver reliability was κ = 0.32. XR interobserver and mean intraobserver reliabilities were κ = 0.30 and κ = 0.59. Although results show acceptable specificity, the reliability and sensitivity of both intraoperative fluoroscopy and postoperative XR in the assessment of ankle articular congruency are low. This calls into question available literature correlating clinical results with articular reduction. During ORIF of an intra-articular ankle fracture, surgeons should be highly critical of fluoroscopic imaging that seems adequately reduced and direct visualization of the articular surface should be used as a reduction aid if possible. Furthermore, in the postoperative period, axial imaging may be warranted in patients who have poor clinical outcomes despite apparent anatomic articular reduction to evaluate for occult joint incongruence.

Malleolar Fractures

Ninety-two intra-articular ankle fractures were randomly selected for either open reduction and internal fixation or closed reduction and plaster cast. The patients were followed for an average of seven years. The initial course was more favorable in surgically reduced fractures. However, follow-up examinations showed little difference in results between the two forms of treatment.