Significant variations in surgical construct and return to sport protocols with syndesmotic injuries: an ISAKOS global perspective.

OBJECTIVES: Although the body of literature on syndesmosis injuries is growing with regard to both the biomechanics and clinical outcomes for various fixation constructs, there is little consensus on the optimal treatment and return to sport strategy for these injuries. We endeavoured to assess the current approaches to managing syndesmotic injuries through a Research Electronic Data Capture survey. METHODS: The survey consisted of 27 questions, including respondent demographics, indications for treatment of syndesmotic injuries, preferred treatment and technique, and postoperative management. Responses were generated through six different athlete scenarios: moderate impact, high impact, and very high impact athletes with/without complete deltoid injury. Frequencies and percentages were calculated for all categorical responses. RESULTS: A total of 742 providers responded to the survey, including 457 American surgeons and 285 members of various international societies. Flexible devices were the preferred fixation construct (47.1%), followed by screws (29.6%), hybrid fixation (e.g. combination of flexible device and screw, 18%), and other (5.3%). Sixty-four percent of respondents noted that their rehabilitation protocols would not change for each athlete scenario. Considerable variability was present in anticipated return to full participation, largely dependent on the presence or absence of a deltoid ligament injury. CONCLUSION: The most common elements used as surgical indications were syndesmosis widening > 2 mm on x-ray, an anterior inferior talofibular ligament injury in combination with a posterior inferior talofinular ligament or deltoid ligament involvement on magnetic resonance imaging, and widening of the distal tibiofibular joint during arthroscopic evaluation. Overall, flexible fixation (e.g. suture button) was the preferred device choice for the repair of an injured syndesmosis. Most respondents did not alter their rehab protocol or anticipated return to play timeline based on the injury severity. However, there was considerable variability between respondents on the time to weight-bearing, running, and full participation. Further pragmatic outcomes data are necessary to guide safe return to play protocols for syndesmotic injuries. LEVEL OF EVIDENCE: Level IV.

Outcomes Following Ankle Fracture Fixation With or Without Ankle Arthroscopy.

BACKGROUND: Ankle fractures are one of the most common orthopedic injuries, and although most patients have a satisfactory outcome following operative fixation, there are patients that have persistent pain despite anatomic reduction. Intra-articular injuries have been suggested as one potential cause of these suboptimal outcomes. Our study assesses the clinical impact of performing an ankle arthroscopy during ankle fracture open reduction and internal fixation (ORIF). METHODS: This was a retrospective chart review of all patients who underwent operative fixation of a bimalleolar or trimalleolar ankle fracture at our institution from 2014 through 2018. We extracted all demographic data, fracture pattern, operative procedures performed, tourniquet times, arthroscopic findings and any arthroscopic interventions. We then conducted a phone and e-mail survey. Our study included 213 total patients (142 traditional ORIF, 71 ORIF plus arthroscopy) with an average age of 40 years. The average follow-up was 32.4 months with a survey follow-up rate of 50.7% (110/213). RESULTS: The average tourniquet time for the arthroscopy cohort was 10 minutes longer (89 minutes vs 79 minutes). During the arthroscopy, there was a 28% (20/71) rate of full-thickness osteochondral lesions, 33% (24/71) rate of loose bodies, and a 49% (35/71) rate of partial-thickness cartilage injury. The mean Patient Reported Outcome Information System (PROMIS) physical function score among Weber B fibula fractures was 45.8 and 42.3 in the arthroscopy and nonarthroscopy groups, respectively (P = .012). In addition, the patient satisfaction rate in Weber B fibula fractures was higher in those patients who underwent arthroscopy compared with ORIF alone (93% vs 75%, P = .05). Patients who had a tibiotalar joint dislocation at the time of the ankle fracture had a significantly higher PROMIS physical function score (46.6 vs 40.2, P = .005) when their surgery included arthroscopy. CONCLUSION: Ankle arthroscopy at the time of ORIF led to statistically significant improvements in patient-reported outcomes for Weber B fibula fractures and ankle dislocations. There was no increase in complication rates and the arthroscopy took 10 minutes longer on average. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Inhibits Major Histocompatibility Complex Class II Expression by Disrupting Enhanceosome Assembly through Binding with the Regulatory Factor X Complex.

UNLABELLED: Major histocompatibility complex class II (MHC-II) molecules play a central role in adaptive antiviral immunity by presenting viral peptides to CD4(+) T cells. Due to their key role in adaptive immunity, many viruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), have evolved multiple strategies to inhibit the MHC-II antigen presentation pathway. The expression of MHC-II, which is controlled mainly at the level of transcription, is strictly dependent upon the binding of the class II transactivator (CIITA) to the highly conserved promoters of all MHC-II genes. The recruitment of CIITA to MHC-II promoters requires its direct interactions with a preassembled MHC-II enhanceosome consisting of cyclic AMP response element-binding protein (CREB) and nuclear factor Y (NF-Y) complex and regulatory factor X (RFX) complex proteins. Here, we show that KSHV-encoded latency-associated nuclear antigen (LANA) disrupts the association of CIITA with the MHC-II enhanceosome by binding to the components of the RFX complex. Our data show that LANA is capable of binding to all three components of the RFX complex, RFX-associated protein (RFXAP), RFX5, and RFX-associated ankyrin-containing protein (RFXANK), in vivo but binds more strongly with the RFXAP component in in vitro binding assays. Levels of MHC-II proteins were significantly reduced in KSHV-infected as well as LANA-expressing B cells. Additionally, the expression of LANA in a luciferase promoter reporter assay showed reduced HLA-DRA promoter activity in a dose-dependent manner. Chromatin immunoprecipitation assays showed that LANA binds to the MHC-II promoter along with RFX proteins and that the overexpression of LANA disrupts the association of CIITA with the MHC-II promoter. These assays led to the conclusion that the interaction of LANA with RFX proteins interferes with the recruitment of CIITA to MHC-II promoters, resulting in an inhibition of MHC-II gene expression. Thus, the data presented here identify a novel mechanism used by KSHV to downregulate the expressions of MHC-II genes. IMPORTANCE: Kaposi's sarcoma-associated herpesvirus is the causative agent of multiple human malignancies. It establishes a lifelong latent infection and persists in infected cells without being detected by the host's immune surveillance system. Only a limited number of viral proteins are expressed during latency, and these proteins play a significant role in suppressing both the innate and adaptive immunities of the host. Latency-associated nuclear antigen (LANA) is one of the major proteins expressed during latent infection. Here, we show that LANA blocks MHC-II gene expression to subvert the host immune system by disrupting the MHC-II enhanceosome through binding with RFX transcription factors. Therefore, this study identifies a novel mechanism utilized by KSHV LANA to deregulate MHC-II gene expression, which is critical for CD4(+) T cell responses in order to escape host immune surveillance.