Controlled Ankle Movement (CAM) Boot Provides Improved Outcomes With Lower Complications Than Short Leg Walking Cast in Low-energy Pediatric Lateral Ankle Injuries: A Prospective, Randomized Study.

BACKGROUND: Low-energy lateral ankle injuries (Salter-Harris 1 distal fibula, distal fibula avulsion fractures, and radiograph-negative lateral ankle injuries) are common in pediatric patients. Patient-based outcomes for the 2 treatment options, short leg walking cast (CAST) and controlled ankle motion (CAM) boot, are unknown. This study aims to determine differences between 2 treatments of low-energy lateral ankle injuries in pediatric patients. METHODS: A prospective, randomized controlled trial comparing the acute outcomes of CAST and CAM treatment for low-energy lateral ankle injuries in pediatric patients was completed. Patients were evaluated in-person at presentation and 4 weeks for ankle range of motion and Oxford foot and ankle score. A novel survey defining patient and parent satisfaction and time away from school/work was also completed. Treatment complications were documented. Patients were called at 8 weeks postinjury to determine other complications and the final time of return to sport. Mixed effects linear regression models evaluated change over time between the 2 treatment groups. RESULTS: After 60 patients were enrolled, 28 patients in the CAST group and 27 patients in the CAM group completed the study. Males comprised 51% (28), with 38 (69%) patients identifying as Hispanic. The patient's average age was 11.3±2.9 years and the average body mass index was 23.At the 4-week evaluation, the CAM group had improved range of motion, higher satisfaction scores (5.26 CAM vs. 4.25 CAST, P <0.05), similar pain scores (0.32 CAST vs. 0.41 CAM, P =0.75), and lower complications (0.54/patient CAST vs. 0.04/patient CAM, P <0.0001) than the CAST group. Female patients had improved inversion with CAM treatment than males ( P <0.05). Patients over age 12 in the CAST group had significantly decreased plantarflexion at week 4 ( P =0.002). Improvement in Oxford scores was similar between the CAST and CAM groups between the initial presentation and 4 weeks, except for increased improvement in CAM group Oxford scores for difficulty running and symptoms with walking/walking. At the 8-week evaluation, patients in the CAST group had a higher rate of continued symptoms than the CAM group (15.4% vs. 0%). CONCLUSIONS: CAM boot treatment of low-energy lateral ankle injuries in pediatric patients results in improved results and lower complications than CAST treatment. LEVEL OF EVIDENCE: Level I -randomized, controlled trial with a statistically significant difference.

Molecular dissection of cis-regulatory modules at the Drosophila bithorax complex reveals critical transcription factor signature motifs.

At the Drosophila melanogaster bithorax complex (BX-C) over 330kb of intergenic DNA is responsible for directing the transcription of just three homeotic (Hox) genes during embryonic development. A number of distinct enhancer cis-regulatory modules (CRMs) are responsible for controlling the specific expression patterns of the Hox genes in the BX-C. While it has proven possible to identify orthologs of known BX-C CRMs in different Drosophila species using overall sequence conservation, this approach has not proven sufficiently effective for identifying novel CRMs or defining the key functional sequences within enhancer CRMs. Here we demonstrate that the specific spatial clustering of transcription factor (TF) binding sites is important for BX-C enhancer activity. A bioinformatic search for combinations of putative TF binding sites in the BX-C suggests that simple clustering of binding sites is frequently not indicative of enhancer activity. However, through molecular dissection and evolutionary comparison across the Drosophila genus we discovered that specific TF binding site clustering patterns are an important feature of three known BX-C enhancers. Sub-regions of the defined IAB5 and IAB7b enhancers were both found to contain an evolutionarily conserved signature motif of clustered TF binding sites which is critical for the functional activity of the enhancers. Together, these results indicate that the spatial organization of specific activator and repressor binding sites within BX-C enhancers is of greater importance than overall sequence conservation and is indicative of enhancer functional activity.