Functional anterior cruciate ligament braces may have a role in select patient groups although there is presently limited evidence supporting or refuting their routine use: A scoping review of clinical practice guidelines and an updated bracing classification.

PURPOSE: The purpose of this study was to perform a scoping review of clinical practice guidelines (CPGs) concerning the use of functional anterior cruciate ligament (ACL) braces and to clarify the nomenclature for bracing relevant to ACL injury treatment in order to support prescribing clinicians. METHODS: A PubMed search for CPGs for the use of braces following ACL injury or reconstruction was performed. CPGs on the treatment of ACL injuries with sufficient attention to postoperative braces were included in this scoping review. The references used for supporting the specific CPG recommendations were reviewed. Specific indications for brace use including brace type, period of use following surgery and activities requiring brace use were collected. RESULTS: Six CPGs were identified and included this this review. Three randomised trials provided the evidence for recommendations on functional brace use following ACL reconstruction in the six CPGs. Functional ACL braces were the primary focus of the three randomised trials, although extension braces (postoperative knee immobilisers) were also discussed. A novel dynamic ACL brace category has been described, although included CPGs did not provide guidance on this brace type. CONCLUSIONS: Guidance on the use of functional ACL braces following ACL reconstruction is provided in six CPGs supported by three randomised trials. However, the brace protocols and patient compliance in the randomised trials render these CPGs inadequate for providing guidance on the use of functional ACL braces in the general and high-risk patient populations when returning to sport after ACL reconstruction. Functional ACL braces are commonly utilised during the course of ACL injury treatment although there is presently limited evidence supporting or refuting the routine use of these braces. Future studies are, therefore, necessary in order to provide guidance on the use of functional and dynamic ACL braces in high-risk patient populations. LEVEL OF EVIDENCE: Level II.

Long-term evaluation of pediatric ACL reconstruction: high risk of further surgery but a restrictive postoperative management was related to a lower revision rate.

INTRODUCTION: The guidelines regarding rehabilitation after pediatric anterior cruciate ligament reconstruction (ACLR) are sparse. The aim of the study was to retrospectively describe the long-term outcome regarding further surgery and with special emphasis on the revision rate after two different postoperative rehabilitation programs following pediatric ACLR. MATERIAL AND METHODS: 193 consecutive patients < 15 years of age who had undergone ACLR at two centers, A (n = 116) and B (n = 77), in 2006-2010 were identified. Postoperative rehabilitation protocol at A: a brace locked in 30° of flexion with partial weight bearing for 3 weeks followed by another 3 weeks in the brace with limited range of motion 10°-90° and full weight bearing; return to sports after a minimum of 9 months. B: immediate free range of motion and weight bearing as tolerated; return to sports after a minimum of 6 months. The mean follow-up time was 6.9 (range 5-9) years. The mean age at ACLR was 13.2 years (range 7-14) years. The primary outcome measurement in the statistical analysis was the occurrence of revision. Multivariable logistic regression analysis was performed to investigate five potential risk factors: surgical center, sex, age at ACLR, time from injury to ACLR and graft diameter. RESULTS: Thirty-three percent had further surgery in the operated knee including a revision rate of 12%. Twelve percent underwent ACLR in the contralateral knee. The only significant variable in the statistical analysis according to the multivariable logistic regression analysis was surgical center (p = 0.019). Eight percent of the patients at center A and 19% of the patients at B underwent ACL revision. CONCLUSIONS: Further surgery in the operated knee could be expected in one third of the cases including a revision rate of 12%. The study also disclosed a similar rate of contralateral ACLR at 12%. The revision rate following pediatric ACLR was lower in a center which applied a more restrictive rehabilitation protocol. LEVEL OF EVIDENCE: Case-control study, Level III.

Genomics based analysis of interactions between developing B-lymphocytes and stromal cells reveal complex interactions and two-way communication.

BACKGROUND: The use of functional genomics has largely increased our understanding of cell biology and promises to help the development of systems biology needed to understand the complex order of events that regulates cellular differentiation in vivo. One model system clearly dependent on the integration of extra and intra cellular signals is the development of B-lymphocytes from hematopoietic stem cells in the bone marrow. This developmental pathway involves several defined differentiation stages associated with specific expression of genes including surface markers that can be used for the prospective isolation of the progenitor cells directly from the bone marrow to allow for ex vivo gene expression analysis. The developmental process can be simulated in vitro making it possible to dissect information about cell/cell communication as well as to address the relevance of communication pathways in a rather direct manner. Thus we believe that B-lymphocyte development represents a useful model system to take the first steps towards systems biology investigations in the bone marrow. RESULTS: In order to identify extra cellular signals that promote B lymphocyte development we created a database with approximately 400 receptor ligand pairs and software matching gene expression data from two cell populations to obtain information about possible communication pathways. Using this database and gene expression data from NIH3T3 cells (unable to support B cell development), OP-9 cells (strongly supportive of B cell development), pro-B and pre-B cells as well as mature peripheral B-lineage cells, we were able to identify a set of potential stage and stromal cell restricted communication pathways. Functional analysis of some of these potential ways of communication allowed us to identify BMP-4 as a potent stimulator of B-cell development in vitro. Further, the analysis suggested that there existed possibilities for progenitor B cells to send signals to the stroma. The functional consequences of this were investigated by co-culture experiments revealing that the co-incubation of stromal cells with B cell progenitors altered both the morphology and the gene expression pattern in the stromal cells. CONCLUSIONS: We believe that this gene expression data analysis method allows for the identification of functionally relevant interactions and therefore could be applied to other data sets to unravel novel communication pathways.

Evaluation of open reduction and internal fixation of proximal humerus fractures using a locking plate with smooth pegs - A retrospective study.

BACKGROUND: Optimal treatment of displaced proximal humeral fractures is controversial. This retrospective study aims to identify complications and clinical outcomes using a locking plate with smooth pegs instead of screws (S3 plate). METHOD: Eighty-two patients with displaced proximal humeral fracture classified with 2-4 fragments (Neer's classification) treated with open reduction and internal fixation (ORIF) with S3 plate were studied retrospectively. Clinical outcome according to constant score; Single Shoulder Value; Disabilities of Arm, Shoulder and Hand; and European Quality of life-5 dimensions and complication rate defined radiologically including peg penetration, avascular necrosis, and loss of reduction was assessed minimum 2.5 years after surgery. RESULTS: A total of 11 peg penetrations were identified (13.6%). Avascular necrosis was seen in 8.5% (n = 7). Mean constant score at follow-up was 64.4 with a relative constant score of 87% (standard deviation 18%) compared to the contralateral uninjured side. The mean Disabilities of Arm, Shoulder and Hand score was 12.7 and mean European Quality of life-5 dimensions score 0.83. The mean Single Shoulder Value was 78.3. No cases of deep infection were seen. CONCLUSIONS: Fixation with S3 plate shows a proper osteosynthesis and the functional outcome is good. Symptomatic peg penetrations are rare and the incidence is lower compared to what has been reported with locked screws.

Exit of pediatric pre-B acute lymphoblastic leukaemia cells from the bone marrow to the peripheral blood is not associated with cell maturation or alterations in gene expression.

BACKGROUND: Childhood pre-B acute lymphoblastic leukemia (ALL) is a bone marrow (BM) derived disease, which often disseminates out of the BM cavity, where malignant cells to a variable degree can be found circulating in the peripheral blood (PB). Normal pre-B cells are absolutely dependent on BM stroma for survival and differentiation. It is not known whether transformed pre-B ALL cells retain any of this dependence, which possibly could impact on drug sensitivity or MRD measurements. RESULTS: Pre-B ALL cells, highly purified by a novel method using surface expression of CD19 and immunoglobulin light chains, from BM and PB show a very high degree of similarity in gene expression patterns, with differential expression of vascular endothelial growth factor (VEGF) as a notable exception. In addition, the cell sorting procedure revealed that in 2 out of five investigated patients, a significant fraction of the malignant cells had matured beyond the pre-B cell stage. CONCLUSION: The transition of ALL cells from the BM into the circulation does not demand, or result in, major changes of gene expression pattern. This might indicate an independence of BM stroma on the part of transformed pre-B cells, which contrasts with that of their normal counterparts.

The CD53 and CEACAM-1 genes are genetic targets for early B cell factor.

Early B cell factor (EBF)-1 is a transcription factor known to be of critical importance for early B lymphocyte development. EBF-1 has been shown to directly interact with and regulate expression of a set of genes involved in the functional formation of the pre-B cell receptor, but the dramatic phenotype observed in the EBF-1-deficient mice suggests that several additional genes are activated by this protein. In order to identify additional target genes for EBF-1, we transduced a hematopoietic progenitor cell line, BaF/3, with an EBF-1-encoding retrovirus and investigated the induced gene expression pattern by micro-arrays. This analysis suggested that among others, the CD53 and the carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-1 genes both were induced by ectopic expression of EBF-1. Identification of the 5' end of the cDNA enabled the identification of promoter elements with functional binding sites for EBF-1 and ability to respond to EBF-1 expression in transient transfection assays. These data suggest that CD53 and CEACAM-1 are direct genetic targets for EBF-1, providing additional information concerning the activity of this crucial transcription factor in hematopoiesis.