Mechanical properties of revision ACL reconstruction.

The aim of this study is to evaluate the mechanical properties of a revision anterior cruciate ligament (ACL) reconstruction after redrilling the original tibial bone tunnel through a retained composite screw compared with initial soft tissue graft fixation. A total of 24 porcine tendons were fixed to porcine tibial tunnels with a 10 × 35 mm composite interference screw. Following the pullout test, a revision tunnel was drilled through the first interference screw and a second graft was fixed in the bone tunnel using a larger composite screw (11 × 35 mm). Following insertion of the revision screw, the graft was reloaded as described for the primary reconstruction. Load versus displacement data were recorded for each test. There were no significant differences between the primary and revision reconstruction constructs for yield load (p = 0.62), linear stiffness (p = 0.18), maximum failure load (p = 0.57), and yield displacement (p = 0.46). These results indicate that the mechanical properties of tibial fixation for ACL reconstruction with a composite screw following a revision provide similar fixation compared with initial reconstruction in this model. Revising a failed composite ACL construct by means of overdrilling and reinstrumenting may provide fixation equivalent to the initial reconstruction.

Biomechanical analysis of Brostrom versus Brostrom-Gould lateral ankle instability repairs.

BACKGROUND: The traditional Brostrom repair and the modified Brostrom-Gould repair are 2 historically reliable procedures used to address lateral ankle instability. The purpose of this study was to evaluate the biomechanical stability conferred by the Brostrom repair as compared to the Brostrom-Gould modification in an unstable cadaveric ankle model. METHODS: A total of 10 cadaveric specimens were placed in a Telos ankle stress apparatus in an anterior-posterior position and then in a lateral position, while a 170 N load was applied to simulate anterior drawer (AD) and talar tilt (TT) tests, respectively. In both circumstances, the ankle was held in 15 degrees of plantarflexion, neutral, and 15 degrees of dorsiflexion, while the movement of the sensors was measured using a video motion analysis system. Measurement of the translation between the talus and tibia in the AD test and the angle between the tibia and talus in the TT test were calculated for specimens in the (1) intact, (2) sectioned (division of the ATFL and CFL), (3) Brostrom repair and (4) Gould modification states. RESULTS: When compared to both the repaired states and the intact states, the sectioned state demonstrated increased inversion and translation at all ankle positions during TT and AD testing. Furthermore, no significant differences were found between the intact state and either of the repaired states. Finally, no difference in the biomechanical stability could be identified between the traditional Brostrom repair and the modified Brostrom-Gould procedure. CONCLUSIONS: Our findings indicate that there is no significant biomechanical difference in initial ankle stability conferred by augmenting the traditional Brostrom repair with the Gould modification in this time-zero cadaveric model. CLINICAL RELEVANCE: These data suggest that the additional reinforcement of an ankle's lateral ligament complex repair of the ankle with the inferior extensor retinaculum may be marginal at the time of surgery.

Adolescent patellar osteochondral fracture following patellar dislocation.

PURPOSE: Patellar dislocations in adolescents may cause osteochondral fractures of the patella. The aim of this study was to review the outcomes of adolescent patients who underwent surgical intervention for patellar osteochondral fracture following patellar dislocation. METHODS: Nine patients who underwent surgery for osteochondral fracture of the patella following dislocation were identified retrospectively. Following arthroscopic examination, if the fragment was large enough to support fixation, headless screws or bioabsorbable pins were used. Otherwise, the loose body was excised, and the donor site was managed with a microfracture. Postoperatively, patients were assessed using the International Knee Documentation Committee (IKDC) and Knee injury and Osteoarthritis Outcome Score (KOOS) outcome measures. RESULTS: The average age of the patients was 14.6 with average follow-up 30.2 months. Four of the nine patients underwent fixation, while five patients underwent removal of loose body with microfracture. The average defect size in the nonfixation group was 1.2 cm(2) compared with 3.2 cm(2) in the fixation group. The IKDC scores for fixation and nonfixation groups were 63.9 (SD = 18) and 76.1 (SD = 11.7), respectively. The KOOS subscale scores for symptoms, function in sports and recreation, and knee-related quality of life were higher for the nonfixation group when compared to the fixation group. CONCLUSIONS: This is the first known series examining surgical outcomes of osteochondral fractures of the patella following patellar dislocations in the adolescent population. While patients without fixation were less symptomatic in this series, this may be attributable to more severe injuries in patients undergoing fracture fixation. LEVEL OF EVIDENCE: Retrospective case series, Level IV.

A suppressive oligodeoxynucleotide enhances the efficacy of myelin cocktail/IL-4-tolerizing DNA vaccination and treats autoimmune disease.

Targeting pathogenic T cells with Ag-specific tolerizing DNA vaccines encoding autoantigens is a powerful and feasible therapeutic strategy for Th1-mediated autoimmune diseases. However, plasmid DNA contains abundant unmethylated CpG motifs, which induce a strong Th1 immune response. We describe here a novel approach to counteract this undesired side effect of plasmid DNA used for vaccination in Th1-mediated autoimmune diseases. In chronic relapsing experimental autoimmune encephalomyelitis (EAE), combining a myelin cocktail plus IL-4-tolerizing DNA vaccine with a suppressive GpG oligodeoxynucleotide (GpG-ODN) induced a shift of the autoreactive T cell response toward a protective Th2 cytokine pattern. Myelin microarrays demonstrate that tolerizing DNA vaccination plus GpG-ODN further decreased anti-myelin autoantibody epitope spreading and shifted the autoreactive B cell response to a protective IgG1 isotype. Moreover, the addition of GpG-ODN to tolerizing DNA vaccination therapy effectively reduced overall mean disease severity in both the chronic relapsing EAE and chronic progressive EAE mouse models. In conclusion, suppressive GpG-ODN effectively counteracted the undesired CpG-induced inflammatory effect of a tolerizing DNA vaccine in a Th1-mediated autoimmune disease by skewing both the autoaggressive T cell and B cell responses toward a protective Th2 phenotype. These results demonstrate that suppressive GpG-ODN is a simple and highly effective novel therapeutic adjuvant that will boost the efficacy of Ag-specific tolerizing DNA vaccines used for treating Th1-mediated autoimmune diseases.

Antigen microarray profiling of autoantibodies in rheumatoid arthritis.

OBJECTIVE: Because rheumatoid arthritis (RA) is a heterogeneous autoimmune disease in terms of disease manifestations, clinical outcomes, and therapeutic responses, we developed and applied a novel antigen microarray technology to identify distinct serum antibody profiles in patients with RA. METHODS: Synovial proteome microarrays, containing 225 peptides and proteins that represent candidate and control antigens, were developed. These arrays were used to profile autoantibodies in randomly selected sera from 2 different cohorts of patients: the Stanford Arthritis Center inception cohort, comprising 18 patients with established RA and 38 controls, and the Arthritis, Rheumatism, and Aging Medical Information System cohort, comprising 58 patients with a clinical diagnosis of RA of <6 months duration. Data were analyzed using the significance analysis of microarrays algorithm, the prediction analysis of microarrays algorithm, and Cluster software. RESULTS: Antigen microarrays demonstrated that autoreactive B cell responses targeting citrullinated epitopes were present in a subset of patients with early RA with features predictive of the development of severe RA. In contrast, autoimmune targeting of the native epitopes contained on synovial arrays, including several human cartilage gp39 peptides and type II collagen, were associated with features predictive of less severe RA. CONCLUSION: Proteomic analysis of autoantibody reactivities provides diagnostic information and allows stratification of patients with early RA into clinically relevant disease subsets.

Immunity to the extracellular domain of Nogo-A modulates experimental autoimmune encephalomyelitis.

Nogo-66, the extracellular 66 aa loop of the Nogo-A protein found in CNS myelin, interacts with the Nogo receptor and has been proposed to mediate inhibition of axonal regrowth. It has been shown that immunization with Nogo-A promotes recovery in animal models of spinal cord injury through induction of Ab production. In this report, studies were performed to characterize the immune response to Nogo-66 and to determine the role of Nogo in experimental autoimmune encephalomyelitis (EAE). Immunization of EAE-susceptible mouse strains with peptides derived from Nogo-66 induced a CNS immune response with clinical and pathological similarities to EAE. The Nogo-66 peptides elicited strong T cell responses that were not cross-reactive to other encephalitogenic myelin Ags. Using a large scale spotted microarray containing proteins and peptides derived from a wide spectrum of myelin components, we demonstrated that Nogo-66 peptides also generated a specific Ab response that spreads to several other encephalitogenic myelin Ags following immunization. Nogo-66-specific T cell lines ameliorated established EAE, via Nogo-66-specific Th2 cells that entered the CNS. These results indicate that some T cell and B cell immune responses to Nogo-66 are associated with suppression of ongoing EAE, whereas other Nogo-66 epitopes can be encephalitogenic.

Protein microarrays guide tolerizing DNA vaccine treatment of autoimmune encephalomyelitis.

The diversity of autoimmune responses poses a formidable challenge to the development of antigen-specific tolerizing therapy. We developed 'myelin proteome' microarrays to profile the evolution of autoantibody responses in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS). Increased diversity of autoantibody responses in acute EAE predicted a more severe clinical course. Chronic EAE was associated with previously undescribed extensive intra- and intermolecular epitope spreading of autoreactive B-cell responses. Array analysis of autoantigens targeted in acute EAE was used to guide the choice of autoantigen cDNAs to be incorporated into expression plasmids so as to generate tolerizing vaccines. Tolerizing DNA vaccines encoding a greater number of array-determined myelin targets proved superior in treating established EAE and reduced epitope spreading of autoreactive B-cell responses. Proteomic monitoring of autoantibody responses provides a useful approach to monitor autoimmune disease and to develop and tailor disease- and patient-specific tolerizing DNA vaccines.