Locking vs. non-locking plate fixation in comminuted talar neck fractures: a biomechanical study using cadaveric specimens.

BACKGROUND: Talar neck fractures are rare but potentially devastating injuries, with early reduction and rigid fixation essential to facilitate union and prevent avascular necrosis. Even small degrees of malunion will alter load transmission and subtalar joint kinematics. Changes in fixation techniques have led to dual plating strategies. While locked plating has perceived advantages in porotic bone and comminution, its biomechanical benefits in talar neck fractures have not been shown. AIM: To compare the strength of locking vs. non-locking plate fixation in comminuted talar neck fractures. METHOD: Seven pairs of cadaveric tali were randomised to locking or non-locking plate fixation. A standardised model of talar neck fracture with medial comminution was created, and fixation performed. The fixed specimens were mounted onto a motorised testing device, and an axial load applied. RESULTS: Peak load to failure, deformation at failure, work done to achieve failure, and stiffness of the constructs were measured. No statistically significant difference was found between locking and non-locking constructs for all parameters. CONCLUSIONS: Both constructs provide similar strength to failure in talar neck fracture fixations. Mean peak load to failure did not exceed the theoretical maximum forces generated of 1.1 kN when weight-bearing. We would advocate caution with early mobilisation in both fixations.

Review of Classification Systems for Adult Acquired Flatfoot Deformity/Progressive Collapsing Foot Deformity and the Novel Development of the Triple Classification Delinking Instability/Deformity/Reactivity and Foot Type.

Background: Classifications of AAFD/PCFD have evolved with an increased understanding of the pathology involved. A review of classification systems helps identify deficiencies and respective contributions to the evolution in understanding the classification of AAFD/PCFD. Methods: Using multiple electronic database searches (Medline, PubMed) and Google search, original papers classifying AAFD/PCFD were identified. Nine original papers were identified that met the inclusion criteria. Results: Johnson's original classification and multiple variants provided a significant leap in understanding and communicating the pathology but remained tibialis posterior tendon-focused. Drawbacks of these classifications include the implication of causality, linearity of progression through stages, an oversimplification of stage 2 deformity, and a failure to understand that multiple tendons react, not just tibialis posterior. Later classifications, such as the PCFD classification, are deformity-centric. Early ligament laxity/instability in normal attitude feet and all stages of cavus feet can present with pain and instability with minor/no deformity. These may not be captured in deformity-based classifications. The authors developed the 'Triple Classification' (TC) understanding that primary pathology is a progressive ligament failure/laxity that presents as tendon reactivity, deformity, and painful impingement, variably manifested depending on starting foot morphology. In this classification, starting foot morphology is typed, ligament laxities are staged, and deformity is zoned. Conclusions: This review has used identified deficiencies within classification systems for AAFD/PCFD to delink ligament laxity, deformity, and foot type and develop the 'Triple classification'. Advantages of the TC may include representing foot types with no deformity, defining complex secondary instabilities, delinking foot types, tendon reactivity/ligament instability, and deformity to represent these independently in a new classification system. Level of Evidence: Level V.

The incidence of congenital pseudarthrosis of the clavicle and review of the literature.

The aim of this study was to identify the hitherto unknown incidence of congenital pseudarthrosis of the clavicle (CPC), based on a cohort of continuous livebirths born in our hospital, to review the literature and investigate if there is evidence supporting the published association between left-sided CPC and dextrocardia. From our electronic medical record and radiology databases, we identified all live births and patients with the diagnosis of CPC born from 2000 to 2016. We reviewed the imaging which included one or both clavicles to search for unrecorded CPC cases and reviewed all retrievable CPC publications listed in PubMed and publications quoted within these publications going back to 1910. We identified 87 407 livebirths of which 41 800 had radiological studies done, 14 885 showing one or both clavicles. We found five cases of CPC, two from the electronic database and three from our imaging review, giving an incidence of 1 of 17 481 livebirths. We identified 138 publications reporting paediatric and adult CPC cases and 12 review articles, including 429 patients (187 female; 159 male; 83 unknown) with 456 CPCs and a minimum of 24 additional patients from case reports for which we could not retrieve details. Two publications reported one case of left-sided CPC with dextrocardia, either not showing left/right marking or only showing the CPC with the aortic knob on the same side. We report the first CPC incidence of 0.0057%, provide the by far most inclusive CPC epidemiology based on 429 patients and could not find reliable proof that there has ever been a patient with left-sided CPC which was associated with dextrocardia.

Live births with cerebral palsy at a tertiary maternity hospital: incidence and associated risk factors over a 17-year period.

The aim of this retrospective study was to establish the incidence and associated risk factors for cerebral palsy (CP) at a tertiary maternity hospital in the UK between 2000-2016. We identified CP patients from our electronic coding system using ICD codes. Multiple independent variables for all live births born during this period were included in a univariate and multivariate logistic regression (LR) to identify associations between these and CP. We identified 130 CP children out of 87318 live births. Univariate LR determined male sex, birth weight <2500 g, gestational age of ≤36 weeks, Small-for-gestational-age, 1-and 5-minute Apgar score <9, neonatal intensive care unit (NICU) admission, multiple births, breech, emergency Caesarean section and delivery between 16.00-20.00 as significant risk factors. In the multivariate LG male sex, 1-minute Apgar <9, 5-minute Apgar <5 and admission to NICU remained as significant risk factors. The risk for delivery between 16.00-19.59 was nearly significant. There was a significant association between NICU admission and moderate-severe CP. Our CP incidence of 0.149% is at the lower end of the incidence spectrum of international comparisons.Impact StatementWhat is already known on this subject? The historic reported incidence of cerebral palsy (CP) ranges from 1.1 to 3.6 cases per 1000 live births, with birth weight <2500g, birth <28 weeks of gestation, Apgar scores ≤4 and male sex having been associated with an increased incidence.What do the results of this study add? This is a large series of live births from a tertiary maternity hospital with a comparative low CP incidence of 0.149%, despite the hospital dealing with many complex pregnancies and deliveries. We identified that already an Apgar score of <9 at 1 minute (significant) and births between 16.00-20.00 (non-significant) were associated with an increased risk to develop CP but not with a specific day of the week.What are the implications of these findings for clinical practice and/or future research? Our significant association between a 1-minute Apgar score of <9 and CP stresses the importance of immediate efficient resuscitation already for babies with a 1-minute score as high as 8. The increased CP risk for deliveries between 16.00-19.59 may be linked to staffing issues and needs further exploration.What this paper addsNew data from a single maternity hospitalAnalysis of risk factorsGMFCS distribution.

Development of temporomandibular joint arthritis: The use of animal models.

Osteoarthritis is the most common joint disease affecting roughly one sixth of the human population. It is also the most common arthritis affecting the temporomandibular joint, often leading to severe pain and the inability to masticate. Animal models are essential to investigate the disease in part because they lend themselves to genetic manipulation and various treatments and also because of the lack of availability of human specimens from various stages of the disease. The wide range of osteoarthritis models alone are a proof of its multifactorial origin. Manipulation of collagen, cytokine, matrix metalloproteinase and small leucine-rich repeat proteoglycan genes can all have an effect on the development and persistence of arthritis. Surgical models also exist, highlighting the importance of normal anatomy and trauma. Here we review the English literature of murine models of temporomandibular joint arthritis with special attention to the genetic and molecular background of osteoarthritis.

Of mice and men: how animal models advance our understanding of T-cell function in RA.

The involvement of autoreactive T cells in the pathogenesis of rheumatoid arthritis (RA) as well as in autoimmune animal models of arthritis has been well established; however, unanswered questions, such as the role of joint-homing T cells, remain. Animal models of arthritis are superb experimental tools in demonstrating how T cells trigger joint inflammation, and thus can help to further our knowledge of disease mechanisms and potential therapies. In this Review, we discuss the similarities and differences in T-cell subsets and functions between RA and mouse arthritis models. For example, various T-cell subsets are involved in both human and mouse arthritis, but differences might exist in the cytokine regulation and plasticity of these cells. With regard to joint-homing T cells, an abundance of synovial T cells is present in humans compared with mice. On the other hand, local expansion of type 17 T-helper (TH17) cells is observed in some animal models, but not in RA. Finally, whereas T-cell depletion therapy essentially failed in RA, antibody targeting of T cells can work, at least preventatively, in most arthritis models. Clearly, additional human and animal studies are needed to fill the gap in our understanding of the specific contribution of T-cell subsets to arthritis in mice and men.

In vivo two-photon imaging of T cell motility in joint-draining lymph nodes in a mouse model of rheumatoid arthritis.

Recent imaging studies on intact lymph nodes (LNs) of naïve T cell receptor (TCR)-transgenic mice have reported that T cells reduce their motility upon contact with relevant antigen-presenting cells (APCs). Using in vivo two-photon imaging of T cells in joint-draining (JD) LNs, we examined whether similar changes in T cell motility are observed in wild type mice. Co-transfer of T cells from naïve mice and antigen-experienced T cells from mice with proteoglycan (PG)-induced arthritis into naïve or arthritic recipients resulted in prolonged interactions of antigen-experienced T cells with APCs upon intra-articular antigen (PG) injection, indicating that T cells from arthritic wild type mice recapitulate the motile behavior reported in naïve TCR-transgenic mice. However, naïve T cells also engaged in stable interactions with APCs in the JDLNs of arthritic recipients, suggesting an enhanced ability of APCs in the JDLNs of arthritic hosts to present antigen to either naïve or antigen-experienced T cells.

B7-H1 expression on non-B and non-T cells promotes distinct effects on T- and B-cell responses in autoimmune arthritis.

The immune system has developed several regulatory mechanisms to maintain homeostasis of adaptive immune responses. T-cell programmed death (PD)-1 recognition of B7-H1 (PD-L1) expressed on APC and non-lymphoid tissue regulates T-cell activation. We show that B7-H1(-/-) mice exhibit exacerbated proteoglycan (PG)-induced arthritis and increased Th-1 CD4(+) T-cell responses. Unexpectedly, the PG-specific antibody response in B7-H1(-/-) mice was diminished. A reduction in the number of peanut agglutinin(+) GC coincided with a decrease in CD19(+) GL-7(+) CD95(+) GC B cells that was a result of increased caspase-induced apoptosis. The percent of CD38(+) CD138(+) emerging plasma cells was decreased. B7-H1(-/-) mice exhibited an increased frequency of CD4(+) PD-1(hi) CXCR5(hi) ICOS(hi) CD62L(lo) T follicular helper cells that displayed a hyperactive phenotype with increased expression of mRNA transcripts for Bcl6, IL-21, and the apoptosis-inducer molecule FasL. In cell transfer of B7-H1(-/-) cells into SCID mice, non-B and non-T cells were sufficient to normalize the antibody response, T-cell hyperactivity, and the development of PG-induced arthritis. These findings indicate that B7-H1 on non-B and non-T cells signals through PD-1 on T effector cells to prevent excessive activation and reduce autoimmune arthritis. Furthermore, these findings demonstrate a novel role for B7-H1 expression in promoting B-cell survival by regulating the activation of T follicular helper cell.

Development of proteoglycan-induced arthritis depends on T cell-supported autoantibody production, but does not involve significant influx of T cells into the joints.

INTRODUCTION: Inflammatory joint destruction in rheumatoid arthritis (RA) may be triggered by autoantibodies, the production of which is supported by autoreactive T cells. Studies on RA and animal models of the disease suggest that T cells recruited in the joints can locally initiate or propagate arthritis. Herein, we investigated the role of joint-homing versus lymphoid organ-homing T cells in the development of proteoglycan-induced arthritis (PGIA), an autoimmune model of RA. METHODS: To identify T cells migrating to the joints before and during development of autoimmune arthritis, we transferred fluorescence-labeled T cells, along with antigen-presenting cells, from BALB/c mice with PGIA to naïve syngeneic severe combined immunodeficient (SCID) mice. We then monitored the recruitment of donor T cells in the ankle joints and joint-draining lymph nodes of the recipients using in vivo two-photon microscopy and ex vivo detection methods. To limit T-cell access to the joints, we selectively depleted T cells in the blood circulation by treatment with FTY720, an inhibitor of lymphocyte egress from lymphoid organs. Reduction of T cell presence in both lymphoid organs and blood was achieved by injection of donor cells from which T cells were removed prior to transfer. T and B cells were quantitated by flow cytometry, and antigen (PG)-specific responses were assessed by cell proliferation and serum antibody assays. RESULTS: Despite development of adoptively transferred arthritis in the recipient SCID mice, we found very few donor T cells in their joints after cell transfer. Treatment of recipient mice with FTY720 left the T-cell pool in the lymphoid organs intact, but reduced T cells in both peripheral blood and joints. However, FTY720 treatment failed to inhibit PGIA development. In contrast, arthritis was not seen in recipient mice after transfer of T cell-depleted cells from arthritic donors, and serum autoantibodies to PG were not detected in this group of mice. CONCLUSIONS: Our results suggest that antigen-specific T cells, which home to lymphoid organs and provide help to B cells for systemic autoantibody production, play a greater role in the development and progression of autoimmune arthritis than the small population of T cells that migrate to the joints.

CCR5 is involved in resolution of inflammation in proteoglycan-induced arthritis.

OBJECTIVE: CCR5 and its ligands (CCL3, CCL4, and CCL5) may play a role in inflammatory cell recruitment into the joint. However, it was recently reported that CCR5 on T cells and neutrophils acts as a decoy receptor for CCL3 and CCL5 to assist in the resolution of inflammation. The aim of this study was to determine whether CCR5 functions as a proinflammatory or antiinflammatory mediator in arthritis, by examining the role of CCR5 in proteoglycan (PG)-induced arthritis (PGIA). METHODS: Arthritis was induced by immunizing wild-type (WT) and CCR5-deficient (CCR5(-/-)) BALB/c mice with human PG in adjuvant. The onset and severity of PGIA were monitored over time. Met-RANTES was used to block CCR5 in vivo. Arthritis was transferred to SCID mice, using spleen cells from arthritic WT and CCR5(-/-) mice. The expression of cytokines and chemokines was measured by enzyme-linked immunosorbent assay. RESULTS: In CCR5(-/-) mice and WT mice treated with the CCR5 inhibitor Met-RANTES, exacerbated arthritis developed late in the disease course. The increase in arthritis severity in CCR5(-/-) mice correlated with elevated serum levels of CCL5. However, exacerbated arthritis was not intrinsic to the CCR5(-/-) lymphoid cells, because the arthritis that developed in SCID mouse recipients was similar to that in WT and CCR5(-/-) mice. CCR5 expression in the SCID mouse was sufficient to clear CCL5, because serum levels of CCL5 were the same in SCID mouse recipients receiving cells from either WT or CCR5(-/-) mice. CONCLUSION: These data demonstrate that CCR5 is a key player in controlling the resolution of inflammation in experimental arthritis.